CN101898982A - Npy y5拮抗剂 - Google Patents
Npy y5拮抗剂 Download PDFInfo
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- CN101898982A CN101898982A CN2010101570894A CN201010157089A CN101898982A CN 101898982 A CN101898982 A CN 101898982A CN 2010101570894 A CN2010101570894 A CN 2010101570894A CN 201010157089 A CN201010157089 A CN 201010157089A CN 101898982 A CN101898982 A CN 101898982A
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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Abstract
本发明提供NPY Y5受体拮抗剂,它们包含通式(I)代表的化合物、其前药、药学上可接受的盐或溶剂化物,其中R1是低级烷基、环烷基等;R2是氢、低级烷基等;n是1或2;X是低级亚烷基、低级亚链烯基、亚芳基、亚环烷基等;Y是CONR7、CSNR7、NR7CO、NR7CS等(其中R7表示氢或低级烷基);及Z是低级烷基、任选取代的烃环基、任选取代的杂环基等。
Description
本申请是以下申请的分案申请:申请日2000年11月21日,申请号00815998.X(PCT/JP00/08197),标题“NPY Y5拮抗剂”。
技术领域
本发明涉及一种用作NPY Y5受体拮抗剂的药用组合物,更详细地讲,是抗肥胖剂以及具有抗肥胖活性的新化合物。
背景技术
神经肽Y(以下称为NPY)是一种由36个氨基酸残基组成的肽,1982年从猪脑中分离出来。NPY广泛分布于人和动物的中枢神经系统和外周组织中。
已报道NPY在中枢神经系统中具有刺激食物摄取活性、抗癫痫发作活性、促进学习活性、抗焦虑活性、抗压力活性等,并且它可能主要与中枢神经系统疾病有关,如抑郁症、阿尔茨海默氏病和帕金森氏病。由于NPY可诱发外周组织中的平滑肌如血管或心肌收缩,所以认为它与心血管疾病有关。另外,还知道NPY与代谢疾病有关,如肥胖症、糖尿病和激素异常(Trends in Pharmacological Sciences,Vol.15,and 153(1994))。因此,期待NPY受体拮抗剂作为预防或治疗与NPY受体有关的各种疾病的药物。
目前已证实Y1、Y2、Y3、Y4、Y5和Y6亚型为NPY受体(Trendsin Pharmacological Sciences,Vol.18,and 372(1997))。一直认为Y5受体至少与饮食行为有关,期待其拮抗剂可作为抗肥胖剂(Peptides,Vol.18,and 445(1997))。
WO97/20820、WO97/20821、WO97/20823等中介绍了与本发明 化合物结构类似并且呈现NPY受体拮抗活性的喹唑啉化合物。另外,WO 99/64349中公开的具有磺酰胺基的脲衍生物和具有磺酰基的酰胺衍生物以及EP 1010691-A中公开的苄基磺酰胺衍生物,均具有NPY拮抗活性。
JP59-16871-A和WO97/15567中公开与本发明化合物结构类似的化合物。这些化合物的活性与本发明化合物的活性有显著差别,这些文献并未提到本发明的内容。
发明公开
本发明的主题是提供用作NPY Y5受体拮抗剂的优良的药用组合物以及具有该活性的新化合物。
本发明提供:
[1]一种用作NPY Y5受体拮抗剂的药用组合物,它包含式(I)化合物、其前药、药学上可接受的盐或溶剂化物:
其中R1是任选取代的低级烷基、任选取代的环烷基或任选取代的芳基,
R2是氢或低级烷基,并且R1和R2可一起形成低级亚烷基,
n是1或2,
X是任选取代的低级亚烷基、任选取代的低级亚链烯基、任选取代的-CO-低级亚烷基、任选取代的-CO-低级亚链烯基或者
其中R3、R4、R5和R6各自独立是氢或低级烷基,
是任选取代的亚环烷基、任选取代的亚环烯基、任选取代的亚双环烷基、任选取代的亚芳基或任选取代的杂环二基,p和q各自独立是0或1,
-NR2-X-可以是
其中
是哌啶二基、哌嗪二基、吡啶二基、吡嗪二基、吡咯烷二基或吡咯二基,U是单键、低级亚烷基或者低级亚链烯基,
Y是OCONR7、CONR7、CSNR7、NR7CO或者NR7CS,
R7是氢或低级烷基,和
Z是任选取代的低级烷基、任选取代的低级链烯基、任选取代的氨基、任选取代的低级烷氧基、任选取代的碳环基或任选取代的杂环基,[2][1]中说明的用作NPY Y5受体拮抗剂的药用组合物,其中R2是氢或低级烷基,Z是任选取代的低级烷基、任选取代的低级链烯基、任选取代的低级烷氧基、任选取代的碳环基、任选取代的杂环基或者任选取代的氨基,条件是当Z是任选取代的氨基时,R1是任选取代的C3-C10烷基,
[3][1]中说明的用作NPY Y5受体拮抗剂的药用组合物,其中R1是任选取代的低级烷基或任选取代的环烷基,X是任选取代的低级亚烷基、任选取代的低级亚链烯基或者
其中
定义与[1]中相同,和
Z是任选取代的低级烷基、任选取代的碳环基或任选取代的杂环基,
[4][1]-[3]中任一项说明的用作NPY Y5受体拮抗剂的药用组合物,其中R1是任选取代的C3-C10烷基,
[5][1]-[4]中任一项说明的用作NPY Y5受体拮抗剂的药用组合物,它是抗肥胖剂,
[6][1]-[4]中任一项说明的用作NPY Y5受体拮抗剂的药用组合物,它是减食欲剂,
[7]一种治疗和/或预防肥胖症的方法,该方法包括给予有效剂量的[1]-[4]中任一项说明的NPY Y5受体拮抗剂,
[8]一种抑制食物摄取的方法,该方法包括给予有效剂量的[1]-[4]中任一项说明的NPY Y5受体拮抗剂,
[9]应用[1]-[4]中任一项说明的NPY Y5受体拮抗剂制备用于治疗和/或预防肥胖症的药物,
[10]应用[1]-[4]中任一项说明的NPY Y5受体拮抗剂制备用于抑制食物摄取的药物,
[11]一种式(I)化合物、其前药、药学上可接受的盐或溶剂化物:
其中X是C2-C6亚烷基或C3-C6亚链烯基,R1是任选取代的C3-C10烷基或任选取代的C5-C6环烷基,其余符号与[1]中定义相同,条件是当Y是NR7CO时,Z不是低级烷基苯基氨基、羟基(低级)烷基苯基氨基和酰基苯基氨基,
[12][11]中说明的化合物、其前药、药学上可接受的盐或溶剂化物,其中Z是任选取代的低级烷基或任选取代的苯基,
[13]一种式(I)化合物、其前药、药学上可接受的盐或溶剂化物:
其中X是
是任选取代的亚环烷基、任选取代的亚环烯基、任选取代的亚双环烷基或任选取代的亚哌啶基,R1是任选取代的C3-C10烷基或任选取代的C5-C6环烷基,其余符号与[1]中定义相同,
[14][13]中说明的化合物、其前药、药学上可接受的盐或溶剂化物,其中
是任选取代的亚环己基或者任选取代的亚哌啶基,p和q同时为0,
[15][13]或[14]中说明的化合物、其前药、药学上可接受的盐或溶剂化物,其中Y是CONH,
[16][13]-[15]中任一项说明的化合物、其前药、药学上可接受的盐或溶剂化物,其中Z是任选取代的低级烷基、任选取代的苯基、任选取代的吡啶基或任选取代的苯并吡喃基,
[17]一种式(I)化合物、其前药、药学上可接受的盐或溶剂化物:
其中X是
R1是任选取代的C3-C10烷基或任选取代的C5-C6环烷基,Z是对-(低级)烷基苯基,其余符号与[1]中定义相同,条件是当R1是异丙基时,Z不是对正丁基苯基,
[18]一种式(I)化合物、其前药、药学上可接受的盐或溶剂化物:
其中X是
是亚杂芳基,R1是任选取代的C3-C10烷基或任选取代的C5-C6环烷基,其余符号与[1]中定义相同,
[19][18]中说明的化合物、其前药、药学上可接受的盐或溶剂化物,其中
是噻吩二基或呋喃二基,和
[20]一种药用组合物,它包含[11]-[19]中任一项说明的化合物、其前药、药学上可接受的盐或溶剂化物。
实施本发明的最佳方式
在本说明书中,术语“卤素”包括氟、氯、溴和碘,优选氟或氯。
在“任选保护的羟基”和“任选保护的羟基(低级)烷基”中的术语“保护基”包括所有常用的羟基保护基。例如,包括酰基如乙酰基、三氯乙酰基和苯甲酰基,低级烷氧基羰基如叔丁氧基羰基,低级烷基磺酰基如甲磺酰基,低级烷氧基(低级)烷基如甲氧基甲基,三烷基甲硅烷基如叔丁基二甲基甲硅烷基。
术语“低级烷基”包括C1-C10直链或支链烷基。“低级烷基”的实例是甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、己基、异己基、正庚基、异庚基、正辛基、异辛基、正壬基和正癸基。
R1代表的“低级烷基”优选是C3-C10烷基,更优选C3-C6烷基,最优选异丙基或叔丁基。
其它情况下,“低级烷基”优选是C1-C6烷基,更优选C1-C4烷基。
Z代表的“任选取代的低级烷基”的取代基的实例是(1)卤素;(2)氰基;
(3)下列基团(i)-(xvi),它们可任选被一个或更多个选自以下定义的“取代基组β”的取代基取代,
(i)羟基,(ii)低级烷氧基,(iii)巯基,(iv)低级烷硫基,(v)酰基,(vi)酰氧基,(vii)羧基,(viii)低级烷氧基羰基,(ix)亚氨基,(x)氨基甲酰基,(xi)硫代氨基甲酰基,(xii)低级烷基氨基甲酰基,(xiii)低级烷硫基氨基甲酰基,(xiv)氨基,(xv)低级烷基氨基或者(xvi) 杂环基羰基;或者
(4)下式基团:
其中R10和R11各自独立是氢或低级烷基,当该基团具有两个或两个以上R10和/或两个或两个以上R11时,各R10和/或R11可以不同,
W是单键、O、S或NR12,
R12是氢、低级烷基或苯基,
是环烷基、双环烷基、环烯基、芳基或杂环基,它们各自可任选被一个或更多个选自以下定义的“取代基组α”的取代基取代,以及s是0-4的整数。
在本说明书中,“取代基组α”为由下列基团组成的组:(1)卤素;(2)氧代基;(3)氰基;(4)硝基;(5)任选由低级烷基或羟基取代的亚氨基;
(6)下列基团(i)-(xxi),它们可任选被一个或更多个选自取代基组β的基团取代,
(i)羟基,(ii)低级烷基,(iii)低级链烯基,(iv)低级烷氧基,(v)羧基,(vi)低级烷氧基羰基,(vii)酰基,(viii)酰氧基,(ix)亚氨基,(x)巯基,(xi)低级烷硫基,(xii)氨基甲酰基,(xiii)低级烷基氨基甲酰基,(xiv)环烷基氨基甲酰基,(xv)硫代氨基甲酰基,(xvi)低级烷基硫代氨基甲酰基,(xvii)低级烷基亚硫酰基,(xviii)低级烷基磺酰基,(xix)氨基磺酰基,(xx)低级烷基氨基磺酰基和(xxi)环烷基氨基磺酰基;
(7)下列基团(i)-(v),它们可任选被取代基组β、低级烷基、低级烷氧基(低级)烷基、任选被保护的羟基(低级)烷基、卤代(低级)烷基,低级烷基磺酰基和/或芳基磺酰基取代,
(i)环烷基,(ii)环烯基,(iii)环烷基氧基,(iv)氨基和(v)亚烷基二 氧基;以及
(8)下列基团(i)-(xii),它们可任选被取代基组β、低级烷基、卤代(低级)烷基和/或氧代基取代,
(i)苯基,(ii)萘基,(iii)苯氧基,(iv)苯基(低级)烷氧基,(v)苯硫基,(vi)苯基(低级)烷硫基,(vii)苯基偶氮基,(viii)杂环基,(ix)杂环氧基,(x)杂环硫基,(xi)杂环羰基和(xii)杂环磺酰基。
作为B环取代基的取代基组α的优选实例是卤素;硝基;羟基;任选取代的低级烷基,其中该取代基是卤素、氰基、苯基、羧基和/或低级烷氧基羰基;低级链烯基;低级烷氧基羰基(低级)链烯基;任选取代的低级烷氧基,其中该取代基是卤素、羟基、低级烷氧基、羧基、低级烷氧基羰基、低级烷基氨基和/或氰基;酰基;羟基亚氨基;低级烷硫基;低级烷基亚硫酰基;氨基磺酰基;任选取代的氨基,其中该取代基是低级烷基、任选被保护的羟基(低级)烷基、苯基和/或酰基;亚烷基二氧基;氰基苯基;杂环基苯基;联苯基;苯氧基;任选被低级烷基取代的苯偶氮基;或者任选取代的杂环基,其中该取代基是任选被保护的羟基、巯基、卤素、低级烷基、环烷基、低级烷氧基羰基、氨基、低级烷氧基羰基氨基、氨基甲酰基、氧代基、苯基、低级烷氧基苯基或杂环基。更优选的实例是卤素;任选被卤素取代的低级烷基;或任选被卤素取代的低级烷氧基。
“取代基组β”为由下列基团组成的组:卤素、任选被保护的羟基、巯基、低级烷氧基、低级链烯基、氨基、低级烷基氨基、低级烷氧基羰基氨基、低级烷硫基、酰基、羧基、低级烷氧基羰基、氨基甲酰基、氰基、环烷基、苯基、苯氧基、低级烷基苯基、低级烷氧基苯基、卤代苯基、萘基和杂环基。
除Z外,任何其它(例如R1)代表“任选取代的低级烷基”的取代基的实例是一个或更多个选自取代基组β的取代基。该低级烷基可在任何可能的位置被这些取代基取代。
“低级烷氧基”、“低级烷氧基羰基”、“低级烷氧基羰基(低 级)烷基”、“低级烷基苯基”、“低级烷氧基苯基”、“低级烷基氨基甲酰基”、“低级烷基硫代氨基甲酰基”、“低级烷基氨基”、“卤代(低级)烷基”、“羟基(低级)烷基”、“苯基(低级)烷氧基”、“低级烷硫基”、“苯基(低级)烷硫基”、“低级烷氧基羰基氨基”、“低级烷氧基羰基(低级)链烯基”、“低级烷基亚硫酰基”、“低级烷基磺酰基”、“芳基(低级)烷氧基羰基”、“低级烷基苯甲酰基”和“低级烷氧基苯甲酰基”中的低级烷基部分与以上“低级烷基”中的定义相同。
“任选取代的低级烷氧基”的取代基实例是一个或更多个选自取代基组β的取代基。优选的实例是苯基、低级烷基苯基、低级烷氧基苯基、萘基和杂环基。
术语“环烷基”包括C3-C8环烷基,优选C5-C6环烷基。实例是环丙基、环丁基、环戊基、环己基、环庚基和环辛基。
“任选取代的环烷基”的取代基实例是一个或更多个选自取代基组α的取代基,该环烷基可在任何可能的位置被这些取代基取代。
术语“双环烷基”包括从含有共同具有两个或两个以上原子的双环的C5-C8脂族环中,除去一个氢原子形成的基团。实施例为双环[2.1.0]戊基、双环[2.2.1]庚基、双环[2.2.2]辛基和双环[3.2.1]辛基。
术语“低级链烯基”包括在任何可能位置上具有一个或更多个双键的C2-C10,优选C2-C8,更优选C3-C6直链或支链链烯基。实例是乙烯基、丙烯基、异丙烯基、丁烯基、异丁烯基、异戊(间)二烯基、丁二烯基、戊烯基、异戊烯基、戊二烯基、己烯基、异己烯基、己二烯基、庚烯基、辛烯基、壬烯基和癸烯基。
“低级烷氧基羰基(低级)链烯基”中的“低级链烯基”部分定义与以上“低级链烯基”中的定义相同。
“任选取代的低级链烯基”的取代基实例是卤素、低级烷氧基、低级链烯基、氨基、低级烷基氨基、低级烷氧基羰基氨基、低级烷硫基、酰基、羧基、低级烷氧基羰基、氨基甲酰基、氰基、环烷基、苯 基、低级烷基苯基、低级烷氧基苯基、萘基和/或杂环基。
术语“酰基”包括(1)C1-C10,优选C1-C6,更优选C1-C4直链或支链烷基羰基或链烯基羰基,(2)C4-C9,优选C4-C7环烷基羰基以及(3)C3-C11芳基羰基。实例为甲酰基、乙酰基、丙酰基、丁酰基、异丁酰基、戊酰基、新戊酰基、己酰基、丙烯酰基、丙酰基、异丁烯酰基、丁烯酰基、环丙基羰基、环己基羰基、环辛基羰基和苯甲酰基。
“酰氧基”中的“酰基”部分定义同上。
术语“环烯基”包括在以上环烷基的任何可能位置上具有至少一个双键的基团。实例是环丙烯基、环丁烯基、环戊烯基、环己烯基和环己二烯基。
“任选取代的环烯基”的取代基实例是一个或更多个选自取代基组β的取代基。
“任选取代的氨基”的取代基实例是取代基组β、任选取代的苯甲酰基和/或任选取代的杂环基羰基,其中该取代基是羟基、低级烷基、低级烷氧基和/或低级烷硫基。
术语“芳基”包括单环或多环芳族碳环基团,实例是苯基、萘基、蒽基和菲基。“芳基”包括与其它非芳族碳环基稠合的芳基,如2,3-二氢化茚基、茚基、联苯基、苊基(acenaphthyl)、四氢萘基和芴基。优选苯基。
“芳基低级烷氧基羰基”中的芳基部分定义同上。
Z代表的术语“任选取代的芳基”和“任选取代的苯基”分别包括以上的“芳基”和“苯基”,它们可被取代基组α或低级烷基取代,该低级烷基可被一个或更多个选自取代基组α的基团取代。
除Z外,任何其它代表“任选取代的芳基”和“任选取代的苯基”的取代基的实例是一个或更多个选自取代基组β的基团。
术语“碳环基”包括以上的“环烷基”、“环烯基”、“双环烷基”和“芳基”。
术语“非芳族碳环基”包括以上的“环烷基”、“环烯基”、和 “双环烷基”。
术语“任选取代的碳环基”包括以上的“任选取代的环烷基”、“任选取代的环烯基”、“任选取代的双环烷基”和“任选取代的芳基”。
术语“杂环基”包括含有至少一个任意选自O、S和N的杂原子的杂环基团。例如,5-或6-元杂芳基,如吡咯基、咪唑基、吡唑基、吡啶基、哒嗪基、嘧啶基、噁唑基、噁二唑基、异噻唑基、噻唑基、噻二唑基、呋喃基和噻吩基;含有两个环的稠合杂环基,如吲哚基、异吲哚基、吲唑基、中氮茚基、二氢吲哚基、异二氢吲哚基、喹啉基、异喹啉基、肉啉基、2,3-二氮杂萘基、喹唑啉基、1,5-二氮杂萘基、喹喔啉基、嘌呤基、蝶啶基、苯并吡喃基、苯并咪唑基、苯并异噁唑基、苯并噁唑基、苯并噁二唑基、苯并异噻唑基、苯并噻唑基、苯并噻二唑基、苯并呋喃基、异苯并呋喃基、苯并噻吩基、苯并三唑基、咪唑并吡啶基、三唑并吡啶基、咪唑并噻唑基、吡嗪并哒嗪基、喹唑啉基、喹啉基、异喹啉基、1,5-二氮杂萘基、二氢吡啶基、四氢喹啉基和四氢苯并噻吩基;由三个环组成的稠合杂环基,如咔唑基、吖啶基、呫吨基、吩噻嗪基、吩氧硫杂环己烯基(phenoxathiinyl)、吩噁嗪基和二苯并呋喃基;以及非芳族杂环基,如二噁烷基、硫杂丙环基、环氧乙烷基、氧硫杂戊环基(oxathiolanyl)、氮杂环丁烷基、thianyl、吡咯烷基、吡咯啉基、咪唑烷基、咪唑啉基、吡唑烷基、吡唑啉基、哌啶基、哌嗪基、吗啉基、吗啉代、硫代吗啉基、硫代吗啉代、二氢吡啶基、四氢呋喃基、四氢吡喃基、四氢噻唑基和四氢异噻唑基。
与一个非杂环的环稠合的“稠合杂环基”(如苯并噻唑基)可在任何可能的位置上连接。
“任选取代的杂环基”的取代基与以上“任选取代的芳基”的那些取代基定义相同。
“杂环基羰基”、“杂环基氧基”、“杂环基硫基”和“杂环基取代的苯基”中的杂环基部分与以上“杂环基”定义相同。
术语“低级亚烷基”包括含有1-6个亚甲基的二价基团,优选含2-6个亚甲基,更优选含3-6个亚甲基。例如,包括亚甲基、亚乙基、1,3-亚丙基、1,4-亚丁基、1,5-亚戊基和1,6-亚己基。优选1,4-亚丁基。
“低级亚烷基二氧基”中的低级亚烷基部分与以上“低级亚烷基”定义相同。优选亚甲基二氧基或亚乙基二氧基。
术语“低级亚链烯基”包括含有2-6个亚甲基,优选含3-6个亚甲基,更优选含4-5个亚甲基,并且包含至少一个双键的二价基团。
术语“亚环烷基”包括从以上“环烷基”中除去一个氢原子形成的二价基团。X代表的亚环烷基的优选实例是1,4-环己烷二基。
术语“亚环烯基”包括在以上亚环烷基中含有至少一个双键的基团。
术语“亚双环烷基”包括从以上“双环烷基”中除去一个氢原子形成的基团。实例是亚双环[2.1.0]戊基、亚双环[2.2.1]庚基、亚双环[2.2.2]辛基和亚双环[3.2.1]辛基。
术语“杂环二基”包括从以上“杂环基”中除去一个氢原子形成的二价基团。优选哌啶二基、哌嗪二基、吡啶二基、嘧啶二基、吡嗪二基、吡咯烷二基或吡咯二基,更优选哌啶二基。
术语“亚芳基”包括从以上“芳基”中除去一个氢原子形成的二价基团。优选亚苯基。
术语“杂亚芳基”包括以上“杂环二基”中的芳族基团。实例是吡咯二基、咪唑二基、吡唑二基、吡啶二基、哒嗪二基、嘧啶二基、吡嗪二基、三唑二基、三嗪二基、异噁唑二基、噁唑二基、噁二唑二 基、异噻唑二基、噻唑二基、噻二唑二基、呋喃二基和噻吩二基。
一个或更多个选自取代基组β的基团是“任选取代的低级亚烷基”、“任选取代的低级亚链烯基”、“任选取代的亚环烷基”、“任选取代的亚环己基”、“任选取代的亚双环烷基”、“任选取代的亚环烯基”、“任选取代的亚苯基”、“任选取代的杂环二基”和“任选取代的亚哌啶基”的取代基实例。优选卤素、羟基、低级烷基、卤代(低级)烷基、低级烷氧基、氨基、低级烷基氨基、酰基、羧基或低级烷氧基羰基。这些取代基可连接在任何可能的位置上。
当-NR2-X-是
U优选是单键或亚甲基。更优选
本发明化合物包括任何能形成的及其药学上可接受的盐。“药学上可接受的盐”的实例是无机酸盐,如盐酸、硫酸、硝酸和磷酸盐;有机酸盐,如对甲苯磺酸、甲磺酸、草酸和柠檬酸盐;有机碱盐,如铵、三甲基铵和三乙基铵盐;碱金属盐,如钠和钾盐;以及碱土金属盐,如钙和镁盐。
本发明化合物包括其溶剂化物。优选水合物,任意数量的水分子可与本发明化合物配位。
本发明化合物包括其前药。前药包括本发明化合物的衍生物,该衍生物具有化学上或代谢上可分解的基团,并能通过水解或者在生理条件下,在体内转化成本发明的药学活性化合物。选择及制备适当前药的方法可见Design of Prodrugs,Elsevier,Amsterdam 1985所述。
当本发明化合物(I)具有羧基时,前药的实例是酯衍生物和酰胺衍 生物,其可通过使具有羧基的化合物(I)分别与适当的醇或适当的胺反应制备。
当本发明化合物(I)具有羟基时,前药的实例是酰氧基衍生物,其可通过使具有羟基的化合物(I)与适当的酰卤或适当的酸酐反应合成。
当本发明化合物(I)具有氨基时,前药的实例是酰胺衍生物,其可通过使具有氨基的化合物(I)与适当的酰卤或适当的混酸酐反应合成。
当本发明化合物(I)具有不对称碳原子时,它包括外消旋体、所有的对映体和所有的立体异构体,如其非对映体、差向异构体和对映体。
当具有一个或更多个双键的本发明化合物(I)形成E异构体或Z异构体时,化合物(I)包括这两种异构体。当X是亚环烷基时,化合物(I)包括顺式异构体和反式异构体。
例如,本发明化合物(I)可通过下列方法合成。
(化合物,其中Y=CONR7)
其中Hal是卤素,Q是氨基保护基,其它符号定义同上。
步骤A
在0-50℃下,在适当的溶剂中,使化合物1与具有所要求取代基Z和R7的氨基化合物2反应数分钟至数小时。作为溶剂,可使用四氢呋喃、二甲基甲酰胺、乙醚、二氯甲烷、甲苯、苯、二甲苯、环己烷、己烷、氯仿、乙酸乙酯、乙酸丁酯、戊烷、庚烷、二氧六环、丙酮、乙腈、水及其混合物等。如果必要,可使用活性剂,如亚硫酰氯、酰卤、酸酐和活性酯。
步骤B
通过常用的方法使化合物3脱保护,然后在0-50℃下,在适当的溶剂中,使其与具有所要求取代基R1的磺酰卤4反应数分钟至数小时,得到化合物(I-A),其中n是2。作为溶剂,可使用四氢呋喃、二甲基甲酰胺、乙醚、二氯甲烷、甲苯、苯、二甲苯、环己烷、己烷、氯仿、乙酸乙酯、乙酸丁酯、戊烷、庚烷、二氧六环、丙酮、乙腈、水及其混合物等。
步骤C
通过化合物3与具有取代基R1的磺酰卤5反应,可合成化合物(I-B),其中n是1。该反应的反应条件与以上步骤B的相同。
步骤D
通过常用的方法,将步骤C中得到的化合物(I-B)氧化,得到化合物(I-A),其中n是2。作为氧化剂,可使用间氯过氧苯甲酸、过乙酸、过氧化氢、三氟过乙酸、高碘酸钠、次氯酸钠、高锰酸钾等,该反应可在0-50℃下进行。溶剂的实例为四氢呋喃、二甲基甲酰胺、乙醚、二氯甲烷、甲苯、苯、二甲苯、环己烷、己烷、氯仿、乙酸乙酯、乙酸丁酯、戊烷、庚烷、二氧六环、丙酮、乙腈、水、甲醇、乙醇、异丙醇及其混合物。
当X是含有至少一个N原子的杂环二基,并且该N原子与化合物(I)中的CONR7-Z相连时,可采用以下反应得到化合物(I-A’)或(I-B’)。可在步骤C或步骤E之后立刻进行步骤D。
其中R是低级烷基或芳基,L是离去基团。
步骤C
可按与以上步骤C类似的方法,使化合物5与化合物6反应,得到化合物7。
步骤E
在适当的溶剂中,将如此得到的化合物7用碱处理,生成化合物8。作为碱,可使用例如氢氧化钡、氢氧化钠、氢氧化钾、肼或丙硫醇锂。作为溶剂,可使用四氢呋喃、二甲基甲酰胺、二氧六环、丙酮、乙腈、甲醇、乙醇、丙醇、水及其混合物等。该反应可在0-100℃下 进行数分钟至数十小时。
步骤F
在0-100℃下,在适当的溶剂中,在碱存在或不存在下,使化合物8与具有离去基团和所要求取代基的化合物9反应数分钟至数日,生成化合物(I-B’)。离去基团的实例是苯氧基、氯代基和三氯甲基。碱的实例是三乙胺、吡啶、二异丙基乙胺、氢氧化钠、碳酸钾和碳酸氢钠。溶剂的实例是四氢呋喃、二甲基甲酰胺、乙醚、二氯甲烷、甲苯、苯、二甲苯、环己烷、己烷、氯仿、乙酸乙酯、乙酸丁酯、戊烷、庚烷、二氧六环、丙酮、乙腈、甲醇、乙醇及其混合物。
步骤D
可按与以上步骤D类似的方法,使化合物(I-B’)反应生成化合物(I-A’)。
(化合物,其中Y=NR7CO)
其中各符号定义同上。
步骤G和步骤B
在与步骤B相同的反应条件下,使化合物10与化合物11反应。按与以上步骤B类似的方法,使如此得到的化合物12反应,生成化合物(I-C),其中n=2。
步骤C和步骤D
按与以上步骤C和步骤D类似的方法,使在步骤G中得到的化合物12反应,合成化合物(I-D)。
(化合物,其中Y=OCONR7)
其中各符号定义同上。
步骤H
在0-100℃下,在适当的溶剂中,在适当的催化剂存在或不存在下,使化合物13与具有取代基Z的异氰酸酯化合物14反应数分钟至数日,生成化合物15。溶剂的实例是四氢呋喃、二甲基甲酰胺、乙醚、二氯甲烷、甲苯、苯、二甲苯、环己烷、己烷、氯仿、乙酸乙酯、乙酸丁酯、戊烷、庚烷、二氧六环、丙酮、乙腈及其混合物。
步骤C和步骤D
可按与步骤C和步骤D类似的方法,使如此得到的化合物15反应生成本发明的化合物(I-E)。
(化合物,其中Y=CSNR7或NR7CS)
在30-100℃下,在适当的溶剂中,通过使用以上任何方法之一合成的化合物(I)(其中Y是CONR7或NR7CO)与Lawesson氏试剂或五硫化二磷反应数分钟至数小时,可合成化合物(I),其中Y是CSNR7或NR7CS。溶剂实例是四氢呋喃、二甲基甲酰胺、乙醚、二氯甲烷、甲苯、苯、二甲苯、环己烷、己烷、氯仿、乙酸乙酯、乙酸丁酯、戊烷、庚烷、二氧六环、丙酮、乙腈及其混合物。
在适当步骤中,采用常用的方法,可将氨基用适当的保护基保护。例如,可使用邻苯二甲酰亚胺、低级烷氧基羰基、低级链烯基氧基羰基、卤代烷氧基羰基、芳基(低级)烷氧基羰基、三烷基甲硅烷基、低级烷基磺酰基、卤代(低级)烷基磺酰基、芳基磺酰基、低级烷基羰基和芳基羰基作为保护基。
将氨基保护后,可使化合物经过以上提到的反应,然后在适当的阶段,在适当的溶剂中,通过用酸或碱处理,将得到的化合物脱保护。溶剂实例是四氢呋喃、二甲基甲酰胺、乙醚、二氯甲烷、甲苯、苯、二甲苯、环己烷、己烷、氯仿、乙酸乙酯、乙酸丁酯、戊烷、庚烷、二氧六环、丙酮、乙腈及其混合物。碱的实例是肼、吡啶、氢氧化钠和氢氧化钾,酸的实例是盐酸、三氟乙酸和氢氟酸。
本发明所有化合物都具有NPY Y5拮抗活性,特别优选以下化合物。
在式(I)中,
化合物,其中R1是任选取代的低级烷基或任选取代的环烷基(以下称之为“R1是R1-1”),
化合物,其中R1是C3-C10烷基或C5-C6环烷基,其各自可被卤素任选 取代(以下称之为“R1是R1-2”),
化合物,其中R1是任选被卤素取代的C3-C10烷基(以下称之为“R1是R1-3”),
化合物,其中R1是异丙基或叔丁基(以下称之为“R1是R1-4”),
化合物,其中R2是氢或C1-C3烷基(以下称之为“R2是R2-1”),
化合物,其中R2是氢(以下称之为“R2是R2-2”),
化合物,其中X是任选取代的低级亚烷基、任选取代的低级亚链烯基或者
其中
是任选取代的亚环烷基、任选取代的亚环烯基、任选取代的亚双环烷基、任选取代的亚苯基或者任选取代的杂环二基(以下称之为“X是X-1”),
化合物,其中X是C2-C6亚烷基、C3-C6亚链烯基或者
其中
是任选取代的亚环烷基、任选取代的亚环烯基、任选取代的亚双环烷基、任选取代的亚苯基、任选取代的亚哌啶基、任选取代的噻吩二基或者任选取代的呋喃二基(以下称之为“X是X-2”),
化合物,其中X是C2-C6亚烷基或者
其中
是任选取代的亚环烷基、任选取代的亚苯基、任选取代的亚哌啶基、任选取代的噻吩二基或者任选取代的呋喃二基(以下称之为“X是X-3”),
化合物,其中X是(i)C2-C6亚烷基或者(ii)亚环烷基或亚苯基,其各自可任选被卤素、羟基、低级烷基或者卤代(低级)烷基取代(以下称之为“X是X-4”),
化合物,其中X是C2-C6亚烷基或C5-C6亚环烷基(以下称之为“X是X-5”),
化合物,其中X是C3-C6亚烷基或1,4-亚环己基(以下称之为“X是X-6”),
化合物,其中Y是CONR7、CSNR7、NR7CO或者NR7CS,R7是氢或者C1-C3烷基(以下称之为“Y是Y-1”),
化合物,其中Y是CONH、CSNH或者NHCO(以下称之为“Y是Y-2”),
化合物,其中Y是CONH(以下称之为“Y是Y-3”),
化合物,其中Z是任选取代的低级烷基、任选取代的碳环基或者任选取代的杂环基(以下称之为“Z是Z-1”),
化合物,其中Z是-(CR8R9)r-W-(CR10R11)s-V
其中R8、R9、R10和R11各自独立是氢或低级烷基,当Z具有两个或两个以上R8、两个或两个以上R9、两个或两个以上R10和/或两个或两个以上R11时,R8、R9、R10和R11各自可以不同,W是单键、O、S或NR12,R12是氢、低级烷基或苯基,V是氢、 任选取代的环烷基、任选取代的双环烷基、任选取代的芳基或任选取代的杂环基,r是1-4的整数,s是0-4的整数
(以下称之为“Z是Z-2”),
化合物,其中Z是-(CH2)r-W-(CH2)s-V
其中W是单键、O、S或NR12,R12是氢或低级烷基,V是任选取代的芳基或任选取代的杂环基,其中该取代基是卤素、羟基、低级烷基、卤代(低级)烷基、低级烷氧基、低级链烯基、氨基、低级烷基氨基、酰基、羧基、低级烷氧基羰基、苯基或单环杂芳基,r是1-4的整数,s是0-4的整数
(以下称之为“Z是Z-3”),
化合物,其中Z是-(CH2)r-W-(CH2)s-V
其中W是单键、O、S、NH或NMe,V是任选取代的苯基或任选取代的杂芳基,其中该取代基是卤素、低级烷基、卤代(低级)烷基、低级烷氧基、氨基或低级烷基氨基,r是1-3的整数,s是0或1的整数
(以下称之为“Z是Z-4”),
化合物,其中Z是任选取代的碳环基,
其中该取代基是卤素;羟基;任选取代的低级烷基,其中该取代基是卤素、羟基、羧基、低级烷氧基羰基、氰基和/或苯基;任选由低级烷氧基羰基取代的低级链烯基;任选取代的低级烷氧基,其中该取代基是卤素、羟基、低级烷氧基、羧基、低级烷氧基羰基、低级烷基氨基、环烷基、氰基和/或杂环基;环烷基;环烷氧基;酰基;低级烷硫基;氨基甲酰基;低级烷基氨基甲酰基;环烷基氨基甲酰基;羟基亚氨基;任选取代的氨基,其中该取代基是低级烷基、任选被保护的羟基(低级)烷基、低级烷氧基 (低级)烷基、酰基、低级烷基磺酰基、芳基磺酰基和/或苯基;任选被卤素、氰基、苯基和/或杂环基取代的苯基;低级烷基亚硫酰基;低级烷基氨基磺酰基;环烷基氨基磺酰基;硝基;氰基;亚烷基二氧基;任选被低级烷基取代的苯基偶氮基;苯氧基;氧代基;任选取代的杂环基,其中该取代基是任选被保护的羟基、巯基、卤素、低级烷基、环烷基、低级烷氧基羰基、酰基、氨基、低级烷氧基羰基氨基、氨基甲酰基、氧代基、苯基、低级烷氧基苯基、卤代苯基、杂环基和/或氧代基;任选被低级烷基取代的杂环基磺酰基;杂环基氧基;任选被低级烷基取代的杂环羰基
(以下称之为“Z是Z-5”)
化合物,其中Z是任选取代的苯基
其中该取代基是卤素;羟基;任选被卤素、羟基、低级烷氧基羰基、氰基和/或苯基取代的低级烷基;低级烷氧基羰基(低级)链烯基;任选被卤素、低级烷氧基、低级烷氧基羰基、环烷基和/或杂环基取代的低级烷氧基;环烷基;环烷基氧基;酰基;低级烷硫基;氨基甲酰基;低级烷基氨基甲酰基;任选被低级烷基、羟基(低级)烷基、酰基、低级烷基磺酰基和/或苯基取代的氨基;任选被卤素、氰基、苯基和/或杂环基取代的苯基;低级烷基氨基磺酰基;环烷基氨基磺酰基;硝基;亚烷基二氧基;任选被低级烷基取代的苯基偶氮基;苯氧基;氧代基;任选被羟基、卤素、低级烷基、低级烷氧基羰基、氨基、氨基甲酰基、苯基、卤代苯基、杂环基和/或氧代基取代的杂环基;杂环基氧基;和/或任选被低级烷基取代的杂环基磺酰基
(以下称之为“Z是Z-6”),
化合物,其中Z是任选取代的苯基
其中该取代基是卤素;任选被卤素、羟基、低级烷氧基羰基和/ 或苯基取代的低级烷基;任选被卤素和/或环烷基取代的低级烷氧基;环烷基;环烷基氧基;酰基;低级烷硫基;低级烷基氨基甲酰基;任选被低级烷基、羟基(低级)烷基、酰基和/或苯基取代的氨基;任选被哌啶基取代的苯基;环烷基氨基磺酰基;亚烷基二氧基;苯氧基;吗啉基或吗啉代,其各自可任选被低级烷基取代;任选被羟基、低级烷基、低级烷氧基羰基、苯基、卤代苯基和/或氧代基取代的哌啶基;任选被羟基、氨基甲酰基和/或氧代基取代的吡咯烷基;任选被苯基或嘧啶基取代的哌嗪基;二氢吡啶基;吡咯基;吡咯啉基;任选被卤素和/或低级烷基取代的咪唑基;吡唑基;噻吩基;噻二唑基;呋喃基;噁唑基;异噁唑基;任选被低级烷基和/或苯基取代的四唑基;二氢吲哚基;吲哚基;四氢喹啉基;任选被低级烷基取代的苯并噻唑基;任选被氧代基取代的四氢异噻唑基;任选被氧代基取代的苯并吡喃基;四氢吡喃氧基;四氢呋喃氧基;任选被低级烷基取代的吗啉代磺酰基;和/或任选被低级烷基取代的哌啶磺酰基
(以下称之为“Z是Z-7”),
化合物,其中Z是任选取代的苯基
其中该取代基是卤素、低级烷基、卤代(低级)烷基、低级烷氧基、环烷氧基、低级烷基氨基甲酰基、苯基、低级烷基吗啉代和/或四氢吡喃氧基
(以下称之为“Z是Z-8”),
化合物,其中Z是任选取代的杂环基
其中该取代基是卤素、羟基、低级烷基、卤代(低级)烷基、低级烷氧基、巯基、低级烷硫基、酰基、羧基、低级烷氧基羰基、氨基、低级烷基氨基、苯基、萘基、任选被卤素取代的苯硫基、任选被卤素取代的苯氧基、氧代基和/或任选被低级烷基取代的杂 环基
(以下称之为“Z是Z-9”),
化合物,其中Z是噻吩基、吡唑基、噻唑基、噻二唑基、吡啶基、嘧啶基、吡嗪基、三嗪基、吲哚基、异吲哚基、二氢吲哚基、异二氢吲哚基、吲唑基、苯并吡喃基、苯并噁唑基、苯并噻吩基、苯并噻唑基、苯并噻唑啉基、苯并噻二唑基、喹啉基、异喹啉基、二氢苯并呋喃基、咔唑基、吖啶基或二苯并呋喃基,其各自可任选被选自以下的取代基取代:低级烷基;卤代(低级)烷基;低级烷氧基;低级烷氧基羰基;酰基;低级烷氧基羰基(低级)烷基;巯基;各自可任选被卤素取代的苯基、萘基、苯硫基或苯氧基;呋喃基;硝基;氧代基和任选被低级烷基取代的吗啉代(以下称之为“Z是Z-10”),
化合物,其中Z是噻吩基、噻唑基、噻二唑基、吡啶基、吡嗪基、吲哚基、异二氢吲哚基、苯并吡喃基、喹啉基、咔唑基、二苯并呋喃基、苯并吡喃基、苯并噻吩基或苯并噻唑基,其各自可任选被一个或更多个选自低级烷基、卤代(低级)烷基、低级烷氧基、低级烷氧基羰基、酰基、苯基、萘基、苯硫基、低级烷基吗啉代和氧代基的取代基取代(以下称之为“Z是Z-11”),
化合物,其中R1是R1-2,R2是R2-2,n是2,X、Y和Z的组合即(X、Y、Z)是以下任何一种:
(X、Y、Z)=(X-3,Y-2,Z-1),(X-3,Y-2,Z-2),(X-3,Y-2,Z-3),(X-3,Y-2,Z-4),(X-3,Y-2,Z-5),(X-3,Y-2,Z-6),(X-3,Y-2,Z-7),(X-3,Y-2,Z-8),(X-3,Y-2,Z-9),(X-3,Y-2,Z-10),(X-3,Y-2,Z-11),(X-3,Y-3,Z-1),(X-3,Y-3,Z-2),(X-3,Y-3,Z-3),(X-3,Y-3,Z-4),(X-3,Y-3,Z-5),(X-3,Y-3,Z-6),(X-3,Y-3,Z-7),(X-3,Y-3,Z-8),(X-3,Y-3,Z-9),(X-3,Y-3,Z-10),(X-3, Y-3,Z-11),(X-4,Y-2,Z-1),(X-4,Y-2,Z-2),(X-4,Y-2,Z-3),(X-4,Y-2,Z-4),(X-4,Y-2,Z-5),(X-4,Y-2,Z-6),(X-4,Y-2,Z-7),(X-4,Y-2,Z-8),(X-4,Y-2,Z-9),(X-4,Y-2,Z-10),(X-4,Y-2,Z-11),(X-4,Y-3,Z-1),(X-4,Y-3,Z-2),(X-4,Y-3,Z-3),(X-4,Y-3,Z-4),(X-4,Y-3,Z-5),(X-4,Y-3,Z-6),(X-4,Y-3,Z-7),(X-4,Y-3,Z-8),(X-4,Y-3,Z-9),(X-4,Y-3,Z-10),(X-4,Y-3,Z-11),(X-5,Y-2,Z-1),(X-5,Y-2,Z-2),(X-5,Y-2,Z-3),(X-5,Y-2,Z-4),(X-5,Y-2,Z-5),(X-5,Y-2,Z-6),(X-5,Y-2,Z-7),(X-5,Y-2,Z-8),(X-5,Y-2,Z-9),(X-5,Y-2,Z-10),(X-5,Y-2,Z-11),(X-5,Y-3,Z-1),(X-5,Y-3,Z-2),(X-5,Y-3,Z-3),(X-5,Y-3,Z-4),(X-5,Y-3,Z-5),(X-5,Y-3,Z-6),(X-5,Y-3,Z-7),(X-5,Y-3,Z-8),(X-5,Y-3,Z-9),(X-5,Y-3,Z-10)或(X-5,Y-3,Z-11),
其药学上可接受的盐、溶剂化物或前药。
本发明的NPY Y5受体拮抗剂对所有与NPY Y5有关的疾病均有效,尤其可用于预防和/或治疗肥胖症和抑制食物摄取。此外,该拮抗剂能有效预防和/或治疗其中肥胖作为危险因素的疾病,如糖尿病、高血压、高脂血症、动脉粥样硬化和急性冠状动脉综合征。
另外,本发明的NPY Y5受体拮抗剂对NPY Y1和Y2受体具有较低的亲和力,并对NPY Y5受体具有高选择性。在外周循环中,NPY能引起持续性血管收缩,该作用主要通过Y1受体进行。由于Y5受体根本不涉及该作用,所以NPY Y5受体拮抗剂对由外周血管收缩引起的副作用具有较低的风险,并期待适合作为安全用药。
NPY Y5受体拮抗剂通过抑制食物摄取显示出抗肥胖作用。因此,该拮抗剂的一个特征是不诱发副作用,如由抑制消化和吸收的抗肥胖药引起的消化不良,以及中枢系统的副作用,如由呈现抗肥胖作用的5-羟色胺转运蛋白抑制剂引起的抗抑郁作用。
本发明化合物可作为抗肥胖药或减食欲剂口服或非肠道给予。口 服给药时,可采用任何常用的形式,如片剂、颗粒剂、散剂、胶囊剂、丸剂、溶液剂、糖浆剂、口含片和舌下片形式。当非肠道给予该化合物时,优选任何常用的形式,如注射剂(如静脉、肌内注射剂)、栓剂、经皮剂和吸入剂。由于本发明化合物呈现出高的口服吸收性,所以特别优选口服给药。
药用组合物可通过将有效量的本发明化合物与各种适于给药形式的药用添加剂,如赋形剂、粘合剂、湿润剂、崩解剂、润滑剂和稀释剂混合制备。当组合物为注射剂时,可将活性组分与适当的载体一起灭菌制得药用组合物。
赋形剂的实例包括乳糖、蔗糖、葡萄糖、淀粉、碳酸钙和晶体纤维素。粘合剂的实例包括甲基纤维素、羧甲基纤维素、羟丙基纤维素、明胶和聚乙烯吡咯烷酮。崩解剂的实例包括羧甲基纤维素、羧甲基纤维素钠、淀粉、藻酸钠、琼脂和十二烷基硫酸钠。润滑剂的实例包括滑石粉、硬脂酸镁和聚乙二醇(macrogol)。可用可可油、聚乙二醇、甲基纤维素等作为栓剂基质材料。当将该组合物制成溶液剂、乳化注射剂或混悬注射剂时,可加入溶解加速剂、悬浮剂、乳化剂、稳定剂、防腐剂、等渗剂等。对于口服给药,可加入甜味剂、矫味剂等。
虽然本发明化合物作为抗肥胖药或减食欲剂的剂量应根据患者的年龄和体重、疾病的类型和程度、给药途径等确定,但是成人的一般口服剂量是0.05-100mg/kg/日,优选0.1-10mg/kg/日。对于非肠道给药,虽然其剂量随给药途径高度变化,但是一般剂量是0.005-10mg/kg/日,优选0.01-1mg/kg/日。该剂量可分每日一至多次给予。
本发明可通过下列实施例和实验进一步说明,但它们并不限制本发明的范围。
实施例
实施例1化合物(I-7)的合成
步骤1
将碳酸钠(995mg,9.38mmol)溶于30ml水中,向其中加入原料氨基酸(1.0g,8.53mmol)和N-乙酯基邻苯二甲酰亚胺(2.49g,11.4mmol)。室温下将混合液搅拌过夜。加入浓盐酸,将混合液pH调节至1。将沉淀的晶体用水洗涤,干燥得到所要求的化合物(1.72g,82%收率)。 1H NMR(CD3OD)δppm:1.59-1.77(m,4H),2.34(t,2H,J=6.3Hz),3.69(t,2H,J=6.6Hz),7.78-7.87(m,4H)。
步骤2
室温下,将步骤1得到的化合物(1.0g,4.0mmol)溶于5ml二氯甲烷中。冰浴冷却下,向该混合液中加入草酰氯(0.459ml,5.2mmol)和微量DMF,在冰浴冷却和室温下,使混合物各反应30分钟。减压除去溶剂后,加入5ml二氯甲烷。冰浴冷却下,向其中加入4-丁基苯胺(664mg,4.4mmol)和三乙胺(0.564ml,4.4mmol),室温下使混合液反应30分钟。将反应物倒入水中,用氯仿提取。将有机层用水洗涤,经无水硫酸镁干燥。减压除去溶剂,残留物经硅胶层析纯化得到所要求的化合物(1.49g,97%收率)。
1H NMR(CDCl3)δppm:0.91(t,3H,J=7.5Hz),1.27-1.39(m,2H),1.51-1.62(m,2H),1.72-1.84(m,4H),2.40-2.46(m,2H),2.56(t,2H,J=7.5Hz),3.76(t,1H,J=5.7Hz),7.12(d,2H,J=7.8Hz),7.33(s,1H),7.42(d,2H,J=8.1Hz),7.71-7.73(m,2H),7.83-7.86(m,2H)。
步骤3
将步骤2得到的化合物(1.49g,3.9mmol)溶于30ml乙醇中,然后加入单水合肼(0.591mg,11.8mmol),在50℃下,使混合液反应3小时。除去溶剂,加入1mol/l NaOH水溶液,将该溶液用乙酸乙酯提取。将有机层用水洗涤,经无水硫酸镁干燥。减压除去溶剂,得到所要求的化合物(808mg,83%收率)。
1H-NMR(CD3OD)δppm:0.93(t,3H,J=7.2Hz),1.28-1.40(m,2H),1.50-1.62(m,4H),1.67-1.77(m,2H),2.37(t,2H,J=7.5Hz),2.56(t,2H,J=7.8Hz),2.68(t,2H,J=7.2Hz),7.11(d,2H,J=8.1Hz),7.42(d,2H,J=8.4Hz)。
步骤4
冰浴冷却下,将步骤3得到的化合物(808mg,3.25mmol)混悬于5ml二氯甲烷中,加入异丙基磺酰氯(696mg,4.9mmol)和三乙胺(494mg,4.9mmol)。冰浴冷却下,使混合液反应1小时,然后将反应物倒入水中,用氯仿提取。将有机层用水洗涤,经无水硫酸镁干燥。减压除去溶剂,残留物经硅胶层析纯化定量得到所要求的化合物。
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.27-1.40(m,2H),1.36(d,6H,J=6.6Hz),1.51-1.69(m,4H),1.77-1.86(m,2H),2.38(t,2H,J=7.2Hz),2.56(t,2H,J=7.5Hz),3.12-3.21(m,3H),4.38(t,1H,J=5.7Hz),7.11(d,2H, J=8.4Hz),7.36-7.41(m,3H)。
实施例2化合物(I-10)的合成
按实施例1步骤4类似的方法,但将叔丁基亚硫酰氯(689mg,4.9mmol)和三乙胺(494mg,4.9mmol)加入到实施例1步骤3得到的化合物中,合成所要求的化合物。
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.5Hz),1.22(s,9H),1.30-1.37(m,2H),1.51-1.68(m,4H),1.76-1.86(m,2H),2.31-2.40(m,2H),2.56(t,2H,J=7.5Hz),3.15-3.26(m,3H),7.11(t,2H,J=8.7Hz),7.42(d,2H,J=8.1Hz),7.54(s,1H)。
实施例3化合物(I-11)的合成
冰冷却下,将实施例2得到的化合物(352mg,1.0mmol)溶于5ml二氯甲烷中,向该溶液中加入mCPBA(259mg,1.5mmol)。室温下,使该溶液反应1小时,滤除不溶物。将滤液用1mol/l NaOH、Na2S2O5和水顺次洗涤,经无水硫酸镁干燥。减压除去溶剂,残留物经硅胶层析纯化,得到所要求的化合物(338mg,92%收率)。
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.5Hz),1.29-1.39(m,2H),1.39(s,9H),1.51-1.68(m,4H),1.76-1.84(m,2H),2.37(t,2H,J=7.5Hz),2.56(t,2H,J=7.8Hz),3.19-3.26(m,2H),4.20(t,1H,J=5.7Hz),7.11(t,2H, J=8.1Hz),7.42(d,2H,J=8.7Hz),7.46(s,1H)。
实施例4化合物(I-72)的合成
步骤1
将原料氨基酸(顺式和反式异构体的混合物)(1.0g,8.53mmol)溶于7.5ml甲醇中。冰冷却下,向该混合液中加入亚硫酰氯(1.0ml,13.7mmol),室温下将混合液搅拌过夜。将该混合液减压浓缩,加入乙醚,过滤得到的沉淀结晶。将该晶体用乙醚洗涤,干燥得到所要求的化合物(1.25g,93%收率)。
1H-NMR(CDCl3)δppm:1.50-2.60(m,9H),3.08-3.36(m,1H),3.67(s,3H,顺式异构体的CO2Me),3.71(s,3H,反式异构体的CO2Me),8.15-8.55(m,3H)。
步骤2
根据实施例1步骤3和实施例2类似的方法,用原料甲酯,合成所要求的磺酰胺(顺式异构体和反式异构体的混合物)。
顺式异构体
1H-NMR(CDCl3)δppm:1.39(s,9H),1.52-1.99(m,8H),2.43-2.53(m,1H),3.42-3.55(m,1H),3.69(s,3H),3.85(d,1H,J=9.0Hz)。
步骤3
将原料磺酰胺(19.4g,70.0mmol,顺式和反式异构体的混合物)溶于30ml甲醇中。向该混合液中加入28%甲醇钠(284ml,140.0mmol),冰冷却下搅拌回流。除去溶剂,然后将残留物用氯仿稀释,冰冷却搅拌下加入1mol/l HCl直至水层pH达到3。将水层用氯仿提取,将有机层用水洗涤,经无水硫酸镁干燥。将得到的粗品晶体用己烷-乙酸乙酯重结晶,得到所要求的磺酰胺(反式异构体,7.75g,40%收率)。
反式异构体
1H-NMR(CD3OD)δppm:1.16-1.32(m,2H),1.39(s,9H),1.44-1.52(m,2H),1.98-2.09(m,2H),2.14-2.29(m,3H),3.18-3.37(m,1H),3.63(d,1H,J=9.0Hz),3.67(s,3H)。
步骤4
将原料甲酯(4.77g,17.2mmol)溶于95ml甲醇中,冰冷却、搅拌下,加入1mol/l NaOH(43ml,43.0mmol)。室温下,将该混合液搅拌过夜,减压浓缩。冰冷却、搅拌下,加入1mol/l HCl直至混合物pH达到3,过滤收集沉淀的结晶,用水洗涤,干燥。将得到的粗品结晶用己烷-乙酸乙酯重结晶,得到所要求的羧酸(4.20g,93%收率)。
1H-NMR(CDCl3)δppm:1.18-1.35(m,2H),1.39(s,9H),1.46-1.63(m,2H),2.01-2.14(m,2H),2.14-2.32(m,3H),3.18-3.35(m,1H),3.80(d,1H,J=9.6Hz)。
步骤5
室温下,将原料羧酸(5.86g,22.3mmol)溶于88ml二氯甲烷中。冰冷却下,向该混合液中加入草酰氯(2.34ml,26.7mmol)和催化量的DMF,室温下搅拌1小时。减压除去溶剂,然后加入二氯甲烷(115ml)、取代的苯胺(5.05g,24.5mmol)和三乙胺(4.65ml,33.4mmol)。室温下,将该混合液搅拌2.5小时,向其中加入冰冷却的水,将该混合液用氯仿提取。将有机层用水洗涤,经无水硫酸镁干燥。减压除去溶剂,向残留物中加入乙酸乙酯和己烷。过滤收集沉淀的晶体,得到所要求的酰胺(7.00g,70%收率)。
1H-NMR(CDCl3)δppm:1.25(d,6H,J=6.3Hz),1.17-1.42(m,2H),1.40(s, 9H),1.60-1.78(m,2H),1.98-2.43(m,7H),3.20-3.43(m,3H),3.67(d,1H,J=9.6Hz),3.74-3.86(m,2H),6.86(d,2H,J=9.0Hz),7.04(s,1H),7.38(d,2H,J=9.0Hz)。
实施例5化合物(I-2)的合成
步骤1
冰冷却下,将原料二胺(461mg,2.5mmol)混悬于二氯甲烷中,加入酰氯(500mg,2.5mmol)和三乙胺(773mg,7.5mmol),使该混合液反应30分钟。向反应物中加入水和二氯甲烷,滤除不溶物。将有机层用水洗涤,经无水硫酸镁干燥。减压除去溶剂,得到残留物,为所要求的化合物(100mg,15%收率)。
1H NMR(CDCl3)δppm:0.93(t,3H,J=7.2Hz),1.30-1.42(m,2H),1.57-1.67(m,2H),2.66(t,2H,J=7.8Hz),3.50(brs,1H),6.57(s,1H),6.68(d,2H,J=8.7Hz),7.26(d,2H,J=8.4Hz),7.39(d,2H,J=8.7Hz),7.68(s,1H),7.75(d,2H,J=8.1Hz)。
步骤2
按实施例1步骤4类似的方法,合成所要求的化合物。
1H-NMR(CDCl3)δppm:0.94(t,3H,J=7.5Hz),1.34-1.44(m,2H),1.40(d,6H,J=6.6Hz),1.59-1.68(m,2H),2.69(t,2H,J=7.8Hz),3.24-3.35(m,1H),6.49(s,1H),7.23-7.32(m,4H),7.6(d,2H,J=8.7Hz),7.79(d,2H,J=8.1Hz),7.85(s,1H)。
实施例6化合物(I-31)的合成
步骤1
室温下,将原料二胺(8.37g,73.3mmol)溶于30ml二氧六环中,加入Boc2O(2g,9.2mmol)的二氧六环(30ml)溶液。室温下,使该混合液反应3日,除去溶剂。向残留物中加入水,将该混合液用氯仿提取。将有机层用水洗涤,经无水硫酸镁干燥。减压除去溶剂,得到残留物,为所要求的化合物(1.8g,以Boc2O计92%收率)。
1H NMR(CDCl3)δppm:1.07-1.26(m,6H),1.44(s,9H),1.84-2.00(m,4H),2.58-2.67(m,1H),3.37(brs,1H),4.43(brs,1H)。
步骤2
按实施例5步骤1类似的方法,合成所要求的化合物。
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.2Hz),1.26-1.42(m,6H),1.45(s,9H),1.54-1.68(m,2H),1.99-2.12(m,4H),2.64(t,2H,J=7.8Hz),3.43(brs,1H),3.90-4.00(m,1H),4.48(d,1H,J=5.7Hz),5.95(d,1H,J=8.4Hz),7.21(d,2H,J=8.4Hz),7.65(d,2H,J=8.4Hz)。
步骤3
冰冷却下,将原料Boc化合物(2.08g,5.55mmol)溶于20ml乙酸乙酯中,加入20ml的4mol/l HCl/AcOEt。使该混合液在室温下反应1小时,减压除去溶剂,得到残留物,为所要求的化合物(1.7g,98%收率)。
1H-NMR(CD3OD)δppm:0.93(t,3H,J=7.2Hz),1.29-1.41(m,2H),1.50-1.66(m,6H),2.02-2.18(m,4H),2.66(t,2H,J=7.8Hz),3.13(brs,1H),3.82-3.94(m,1H),7.26(d,2H,J=8.7Hz),7.72(d,2H,J=8.4Hz)。
步骤4
按实施例1步骤4类似的方法,合成所要求的化合物。
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.5Hz),1.21(s,9H),1.28-1.62(m,8H),2.07-2.14(m,4H),2.64(t,2H,J=7.8Hz),3.11(d,1H,J=5.1Hz),3.20(brs,1H),3.90-4.04(m,1H),6.06-6.14(m,1H),7.21(t,2H,J=8.1Hz),7.67(t,2H,J=8.4Hz)。
实施例7化合物(I-32)的合成
按实施例3类似的方法,用实施例6得到的化合物,合成所要求的化合物。
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.2Hz),1.27-1.65(m,8H),1.40(s,9H),2.10-2.23(m,4H),2.65(t,2H,J=7.5Hz),3.23-3.35(m,1H),3.49(s,1H),3.88-4.02(m,1H),5.84-5.92(m,1H),7.13(t,2H,J=8.4Hz),7.65(d,2H,J=8.1Hz)。
实施例8化合物(I-5)的合成
步骤1
按实施例1步骤2类似的方法,合成所要求的化合物。
1H NMR(CDCl3)δppm:0.94(t,3H,J=7.5Hz),1.30-1.42(m,2H),1.50-1.65(m,2H),2.61(t,2H,J=7.8Hz),7.20(d,2H,J=7.2Hz),7.48-7.51(m,3H),7.72(s,1H),7.88-7.90(m,1H)。
步骤2
向原料硝基化合物(593mg,1.95mmol)和锡(358mg,3.0mmol)的混合物中,加入30ml 6mol/l HCl和6ml THF,在50℃下反应3小时。冷却,然后除去溶剂,将残留物用10%NaOH中和,用氯仿提取。将有机层用水洗涤,经无水硫酸镁干燥。减压除去溶剂,残留物经硅胶层析纯化,得到所要求的化合物(110mg,21%收率)。
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.26-1.39(m,2H),1.49-1.59(m,2H),2.50(t,2H,J=7.8Hz),4.37(s,1H),6.65(d,2H,J=8.4Hz),6.97(d,2H,J=8.4Hz),7.14(d,1H,J=8.4Hz),7.43(d,1H,J=8.7Hz)。
步骤3
按实施例1步骤4类似的方法,合成所要求的化合物。
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.2Hz),1.28-1.41(m,2H),1.46(d,6H,J=6.9Hz),1.53-1.63(m,2H),2.59(t,2H,J=7.8Hz),3.35-3.44(m,1H),7.15(d,2H,J=8.7Hz),7.38(s,1H),7.45(d,2H,J=8.7Hz),7.57(s,1H)。
实施例9化合物(I-4)的合成
步骤1
按实施例1步骤4的类似方法,合成所要求的化合物。
1H NMR(CDCl3)δppm:1.44(d,6H,J=6.9Hz),3.33-3.43(m,1H),3.88(s,9H),6.24-6.26(m,1H),7.11-7.14(m,2H)。
步骤2
按实施例4步骤4类似的方法,合成所要求的化合物。
1H-NMR(CDCl3)δppm:1.44(d,6H,J=6.3Hz),3.33-3.45(m,1H),6.25-6.28(m,1H),7.27-7.28(m,1H),7.51(s,1H)。
步骤3
按实施例1步骤2类似的方法,合成所要求的化合物。
1H-NMR(CD3OD)δppm:0.92(t,3H,J=6.9Hz),1.28-1.41(m,2H),1.46(d,6H,J=6.3Hz),1.53-1.63(m,2H),2.58(t,2H,J=7.8Hz),3.33-3.43(m,1H),6.27-6.29(m,1H),7.14-7.16(m,3H),7.50(d,2H,J=8.4Hz),7.90(s,1H)。
实施例10化合物(I-28)的合成
步骤1
按实施例1步骤1类似的方法,合成所要求的化合物。
1H-NMR(CDCl3)δppm:1.37-1.52(m,3H),1.74-1.79(m,2H),2.07-2.13(m,2H),2.28-2.42(m,2H),3.72-3.81(m,1H),4.09-4.20(m,1H),7.68-7.73(m,2H),7.81-7.85(m,2H)。
步骤2
将异氰酸4-丁基苯酯(2.85g,16.3mmol)溶于30ml THF中,加入原料醇(1.0g,4.08mmol)和氧化二(三丁基锡)(972mg,1.63mmol)。将混合物搅拌过夜后,除去溶剂,加入水,将该溶液用氯仿提取。将有机层用水洗涤,经无水硫酸镁干燥。减压除去溶剂,残留物经硅胶层析纯化,得到所要求的化合物(332mg,19%收率)。
1H-NMR(CDCl3)δppm:0.92(t,3H,J=6.9Hz),1.30-1.40(m,2H),1.48-1.62(m,4H),1.79-1.83(m,2H),2.21-2.25(m,2H),2.37-2.50(m,2H),2.57(t,2H,J=7.8Hz),4.11-4.22(m,1H),4.77-4.87(m,1H),6.49(s,1H),7.11(d,2H,J=8.7Hz),7.28(d,2H,J=8.7Hz),7.69-7.73(m,2H),7.80-7.84(m,2H)。
步骤3
按实施例1步骤3和实施例2类似的方法,合成所要求的化合物。
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.21(s,9H),1.30-1.62(m,8H),2.08(d,4H,J=11.1Hz),2.56(t,2H,J=7.8Hz),3.04(d,1H,J=4.8Hz), 3.20-3.30(m,1H),4.65-4.76(m,1H),6.57(s,1H),7.10(d,2H,J=8.7Hz),7.26(d,2H,J=8.1Hz)。
实施例11化合物(I-29)的合成
按实施例3类似的方法,合成所要求的化合物。
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.23-1.62(m,8H),1.40(s,9H),2.12(d,4H,J=14.4Hz),2.56(t,2H,J=7.8Hz),3.28-3.40(m,1H),3.90(s,1H),4.60-4.73(m,1H),6.57(s,1H),7.10(d,2H,J=8.4Hz),7.25(d,2H,J=8.4Hz)。
实施例12化合物(I-114)的合成
向按实施例1类似方法合成的100mg化合物(I-110)的甲苯(2.7ml)溶液中,加入Lawesson氏试剂[2,4-双(4-甲氧基苯基)-1,3-二硫代-2,4-二磷烷-2,4-二硫化物](132mg),在80℃下,将该混合物搅拌3小时。减压浓缩反应物,残留物经硅胶层析(乙酸乙酯∶正己烷=1∶1)纯化,得到浅黄色晶体(82.3mg,79%)。将该晶体用二氯甲烷-二异丙基醚重结晶,得到所要求的化合物,为无色针状物(50.5mg,48%)。
实施例13化合物(I-120)的合成
步骤1
将4-氨基-1-哌啶甲酸乙酯(300mg)和三乙胺(258mg)溶于5ml二氯甲烷中。向该混合液中加入2ml叔丁基亚硫酰氯(222mg)的二氯甲烷溶液,室温下将该混合液搅拌4小时。将该溶液在硫酸氢钾水溶液和乙酸乙酯之间分配。将有机层用盐水洗涤,经无水硫酸镁干燥。减压除去溶剂,残留物经硅胶层析纯化,得到378mg的4-叔丁基亚硫酰基氨基-1-乙氧基羰基哌啶。
步骤2
在5ml 2-丙醇和5ml水混合液中,混悬入378mg的4-叔丁基亚硫酰基氨基-1-乙氧基羰基哌啶,加入1.77g氢氧化钡。搅拌、加热下,将该混合液回流4小时。将混合液用甲醇稀释,滤除不溶物。减压除去溶剂得到4-叔丁基亚硫酰基氨基哌啶。不需纯化,将得到的物质溶于5ml THF中,加入984mg N-苯氧基羰基-4-丁基苯胺和236mg二异丙基乙胺,然后在室温下搅拌过夜。向该混合液中加入硫酸氢钾水溶液,将混合液用乙酸乙酯提取。将有机层用盐水洗涤,经无水硫酸镁干燥。减压除去溶剂,残留物经硅胶层析纯化,得到291mg 4-叔丁基亚硫酰基氨基哌啶-1-甲酸(4-叔丁基苯基)酰胺。
1H-NMR(CDCl3)δppm:0.89(t,3H,J=7.3Hz),1.19(s,9H),1.25-1.38(m,4H),1.40-1.60(m,4H),1.89-2.03(m,3H),2.52(t,2H,J=7.7Hz),2.89-3.04(m,2H),3.14(d,1H,J=5.2Hz),3.37(m,1H),3.96(m,2H),6.67(s,1H),7.05(d,2H,J=8.5Hz),7.22(d,2H,J=8.5Hz)。
步骤3
在2ml甲醇和2ml二氯甲烷混合液中,溶入291mg的4-叔丁基亚硫酰基氨基哌啶-1-甲酸(4-叔丁基苯基)酰胺。向该混合液中,加入570mg的80%-MMPP(一过氧化邻苯二甲酸镁六水合物),室温下将该混合液搅拌2小时。将该溶液用水稀释,用乙酸乙酯提取。将有机层用盐水洗涤,经无水硫酸镁干燥。减压除去溶剂,残留物经硅胶层析纯化,得到130mg 4-叔丁基磺酰基氨基哌啶-1-甲酸(4-丁基苯基)酰胺(I-120)。
可根据类似的方法合成其它化合物(I)。结构和物理性质如下所示。
I-2
1H-NMR(CDCl3)δppm:0.94(t,3H,J=7.5Hz),1.34-1.44(m,2H),1.40(d,6H,J=6.6Hz),1.59-1.68(m,2H),2.69(t,2H,J=7.8Hz),3.24-3.35(m,1H),6.49(s,1H),7.23-7.32(m,4H),7.6(d,2H,J=8.7Hz),7.79(d,2H,J=8.1Hz),7.85(s,1H)
I-3
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.2Hz),1.30-1.39(m,2H),1.37(d,6H,J=6.9Hz),1.57(五重峰,2H,J=7.5Hz),1.96(五重峰,2H,J=6.6Hz),2.49(t,2H,J=6.6Hz),2.57(t,2H,J=7.8Hz),3.16-3.26(m,3H),4.62(brs,1H),7.12(d,2H,J=8.1Hz),7.43(d,2H,J=8.4Hz),7.64(s,1H).
I-4
1H-NMR(CD3OD)δppm:0.92(t,3H,J=6.9Hz),1.28-1.41(m,2H),1.46(d,6H,J=6.3Hz),1.53-1.63(m,2H),2.58(t,2H,J=7.8Hz),3.33-3.43(m,1H),6.27-6.29(m,1H),7.14-7.16(m,3H),7.50(d,2H,J=8.4Hz),7.90(s,1H).
I-5
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.2Hz),1.28-1.41(m,2H),1.46(d,6H,J=6.9Hz),1.53-1.63(m,2H),2.59(t,2H,J=7.8Hz),3.35-3.44(m,1H),7.15(d,2H,J=8.7Hz),7.38(s,1H),7.45(d,2H,J=8.7Hz),7.57(s,1H).
I-6
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.5Hz),1.29-1.39(m,2H),1.37(d,6H,J=6.9Hz),1.55(五重峰,2H,J=7.5Hz),2.55(t,2H,J=5.1Hz),3.18-3.27(m,1H),3.92(d,2H,J=6.0Hz),5.51(t,1H,J=5.7Hz),7.10(d,2H,J=8.4Hz),7.39(d,2H,J=8.4Hz),8.23(s,1H).
I-7
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.28-1.38(m,2H),1.37(d,6H,J=6.9Hz),1.51-1.67(m,4H),1.78-1.88(m,2H),2.39(t,2H,J=7.2Hz),2.57(t,2H,J=7.5Hz),3.12-3.22(m,3H),4.30-4.37(m,1H),7.12(d,2H,J=8.4Hz),7.36-7.42(m,3H)
I-8
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.5Hz),1.21-1.47(m,4H),1.35(d,6H,J=6.6Hz),1.51-1.63(m,4H),1.67-1.77(m,2H),2.34(t,2H,J=7.5Hz),2.55(t,2H,J=7.8Hz),3.08-3.17(m,3H),4.71(t,1H,J=6.0Hz),7.09(d,2H,J=8.1Hz),7.43(d,2H,J=8.4Hz),7.74(s,1H).
I-9
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.29-1.39(m,2H),1.35(d,6H,J=6.9Hz),1.50-1.60(m,2H),2.54(t,2H,J=7.8Hz),2.64(t,2H,J=5.7Hz),3.14-3.23(m,1H),3.41-3.47(m,2H),5.29(t,1H,J=6.3Hz),7.10(d,2H,J=8.4Hz),7.39(d,2H,J=8.4Hz),7.91(s,1H).
I-10
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.5Hz),1.22(s,9H),1.30-1.37(m,2H),1.51-1.68(m,4H),1.76-1.86(m,2H),2.31-2.40(m,2H),2.56(t,2H,J=7.5Hz),3.15-3.26(m,3H),7.11(t,2H,J=8.7Hz),7.42(d,2H,J=8.1Hz),7.54(s,1H).
I-11
mp:128-129℃
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.5Hz),1.29-1.39(m,2H),1.39(s,9H),1.51-1.68(m,4H),1.76-1.84(m,2H),2.37(t,2H,J=7.5Hz),2.56(t,2H,J=7.8Hz),3.19-3.26(m,2H),4.20(t,1H,J=5.7Hz),7.11(d,2H,J=8.1Hz),7.42(d,2H,J=8.7Hz),7.46(s,1H).
I-12
1H-NMR(CDCl3)δppm:0.91(t,8H,J=7.5Hz),1.28-1.37(m,2H),1.47-1.68(m,6H),2.23(t,2H,J=7.2Hz),2.56(t,2H,J=7.5Hz),2.90-2.97(m,2H),5.10(brs,1H),7.11(d,2H,J=8.4Hz),7.36(d,2H,J=8.1Hz),7.50-7.68(m,3H),7.93(d,1H,J=8.1Hz),8.06(d,1H,J=8.4Hz),8.24(d,1H,J=7.5Hz),8.66(d,1H,J=8.7Hz).
I-13
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.5Hz),1.28-.40(m,2H),1.45-1.73(m,6H),2.23(t,2H,J=7.5Hz),2.56(t,2H,J=7.8Hz),2.88(s,6H),2.88-2.95(m,2H),5.04(brs, 1H),7.10(d,2H,J=8.1Hz),7.17(d,1H,J=7.2Hz),7.37(d,2H,J=8.4Hz),7.48-7.54(m,2H),8.23(d,1H,J=7.2Hz),8.30(d,1H,J=8.7Hz),8.53(d,1H,J=8.4Hz).
I-14
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.30-1.43(m,6H),1.36(d,6H,J=6.6Hz),1.51-1.62(m,4H),1.67-1.78(m,2H),2.34(t,2H,J=7.5Hz),2.56(t,2H,J=7.8Hz),3.09-3.20(m,3H),4.34(brs,1H),7.10(d,2H,J=8.4Hz),7.41-7.44(m,3H).
I-15
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.5Hz),1.23(s,9H),1.27-1.80(m,12H),2.30-2.88(m,2H),2.56(t,2H,J=7.5Hz),3.15(brs,2H),7.11(d,2H,J=7.8Hz),7.43(d,2H,J=7.8Hz),7.59(s,1H).
I-16
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.5Hz),1.29-1.44(m,6H),1.39(s,9H),1.51-1.61(m,4H),1.68-1.78(m,2H),2.35(t,2H,J=7.5Hz),2.56(t,2H,J=8.1Hz),3.15-3.21(m,2H),4.14-4.23(m,1H),7.11(d,2H,J=7.8Hz),7.86-7.44(m,3H).
I-19
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.5Hz),1.21(s,9H),1.30-1.40(m,2H),1.55-1.72(m,6H),2.64(t,2H,J=7.8Hz),3.08-3.33(m,3H),3.42-3.50(m,2H),6.39(s,1H),7.22(d,2H,J=8.4Hz),7.69(d,2H,J=8.1Hz).
I-20
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.2Hz),1.31-1.39(m,2H),1.39(s,9H).1.55-1.72(m,6H),2.64(t,2H,J=7.8Hz),3.24(四重峰,2H,J=6.6Hz),3.48(四重峰,2H,J=6.6Hz),4.21(t,1H,J=6.3Hz),6.29(s,1H),7.22(d,2H,J=7.8Hz),7.67(d,2H,J=8.1Hz).
I-21
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.23(s,9H),1.30-1.42(m,2H),1.50-2.02(m,10H),2.30-2.42(m,1H),2.57(t,2H,J=8.1Hz),3.10(brs,1H),3.57(brs,1H),7.12(d,2H,J=8.4Hz),7.41(d,2H,J=7.8Hz).
I-22
mp:78-79℃
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.30-1.40(m,2H),1.40(s,9H),1.50-1.65(m,4H),1.70-1.98(m,8H),2.30-2.40(m,1H),2.57(t,2H,J=7.5Hz),3.58-3.70(m,1H),4.16(d,1H,J=9.3Hz),7.11-7.15(m,3H),7.40(d,2H,J=8.1Hz).
I-23
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.21(s,9H),1.21-141(m,4H),1.51-1.64(m,4H),1.86-2.01(m,4H),2.12-2.25(m,1H),2.56(t,2H,J=7.5Hz),2.87-2.96(m,1H),3.00-3.12(m,1H),3.23-3.34(m,1H),3.67-3.75(m,1H),7.11(d,2H,J=8.1Hz),7.40(d,2H,J=8.4Hz).
I-24
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.25-1.37(m,2H),1.40(s,9H),1.48-1.65(m,6H),1.90(d,2H,J=11.7Hz),2.02(d,2H,J=11.7Hz),2.12-2.24(m,1H),2.56(t,2H,J=7.5Hz),3.04(t,2H,J=6.3Hz),4.31(t,1H,J=5.7Hz),7.11(d,2H,J=8.1Hz),7.42(d,2H,J=8.4Hz).
I-25
mp:232-233℃
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.5Hz),1.23-1.40(m,4H),1.40(s,9H),1.51-1.76(m,4H),2.01-2.26(m,5H),2.56(t,2H,J=7.5Hz),3.22-3.38(m,1H),3.79(d,1H,J=9.3Hz),7.11(d,2H,J=8.7Hz),7.17(s,1H),7.40(d,2H,J=8.4Hz).
I-26
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.22(s,9H),1.28-1.40(m,2H),1.52-1.62(m,2H),1.85-1.96(m,1H),2.00-2.14(m,1H),2.38-2.53(m,2H),2.56(t,2H,J=7.5Hz),3.22-3.37(m,3H),7.11(d,2H,J=8.4Hz),7.45(d,2H,J=8.4Hz),8.19(s,1H).
I-27
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.30-1.40(m,2H),1.40(s,9H),1.52-1.61(m,2H),1.95(五重峰,2H,J=6.3Hz),2.50(t,2H,J=6.9Hz),2.56(t,2H,J=7.8Hz),3.31(四重峰,2H,J=6.0Hz),4.30-4.36(m,1H),7.12(d,2H,J=8.4Hz),7.43(d,2H,J=8.4 Hz),7.65(s,1H).
I-28
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.21(s,9H),1.30-1.62(m,8H),2.08(d,4H,J=11.1Hz),2.56(t,2H,J=7.8Hz),3.04(d,1H,J=4.8Hz),3.20-3.30(m,1H),4.65-4.76(m,1H),6.57(s,1H),7.10(d,2H,J=8.7Hz),7.26(d,2H,J=8.1Hz).
I-29
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.2Hz),1.23-1.62(m,8H),1.40(s,9H),2.12(d,4H,J=14.4Hz),2.56(t,2H,J=7.8Hz),3.28-3.40(m,1H),3.90(s,1H),4.60-4.73(m,1H),6.57(s,1H),7.10(d,2H,J=8.4Hz),7.25(d,2H,J=8.4Hz).
I-30
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.5Hz),1.26-1.39(m,2H),1.51-1.64(m,4H),1.72-1.81(m,2H),2.34(t,2H,J=6.9Hz),2.56(t,2H,J=7.8Hz),2.95-3.01(m,2H),4.84(t,1H,J=5.7Hz),6.99-7.12(m,6H),7.19-7.24(m,1H),7.30(s,1H),7.38-7.43(m,4H),7.79(d,2H,J=8.7Hz).
I-31
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.5Hz),1.21(s,9H),1.28-1.62(m,8H),2.07-2.14(m,4H),2.64(t,2H,J=7.8Hz),3.11(d,1H,J=5.1Hz),2.20(brs,1H),3.90-4.04(m,1H),6.06-6.14(m,1H),7.21(t,2H,J=8.1Hz),7.67(t,2H,J=8.4Hz)
I-32
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.2Hz),1.27-1.65(m,8H),1.40(s,9H),2.10-2.23(m,4H),2.65(t,2H,J=7.5Hz),3.23-3.35(m,1H),3.49(s,1H),3.88-4.02(m,1H),5.84-5.92(m,1H),7.13(t,2H,J=8.4Hz),7.65(d,2H,J=8.1Hz).
I-33
1H-NMR(CDCl3)δppm:0.94(t,3H,J=7.2Hz),1.30-1.42(m,2H),1.32(s,9H),1.57-1.66(m,2H),2.67(t,2H,J=7.8Hz),5.61(s,1H),6.93(d,2H,J=8.7Hz),7.25(d,2H,J=8.4Hz),7.49(d,2H,J=9.0Hz),7.80(d,2H,J=8.1Hz),8.22(s,1H)
I-34
1H-NMR(CD3OD)δppm:0.95(t,3H,J=7.5Hz),1.35(s,9H),1.35-1.44(m,2H),1.57-1.69(m,2H),2.69(t,2H,J=7.5Hz),7.28-7.33(m,4H),7.56(d,2H,J=9.0Hz),7.83(d,2H,J=8.4Hz).
I-36
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.5Hz),1.31-1.70(m,11H),1.39(s,9H),1.75-1.85(m,1H),2.65(t,2H,J=8.1Hz),3.13(t,2H,J=6.6Hz),3.40(t,2H,J=7.2Hz),4.10(t,1H,J=5.7Hz),6.21(t,1H,J=5.7Hz),7.23(d,2H,J=8.1Hz),7.67(d,2H,J=8.4Hz).
I-37
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.5Hz),0.95-1.10(m,2H),1.31-1.40(m,2H),1.39(s,9H),1.55-1.63(m,4H),1.80-1.92(m,4H),2.65(t,2H,J=7.8Hz),3.03(t,2H,J=6.6Hz),3.31(t,2H,J=6.6Hz),4.06(t,1H,J=6.0Hz),6.22(t,1H,J=6.0Hz),7.23(d,2H,J=8.4Hz),7.67(d,2H,J=8.1Hz).
I-39
1H-NMR(CDCl3)δppm:1.13(t,3H,J=7.2Hz),1.39(s,9H),1.69-1.97(m,8H),2.27-2.38(m,1H),3.29-3.35(m,4H),3.60-3.70(m,1H),4.52(d,1H,J=9.3Hz),6.64(d,2H,J=8.4Hz),7.22(s,1H),7.31(d,2H,J=9.0Hz).
I-40
1H-NMR(CDCl3)δppm:1.38(s,9H),1.68-1.96(m,8H),2.30-2.40(m,1H),3.11(t,4H,J=4.8Hz),3.60-3.72(m,1H),3.86(t,4H,J=4.8Hz),4.51(brs,1H),6.89(d,2H,J=9.0Hz),7.42(d,2H,J=8.7Hz).
I-41
mp:>278℃(分解)
1H-NMR(CDCl3)δppm:1.18-1.40(m,2H),1.40(s,9H),1.62-1.75(m,2H),2.01-2.27(m,5H),3.10-3.13(m,4H),3.22-3.38(m,1H),3.72(d,1H,J=9.3Hz),3.85-3.88(m,4H),6.87(d,2H,J=9.0Hz),7.10(s,1H),7.40(d,2H,J=9.0Hz).
I-42
1H-NMR(CDCl3)δppm:1.40(s,9H),1.61-1.97(m,8H),2.16(s,3H),2.33-2.43(m,1H),3.60-3.70(m,1H),4.66(brs,1H),7.12(d,1H,J=8.7Hz),7.46-7.50(m,1H),7.62(s,H),7.75-7.78(m,1H),7.86-7.91(m,2H).
I-43
1H-NMR(CDCl3)δppm:1.40(s,9H),1.62-2.00(m,8H),1.87(s,3H),2.36-2.47(m,1H),3.24(s,3H),3.64-3.74(m,1H),4.87(brs,1H),7.13(d,2H,J=9.0Hz),7.64(d,2H,J=8.4Hz),7.81(s,H).
I-44
mp:235-236℃
1H-NMR(CDCl3)δppm:1.13(t,6H,J=6.9Hz),1.18-1.33(m,2H),1.40(s,9H),1.60-1.77(m,2H),2.00-2.26(m,5H),3.28-3.35(m,4H),3.73(d,1H,J=9.3Hz),6.60-6.70(m,2H),7.03(brs,1H),7.31(d,2H,J=7.8Hz).
I-45
mp:>268C(分解)
1H-NMR(CDCl3)δppm:1.20-1.34(m,2H),1.40(s,9H),1.56-1.76(m,8H),2.00-2.26(m,5H),3.06-3.14(m,4H),3.24-3.36(m,1H),3.72(d,1H,J=9.3Hz),6.90(d,2H,J=8.7Hz),7.09(s,1H),7.36(d,2H,J=8.7Hz).
I-46
mp:>272℃(分解)
1H-NMR(DMSO-d6)δppm:1.28(s,9H),1.31-1.59(m,7H),1.87-2.00(m,4H),2.23-2.34(m,1H),3.00-3.16(m,1H),4.35-4.45(m,2H),6.81(d,1H,J=9.0Hz),7.16(t,1H,J=7.2Hz),7.43(t,1H,J=8.4Hz),7.52-7.58(m,3H),8.04(d,1H,J=7.8Hz),8.43(s,1H).
I-47
1H-NMR(CDCl3)δppm:1.20-1.36(m,2H),1.40(s,9H),1.62-1.77(m,2H),1.98-2.32(m,5H),3.31-3.40(m,1H),3.62(d,1H,J=9.0Hz),7.08(s,1H),7.29(d,2H,J=9.0Hz),7.61(d,2H,J=9.0Hz).
I-48
1H-NMR(CDCl3)δppm:1.22-1.36(m,2H),1.40(s,9H),1.62-1.77(m,2H),2.00-2.31(m,5H),3.24-3.40(m,1H),3.62(d,1H,J=10.2Hz),7.01(t,2H,J=8.7Hz),7.09(s,1H),7.42-7.50(m,2H).
I-49
mp:270℃(分解)
1H-NMR(CDCl3)δppm:1.20-1.36(m,2H),1.40(s,9H),1.61-1.77(m,2H),1.95-2.30(m,9H),3.17-3.38(m,5H),3.67(d,1H,J=9.3Hz),6.50(d,2H,J=9.0Hz),6.97(s,1H),7.30(d,2H,J=9.0Hz).
I-50
mp:252-253℃
1H-NMR(CDCl3)δppm:1.21-1.37(m,2H),1.40(s,9H),1.62-1.78(m,2H),1.98-2.32(m,5H),3.26-3.40(m,1H),3.68(d,1H,J=9.6Hz),6.94-7.02(m,4H),7.08(t,1H,J=7.5Hz),7.13(s,1H),7.31(t,2H,J=7.5Hz),7.46(d,2H,J=9.0Hz).
I-51
mp:278-279℃
1H-NMR(CDCl3)δppm:1.02(d,6H,J=6.9Hz),1.35(s,9H),1.39-1.71(m,6H),1.90-2.09(m,2H),3.16-3.30(m,1H),3.46(d,1H,J=9.0Hz),4.92-5.01(m,1H),6.91-6.95(m,2H),7.00-7.07(m,3H),7.13-7.16(m,2H),7.30-7.36(m,2H).
I-52
mp:276-277℃
1H-NMR(CDCl3)δppm:1.20-1.36(m,2H),1.40(s,9H),1.60-1.78(m,2H),1.98-2.30(m,5H),2.36(s,3H),2.58(t,4H,J=4.5Hz),3.17(t,4H,J=4.5Hz),3.21-3.40(m,1H),3.64(d,1H,J=9.0Hz),6.88(d,2H,J=9.0Hz),7.01(s,1H),7.37(d,2H,J=9.0Hz).
I-53
mp:>300℃
1H-NMR(DMSO-d6)δppm:1.20-1.54(m,4H),1.27(s,9H),1.73-1.88(m,2H),1.89-2.01(m,2H),2.13-2.25(m,1H),2.98-3.12(m,1H),3.15-3.31(m,8H),6.76-6.84(m,2H),6.93(d, 2H,J=9.0Hz),6.99(d,2H,J=8.1Hz),7.24(d,2H,J=8.1Hz),7.46(d,2H,J=9.0Hz),9.60(s,1H).
I-54
mp:>215℃(分解)
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.27-2.00(m,18H),2.14-2.26(m,1H),2.53-2.84(m,4H),2.86-3.30(m,2H),3.46-3.54(m,1H),3.62-3.74(m,2H),6.78(d,1H,J=8.7Hz),6.87(d,2H,J=7.8Hz),7.42(d,2H,J=87Hz),9.58(s,1H).
I-55
mp:>290℃(分解)
1H-NMR(CDCl3)δppm:1.23-1.40(m,2H),1.40(s,9H),1.60-1.76(m,2H),2.02-2.27(m,5H),3.20(t,4H,J=5.4Hz),3.21-3.32(m,1H),3.67(d,1H,J=9.3Hz),3.98(t,4H,J=4.8Hz),6.52(t,1H,J=4.8Hz),6.93(d,2H,J=8.4Hz),7.06(s,1H),7.41(d,2H,J=8.7Hz),8.33(d,2H,J=4.8Hz)
I-56
mp:>232℃(分解)
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.27-1.48(m,4H),1.80-1.99(m,4H),2.14-2.25(m,1H),3.04-3.24(m,8H),3.68(s,3H),3.76(s,3H),6.44-6.47(m,1H),6.66(s,1H),6.76-6.84(m,2H),6.92(d,2H,J=8.4Hz),7.46(d,2H,J=8.4Hz),9.61(s,1H).
I-57
mp:284-285℃(分解)
1H-NMR(CDCl3)δppm:1.27(t,3H,J=7.2Hz),1.40(s,9H),1.61-2.24(m,9H),2.35-2.49(m,1H),2.76(t,2H,J=10.2Hz),3.04-3.15(m,2H),3.20-3.36(m,1H),3.55-3.59(m,2H),3.87(d,1H,J=9.6Hz),4.12-4.19(m,2H),6.90(d,2H,J=8.7Hz),2.79(s,1H),7.40(d,2H,J=8.7Hz).
I-58
mp:>299℃(分解)
1H-NMR(CDCl3)δppm:1.26-1.33(m,2H),1.40(s,9H),1.56-2.42(m,19H),2.73-2.81 (m,4H),3.16-3.26(m,4H),3,64(d,1H,J=9.6Hz),6.87(d,2H,J=8.7Hz),7.04(s,1H),7.37(d,2H,J=9.0Hz).
I-59
mp:>270℃(分解)
1H-NMR(CDCl3)δppm:1.26-1.47(m,2H),1.47(s,9H),1.60-1.80(m,4H),2.01-2.32(m,5H),3.28-3.40(m,3H),3.52-3.74(m,3H),5.74-5.96(m,2H),6.92(d,2H,J=8.7Hz),7.13(s,1H),7.39(d,2H,J=9.0Hz).
I-60
mp:247-250℃(分解)
1H-NMR(CDCl3)δppm:1.20-1.37(m,2H),1.40(s,9H),1.60-1.78(m,2H),1.98-2.33(m,5H),2.93-3.03(m,2H),3.22-3.40(m,1H),3.52(t,2H,J=6.0Hz),3.62(d,1H,J=8.4Hz),4.36(s,2H),6.93(d,2H,J=8.7Hz),7.00(s,1H),7.11-7.22(m,4H),7.39(d,2H,J=8.7Hz).
I-61
mp:280-281℃
1H-NMR(CDCl3)δppm:1.21-1.38(m,2H),1.41(s,9H),1.64-1.80(m,2H),2.02-2.33(m,5H),3.24-3.40(m,1H),3.61(d,1H,J=9.0Hz),6.33(t,2H,J=2.1Hz),7.04(t,2H,J=2.1Hz),7.14(s,1H),7.34(d,2H,J=9.0Hz),7.56(d,2H,J=9.0Hz).
I-62
mp:260-262℃
1H-NMR(CDCl3)δppm:1.22-1.39(m,2H),1.41(s,9H),1.64-1.82(m,2H),2.02-2.35(m,5H),3.24-3.40(m,1H),3.62(d,1H,J=9.6Hz),7.31(d,2H,J=9.0Hz),7.51(s,1H),7.69(d,2H,J=9.0Hz).
I-63
mp:248℃
1H-NMR(CDCl3)δppm:1.20-1.38(m,2H),1.40(s,9H),1.61-1.78(m,2H),1.98-2.32(m,5H),3.22-3.45(m,1H),3.64(d,1H,J=9.3Hz),7.11(s,1H),7.37-7.46(m,4H).
I-64
mp:272-275℃(分解)
1H-NMR(DMSO-d6)δppm:1.20-1.53(m,4H),1.27(s,9H),1.75-1.88(m,2H),1.88-2.00(m,2H),2.11-2.24(m,1H),2.96-3.12(m,1H),5.96(s,2H),6.77(d,1H,J=8.7Hz),6.82(d,1H,J=8.4Hz),6.95(dd,1H,J=1.8,8.4Hz),7.29(d,1H,J=1.8Hz),9.70(s,1H).
I-65
mp:293-296℃(分解)
1H-NMR(DMSO-d6)δppm:1.20-1.70(m,10H),1.27(s,9H),1.79-2.038(m,4H),2.18-2.33(m,1H),2.98-3.30(m,5H),6.79(d,1H,J=9.0Hz),6.97(d,2H,J=8.1Hz),7.43-7.57(m,4H),7.62(d,2H,J=8.1Hz),9.82(s,1H).
I-66
mp:>300℃
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.27-1.53(m,4H),1.86-1.99(m,4H),2.22-2.34(m,1H),2.39(s,3H),3.00-3.14(m,1H),6.25(s,1H),6.79(d,1H,J=9.0Hz),7.47-7.50(m,1H),7.69-7.76(m,1H),10.27(s,1H).
I-67
mp:248-249℃
1H-NMR(DMSO-d6)δppm:1.20-1.54(m,4H),1.27(s,9H),1.77-1.90(m,2H),1.90-2.02(m,2H),2.02(s,3H),2.17-2.32(m,1H),2.96-3.13(m,1H),6.78(d,1H,J=8.7Hz),7.12-7.30(m,3H),7.89(s,1H),9.79(s,1H),9.88(s,1H).
I-68
mp:>300℃
1H-NMR(DMSO-d6)δppm:1.20-1.54(m,4H),1.27(s,9H),1.77-1.89(m,2H),1.89-2.03(m,2H),2.00(s,3H),2.14-2.28(m,1H),2.95-3.13(m,1H),6.78(d,1H,J=8.7Hz),7.40-7.54(m,4H),9.72(s,1H),9.83(s,1H).
I-69
mp:199-201℃
1H-NMR(DMSO-d6)δppm:1.21-1.53(m,4H),1.27(s,9H),1.76-1.89(m,2H),1.89-2.02(m,2H),2.13-2.30(m,1H),2.85(s,6H),2.94-3.14(m,1H),6.40(dd,1H,J=2.4,8.4Hz),6.78(d,1H,J=8.7Hz),6.90(d,1H,J=8.4Hz),7.05(t,2H,J=8.4Hz),9.60(s,1H).
I-70
mp:227-230℃
1H-NMR(DMSO-d6)δppm:1.22-1.52(m,4H),1.27(s,9H),1.72-1.87(m,2H),1.87-2.01(m,2H),2.12-2.29(m,1H),2.96-3.12(m,1H),5.00(s,2H),6.22(d,1H,J=7.5Hz),6.66(d,1H,J=7.5Hz),6.78(d,1H,J=9.0Hz),6.86(d,1H,J=7.5Hz),6.89-6.95(m,1H),9.46(s,1H).
I-71
mp:270-272℃
1H-NMR(DMSO-d6)δppm:1.22-1.52(m,4H),1.26(s,9H),1.73-1.86(m,2H),1.88-2.00(m,2H),2.08-2.22(m,1H),2.95-3.11(m,1H),4.80(s,2H),6.47(d,2H,J=8.4Hz),6.77(d,1H,J=8.4Hz),7.20(d,2H,J=8.4Hz),9.35(s,1H).
I-72
mp:262-263℃
1H-NMR(CDCl3)δppm:1.25(d,6H,J=6.3Hz),1.17-1.42(m,2H),1.40(s,9H),1.60-1.78(m,2H),1.98-2.43(m,7H),3.20-3.43(m,3H),3.67(d,1H,J=9.6Hz),3.74-3.86(m,2H),6.86(d,2H,J=9.0Hz),7.04(s,1H),7.38(d,2H,J=9.0Hz).
I-73
mp:218-219℃
1H-NMR(CD3OD)δppm:1.36(s,9H),1.36-1.69(m,4H),1.45(s,9H),1.88-2.02(m,3H),2.06-2.30(m,4H),3.05-3.44(m,3H),3.46-3.56(m,1H),4.16-4.26(m,1H),6.51(d,2H,J=9.0Hz),7.30(d,2H,J=8.7Hz).
I-74
mp:295-296℃(分解)
1H-NMR(CD3OD)δppm:1.36(s,9H),1.36-1.67(m,4H),1.92-2.13(m,4H),2.26-2.40(m, 2H),2.62-2.75(m,1H),3.16-3.25(m,1H),3.58-3.98(m,4H),4.16-4.25(m,1H),7.20-7.30(m,2H),7.62(d,2H,J=9.0Hz).
I-75
mp:250-251℃
1H-NMR(DMSO-d6)δppm:1.23-1.55(m,4H),1.27(s,9H),1.78-1.90(m,2H),1.90-2.02(m,2H),2.15-2.28(m,1H),2.98-3.14(m,1H),3.06(t,2H,J=8.4Hz),3.87(t,2H,J=8.4Hz),6.67(dd,1H,J=1.5,7.2Hz),6.80(d,1H,J=8.4Hz),6.94-7.05(m,2H),7.12-7.19(m,1H),7.16(d,2H,J=9.3Hz),7.57(d,2H,J=9.3Hz),9.73(s,1H).
I-76
mp:265-266℃
1H-NMR(DMSO-d6)δppm:1.23-1.58(m,4H),1.28(s,9H),1.83-2.04(m,4H),2.20-2.36(m,1H),2.97-3.16(m,1H),6.67(d,1H,J=3.0Hz),6.82(d,1H,J=8.4Hz),7.07-7.22(m,2H),7.47-7.53(m,1H),7.50(d,2H,J=9.0Hz),7.58(d,1H,J=3.0Hz),7.64(d,1H,J=7.5Hz),7.79(d,2H,J=9.0Hz),10.02(s,1H).
I-77
mp:281℃
1H-NMR(DMSO-d6)δppm:1.21-1.56(m,4H),1.27(s,9H),1.80-2.03(m,4H),2.18-2.31(m,1H),2.97-3.14(m,1H),6.51(dd,1H,J=2.1,2.7Hz),6.81(d,1H,J=9.0Hz),7.67-7.78(m,5H),8.41(d,1H,J=2.1Hz),9.96(s,1H).
I-78
mp:>300℃(分解)
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.27-1.52(m,4H),1.74-2.04(m,7H),2.10-2.25(m,2H),2.96-3.20(m,2H),3.48-3.58(m,1H),3.75-3.84(m,1H),6.39(d,2H,J=8.4Hz),6.79(d,1H,J=8.4Hz),7.02(s,1H),7.30(s,1H),7.36(d,2H,J=8.1Hz),9.48(s,1H)
I-79
mp:248-250℃(分解)
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.27-1.54(m,4H),1.85-1.99(m,4H),2.24-2.33 (m,1H),3.00-3.14(m,1H),6.82(d,1H,J=8.7Hz),7.77(d,2H,J=8.4Hz),8.07(d,2H,J=8.4Hz).
I-80
mp:>300℃
1H-NMR(DMSO-d6)δppm:1.22-1.58(m,4H),1.27(s,9H),1.80-2.03(m,4H),2.18-2.32(m,1H),2.98-3.14(m,1H),6.80(d,1H,J=8.7Hz),7.35-7.50(m,2H),7.99(s,1H),8.11(s,1H),9.79(s,1H),12.94(s,1H),
I-81
mp:261-262℃
1H-NMR(DMSO-d6)δppm:1.21-1.57(m,4H),1.27(s,9H),1.78-2.02(m,4H),2.17-2.30(m,1H),2.96-3.16(m,1H),6.34(s,1H),6.80(d,1H,J=8.7Hz),7.14-7.32(m,3H),7.85(s,1H),9.58(s,1H),10.95(s,1H).
I-82
1H-NMR(CDCl3)δppm:0.86(s,18H),1.24-1.37(m,2H),1.37(s,9H),1.56-1.74(m,2H),1.95-2.19(m,5H),3.18-3.32(m,1H),3.44(t,4H,J=6.3Hz),3.70(t,4H,J=6.3Hz),4.39(d,1H,J=9.0Hz),6.59(d,2H,J=9.0Hz),7.31(d,2H,J=8.7Hz),7.43(s,1H).
I-83
mp:264-265℃
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.27-1.52(m,4H),1.78-1.88(m,2H),1.90-2.00(m,2H),2.14-2.26(m,1H),2.96-3.14(m,1H),6.72-6.82(m,2H),6.99(t,4H,J=7.8Hz),7.18(t,2H,J=7.5Hz),7.46(d,2H,J=9.0Hz),8.00(s,1H),9.65(s,1H).
I-84
mp:257℃(分解)
1H-NMR(DMS0-d6)δppm:1.23-1.57(m,4H),1.27(s,9H),1.83-2.03(m,4H),2.23-2.35(m,1H),2.98-3.15(m,1H),6.80(d,1H,J=8.1Hz),7.87(d,2H,J=9.0Hz),8.34(d,2H,J=9.0Hz),9.21(s,1H),10.20(s,1H).
I-85
mp:256-258℃
1H-NMR(DMSO-d6)δppm:1.22-1.58(m,4H), 3H),2.28-2.42(m,1H),2.97-3.02(m,1H),6.71(d,1H,J=0.9Hz),6.80(d,1H,J=8.1Hz),11.91(s,1H).
I-86
mp:228-230℃
1H-NMR(CD3OD)δppm:1.36(s,9H),1.36-1.48(m,2H),1.55-1.70(m,2H),1.87-1.98(m,2H),2.08-2.17(m,2H),2.20-2.32(m,1H),3.15-3.27(m,1H),3.50(t,4H,J=5.7Hz),3.69(t,4H,J=5.7Hz),6.72(d,2H,J=9.0Hz),7.29-7.33(m,2H),
I-87
mp:183-184℃
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.27-1.48(m,4H),1.73-1.89(m,4H),1.90-2.00(m,2H),2.16-2.28(m,1H),2.28(t,2H,J=7.5Hz),2.51-2.54(m,2H),2.97-3.13(m,1H),3.58(s,3H),6.79(d,1H,J=8.7Hz),7.08(d,2H,J=8.7Hz),7.49(d,2H,J=8.4Hz),9.73(s,1H).
I-88
mp:217-218℃
1H-NMR(CD3OD)δppm:1.36(s,9H),1.36-1.46(m,2H),1.55-1.69(m,2H),1.83-2.00(m,4H),2.07-2.18(m,2H),2.26-2.36(m,3H),2.61(t,2H,J=7.5Hz),3.14-3.26(m,1H),7.13(d,2H,J=8.1Hz),7.44(d,2H,J=8.1Hz).
I-89
1H-NMR(CDCl3)δppm:0.08(d,6H,J=3.3Hz),0.88(s,9H),1.21-1.36(m,2H),1.39(s,9H),1.61-1.74(m,2H),1.88-2.23(m,6H),3.06-3.11(m,1H),3.24-3.74(m,4H),3.92(d,1H,J=9.6Hz),4.48-4.56(m,1H),6.47(d,2H,J=9.0Hz),7.17(s,1H),7.32(d,2H,J=9.0Hz).
I-90
mp:无定型
1H-NMR(CD3OD)δppm:1.36(s,9H),1.36-1.47(m,2H),1.56-1.70(m,3H),1.88-2.30(m,6H),3.05-3.49(m,5H),4.50(bra,1H),6.50(d,2H,J=9.0Hz),7.29(d,2H,J=9.0Hz).
I-91
mp:105-106℃
1H-NMR(CDCl3)δppm:0.92(t,8H,J=7.3Hz),1.25-1.27(m,2H),1.36(d,6H,J=6.9Hz),1.51-1.59(m,2H),2.56(t,2H,J=7.8Hz),3.27(七重峰,1H,J=6.9Hz),7.12(d,2H,J=8.6Hz),7.32(t,1H,J=7.8Hz),7.45(brd,1H,J=7.8Hz),7.53(d,2H,J=8.6Hz),7.58(d,1H,J=7.8Hz),7.71-7.72(m,2H),8.27(s,1H),
I-92
mp:163-164℃
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.3Hz),1.32-1.39(m,2H),1.55-1.65(m,2H),1.87(s,3H),1.95(s,3H),2.60(t,2H,J=7.6Hz),7.07(d,2H,J=8.4Hz),7.18(d,2H,J=8.5Hz),7.54(d,2H,J=8.5Hz),7.91(brs,1H),8.18(d,2H,J=8.4Hz),8.77(s,1H).
I-93
mp:173℃
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.3Hz),1.32-1.40(m,2H),1.39(d,6H,J=6.9Hz),1.55-1.62(m,2H),2.60(t,2H,J=7.8Hz),3.13(七重峰,1H,J=6.9Hz),4.39(d,2H,J=6.3Hz),4.45(t,1H,J=6.3Hz),7.18(d,2H,J=8.7Hz),7.46(d,2H,J=8.7Hz),7.54(d,2H,J=8.7Hz),7.80(s,1H),7.85(d,2H,J=8.7Hz).
I-94
mp:159-160℃
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.3Hz),1.32-1.39(m,2H),1.54-1.80(m,2H),1.79(s,3H),1.80(s,3H),2.60t,2H,J=7.7Hz),3,18(s,3H),7.18(d,2H,J=8.5Hz),7.30(d,2H,J=8.8Hz),7.52(d,2H,J=8.5Hz),7.70(brs,1H),7.84(d,2H,J=8.8Hz),8.77(s,1H).
I-95
mp:177-178℃
1H-NMR(CDCl3)δppm:0.94(t,3H,J=7.2Hz),1.31-1.48(m,8H),1.54-1.66(m,2H), 2.55(s,3H),2.62(t,2H,J=7.6Hz),3.92(七重峰,1H,J=6.6Hz),7.20(d,2H,J=8.45Hz),7.74(d,2H,J=8.5Hz),9.01(brs,1H),9.17(s,1H).
I-96
mp:220-223℃
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.3Hz),1.28-1.42(m,2H),1.50(d,6H,J=6.8Hz),1.54-1.65(m,2H),2.62(t,2H,J=7.6Hz),4.08(七重峰,1H,J=7.1Hz),7.20(d,2H,J=8.5Hz),7.48(d,2H,J=8.5Hz),7.71(brs,1H),8.51(brs,1H),8.95(s,1H).
I-97
mp:195-197℃
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.6Hz),0.94(t,3H,J=7.3Hz),1.32-1.44(m,6H),1.54-1.64(m,2H),1.66-1.78(m,2H),2.62(t,2H,J=7.7Hz),2.86(brs,2H),3.98(七重峰1H,J=7.1Hz),7.19(d,2H,J=8.5Hz),7.63(d,2H,J=8.4Hz),8.72(brs,1H),8.81(brs,1H).
I-98
mp:216-218℃
1H-NMR(CDCl3+CD3OD)δppm:0.93(t,3H,J=7.4Hz),1.29-1.40(m,2H),1.43(d,2H,J=6.9Hz),1.51-1.63(m,2H),2.60(t,2H,J=7.8Hz),3.65(七重峰,1H,J=6.9Hz),7.18(d,2H,J=8.5Hz),7.22(d,1H,J=8.8Hz),7.55(d,2H,J=8.5Hz),8.18(dd,1H,J=8.8,2.4Hz),8.63(d,1H,J=2.4Hz).
I-99
mp:201-202℃
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.3Hz),1.22-1.40(m,2H),1.49(d,2H ,J=7.1Hz),1.51-1.63(m,2H),2.59(t,2H,J=7.7Hz),4.22(七重峰,1H,J=7.1Hz),7.16(d,2H,J=8.4Hz),7.41(brs,1H),7.52(d,2H,J=8.4Hz),8.10(brs,1H),8.13(d,1H,J=2.2Hz),8.61(brs,1H).
I-100
mp:160-162℃
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.3Hz),1.22-1.42(m,2H),1.45(d,2H,J=6.9Hz),1.51-1.63(m,2H),2.61(t,2H,J=7.8Hz),3.37(七重峰,1H,J=6.9Hz),6.89(brs,1H),7.19(d, 2H,J=8.4Hz),7.65(d,2H,J=8.4Hz),7.80(dd,1H,J=8.4,2.4Hz),8.27(d,1H,J=8.4Hz),8.45(d,1H,J=2.4Hz),9.75(brs,1H).
I-101,I-214
mp:192-194℃
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.3Hz),1.27-1.41(m,2H),1.35(s,9H),1.50-1.66(m,2H),2.60(t,2H,J=7.6Hz),5.58(brs,1H),7.07(d,2H,J=8.5Hz),7.17(d,2H,J=8.5Hz),7.52(d,2H,J=8.5Hz),7.71(brs,1H),7.79(d,2H,J=8.5Hz).
I-102
mp:216-217℃
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.3Hz),1.26-1.42(m,2H),1.45(s,9H),1.70-1.83(m,2H),2.60(t,2H,J=7.7Hz),6.42(brs,1H),7.18(d,2H,J=8.5Hz),7.35(d,2H,J=8.5Hz),7.51(d,2H,J=8.5Hz),7.68(brs,1H),7.82(d,2H,J=8.5Hz).
I-103
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.3Hz),1.28-1.36(m,2H),1.32(d,6H,J=6.9Hz),1.49-1.59(m,2H),2.54(t,2H,J=7.7Hz),3.23(七重峰,1H,J=6.9Hz),3.48(s,3H),6.76(brs,1H),6.91(d,2H,J=8.2Hz),6.99(d,2H,J=8.8Hz),7.03(d,2H,J=8.2Hz),7.25(d,2H,J=8.8Hz).
I-104
mp:182-183℃
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.3Hz),1.28-1.40(m,2H),1.51-1.63(m,2H),1.64-1.88(m,4H),1.90-2.23(m,4H),2.60(t,2H,J=7.6Hz),3.39(m,1H),6.16(brs,1H),7.07(d,2H,J=8.5Hz),7.16(d,2H,J=8.5Hz),7.52(d,2H,J=8.5Hz),7.74(brs,1H),7.77(d,2H,J=8.5Hz).
I-105
mp:190-191℃
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.3Hz),1.28-1.41(m,2H),1.52-1.69(m,4H),1.75-1.90(m,2H),1.92-2.07(m,4H),2.58(t,2H,J=7.6Hz),3.59(m,1H),6.53(brs,1H), 7.18(d,2H,J=8.5Hz),7.31(d,2H,J=8.5Hz),7.52(d,2H,J=8.5Hz),7.67(brs,1H),7.84(d,2H,J=8.5Hz).
I-106
mp:194-197℃
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.3Hz),1.22-1.41(m,2H),1.53-1.65(m,2H),1.90(s,6H),2.60(t,2H,J=7.8Hz),6.86(brs,1H),7.18(d,2H,J=8.5Hz),7.43(d,2H,J=8.5Hz),7.51(d,2H,J=8.5Hz),7.71(brs,1H),7.84(d,2H,J=8.5Hz).
I-107
mp:211-212℃
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.3Hz),1.24-1.40(m,2H),1.50-1.62(m,2H),2.60(t,2H,J=7.6Hz),6.19(brs,1H),7.17(d,2H,J=8.5Hz),7.18(d,2H,J=8.5Hz),7.51(d,2H,J=8.5Hz),7.66(brs,1H),7.86(d,2H,J=8.5Hz).
I-108
mp:298-300℃
1H-NMR(DMSO-d6)δppm:0.90(t,3H,J=7.3Hz),1.22-1.39(m,2H),1.48-1.60(m,2H),2.54(t,2H,J=7.3Hz),7.04(d,2H,J=8.8Hz),7.12(d,2H,J=8.5Hz),7.64(d,2H,J=8.5Hz),7.69(d,2H,J=8.8Hz),9.80(s,1H).
I-109
mp:122-123℃
1H-NMR(CDCl3)δppm:0.90(t,3H,J=7.4Hz),0.97(t,3H,J=7.7Hz),1.26-1.38(m,2H),1.30(s,6H),1.50-1.66(m,4H),1.72-1.83(m,4H),2.34(t,2H,J=7.1Hz),2.55(t,2H,J=7.6Hz),3.19(q,1H,J=6.0Hz),4.60(brs,1H),7.08(d,2H,J=8.5Hz),7.42(d,2H,J=8.5Hz),7.85(s,1H).
I-110
mp:109-110℃
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.4Hz),1.10(d,6H,J=6.7Hz),1.29-1.38(m,2H),1.55(s,9H),1.60-1.70(m,2H),1.78-1.89(m,2H),2.26(m,1H),2.39(t,2H,J=7.0Hz),2.57(t, 2H,J=7.7Hz),2.90(d,2H,J=6.6Hz),3.16(brs,1H),4.24(brs,1H),7.12(d,2H,J=8.5Hz),7.40(d,2H,J=8.5Hz).
I-111
mp:64-65℃
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.3Hz),1.02(t,3H,J=7.5Hz),1.35(d,3H,J=6.7Hz),1.26-1.38(m,2H),1.48-1.69(m,5H),1.76-1.87(m,2H),2.04(m,1H),2.38(t,2H,J=7.3Hz),2.56(t,2H,J=7.6Hz),2.91(m,1H),3.16(brs,2H),4.42(brs,1H),7.11(d,2H,J=8.5Hz),7.42(d,2H,J=8.5Hz),7.47(brs,1H).
I-112
mp:79-80℃
1H-NMR(CDCl3)δppm:1.36(s,9H),1.52-1.62(m,2H),1.67-1.76(m,2H),2.22(t,2H,J=7.4Hz),3.16(q,2H,J=6.3Hz),3.78(s,3H),4.33(d,2H,J=5.4Hz),4.62(brs,1H),6.20(brs,1H),6.85(d,2H,J=8.8Hz),7.19(d,2H,J=8.8Hz).
I-113
mp:125-126℃
1H-NMR(CDCl3)δppm:1.38(s,9H),1.62-1.70(m,2H),1.76-1.88(m,2H),2.46(t,2H,J=7.4Hz),3.22(q,2H,J=6.1Hz),4.22(t,1H,J=6.1Hz),7.24(dd,1H,J=8.9,2.3Hz),7.36(d,1H,J=2.3Hz),7.65(brs,1H),8.29(d,1H,J=8.9Hz).
I-114
mp:89-91℃
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.0Hz),1.06(d,6H,J=7.0Hz),1.36(m,1H),1.50-1.72(m,5H),1.94-2.06(m,2H),2.26(m,1H),2.60(t,2H,J=7.7Hz),2.84(t,2H,J=7.7Hz),2.93(d,2H,J=6.3Hz),3.20(t,2H,J=6.6Hz),4.30(brs,1H),7.19(d,2H,J=8.5Hz),7.63(d,2H,J=8.5Hz),9.15(brs,1H).
I-115
mp:94-95℃
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.5Hz),1.03(t,3H,J=7.5Hz),1.23-1.40 (m,5H),1.42-1.65(m,6H),1.75(m,1H),2.02(m,1H),2.24(t,2H,J=7.0Hz),2.59(t,2H,J=8.0Hz),2.90(m,1H),3.14(q,2H,J=6.6Hz),4.20(m,1H),4.40(d,2H,J=5.4Hz),5.70(brs,1H),7.14(d,2H,J=8.1Hz),7.18(d,2H,J=8.1Hz).
I-116
mp:89-91℃
1H-NMR(CDCl3)δppm:0.97(t,3H,J=7.3Hz),1.02(t,3H,J=7.5Hz),1.35(d,3H,J=7.0Hz),1.40-1.90(m,9H),2.04(m,1H),2.37(t,2H,J=7.0Hz),2.90(m,1H),3.17(q,2H,J=6.6Hz),3.93(t,2H,J=6.6Hz),4.32(m,1H),6.84(d,2H,J=9.0Hz),7.31(brs,1H),7.40(d,2H,J=9.0Hz).
I-117
mp:110-111℃
1H-NMR(CDCl3)δppm:1.02(t,3H,J=7.5Hz),1.34(d,3H,J=6.6Hz),1.45-1.70(m,3H),1.75-1.85(m,2H),2.05(m,1H),2.36(t,2H,J=7.5Hz),2.90(m,1H),3.16(q,2H,J=6.6Hz),3.78(s,3H),4.50(m,1H),6.84(d,2H,J=6.8Hz),7.42(d,2H,J=6.8Hz),7.48(brs,1H).
I-118
mp:113-115℃
1H-NMR(CDCl3)δppm:0.92(t,3H,J=7.0Hz),1.20-1.34(m,1H),1.37(d,6H,J=7.0Hz),1.48-1.70(m,3H),2.43(q,2H,J=6.6Hz),2.58(t,2H,J=7.7Hz),3.10-3.31(m,3H),4.75(m,1H),6.04(d,1H,J=15.0Hz),6.77(dt,1H,J=7.7,15.0Hz),7.14(d,2H,J=8.4Hz),7.55(d,2H,J=8.4Hz),7.85(brs,1H).
I-119
mp:139-140℃
1H-NMR(CDCl3)δppm:1.19(s,9H),1.47(m,2H),1.61(m,2H),2.18(t,2H,J=7.6Hz),3.03(q,2H,J=6.3Hz),4.09(t,1H,J=5.9Hz),6.85(brd,1H,J=8.0Hz),7.00(t,1H,J=8.0Hz),7.16(brd,1H,J=8.0),7.48(brs,1H),7.57(brs,1H).
I-120
mp:183℃
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.3Hz),1.20-1.58(m,6H),1.40(s,9H),2.07(dd,1H,J=12.9,3.1Hz),2.52(t,2H,J=7.7Hz),2.95(dd,2H,J=11.5,2.5Hz),3.46(m,1H),3.88-4.07(m,3H),6.47(s,1H),7.08(d,2H,J=8.5Hz),7.22(d,2H,J=8.5Hz).
I-121
mp:163-166℃
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.3Hz),1.32-1.62(m,6H),1.45(s,9H),1.95-2.07(H,3H),2.20(m,1H),2.46(td,1H,J=10.4,3.7Hz),2.37(t,2H,J=7.6Hz),3.43(brd,2H,J=10.4Hz),4.80(s,1H),7.12(d,2H,J=8.4Hz),7.14(s,1H),7.39(d,2H,J=8.4Hz),
I-122
mp:188-189℃
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.5Hz),1.25-1.41(m,2H),1.42(s,9H),1.50-1.62(m,2H),1.78-1.95(m,4H),2.00-2.20(m,6H),2.57(t,2H,J=7.5Hz),3.99(brs,1H),7.10(brs,1H),7.12(d,2H,J=6.5Hz),7.41(d,2H,J=6.5Hz).
I-123
mp:197-198℃
1H-NMR(CDCl3)δppm:0.91(t,3H,J=7.5Hz),1.24-1.40(m,2H),1.39(s,9H),1.50-1.70(m,2H),1.99(brs,12H),2.56(t,2H,J =7.5Hz),3.47(brs,1H),7.10(s,1H),7.11(d,2H,J=8.5Hz),7.38(d,2H,J=8.5Hz).
I-124
mp:258-260℃
1H-NMR(CDCl3)δppm:1.20-1.40(m,2H),1.41(s,9H),1.62-1.81(m,2H),2.03-2.35(m,5H),2.37(s,3H),2.71(s,3H),3.32(m,1H),3.64(d,1H,J=8.4Hz),7.08(brs,1H),7.24(m,1H,7.33(m,2H),7.60(d,1H,J=8.1Hz),7.77(s,1H),7.80(d,1H,J=8.4Hz),8.14(m,1H).
I-125
mp:297-299℃
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.28-1.56(m,4H),1.80-2.01(m,4H),2.47(m,1H),2.76(brs,1H),3.05(m,2H),6.78(d,1H,J=9.0Hz),7.23(d,1H,J=9.0Hz),7.46(dd,1H,J=2.0,9.0Hz),8.03(d,1H,J=2.0Hz).
I-126
mp:198-199℃
1H-NMR(CDCl3)δppm:1.18-1.39(m,2H),1.40(s,9H),1.60-1.79(m,2H),1.98-2.35(m,5H),3.30(m,1H),3.67(d,1H,J=9.6Hz),5.89(tt,1H,J=3.0,50.0Hz),6.97(d,1H,J=7.8Hz),7.21(s,1H),7.30-7.40(m,2H),7.55(s,1H)
I-127
mp:262-264℃
1H-NMR(CDCl3)δppm:1.20-1.39(m,2H),1.41(s,9H),1.60-1.80(m,2H),2.00-2.36(m,5H),2.57(s,3H),3.33(m,1H),3.62(d,1H,J=8.7Hz),7.28(brs,1H),7.62(d,2H,J=8.7Hz),7.94(d,2H,J=8.7Hz).
I-128
mp:252-254℃
1H-NMR(CDCl3)δppm:1.18-1.39(m,2H),1.40(s,9H),1.58-1.79(m,2H),1.99-2.30(m,5H),2.46(s,3H),3.32(m,1H),3.64(m,1H),7.11(brs,1H),7.23(d,2H,J=9.0Hz),7.44(d,2H,J=9.0Hz).
I-129
mp:>300℃
1H-NMR(CDCl3+CD3OD)δppm:1.30-1.45(m,2H),1.42(s,9H),1.70-1.88(m,2H),2.10-2.37(m,4H),2.52(m,1H),3.34(m,1H),7.43-7.54(m,3H),7.82(d,1H,J=6.7Hz),7.88(d,1H,J=8.5Hz),7.98-8.07(m,2H),8.44(s,1H),8.46(s,1H).
I-130
mp:123-124℃
1H-NMR(CDCl3)δppm:1.18-1.84(m,2H),1.40(s,9H),1.62-1.75(m,2H),2.00-2.28(m,5H),3.31(m,1H),3.61(d,1H,J=9.5Hz),5.59(s,1H),7.17(s,1H),7.30-7.37(m,6H),7.41(d, 1H,J=8.5Hz),7.84(d,1H,J=2.1Hz).
I-131
mp:202-204℃
1H-NMR(CDCl3)δppm:1.27-1.38(m,2H),1.38(s,9H),1.62-1.75(m,2H),1.97-2.04(m,2H),2.18-2.27(m,3H),3.26(m,1H),3.81(s,3H),4.62(d,1H,J=7.9Hz),7.12(d,1H,J=7.8Hz),7.40(t,1H,J=7.8Hz),7.51(s,3H),7.61(d,1H,J=7.8Hz),7.71(s,1H),8.21(brs,1H).
I-132
mp:236-237℃
1H-NMR(CDCl3)δppm:1.23-1.43(m,2H),1.41(s,9H),1.66-1.80(m,2H),2.08-2.12(m,2H),2.23-2.31(m,3H),3.34(m,1H),3.87(d,1H,J=9.5Hz),4.02(s,3H),7.30(td,1H,J=7.3,1.1Hz),7.36(s,1H),7.39(td,1H,J=7.3,1.5Hz),7.53(brd,1H,J=7.3Hz),7.84(brd,1H,J=7.3Hz),8.05(s,1H),8.73(s,1H).
I-133
mp:198-200℃
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.3Hz),0.97(t,3H,J=6.7Hz),1.18-1.81(m,7H),1.39(s,9H),1.98-2.05(m,2H),2.21-2.24(m,3H),3.29(m,1H),4.00(dd,1H,J=10.7,6.7Hz),4.09(dd,1H,J=10.7,6.1Hz),4.27(d,1H,J=9.8Hz),6.37(d,1H,J=15.9Hz),7.47(d,2H,J=8.5Hz),7.59(d,2H,J=8.5Hz),7.62(d,1H,J=15.9Hz),7.83(brs,1H).
I-134
mp:212-213℃
1H-NMR(CDCl3)δppm:1.21-1.32(m,2H),1.39(s,9H),1.59-1.73(m,2H),1.99-2.04(m,2H),2.10-2.26(m,3H),3.26(m,1H),3.72(d,1H,J=9.6Hz),6.74(m,1H),7.02(d,2H,J=7.4Hz),7.11(t,1H,J=7.4Hz),7.13-7.19(m,2H),7.22-7.26(m,2H),7.34(t,2H,J=7.4Hz).
I-135
mp:294-296℃
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.28-1.55(m,4H),1.81-2.05(m,4H),2.26(m, 1H),2.98-3.20(m,2H),6.78(d,1H,J=9.0Hz),7.31(t,1H,J=7.5Hz),7.54-7.72(m,5H),7.94(brs,1H).
I-136
mp:>300℃
1H-NMR(DMSO-d6)δppm:1.28(s,9H),1.29-1.59(m,4H),1.81-2.02(m,4H),2.27(m,1H),3.06(m,1H),6.81(d,1H,J=8.7Hz),7.38(t,1H,J=7.2Hz),7.48(t,2H,J=7.2Hz),7.62-7.81(m,10H),9.93(brs.1H).
I-137
mp:291-292℃
1H-NMR(CDCl3)δppm:1.25-1.39(m,2H),1.41(s,9H),1.61-1.80(m,2H),2.01-2.36(m,5H),3.32(m,1H),3.63(d,1H,J=9.3Hz),7.20(brs,1H),7.53-7.74(m,8H).
I-138
mp:259-262℃
1H-NMR(CD3OD)δppm:1.40(s,9H),1.40-1.80(m,4H),2.00-2.30(m,4H),2.45(m,1H),3.00(s,3H),3.15-3.30(m,2H),7.90(d,1H,J=8.4Hz),8.12(d,1H,J=9.0Hz),8.39(d,1H,J=9.0Hz),8.72(s,1H),8.92(d,1H,J=8.4Hz),10.4(s,1H).
I-139
mp:265-268℃
1H-NMR(CDCl3)δppm:1.25-1.40(m,2H),1.40(s,9H),168-1.81(m,2H),2.05-2.10(m,2H),2.23-2.37(m,3H),3.32(m,1H),4.27(d,1H,J=9.1Hz),7.53(t,1H,J=7.9Hz),7.63(td,1H,J=7.9,1.4Hz),7.77(d,1H,J=7.9Hz),8.03(d,1H,J=7.9Hz),8.37(brs,1H),8.85-8.86(m,2H).
I-140
mp:258-260℃
1H-NMR(CDCl3)δppm:1.20-1.40(m,2H),1.41(s,9H),1.52-1.85(m,2H),2.08-2.35(m,5H),3.34(m,1H),3.75(m,1H),7.35-7.66(m,3H),8.05(d,1H,J=9.0Hz),8.11(d,1H,J=9.0Hz),8.40(brs,1H),8.83(s,1H).
I-141
mp:205-206℃
1H-NMR(CDCl3)δppm:1.20-1.37(m,2H),1.40(s,9H),1.43-1.62(m,2H),1.90-2.01(m,2H),2.02-2.23(m,3H),3.27(m,1H),8.63(d,1H,J=9.6Hz),3.70(s,3H),6.64(d,1H,J=8.8Hz),7.28-7.41(m,5H),7.45(brs,1H),8.26(d,1H J=8.8Hz).
I-142
mp:277-280℃
1H-NMR(CDCl3)δppm:0.23-0.34(m,2H),1.34(s,9H),1.34-1.55(m,5H),1.76-1.80(m,2H),2.97(m,1H),3.31(d,1H,J=9.6Hz),7.18(s,1H),7.50-7.59(m,4H),7.77(dd,1H,J=7.4,1.0Hz),7.91-7.98(m,2H),8.39(dd,1H,J=7.4,1.9Hz).
I-143
mp:202-203℃
1H-NMR(CDCl3)δppm:1.23-1.40(m,2H),1.40(s,9H),1.57-1.71(m,2H),2.05-2.10(m,2H),2.18-2.28(m,3H),3.31(m,1H),3.91(s,3H),3.93(s,3H),4.05(d,1H,J=9.5Hz),8.15(s,1H),9.56(s,1H).
I-144
mp:177-178℃
1H-NMR(CDCl3)δppm:1.27-1.39(m,2H),1.40(s,9H),1.65-1.79(m,2H),2.04-2.07(m,2H),2.12-2.34(m,3H),3.22(m,1H),3.93(d,1H,J=9.1Hz),6.90-7.03(m,3H),7.25(m,1H),7.77(dd,1H,J=4.9,1.7Hz),7.81(brs,1H),8.72(dd,1H,J=7.8,1.5Hz).
I-145
mp:>300℃
1H-NMR(DMSO-d6)δppm:1.30(s,9H),1.44-1.70(m,4H),2.05-2.19(m,4H),2.73(m,1H),3.18(m,1H),6.86(d,1H,J=8.8Hz),7.62(t,2H,J=8.5Hz),7.86(t,2H,J =8.5Hz),7.89(d,2H,J=8.5Hz),8.16(d,2H,J=8.5Hz).
I-146
mp:240-242℃
1H-NMR(DMSO-d6)δppm:1.26-1.53(m,4H),1.27(s,9H),1.74-1.83(m,2H),1.90-1.97(m,2H),2.26(m,1H),3.04(m,1H),6.59(brs,1H),6.74-6.79(m,3H),7.74(s,1H),10.32(s,1H),12.80(s,1H).
I-147
mp:167-169℃
1H-NMR(CDCl3)δppm:1.05-1.28(m,2H),1.38(s,9H),1.47-1.70(m,2H),1.80-2.00(m,3H),2.13-2.25(m,2H),2.75(t,2H,J=6.9Hz),3.24(m,1H),3.49(dt,2H,J=6.3,6.9Hz),3.58(d,1H,J=8.7Hz),3.87(s,6H),5.40(brs,1H),6.71(m,2H),6.82(d,1H,J=8.7Hz).
I-148
mp:171-172℃
1H-NMR(CDCl3)δppm:1.16-1.38(m,2H),1.39(s,9H),1.50-1.79(m,4H),1.85-2.02(m,3H),2.15-2.30(m,2H),2.35-2.56(m,6H),3.25(m,1H),3.33(q,2H,J=6.0Hz),3.63(d,1H,J=9.0Hz),3.72(t,4H,J=4.6Hz),6.77(brs,1H).
I-149
1H-NMR(CDCl3)δppm:1.20-1.36(m,2H),1.28(t,2H,J=7.2Hz),1.39(s,9H),1.45-1.70(m,2H),1.85-2.30(m,7H),2.43(s,3H),3.05-3.42(m,3H),3.46-3.80(m,3H),7.31(d,1H,J=7.2Hz),7.40-7.52(m,3H),8.18(brs,1H).
I-150
mp:203-204℃
1H-NMR(CDCl3)δppm:1.15-1.37(m,2H),1.39(s,9H),1.42-1.70(m,2H),1.85-2.29(m,5H),2.76(t,2H,J=6.0Hz),3.26(m,1H),3.49(q,2H,J=6.0Hz),3.61(m,1H),4.03(s,2H),5.88(brs,1H),7.15(dd,1H,J=7.0,8.8Hz),7.30-7.35(m,2H).
I-151
mp:181-183℃
1H-NMR(CDCl3)δppm:1.15-1.30(m,2H),1.39(s,9H),1.45-1.64(m,2H),1.88-2.05(m,3H),2.15-2.25(m,2H),2.69(t,2H,J=6.0Hz),3.28(m,1H),3.47(q,2H,J=6.0Hz),3.58(d,1H,J=9.9Hz),3.87(s,2H),5.83(brs,1H),7.00(m,1H),7.20(m,2H).
I-152
mp:222-224℃
1H-NMR(CDCl3)δppm:1.16-1.37(m,2H),1.39(s,9H),1.49-1.70(m,2H),1.90-2.25(m,5H),3.26(m,1H),3.36(t,2H,J=6.4Hz),3.66(dt,3H,J=6.0,6.4Hz),5.87(t,1H,J=6.0Hz),7.58(s,1H),7.68(dd,1H,J=7.0,8.5Hz),7.83(dd,1H,J=7.0,8.5Hz),8.19(t,2H,J=8.5Hz).
I-153
mp:207-209℃
1H-NMR(CDCl3)δppm:1.05-1.25(m,2H),1.38(s,9H),1.40-2.03(m,10H),2.05-2.25(m,2H),2.58(s,3H),2.76(m,1H),3.05-3.35(m,2H),3.97(d,1H,J=9.5Hz),4.94(t,1H,J=4.0Hz),8.42(d,1H,J=5.5Hz),8.97(d,1H,J=5.5Hz).
I-154
mp:184-185℃
1H-NMR(CDCl3)δppm:1.05-1.25(m,2H),1.37(s,9H),1.50-1.69(m,2H),1.85-2.05(m,3H),2.10-2.21(m,2H),3.24(m,1H),3.64(m,1H),4.87(s,1H),4.88(s,1H),5.67(brs,1H),7.42(d,2H,J=5.5Hz),7.52(m,2H),7.78(m,1H),7.82(m,1H),7.95(d,1H,J=7.0Hz).
I-155
mp:208-210℃
1H-NMR(DMSO-d6)δppm:1.26(s,9H),1.27-1.50(m,4H),1.75-2.00(m,4H),2.16(m,1H),2.81(s,3H),3.02(m,1H),6.79(d,1H,J=8.5Hz),10.00(s,1H),10.66(s,1H).
I-156
mp:256-257℃
1H-NMR(CDCl3)δppm:1.20-1.39(m,2H),1.41(s,9H),1.60-1.81(m,2H),2.01-2.35(m,5H),2.69(t,2H,J=6.0Hz),3.11(t,2H,J=6.0Hz),3.30(m,1H),3.61(d,1H,J=9.3Hz),7.21(d,1H,J=8.0Hz),7.31(s,1H),7.70(d,1H,J=8.0Hz),7.99(s,1H).
I-157
mp:269-271℃
1H-NMR(CDCl3)δppm:1.20-1.45(m,2H),1.41(s,9H),1.70-1.90(m,2H),2.10-2.45(m,5H),3.37(m,1H),3.68(m,1H),7.45(dd,1H,J=4.0,8.0Hz),7.53(brs,1H),7.72(t,1H,J=8.0Hz),7.83(d,1H,J=8.0Hz),8.02(d,1H,J=8.0Hz),8.18(d,1H,J=8.0Hz),8.93(d,1H,J=4.0Hz).
I-158
mp:253-255℃
1H-NMR(CDCl3)δppm:1.20-1.40(m,2H),1.42(s,9H),1.60-1.90(m,2H),2.06-2.50(m,5H),2.72(s,3H),3.33(m,1H),3.78(d,1H,J=9.2Hz),7.52(t,1H,J=7.0Hz),7.62-7.80(m,2H),7.94(brs,1H),8.05(d,1H,J=8.5Hz),8.20(s,1H).
I-159
mp:253-255℃
1H-NMR(CDCl3)δppm:1.20-1.39(m,2H),1.40(s,9H),1.60-1.80(m,2H),1.98-2.30(m,5H),2.71(s,3H),3.31(m,1H),3.68(d 1H,J=9.0Hz),7.41(brs,1H),7.61(d,2H,J=9.0Hz),7.70(d,2H,J=9.0Hz).
I-160
mp:211-212℃
1H-NMR(CDCl3)δppm:1.20-1.32(m,2H),1.39(t,3H,J=7.0Hz),1.40(s,9H),1.55-1.79(m,2H),1.98-2.35(m,5H),3.31(m,1H),3.65(d,1H,J=9.5Hz),4.03(q,2H,J=7.0Hz),6.64(d,1H,J=8.0Hz),6.92(d,1H,J=8.0Hz),7.10(s,1H),7.19(t,1H,J=8.0Hz),7.30(brs,1H).
I-161
mp:202-203℃
1H-NMR(CDCl3)δppm:0.96(t,1H,J=7.3Hz),1.29-1.39(m,2H),1.40(s,9H),1.41-1.58(m,2H),1.60-1.80(m,4H),1.98-2.31(m,5H),3.31(m,1H),3.66(d,1H,J=8.5Hz),3.96(t,2H,J=6.4Hz),6.64(d,1H,J=8.0Hz),6.90(d,1H,J=8.0Hz),7.11(s,1H),7.19(t,1H,J=8.0Hz),7.31(brs,1H).
I-162
mp:177-180℃
1H-NMR(CDCl3)δppm:1.18-1.38(m,2H),1.39(s,9H),1.59-1.78(m,2H),1.95-2.05(m,2H),2.07-2.25(m,3H),3.26(m,1H),3.46(s,3H),4.17(d,1H,J=9.5Hz),5.15(s,2H),6.77(d,1H,J=8.0Hz),7.10-7.23(m,2H),7.34(s,1H),7.58(s,1H).
I-163
mp:175-178℃
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.28-1.50(m,4H),1.78-2.00(m,4H),2.22(m,1H),2.96-3.15(m,2H),6.67(m,1H),6.79(d,1H,J=8.5Hz),7.18(m,2H),7.38(s,1H),9.81(s,1H).
I-164
mp:232-233℃
1H-NMR(CDCl3)δppm:0.97(t,3H,J=7.3Hz),1.22-1.30(m,2H),1.40(s,9H),1.44-1.51(m,2H),1.67-1.77(m,4H),2.02-2.24(m,5H),3.22(m,1H),3.62(d,1H,J=9.6Hz),4.25(t,2H,J=6.8Hz),6.71(d,1H,J=8.4Hz),7.01(brs,1H),7.91(dd,1H,J=8.4,3.3Hz),8.08(d,1H,J=3.3Hz).
I-165
mp:199-200℃
1H-NMR(CDCl3)δppm:0.96(t,3H,J=7.4Hz),1.24-1.50(m,4H),1.40(s,9H),1.67-1.76(m,3H),2.03-2.08(m,2H),2.24-2.35(m,3H),3.29(m,1H),3.76(d,1H,J=9.1Hz),3.91(t,2H,J=6.6Hz),6.41(dd,1H,J=8.8,2.5Hz),6.55(d,1H,J=2.5Hz),6.82(d,1H,J=8.8Hz),7.43(s,1H),8.95(s,1H).
I-166
mp:215-218℃
1H-NMR(CDCl3+CD3OD)δppm:0.97(t,3H,J=7.4Hz),1.24-1.40(m,4H),1.39(s,9H),1.42-1.50(m,2H),1.54-1.72(m,2H),1.76-1.82(m,2H),1.91-2.00(m,2H),2.06-2.22(m,3H),3.24(m,1H),4.00(t,2H,J=6.6Hz),6.78(d,1H,J=8.8Hz),6.98(dd,1H,J=8.8,2.5Hz), 7.09(d,1H,J=8.8Hz).
I-167
mp:212-213℃
1H-NMR(CDCl3)δppm:0.96(t,3H,J=7.5Hz),1.26-1.34(m,2H),1.40(s,9H),1.45-1.50(m,2H),1.68-1.77(m,4H),2.03-2.08(m,2H),2.17(m,1H),2.26-2.29(m,2H),3.29(m,1H),3.60(d,1H,J=9.0Hz),4.25(t,2H,J=6.8Hz),6.71(d,1H,J=8.4Hz),7.01(brs,1H),7.91(dd,1H,J=8.4,3.3Hz),8.08(d,1H,J=3.3Hz).
I-168
mp:230-232℃
1H-NMR(CDCl3)δppm:1.22-1.35(m,2H),1.40(s,9H),1.63-1.77(m,2H),2.03-2.08(m,2H),2.15-2.29(m,3H),3.31(m,1H),3.63(d,1H,J=9.3Hz),6.89(d,1H,J=9.4Hz),7.10(brd,2H,J=7.4Hz),7.12(brs,1H),7.18(t,1H,J=7.4Hz),7.36(brt,2H,J=7.4Hz),8.09-8.15(m,2H).
I-169
mp:159-160℃
1H-NMR(CDCl3)δppm:0.97(t,3H,J=7.3),1.20-1.35(m,2H),1.40(s,9H),1.37-1.49(m,2H),1.61-1.78(m,4H),2.05-2.08(m,2H),2.23-2.26(m,2H),2.36(s,3H),2.97(brs,1H),3.32(m,1H),3.36(brs,1H),4.30(t,2H,J=6.5Hz),6.25(s,1H),7.92(brs,1H).
I-170
mp:180-181℃
1H-NMR(CDCl3)δppm:0.88-0.89(m,2H),1.39(s,9H),1.42-1.60(m,2H),1.86-1.90(m,2H),2.04-2.09(m,2H),2.42(s,3H),2.91(m,1H),3.20(m,1H),3.63(d,1H,J=9.2Hz),6.38s,1H),7.15(m,2H),7.28(m,1H),7.45(m,2H),7.84(brs,1H).
I-171
mp:173-174℃
1H-NMR(CDCl3)δppm:0.98(t,3H,J=7.5Hz),1.29-1.40(m,2H),1.40(s,9H),1.55(m,2H),1.62-1.83(m,4H),2.09-2.12(m,2H),2.24-2.32(m,3H),3.32(m,1H),3.63(d,1H,J= 9.5Hz),3.99(t,2H,J=6.4Hz),7.22(d d,1H,J=9.4,2.7Hz),7.66(d,1H,J=2.7Hz),8.63(d,1H,J=9.4Hz),10.17(s,1H).
I-172
mp:238-242℃
1H-NMR(CDCl3)δppm:0.96(t,3H,J=7.3Hz),1.23-1.52(m,4H),1.40(s,9H),1.61-1.78(m,4H),2.05-2.28(m,5H),3.30(m,1H),3.66(d,1H,J=9.4Hz),3.84(brs,2H),3.90(t,2H,J=6.4Hz),6.32-6.35(m,2H),6.96(brs,1H),6.97(d,1H,J=9.4Hz).
I-173
mp:165-166℃
1H-NMR(CDCl3)δppm:1.23-1.26(m,2H),1.40(s,9H),1.67-1.72(m,2H),2.01-206(m,2H),2.11-2.28(m,3H),3.31(m,1H),3.60(s,2H),3.69(s,3H),4.02(brs,1H),7.01(d,1H,J=8.0Hz),7.25(t,1H,J=8.0Hz),7.43(d,1H,J=8.0Hz),7.49(brs,1H),7.51(brs,1H).
I-174
mp:264-265℃
1H-NMR(CDCl3+CD3OD)δppm:1.26-1.29(m,2H),1.39(s,9H),1.62-1.69(m,2H),1.96-2.00(m,2H),2.18-2.21(m,3H),3.25(m,1H),3.58(s,2H),7.01(d,1H,J=7.5Hz),7.26(t,1H,J=7.5Hz),7.42(brs,1H),7.50(d,1H,J=7.5Hz).
I-175
mp:90-94℃
1H-NMR(CDCl3)δppm:1.16-1.23(m,2H),1.37(s,9H),1.44-1.56(m,2H),1.73-1.85(m,3H),2.11-2.15(m,2H),3.57(t,2H,J=6.4Hz),3.21(m,1H),3.58(m,2H),3.84(d,1H,J=9.3Hz),5.56(brs,1H),7.01(s,1H),7.11(t,1H,J=7.5Hz),7.21(t,1H,J=7.5Hz),7.38(d,1H,J=7.5Hz),7.59(d,1H,J=7.5Hz),8.24(brs,1H).
I-176
mp:116-118℃
1H-NMR(CDCl3)δppm:1.18-1.38(m,2H),1.40(s,9H),1.60-1.79(m,2H),1.95-2.30(m,5H),3.30(m,1H),3.69(m,1H),3.80(s,3H),4.64(s,2H),6.67(d,1H,J=8.0Hz),7.00(d, 1H,J=8.5Hz),7.15-7.24(m,2H),7.32(brs,1H).
I-177
mp:219-220℃
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.28-1.50(m,4H),1.75-2.01(m,4H),2.18-2.30(m,1H),2.95-3.15(m,2H),4.61(s,2H),6.56(m,1H),6.80(d,1H,J=8.5Hz),7.16(m,2H),7.28(brs,1H),9.87(brs,1H).
I-178
mp:170-173℃
1H-NMR(CDCl3)δppm:1.18-1.39(m,2H),1.40(s,9H),1.50-1.80(m,2H),1.90-2.33(m,5H),2.36(s,6H),2.75(t,2H,J=5.5Hz),3.30(m,1H),3.70(m,1H),4.08(t,2H,J=5.5Hz),6.68(d,1H,J=8.0Hz),6.94(d,1H,J=7.5Hz),7.15-7.23(m,2H),7.33(brs,1H).
I-179
mp:191-193℃
1H-NMR(CDCl3)δppm:1.20-1.39(m,2H),1.40(s,9H),1.58-1.80(m,2H),1.98-2.32(m,5H),3.30(m,1H),3.70(d,1H,J=9.5Hz),4.77(s,2H),6.73(d,1H,J=8.0Hz),7.04(d,1H,J=8.0Hz),7.20-7.31(m,2H),7.48(brs,1H).
I-180
mp:174-176℃
1H-NMR(CDCl3)δppm:1.10-1.30(m,2H),1.40(s,9H),1.45-1.65(m,2H),1.81-2.02(m,3H),2.15-2.30(m,2H),2.58(t,2H,J=6.5Hz),3.25(m,1H),3.37(dt,2H,J=5.5,6.5Hz),3.60(d,1H,J=9.5Hz),3.71(s,2H),5.73(brs,1H),7.20-7.40(m,5H).
I-181
mp:176-178℃
1H-NMR(CDCl3)δppm:1.15-1.30(m,2H),1.39(s,9H),1.45-1.70(m,6H),1.85-2.01(m,3H),2.15-2.28(m,2H),2.63(t,2H,J=7.0Hz),3.25(dt,2H,J=6.0,7.0Hz),3.27(m,1H),3.63(m,1H),5.35(brs,1H),7.17(m,3H),7.29(m,2H).
I-182
mp:152-154℃
1H-NMR(CDCl3)δppm:1.15-1.30(m,2H),1.39(s,9H),1.45-1.65(m,2H),1.85-2.05(m,3H),2.09-2.25(m,2H),3.25(m,1H),3.45(dt,2H,J=5.0,5.0Hz),3.55(t,2H,J=5.0Hz),3.60(m,1H),4.51(s,2H),5.81(brs,1H),7.29-7.40(m,5H).
I-183
mp:208-211℃
1H-NMR(CDCl3)δppm:1.20-1.31(m,2H),1.39(s,9H),1.62-1.68(m,2H),1.98-2.25(m,5H),3.30(m,1H),3.57(d,1H,J=9.2Hz),4.59(d,2H,J=5.8Hz),5.76(brs,1H),7.37(dd,1H,J=8.4,2.0Hz),7.46-7.52(m,2H),7.69(brs,1H),7.78-7.83(m,3H).
I-184
mp:180-182℃
1H-NMR(CDCl3)δppm:1.22-1.37(m,2H),1.40(s,9H),1.60-1.69(m,2H),2.05-2.09(m,2H),2.21-2.27(m,3H),3.45(m,1H),3.64(d,1H,J=9.6Hz),4.77(d,2H,J=4.9Hz),7.43(d,1H,J=8.6Hz),7.46(brs,1H),7.61(t,1H,J=7.7Hz),7.73(t,1H,J=7.7Hz),7.87(t,1H,J=7.7Hz),8.20(t,1H,J=7.7Hz),8.24(d,1H,J=8.6Hz).
I-185
mp:260-261℃
1H-NMR(CDCl3)δppm:1.22-1.32(m,2H),1.39(s,9H),1.60-1.70(m,2H),1.97-2.01(m,2H),2.11(m,1H),2.21-2.24(m,2H),3.30(m,1H),3.61(d,1H,J=9.3Hz),4.95(d,2H,J=6.0Hz),5.85(brs,1H),7.33(d,1H,J=4.8Hz),7.62(dd,1H,J=8.4,6.9Hz),7.75(dd,1H,J=8.1,6.9Hz),8.00(d,1H,J=8.1Hz),8.20(d,1H,J=8.4Hz),8.42(d,1H,J=4.8Hz).
I-186
mp:231-233℃
1H-NMR(CDCl3)δppm:1.23-1.40(m,2H),1.40(s,9H),1.62-1.76(m,2H),2.04-2.10(m,2H),2.22-2.32(m,3H),3.30(m,1H),3.95(d,1H,J=9.3Hz),5.04(d,2H,J=4.1Hz),7.61(d,1H,J=5.8Hz),7.63(brs,1H),7.65(dd,1H,J=8.2,6.9Hz),7.73(dd,1H,J=8.5,6.9Hz),7.86(d,1H,J=8.2Hz),8.10(d,1H,J=8.5Hz),8.42(d,1H,J=5.8Hz).
I-187
mp:184-187℃
1H-NMR(CDCl3)δppm:0.97(t,3H,J=7.3Hz),1.18-1.30(m,2H),1.39(s,9H),1.42-1.65(m,4H),1.70-1.80(m,2H),1.94-2.08(m,8H),2.18-2.26(m,2H),3.29(m,1H),3.61(d,1H,J=9.5Hz),3.93(t,2H,J=6.4Hz),4.39(d,2H,J=5.5Hz),5.67(brs,1H),6.79-6.83(m,3H),7.23(t,1H,J=7.6Hz).
I-188
mp:224-226℃
1H-NMR(CDCl3)δppm:16-1.31(m,2H),1.38(s,9H),1.55-1.70(m,2H),1.92-2.07(m,3H),2.17-2.23(m,2H),3.21(m,1H),3.81(s,3H),3.83(s,6H),4.05(d,1H,J=9.8Hz),4.34(d,2H,J=5.8Hz),5.96(brs,1H),6.47(s,2H).
I-189
mp:217-218℃
1H-NMR(CDCl3)δppm:1.15-1.30(m,2H),1.37(s,9H),1.52-1.66(m,2H),1.90-2.06(m,3H),2.13-2.20(m,2H),2.93(s,6H),3.24(m,1H),3.94(d,1H,J=9.5Hz),4.30(d,2H,J=5.5Hz),5.73(brs,1H),6.69(d,2H,J=8.9Hz),7.12(d,2H,J=8.9Hz).
I-190
mp:无定形固体
1H-NMR(CDCl3)δppm:1.17-1.32(m,2H),1.39(s,9H),1.54-1.72(m,2H),1.96-2.13(m,3H),2.18-2.27(m,2H),3.30(m,1H),3.63(d,1H,J=9.2Hz),4.51(d,2H,J=5.8Hz),5.82(brs,1H),7.40(d,2H,J=8.5Hz),8.02(d,2H,J=8.5Hz),8.64(s,1H),
I-191
mp:126-128℃
1H-NMR(CDCl3)δppm:0.97(t,3H,J=7.4Hz),1.10-1.28(m,2H),1.36(s,9H),1.42-1.86(m,9H),2.06-2.18(m,2H),3.22(m,1H),3.95(t,2H,J=4.5Hz),4.16(brs,1H),4.85(s2H),6.82-6.95(m,3H),7.26(t,1H,J=7.8Hz),8.54(brs,1H).
I-192
mp:178-181℃
1H-NMR(CDCl3)δppm:0.96(t,3H,J=7.3Hz),1.18-1.52(m,4H),1.39(s,9H),1.58-1.76(m,4H),1.92-2.00(m,2H),2.02-2.29(m,3H),3.28(m,1H),3.78(d,1H,J=9.5Hz),3.89(t,2H,J=6.6Hz),6.00(brs,1H),6.78(s,4H),7.35(brs,1H).
I-193
mp:187-188℃
1H-NMR(CDCl3+CD3OD)δppm:1.21-1.40(m,2H),1.38(s,9H),1.52-1.69(m,2H),1.90-2.00(m,2H),2.02-2.20(m,3H),3.22(m,1H),3.75(s,3H),6.79(s,4H).
I-194
mp:251-253℃
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.24-1.50(m,4H),1.72-1.83(m,2H),1.91-1.99(m,2H),2.16(m,1H),3.02(m,1H),3.82(s,3H),6.79(d,1H,J=8.2Hz),7.01(d,2H,J=8.8Hz),7.85(d,2H,J=8.8Hz),9.72(brs,1H),8.64(brs,1H).
I-195
mp:183-185℃
1H-NMR(CDCl3)δppm:1.22-1.37(m,2H),1.40(s,9H),1.58-1.75(m,2H),2.05-2.10(m,2H),2.20-2.30(m,3H),3.32(m,1H),3.70(s,2H),3.73(s,3H),6.79(s,1H),8.83(brs,1H).
I-196
mp:185-187℃
1H-NMR(CDCl3)δppm:1.20-1.39(m,2H),1.40(s,9H),1.44(t,6H,J=7.0Hz),1.60-1.80(m,2H),1.95-2.35(m,5H),3.30(m,1H),3.62(d,1H,J=8.9Hz),4.06(q,2H,J=7.0Hz),4.09(q,2H,J=7.0Hz),6.08(s,1H),7.02(s,1H),7.36(s,1H).
I-197
mp:211-213℃
1H-NMR(CDCl3)δppm:1.20-1.40(m,2H),1.41(s,9H),1.60-1.80(m,2H),2.00-2.36(m,5H),2.61(s,3H),3.32(m,1H),3.64(d,1H,J=9.2Hz),7.28(s,1H),7.43(t,1H,J=7.5Hz),7.69(d,1H,J=7.5Hz),7.85(d,1H,J=7.5Hz),8.02(s,1H).
I-198
mp:268-269℃
1H-NMR(CDCl3)δppm:1.20-1.39(m,2H),1.40(s,9H),1.42-2.32(m,7H),2.90-3.10(m,4H),3.30(m,1H),3.68(d,1H,J=8.8Hz),6.59(s,1H),7.18(d,1H,J=8.7Hz),7.59(d,1H,J=8.7Hz),7.77(brs,1H).
I-199mp:221-224℃
I-200mp:237-240℃
I-201mp:87-90℃
I-202mp:222-223℃
I-203mp:255-257℃
I-204mp:234-236℃
I-205mp:208-210℃
I-206mp:217-218℃
I-207mp:275-279℃
I-208mp:248-250℃
I-209mp:256-258℃
I-210mp:270-271℃
I-211mp:219-220℃
I-212mp:260-261℃
I-213mp:>300℃
I-214mp:206-207℃
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.4Hz),1.30-1.42(m,2H),1.49(d,6H,J=6.9Hz),1.53-1.65(m,2H),2.61(t,2H,J=7.7Hz),4.15(七重峰,1H,J=6.9Hz),7.04(d,1H,J=8.2Hz),7.20(d,2H,J=8.2Hz),7.51(d,2H,J=8.2Hz),7.89(d,1H,J=8.8Hz),8.18(s,1H),10.55(s,1H).
I-215
1H-NMR(CDCl3)δppm:0.93(t,3H,J=7.3Hz),1.30-1.41(m,2H),1.52-1.63(m,2H), 1.95(s,6H),2.61(t,2H,J=7.8Hz),6.99(brs,1H),7.20(d,2H,J=8.5Hz),7.65(d,2H,J=8.5Hz),7.93(dd,1H,J=8.5,2.5Hz),8.28(d,1H,J=8.5Hz),8.55(d,1H,J=2.5Hz),9.76(brs,1H).
Ia-1
mp 221-224℃
1H-NMR(CDCl3)δppm:1.19-.38(m,2H),1.40(s,9H),1.62-1.77(m,2H),2.00-2.31(m,5H),3.18(t,4H,J=4.8Hz),3.21-3.38(m,1H),3.85(t,4H,J=4.8Hz),6.64-6.32(m,2H),7.11(s,1H),7.20(t,1H,J=7.8Hz),7.45(s,1H).
Ia-3
mp 87-90℃
1H-NMR(CDCl3)δppm:1.25(d,6H,J=6.3Hz),1.37(d,6H,J=6.9Hz),1.59-1.70(m,2H),1.76-1.88(m,2H),2.32-2.42(m,4H),3.11-3.23(m,3H),3.39(d,2H,J=10.8Hz),3.74-3.86(m,2H),4.34(t,1H,J=9.0Hz),6.86(d,2H,J=9.0Hz),7.30(s,1H),7.40(d,2H,J=9.0Hz).
Ia-4
mp 233-234℃
1H-NMR(CDCl3)δppm:1.25(d,6H,J=6.3Hz),1.40(s,9H),1.26-1.37(m,2H),1.62-1.78(m,2H),2.00-2.22(m,5H),2.42(t,2H,J=11.7Hz),3.20-3.40(m,1H),3.46(d,2H,J=10.5Hz),3.67(d,1H,J=9.3Hz),3.72-3.84(m,2H),6.62-6.76(m,2H),7.10(s,1H),7.18(t,1H,J=7.8Hz),7.42(s,1H).
Ia-5
mp 125-126℃
1H-NMR(CDCl3)δppm:1.25(d,6H,J=6.3Hz),1.40(s,9H),1.59-1.70(m,2H),1.77-1.84(m,2H),2.30-2.46(m,4H),3.24(q,2H,J=6.6Hz),3.38(d,2H,J=11.7Hz),3.74-3.88(m,2H),4.08(t,1H,J=5.7Hz),6.87(d,2H,J=8.7Hz),7.30(s,1H),7.41(d,2H,J=8.7Hz).
Ia-6
mp 229-230℃
1H-NMR(CDCl3)δppm:1.25(d,6H,J=6.3Hz),1.26-1.34(m,2H), Hz),1.61-1.77(m,2H),1.98-1.26(m,5H),2.32-246(m,2H),3.15(五重峰,1H,J=6.6Hz),3.22-3.35(m,1H),3.39(d,2H,J=11.4Hz),3.74-3.92(m,2H),3.88(d,1H,J=8.4Hz),6.96-6.71(m,2H),7.05(brs,1H),7.39(d,2H,J=9.3Hz).
Ia-7
mp 253-254℃
1H-NMR(DMSO)δppm:1.24-1.60(m,4H),1.27(s,9H),1.77-2.07(m,4H),2.16-2.34(m,1H),2.97-3.15(m,1H),6.78(d,1H,J=7.2Hz),7.01(t,1H,J=6.0Hz),7.27(t,2H,J=6.6Hz),7.58(d,2H,J=7.5Hz),9.78(s,1H).
Ia-8
mp 257-258℃
1H-NMR(DMSO)δppm:1.22-1.54(m,4H),1.27(s,9H),1.77-1.88(m,2H),1.88-2.00(m,2H),2.16-2.34(m,1H),2.23(s,3H),2.92-3.14(m,1H),6.77(d,1H,J=8.4Hz),7.07(d,2H,J=8.4Hz),7.46(d,2H,J=8.1Hz),9.68(s,1H).
Ia-9
mp 231-232℃
1H-NMR(CDCl3)δppm:1.21(t,3H,J=7.5Hz),1.22-1.38(m,2H),1.40(s,9H),1.62-1.78(m,2H),1.98-2.31(m,5H),2.61(q,2H,J=7.5Hz),3.24-3.38(m,1H),3.70(d,1H,J=9.9Hz),7.11(s,1H),7.14(d,2H,J=8.7Hz),7.40(d,2H,J=8.7Hz).
Ia-10
mp 233-234℃
1H-NMR(CDCl3)δppm:0.96(t,3H,J=7.2Hz),1.20-1.37(m,2H),1.40(s,9H),1.56-1.78(m,4H),1.98-2.32(m,5H),2.54(t,2H,J=7.2Hz),3.23-3.39(m,1H),3.66(d,1H,J=9.6Hz),7.08(s,1H),7.12(d,2H,J=8.4Hz),7.39(d,2H,J=8.4Hz).
Ia-11
mp 243-244℃
1H-NMR(CDCl3)δppm:1.22(d,6H,J=6.9),1.22-1.77(m,4H),1.40(s,9H),2.01-2.30(m,5H),2.83-2.92(m,1H),3.24-3.40(m,1H),3.66-3.69(m,1H),7.09(s,1H),7.17(d,2H,J=8.4Hz),7.41(d,2H,J=8.1Hz).
Ia-12
mp 246-247℃
1H-NMR(CDCl3)δppm:0.80(t,3H,J=7.5),1.20(d,3H,J=7.2),1.26-1.77(m,6H),1.40(s,9H),2.01-2.27(m,5H),2.51-2.60(m,1H),3.20-3.38(m,1H),3.64-3.69(m,1H),7.08(s,1H),7.12(d,2H,J=8.4Hz),7.41(d,2H,J=8.4Hz).
Ia-13
mp 278-279℃
1H-NMR(CDCl3)δppm:1.22-1.52(m,4H),1.29(s,9H),1.40(s,9H),1.61-1.77(m,2H),2.02-2.30(m,5H),3.20-3.38(m,1H),3.66-3.69(m,1H),7.10(s,1H),7.33(d,2H,J=9.0Hz),7.42(d,2H,J=8.7Hz).
Ia-14
mp 263-264℃
1H-NMR(DMSO)δppm:1.24-1.51(m,4H),1.27(s,9H),1.82-1.99(m,4H),2.19-2.28(m,1H),2.98-3.12(m,1H),6.78(d,1H,J=8.7Hz),7.33(d,2H,J=8.7Hz),7.61(d,2H,J=9.0Hz),9.94(s,1H).
Ia-15
mp 209-210℃
1H-NMR(CDCl3)δppm:1.25(d,6H,J=6.3Hz),1.40(s,9H),1.70-1.98(m,8H),2.19-2.38(m,3H),3.39(d,2H,J=11.7Hz),3.58-3.92(m,3H),4.12-4.26(m,1H),6.82-6.96(m,2H),7.10(br,1H),7.41(d,2H,J=8.1Hz).
Ia-16
mp 238-240℃
1H-NMR(DMSO)δppm:1.22-1.52(m,4H),1.27(s,9H),1.81-1.84(m,2H),1.98-1.97(m,2H),2.16-2.23(m,1H),2.95-3.12(m,1H),3.70(s,3H),6.77(d,1H,J=8.4Hz),6.85(d,2H, J=9.0Hz),7.48(d,2H,J=9.3Hz),9.64(s,1H).
Ia-17
mp 245-246℃
1H-NMR(DMSO)δppm:1.22-1.52(m,4H),1.27(s,9H),1.83-1.87(m,2H),1.94-1.99(m,2H),2.20-2.28(m,1H),2.98-3.12(m,1H),6.78(d,1H,J=8.7Hz),7.28(d,2H,J=8.7Hz),7.69(d,2H,J=9.0Hz),9.64(s,1H).
Ia-18
mp240-241℃
1H-NMR(CDCl3)δppm:1.22-1.78(m,4H),1.40(s,9H),2.05-2.33(m,5H),3.22-3.44(m,1H),3.64-3.67(m,1H),6.61(s,1H),6.69-6.77(m,2H).
Ia-19
mp 240-241℃
1H-NMR(CDCl3)δppm:1.24-1.77(m,4H),1.40(s,9H),2.05-2.30(m,5H),3.22-3.38(m,1H),3.70-3.74(m,1H),7.00-7.15(m,3H),7.36(s,1H),8.29-8.34(m,1H).
Ia-20
mp 239-240℃
1H-NMR(CDCl3)δppm:1.24-1.78(m,4H),1.40(s,9H),2.02-2.30(m,5H),3.22-3.40(m,1H),3.63-3.66(m,1H),6.89-6.84(m,1H),7.10-7.17(m,2H),7.22-7.34(m,1H),7.48-7.51(m,1H).
Ia-21
mp 259-260℃
1H-NMR(CDCl3/DMSO)δppm:1.21(d,6H,J=6.0Hz),1.22-1.44(m,2H),1.40(s,9H),1.60-1.78(m,2H),1.87-2.03(m,2H),2.08-2.29(m,3H),2.39(t,2H,J=10.2Hz),3.14-3.32(m,1H),3.19(d,2H,J=11.4Hz),3.77-3.93(m,2H),5.33(d,1H,J=9.0Hz),6.84(dd,1H,JFH,HH=8.1,8.1Hz),7.20(d,1H,J=7.8Hz),7.49(d,1H,JFH=14.7Hz),8.86(s,1H).
Ia-22
mp 234-235℃
1H-NMR(CDCl3)δppm:1,20(d,6H,J=5.7Hz),1.22-1.44(m,2H),1.38(s,9H),1.54-1.76(m,2H),1.94-2.32(m,5H),2.27(s,3H),2.39(t,2H,J=10.8Hz),2.87(d,2H,J=11.4Hz),3.20-3.40(m,1H),3.76-3.92(m,2H),3.91(d,1H,J=9.3Hz),6.93(d,1H,J=8.1Hz),7.21(brs,1H),7.27(brs,1H),7.36(brs,1H).
Ia-23
mp195-196℃
1H-NMR(CDCl3)δppm:1.20-1.44(m,4H),1.41(s,9H),1.59-1.76(m,2H),2.03-2.14(m,2H),2.15-2.33(m,3H),3.20-3.40(m,1H),3.64(s,1H,J=9.0Hz),7.19-7.24(m,1H),7.44(brs,1H),7.52-7.63(m,2H),8.17(d,1H,J=8.7Hz).
Ia-24
mp 209-210℃
1H-NMR(CDCl3)δppm:1.22-1.39(m,2H),1.56(s,9H),1.61-1.78(m,2H),2.00-2.12(m,2H),2-17-2-33(m,3H),3.24-3.39(m,1H),3.67(d,1H,J=9.6Hz),6.90-7.01(m,1H),7.21(s,1H),7.95-8.06(m,1H).
Ia-25
mp 278-281℃
1H-NMR(DMSO-d6)δppm:1.10(d,6H,J=6.3Hz),1.27(s,9H),1.28-1.55(m,4H),1.78-2.00(m,4H),2.11-2.26(m,1H),2.31(t,2H,J=11.1Hz),3.00-3.10(m,1H),3.08(d,1H,J=10.8Hz),3.67-3.80(m,2H),6.78(d,1H,J=8.7Hz),7.08(d,1H,J=9.0Hz),7.41(dd,1H,J=2.4,8.7Hz),7.78(d,1H,J=8.7Hz),9.85(s,1H).
Ia-26
mp 253-255℃
1H-NMR(DMSO-d6)δppm:1.13(d,6H,J=6.0Hz),1.27(s,9H),1.28-1.52(m,4H),1.78-2.00(m,4H),2.21(t,2H,J=11.1Hz),2.26-2.36(m,1H),2.96-3.10(m,1H),3.56(d,1H,J=12.3Hz),3.60-3.72(m,2H),6.66-6.84(m,4H),7.47(t,1H,J=9.3Hz),9.28(s,1H).
Ia-27
mp 223-226℃
1H-NMR(DMSO-d6)δppm:1.09(d,6H,J=6.3Hz),1.27(s,9H),1.28-1.54(m,4H),1.77-2.01(m,4H),2.32(t,2H,J=11.1Hz),2.32-2.42(m,1H),2.90(d,1H,J=11.4Hz),2.96-3.12(m,1H),3.76-3.92(m,2H),6.78-6.98(m,3H),7.68(dd,1H,J=3.3,8.7Hz),8.84(s,1H)
Ia-28
mp 237-238℃
1H-NMR(CDCl3)δppm:1.22-1.44(m,2H),1.25(d,6H,J=6.3Hz),1.40(s,9H),1.61-1.79(m,2H),2.05-2.32(m,5H),2.21(s,3H),2.38(t,2H,J=10.2Hz),3.22-3.42(m,1H),3.40(d,2H,J=11.1Hz),3.65(d,1H,J=9.3Hz),3.72-3.90(m,2H),6.70-6.78(m,2H),6.81(brs,1H),7.50(d,1H,J=9.6Hz).
Ia-29
mp 208-209℃
1H-NMR(CDCl3)δppm:1.22(d,6H,J=6.0Hz),1.23-1.40(m,2H),1.40(s,9H),1.60-1.78(m,2H),2.00-2.16(m,2H),2.14-2.33(m,3H),2.45(t,2H,J=11.1Hz),3.21(d,2H,J=10.8Hz),3.24-3.38(m,1H),3.63(d,1H,J=9.3Hz),3.80-3.94(m,2H),5.33(d,1H,J=9.0Hz),6.66(dd,1H,JFH,HH=6.6,6.6Hz),7.16(brs,1H),7.89(dd,1H,JFH,HH=9.0,9.0Hz).
Ia-30
mp 284-287℃
1H-NMR(DMSO-d6)δppm:1.08(d,6H,J=6.0Hz),1.26(s,9H),1.28-1.53(m,4H),1.82-2.22(m,4H),2.25-2.39(m,1H),2.78(t,2H,J=10.5Hz),2.97-3.14(m,1H),3.18(d,2H,J=11.4Hz),3.65-3.76(m,2H),6.79(d,1H,J=8.7Hz),9.75(s,1H)
Ia-31
mp 200-201℃
1H-NMR(CDCl3)δppm:1.22-1.40(m,2H),1.40(s,9H),1.62-1.76(m,2H),2.04-2.32(m,5H),3.22-3.40(m,1H),3.62-3.66(m,1H),7.22-7.24(m,1H),7.38-7.38(m,1H),7.60(s, 1H),8.33-8.36(m,1H).
Ia-32
mp 260-261℃
1H-NMR(CDCl3/DMSO)δppm:1.25-1.42(m,2H),1.38(s,9H),1.64(q,2H,J=13.5Hz),1.95(d,2H,J=12.3Hz),2.16(d,2H,J=10.5Hz),2.18-2.32(m,1H),3.14-3.30(m,1H),5.53(d,1H,J=9.0Hz),7.31(d,1H,J=8.7Hz),7.46(dd,1H,J=2.4,8.7Hz),7.90(d,1H,J=2.1Hz),9.35(s,1H).
Ia-33
mp 227℃
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.30-1.56(m,4H),1.78-2.01(m,2H),2.12-2.36(m,2H),2.96-3.13(m,1H),3.70(s,3H),3.71(s,3H),6.77(d,1H,J=8.7Hz),6.85(d,1H,J=8.7Hz),7.06(dd,1H,J=2.4,8.7Hz),7.33(d,1H,J=2.4Hz),9.65(s,1H).
Ia-35
mp 214-216℃
1H-NMR(CDCl3)δppm:1.23-1.38(m,2H),1.40(s,9H),1.60-1.76(m,2H),2.00-2.12(m,2H),2.20-2.32(m,3H),3.24-3.39(m,1H),3.68(d,1H,J=9.0Hz),6.77(d,1H,J=8.7Hz),7.00(dd,1H,J=2.4,8.7Hz),7.77(s,1H),8.45(d,1H,J=2.4Hz).
Ia-36
mp 241-242℃
1H-NMR(CDCl3/DMSO)δppm:1.25-1.42(m,2H),1.37(s,9H),1.62(q,2H,J=11.7Hz),1.93(d,2H,J=12.0Hz),2.12(d,2H,J=10.8Hz),2.16-2.30(m,1H),3.12-3.28(m,1H),3.84(s,3H),6.07(d,1H,J=8.4Hz),6.89(dd,1H,JFH,HH=9.3,9.3Hz),7.24(d,1H,J=8.7Hz),7.55(d,1H,JFH=13.5Hz),9.32(s,1H).
Ia-37
mp 248-249℃
1H-NMR(CDCl3)δppm:0.60-0.73(m,1H),0.91(d,6H,J=6.6),1.12-1.40(m,2H),1.40(s,9H),1.54-1.88(m,5H),1.98-2.29(m,7H),3.22-3.37(m,1H),3.51-3.54(m,2H),3.72(d, 1H,J=9.6),6.88(d,1H,J=8.7),7.06(s,1H),7.35(d,1H,J=9.0).
Ia-38
mp 237-238℃
1H-NMR(CDCl3)δppm:1.01(d,6H,J=6.6),1.20-1.40(m,2H),1.40(s,9H),1.60-1.74(m,4H),1.99-2.28(m,7H),2.69-2.82(m,2H),3.02-3.14(m,2H),3.20-3.38(m,1H),3.80-3.90(m,1H),6.83-6.86(m,2H),7.14(s,1H),7.34(d,1H,J=8.4).
Ia-39
mp 284-235℃
1H-NMR(CDCl3)δppm:1.20-1.36(m,2H),1.40(s,9H),1.60-1.77(m,2H),1.90-2.32(m,5H),3.21-3.39(m,1H),8.65(d,1H,J=9.6Hz),6.87(d,1H,J=8.7Hz),7.04(s,1H),7.37(dd,1H,J=2.7,8.7Hz),7.56(d,1H,J=2.7Hz).
Ia-40
mp 257-258℃
1H-NMR(DMSO-d6)δppm:1.14(d,6H,J=6.0Hz),1.27(s,9H),1.28-1.53(m,4H),1.78-2.00(m,4H),2.13-2.256(m,1H),2.30(t,2H,J=11.7Hz),2.97-3.12(m,1H),3.53-3.67(m,2H),4.01(d,1H,J=12.3Hz),6.80(dd,1H,J=3.0,9.0Hz),7.79(d,1H,J=9.0Hz),8.27(s,1H),9.66(s,1H).
Ia-41
mp 245-246℃
1H-NMR(CDCl3/DMSO)δppm:1.25-1.42(m,2H),1.37(s,9H),1.62(q,2H,J=12.6Hz),1.94(d,2H,J=11.1Hz),2.13(d,2H,J=11.1Hz),2.18-2.35(m,1H),3.11-3.29(m,1H),6.07(d,1H,J=8.1Hz),6.95-7.06(m,1H),7.14-7.27(m,1H),7.44(d,1H,J=7.2Hz),7.79(s,1H),9.48(s,1H).
Ia-43
mp294-295℃
1H-NMR(DMSO-d6)δppm:1.26(s,9H),1.28-1.53(m,4H),1.76-1.87(m,2H),1.89-2.00(m,2H),2.13-2.25(m,1H),2.96-3.10(m,5H),3.52-3.60(m,4H),6.78(d,1H,J=9.0Hz), 6.88(d,2H,J=9.0Hz),7.44(d,2H,J=9.0Hz),9.59(s,1H).
Ia-44
mp 250-252℃
1H-NMR(CDCl3)δppm:1.13(d,6H,J=6.3Hz),1.21-1.38(m,2H),1.41(s,9H),1.63-1.80(m,2H),1.93(t,2H,J=10.8Hz),2.00-2.10(m,2H),2.16-2.32(m,3H),3.24-3.39(m,1H),3.54(d,2H,J=10.2Hz),3.64-3.78(m,3H),7.47(s,1H),7.69(d,2H,J=9.0Hz),7.73(d,2H,J=9.0Hz).
Ia-45
mp 193℃
1H-NMR(DMSO-d6)δppm:1.10(t,6H,J=7.2Hz),1.26(s,9H),1.28-1.52(m,4H),1.75-1.86(m,2H),1.89-2.01(m,2H),2.10-2.22(m,1H),2.96-3.10(m,1H),3.30-3.52(m,12H),6.60(d,2H,J=9.0Hz),6.80(d,1H,J=9.0Hz),7.33(d,2H,J=9.0Hz),9.46(s,1H).
Ia-46
mp>300℃
1H-NMR(DMSO-d6)δppm:1.28(s,9H),1.28-1.58(m,4H),1.83-2.04(m,4H),2.23-2.36(m,1H),2.46(s,3H),3.00-3.14(m,1H),6.79(d,1H,J=8.7Hz),7.34(d,1H,J=8.7Hz),7.78(d,2H,J=8.7Hz),7.89(d,1H,J=8.4Hz),7.91(s,1H),8.00(d,2H,J=8.7Hz),10.13(s,1H).
Ia-47
mp 236-237℃
1H-NMR(CDCl3)δppm:0.97(d,6H,J=6.6Hz),1.01(d,6H,J=6.6Hz),1.20-1.37(m,2H),1.40(s,9H),1.60-1.84(m,3H),1.97-2.31(m,5H),2.50(t,1H,J=10.8Hz),2.78(dt,1H,J=3.3,11.4Hz),3.25-3.38(m,1H),3.45(d,1H,J=11.4Hz),3.75(dt,1H,J=2.4,11.4Hz),4.02(dt,1H,J=2.4,11.4Hz),6.88(d,2H,J=9.0Hz),7.05(s,1H),7.39(d,2H,J=9.0Hz).
Ia-48
mp 228-229℃
1H-NMR(CDCl3)δppm:0.88(t,6H ,J=7.2Hz),1.19-1.45(m,4H),1.48(s,9H),1.45-1.76(m,4H),1.76-1.92(m,1H),1.96-2.30(m,5H),2.66-3.20(m,3H),3.20-3.40(m,1H),3.78(d,1H,J=9.3Hz),3.82(s,1H),6.62-6.98(m,2H),7.09(brs,1H),7.37(d,2H,J=7.8Hz).
Ia-49
mp 262-263℃
1H-NMR(CDCl3/DMSO)δppm:1.21(d,6H,J=5.7Hz),1.26-1.34(m,2H),1.37(d,6H,J=5.4Hz),1.52-1.76(m,2H),1.85-2.08(m,2H),2.03-2.30(m,3H),2.30-2.53(m,2H),3.02-3.33(m,4H),3.75-3.98(m,2H),5.70(brs,1H),6.73-6.98(m,1H),7.14-7.25(m,1H),7.52(d,1H,JH=13.5Hz),8.86(brs,1H).
Ia-50
mp 232-233℃
1H-NMR(CDCl3)δppm:1.21(d,6H,J=6.3Hz),1.22-1.37(m,2H),1.38(d,6H,J=6.9Hz),1.68(q,2H,J=12.6Hz),1.98-2.26(m,5H),2.29(s,3H),2.41(t,2H,J=10.2Hz),2.88(d,2H,J=11.1Hz),3.15(七重峰,1H,J=6.6Hz),3.21-3.37(m,1H),3.77-3.92(m,2H),3.87(d,1H,J=7.8Hz),6.88-7.06(m,3H),7.35(s,1H).
Ia-51
mp 211-212℃
1H-NMR(CDCl3)δppm:1.20-1.42(m,2H),1.26(d,6H,J=6.3Hz),1.38(d,6H,J=6.9Hz),1.62-1.78(m,2H),1.99-2.28(m,5H),2.49(dd,2H,J=10.5,10.5Hz),3.17(五重峰,1H,J=6.9Hz),3.20-3.38(m,1H),3.66-3.99(m,2H),3.90-4.01(m,3H),6.62(d,1H,J=9.0Hz),7.06(s,1H),7.90(dd,1H,J=2.4,9.0Hz),8.09(d,1H,J=2.4Hz).
Ia-52
mp 247-249℃
1H-NMR(CDCl3)δppm:1.21-1.36(m,2H),1.40(s,9H)1.62-1.78(m,2H),1.98-2.32(m,5H),2.55(t,4H,J=6.0Hz),3.23-3.38(m,1H),3.55(t,4H,J=6.0Hz),3.72(d,1H,J=9.6 Hz),6.94(d,2H,J=9.0Hz),7.10(s,1H),7.42(d,1H,J=9.0Hz).
Ia-53
mp 234-235℃
1H-NMR(CDCl3)δppm:1.22-1.38(m,2H),1.41(s,9H)1.64-1.80(m,2H),2.00-2.32(m,5H),3.25-3.40(m,1H),3.73(d,1H,J=9.3Hz),7.43(s,1H),7.48(t,2H,J=7.5Hz),7.55-7.66(m,3H),7.68-7.89(m,4H).
Ia-54
mp 235-236℃
1H-NMR(CDCl3)δppm:1.24-1.39(m,2H),1.25(d,6H,J=6.3Hz),1.39(d,6H,J=6.9Hz),1.60-1.80(m,2H),2.00-2.28(m,5H),2.21(s,3H),2.38(t,2H,J=10.8Hz),3.15(七重峰,1H,J=6.3Hz),3.23-3.38(m,1H),3.40(d,2H,J=11.7Hz),3.72-3.88(m,2H),3.87(d,1H,J=9.3Hz),6.78-6.86(m,3H),7.50(d,1H,J=9.6Hz).
Ia-55
mp 185-186℃
1H-NMR(CDCl3)δppm:1.14(d,6H,J=6.3Hz),1.22-1.38(m,2H),1.41(s,9H),1.62-1.78(m,2H),2.02(t,2H,J=10.5Hz),2.02-2.10(m,2H),2.16-2.31(m,3H),3.24-3.39(m,1H),3.56(d,2H,J=9.3Hz),3.63-3.80(m,3H),7.46(dd,1H,J=1.5,8.1Hz),7.51(t,1H,J=8.1Hz),7.63(s,1H),7.81(t,1H,J=1.8Hz),7.98(dt,1H,J=1.8,8.1Hz).
Ia-56
mp 229-230℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.28-1.54(m,4H),1.38(s,6H),1.78-1.84(m,2H),1.90-2.00(m,2H),2.15-2.30(m,1H),2.97-3.13(m,1H),4.90(s,1H),6.79(d,1H,J=9.0Hz),7.34(d,2H,J=8.7Hz),7.48(d,2H,J=8.4Hz),9.72(s,1H),
Ia-57
mp 211-212℃
1H-NMR(CDCl3/DMSO)δppm:1.24-1.40(m,2H),1.38(s,9H),1.57-1.74(m,2H),1.91(s,3H),1.92-2.01(m,2H),2.12-2.24(m,2H),2.51(brs,1H),3.18-3.33(m,1H),4.96(d,1H, J=9.3Hz),7.16-7.53(m,9H),7.41(s,1H).
Ia-58
mp 298-299℃
1H-NMR(DMSO-d6)δppm:1.24(s,9H),1.27(s,9H),1.28-1.54(m,4H),1.75-2.02(m,4H),2.14-2.28(m,1H),2.97-3.11(m,1H),6.78(d,1H,J=8.4Hz),7.18(d,2H,J=9.0Hz),7.48(d,2H,J=9.0Hz),9.46(s,1H),9.76(s,1H).
Ia-59
mp 253-254℃
1H-NMR(CDCl3)δppm:1.22-1.40(m,2H),1.41(s,9H),1.65-1.81(m,2H),2.04-2.16(m,2H),2.22-2.36(m,2H),3.24-3.41(m,1H),3.74(d,1H,J=9.6Hz),7.40-7.54(m,3H),7.88-8.01(m,3H),8.66(d,1H,J=1.5Hz),9.57(d,1H,J=1.2Hz).
Ia-60
mp213-214℃
1H-NMR(DMSO)δppm:1.32-1.50(m,2H),1.35(s,9H),1.52-1.70(m,2H),1.88-2.00(m,2H),2.04-2.16(m,2H),2.22-2.38(m,1H),2.65(s,3H),2.99-3.15(m,1H),6.46(d,1H,J=9.3Hz),7.28(d,1H,J=9.0Hz),7.81(s,1H),8.20(s,1H),8.47(s,1H),9.89(s,1H).
Ia-61
mp 274-275℃
1H-NMR(DMSO)δppm:1.27(s,1H),1.28-1.58(m,4H),1.84-2.08(m,4H),2.22-2.40(m,1H),2.99-3.15(m,1H),3.01(s,3H),6.81(d,1H,J=8.1Hz),7.78(d,2H,J=7.8Hz),7.84(d,2H,J=8.4Hz),8.18(s,1H),10.43(s,1H).
Ia-62
mp 235-236℃
1H-NMR(CDCl3)δppm:1.22-1.39(m,2H),1.41(s,3H),1.66-1.80(m,2H),2.01-2.12(m,2H),2.14-2.22(m,1H),2.23-2.34(m,2H),3.24-3.42(m,1H),3.69(d,1H,J=9.5Hz),6.44(d,1H,J=9.3Hz),7.27(brs,1H),7.28(d,1H,J=9.3Hz),7.37(dd,1H,J=2.4,9.0Hz),7.68(d,1H,J=9.6Hz),8.04(d,1H,J=2.4Hz).
Ia-63
mp 277-279℃
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.28-1.54(m,4H),1.77-2.02(m,4H),2.15-2.29(m,1H),2.90(s,3H),2.96-3.13(m,1H),6.79(d,1H,J=8.7Hz),7.12(d,2H,J=9.0Hz),7.54(d,2H,J=9.0Hz),9.50(s,1H),9.81(s,1H).
Ia-64
mp 259-260℃
1H-NMR(DMSO-d6)δppm:1.26(s,9H),1.26-1.50(m,4H),1.74-1.99(m,4H),2.10-2.25(m,1H),2.95-3.10(m,1H),6.78(d,1H,J=8.7Hz),6.97(d,2H,J=9.0Hz),7.42(d,2H,J=9.0Hz),7.50-7.71(m,5H),9.73(s,1H),10.05(s,1H).
Ia-65
mp 292-293℃
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.28-1.54(m,4H),1.62-1.72(m,2H),1.77-1.87(m,2H),1.91-2.10(m,4H),2.13-2.25(m,1H),2.98-3.12(m,1H),3.41-3.52(m,2H),5.09(s,1H),6.79(d,1H,J=9.0Hz),6.91(d,2H,J=9.0Hz),7.37(d,2H,J=9.0Hz),7.42(d,2H,J=9.0Hz),7.51(d,2H,J=9.0Hz),9.56(s,1H).
Ia-66
mp>300℃
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.28-1.58(m,4H),1.85-2.02(m,4H),2.40-2.52(m,1H),3.00-3.16(m,1H),6.81(d,1H,J=9.0Hz),7.50-7.58(m,3H),7.90-7.97(m,2H),12.58(s,1H).
Ia-67
mp 199-200℃
1H-NMR(DMSO-d6)δppm:1.14(d,6H,J=6.3Hz),1.28(s,9H),1.31-1.48(m,4H),1.76-1.88(m,2H),2.17(t,2H,J=11.1Hz),2.82(t,2H,J=11.7Hz),3.46(d,2H,J=11.4Hz),3.20-3.36(m,1H),3.62-3.74(m,2H),4.02(d,2H,J=12.9Hz),6.83(d,2H,J=9.0Hz),6.89(d,1H,J=8.7Hz),7.28(d,2H,J=9.0Hz),8.27(s,1H).
Ia-68
mp 237-239℃
1H-NMR(CDCl3/DMSO)δppm:1.40(s,9H),1.49-1.65(m,2H),1.99-2.10(m,2H),2.95(t,2H,J=11.1Hz),3.36-3.52(m,1H),4.17(d,1H,J=12.9Hz),5.84(d,1H,J=8.7Hz),6.39(d,1H,J=9.6Hz),7.21(d,1H,J=9.3Hz),7.51(dd,1H,J=2.4,9.3Hz),7.72(d,1H,J=9.9Hz),7.85(d,1H,J=2.7Hz),8.04(s,1H).
Ia-69
mp 259-260℃
1H-NMR(DMSO)δppm:1.25-1.55(m,4h),1.27(s,9H),1.82-2.05(m,4H),2.22-2.36(m,1H),2.98-3.17(m,1H),4.16(s,3H),6.80(d,1H,J=8.4Hz),7.77-7.87(m,4H),10.16(s,1H).
Ia-70
mp 259-260℃
1H-NMR(DMSO)δppm:1.28(s,9H),1.36-1.56(m,2H),1.80-1.92(m,2H),2.86-3.02(m,2H),3.36-3.52(m,1H),4.04-4.20(m,2H),6.92(d,1H,J=7.5Hz),7.38-7.58(m,3H),8.00-8.14(m,2H),8.90(s,1H),9.08(s,1H),9.63(s,1H).
Ia-71
mp 228-229℃
1H-NMR(CDCl3/DMSO)δppm:1.27-1.42(m,2H),1.38(s,9H),1.57-1.75(m,2H),1.90-2.02(m,2H),2.12-2.34(m,3H),3.14-3.32(m,1H),5.37(d,1H,J=9.3Hz),7.38-7.43(m,3H),7.46(d,2H,J=8.7Hz),7.51-7.60(m,2H),7.68(d,2H,J=9.0Hz),9.33(s,1H).
Ia-75
mp 169-170℃
1H-NMR(CDCl3)δppm:0.58-0.72(m,1H),0.80(d,3H,J=6.6Hz),0.94(d,3H,J=6.0Hz),1.14-1.35(m,3H),1.39(s,9H),1.48-1.66(m,2H),1.74-2.06(m,5H),2.06-2.44(m,6H),3.18-3.35(m,1H),3.64-3.74(m,1H),4.46-4.60(m,1H),6.98-7.38(m,5H).
Ia-76
mp 236-237℃
1H-NMR(CDCl3/DMSO)δppm:1.27-1.42(m,2H),1.38(d,6H, J=6.6Hz),1.60-1.78(m,2H),1.94-2.06(m,2H),2.12-2.30(m,3H),3.06-3.34(m,2H),5.10(brs,1H),6.41(d,1H,J=9.9Hz),7.25(d,1H,J=8.4Hz),7.48(dd,1H,J=2.4,8.7Hz),7.68(d,1H,J=9.9Hz),8.12(d,1H,J=2.4Hz),8.88(brs,1H).
Ia-77
mp 117-118℃
1H-NMR(CDCl3)δppm:1.38(d,6H,J=6.9Hz),1.65(五重峰,2H,J=5.4Hz),1.75-1.91(m,2H),2.42(t,2H,J=7.4Hz),3.10-3.24(m,3H),4.77(brs,1H),6.41(d,1H,J=9.6Hz),7.18-7.26(m,1H),7.48(d d,1H,J=1.8,8.7Hz),7.67(d,1H,J=9.9Hz),8.01(s,1H),8.23(brs,1H).
Ia-78
mp 138-139℃
1H-NMR(CDCl3)δppm:1.41(s,9H),1.64(五重峰,2H,J=6.6Hz),1.84(五重峰,2H,J=7.3Hz),2.42(t,2H,J=7.5Hz),3.26(q,2H,J=6.5Hz),4.59(brs,1H),6.41(d,1H,J=9.3Hz),7.23(d,1H,J=8.7Hz),7.49(dd,1H,J=2.4,9.0Hz),7.67(d,1H,J=9.9Hz),8.03(d,1H,J=2.4Hz),8.28(brs,1H).
Ia-79
mp 289-290℃
1H-NMR(DMSO)δppm:1.24-1.63(m,4H),1.28(s,9H),1.84-2.08(m,4H),2.24-2.41(m,1H),3.00-3.16(m,1H),6.82(d,1H,J=8.1Hz),7.36-7.60(m,5H),7.86-7.99(m,2H),8.28(s,1H),10.50(s,1H).
Ia-80
mp 239-240℃
1H-NMR(DMSO)δppm:1.22(d,1H,J=6.6Hz),1.23-1.40(m,2H),1.40-1.59(m,2H),1.83-2.04(m,4H),2.23-2.39(m,1H),2.98-3.23(m,2H),7.00(d,1H,J=7.8Hz),7.36-7.59(m,5H),7.85-7.97(m,2H),8.29(s,1H),10.50(s,1H).
Ia-81
mp 205-206℃
1H-NMR(CDCl3/DMSO)δppm:1.40(s,9H),1.66(五重峰,2H,J=7.0Hz),1.85(五重峰,2H,J=7.2Hz),2.45(t,2H,J=7.5Hz),3.24(t,2H,J=6.5Hz),5.17(brs,1H),7.36-7.54(m,5H),7.85(d,1H,J=8.4Hz),8.07(dd,1H,J=1.8,8.1Hz),8.23(d,1H,J=1.8Hz),9.61(s,1H).
Ia-82
mp 216-217℃
1H-NMR(DMSO-d6)δppm:1.14(d,6H,J=6.3Hz),1.22(d,6H,J=6.9Hz),1.22-1.53(m,4H),1.76-1.98(m,2H),2.21(t,2H,J=10.8Hz),2.22-2.36(m,1H),2.96-3.20(m,2H),3.57(d,2H,J=12.0Hz),3.60-3.74(m,1H),6.66-6.85(m,2H),6.98(d,1H,J=7.8Hz),747(d,1H,J=8.7Hz),9.30(s,1H).
Ia-83
mp 118-119℃
1H-NMR(DMSO-d6)δppm:1.41(d,6H,J=6.3Hz),1.26(s,9H),1.40-1.67(m,4H),2.17-2.36(m,3H),2.97-3.10(m,2H),3.57(d,2H,J=12.0Hz),3.61-3.74(m,1H),6.67-6.92(m,3H),7.48(t,1H,J=9.0Hz),9.37(s,1H).
Ia-84
mp 265-267℃
1H-NMR(DMSO-d6)δppm:1.21(d,6H,J=6.6Hz),1.20-1.57(m,4H),1.60-2.30(m,9H),2.99-3.20(m,4H),3.40-8.52(m,2H),5.09(s,1H),6.91(d,2H,J=8.7Hz),6.98(d,1H,J=7.5Hz),7.37(d,2H,J=8.7Hz),7.42(d,2H,J=8.7Hz),7.51(d,2H,J=8.7Hz),9.56(s,1H).
Ia-85
mp 185-186℃.
1H-NMR(DMSO-d6)δppm:1.26(s,8H),1.42-1.72(m,6H),1.96-2.10(m,2H),2.26(t,2H,J=6.9Hz),2.96-3.12(m,4H),3.41-3.52(m,2H),5.09(s,1H),6.88(d,1H,J=8.7Hz), 6.92(d,2H,J=9.0Hz),7.37(d,2H,J=8.7Hz),7.43(d,2H,J=9.0Hz),7.52(d,2H,J=8.7Hz),9.63(s,1H),
Ia-86
mp 162-164℃
1H-NMR(DMSO-d6)δppm:1.21(d,6H,J=6.6Hz),1.41-1.73(m,6H),1.96-2.10(m,2H),2.26(t,2H,J=7.2Hz).2.91-3.20(m,5H),3.42-3.52(m,2H),5.09(s,1H),6.92(d,2H,J=9.3Hz),6.99(t,1H,J=6.0Hz),7.37(d,2H,J=8.7Hz),7.43(d,2H,J=9.3Hz),7.52(d,2H,J=8.7Hz),9.64(s,1H).
Ia-87
mp245-247℃
1H-NMR(DMSO-d6)δppm:1.22(d,6H,J=6.6Hz),1.22-1.58(m,4H),1.81-2.02(m,4H),2.22-2.36(m,1H),3.00-3.20(m,2H),3.01(s,3H),6.99(d,1H,J=8.4Hz),7.75-7.88(m,2H),8.19(d,1H,J=1.2Hz),10.43(s,1H).
Ia-88
mp 208-209℃
1H-NMR(DMSO-d6)δppm:1.22(d,6H,J=6.9Hz),1.22-1.55(m,4H),1.75-1.98(m,4H),2.11-2.24(m,1H),2.98-3.20(m,2H),5.96(s,2H),6.82(d,1H,J=8.4Hz),6.91-7.03(m,2H),7.30(d,1H,J=1.8Hz),9.72(s,1H).
Ia-89
mp 142-143℃
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.40-1.66(m,4H),2.26(t,2H,J=7.5Hz),3.02(q,2H,J=6.6Hz),5.96(s,2H),6.82(d,1H,J=8.4Hz),6.88(t,1H,J=8.4Hz),6.94(dd,1H,J=1.8,8.4Hz),7.30(d,1H,J=1.8Hz),9.78(s,1H).
Ia-90
mp 100℃
1H-NMR(DMSO-d6)δppm:1.20(d,6H,J=6.9Hz),1.40-1.66(m,4H),2.26(t,2H,J=7.5Hz),2.89-2.99(m,2H),3.13(五重峰,1H,J=6.6Hz),5.96(s,2H),6.83(d,1H,J=8.1 Hz),6.91-7.02(m,2H),7.30(d,1H,J=1.8Hz),9.78(s,1H).
Ia-91
mp 189-190℃
1H-NMR(DMSO-d6)δppm:1.26(s,9H),1.43-1.71(m,4H),2.40(t,2H,J=7.5Hz),2.97-3.09(m,2H),3.01(s,3H),6.85-6.93(m,1H),7.76-7.88(m,2H),8.20(d,1H,J=1.2Hz),10.49(s,1H).
Ia-104
mp 238-241℃
1H-NMR(DMSO)δppm:1.27(s.9H),1.3-1.5(m,4H),1.8-2.0(m,4H),2.50(m,1H),3.05(m,1H),6.55(br s,1H),6.79(d,1H,J=8.2),7.15(t,1H,J=4.8),8.64(d,2H,J=4.8),
Ia-105
mp 232-234℃
1H-NMR(DMSO)δppm:1.26(s,9H),1.2-1.5(m,4H),1.8-2.0(m,4H),2.55(m,1H),3.05(m,1H),6.77(d,1H,J=8.7),9.92(s,2H),10.93(s,1H).
Ia-106
mp 226-228℃
1H-NMR(DMSO)δppm:1.28(s,9H),1.22-1.58(m,4H),1.82-2.04(m,4H),2.29(m,1H),3.07(m,1H),6.79(d,1H,J=8.7Hz),7.61(d-d,1H,J=1.8Hz,8.7Hz),8.04(d,1H,J=8.7Hz),8.48(d,1H,2.1Hz),9.35(s,1H),10.05(s,1H).
Ia-107
mp 282-283℃
1H-NMR(DMSO)δppm:1.22-1.57(m,4H),1.27(s,9H),1.80-2.04(m,4H),2.27(m,1H),3.06(m,1H),6.81(d,1H,J=8.7Hz),7.32(m,1H),7.44(t,2H,J=7.5Hz),7.57-7.72(m,6H),9.91(s,1H).
Ia-108
mp 191-192℃
1H-NMR(DMSO)δppm:1.24-1.58(m,4H),1.28(s,9H),1.86-2.04(m,4H),2.70(m,1H), 3.08(m,1H),6.83(d,1H,J=8.7Hz),7.63-7.79(m,2H),8.31(d,1H,J=7.2Hz),10.27(s,1H).
Ia-109
mp 283-285℃
1H-NMR(DMSO)δppm:1.24-1.60(m,4H),1.28(s,9H),1.87-2.04(m,4H),2.42(m,1H),3.09(m,1H),3.87(s,2H),6.82(d,1H,J=8.7Hz),7.28-7.43(m,3H),7.60(d,2H,J=7.8Hz),7.68(d,1H,J=7.2Hz),7.89(d,1H,J=7.5Hz),9.48(s,1H).
Ia-110
mp 263-265℃
1H-NMR(DMSO)δppm:1.24-1.54(m,4H),1.27(s,9H),1.76-1.87(m,2H),1.89-2.01(m,2H),2.17(m,1H),3.04(m,1H),4.01(s,4H),6.01(s,2H),6.44(d,2H,J=8.7Hz),6.77(d,1H,J=8.7Hz),7.39(d,2H,J=9,0Hz),9.44(s,1H).
Ia-111
mp 239-241℃
1H-NMR(DMSO)δppm:1.24-1.54(m,4H),1.27(s,9H),1.62-1.76(m,4H),1.80-2.02(m,4H),2.30(m,1H),2.47-2.59(m,2H),2.66-2.76(m,2H),6.08(m,1H),6.79(d,1H,J=9.0Hz),6.88(d,1H,J=6.9Hz),7.02(t,1H,J=7.5Hz),7.13(d,1H,J=7.5Hz),8.98(s,1H).
Ia-124
mp247-249℃
1H-NMR(DMSO)δppm:1.15(d,6H,J=6.3Hz),1.30(s,9H),2.15-2.26(m,2H),3.48-3.57(m,2H),3.63-3.76(m,2H),6.92(d,2H,J=8.7Hz),7.59(d,2H,J=9.0Hz),7.38(d,2H,J=9.0Hz),7.87(d,2H,J=8.7Hz),9.92(brs,1H),9.98(brs,1H).
Ia-125
mp 228-232℃
1H-NMR(DMSO)δppm:1.30(s,9H),1.95-2.08(m,2H),2.77-2.89(m,4H),7.17(d,1H,J=8.4Hz),7.39(d,2H,J=9.0Hz),7.42-7.48(m,1H),7.64(brs,1H),7.87(d,2H,J=9.0 Hz),9.99(brs,2H),
Ia-126
mp 244-246℃
1H-NMR(DMSO)δppm:1.31(s,9H),7.42(d,2H,J=8.4Hz),7.81(d-d,1H,J=2.1Hz,8.7Hz),7.93(d,2H,J=9.0Hz),8.05(d,1H,J=9.0Hz),8.66(d,1H,J=2.1Hz),9.29(s,1H),10.05(brs,1H),10.39(brs,1H).
Ia-127
mp 238-239℃
1H-NMR(DMSO)δppm:1.30(s,9H),4.18-4.27(m,4H),6.81(d,1H,J=8.4Hz),7.16(d-d,1H,J=2.7Hz,9.0Hz),7.84-7.42(m,3H),7.85(d,2H,J=8.4Hz),9.94(brs,1H),9.99(brs,1H).
Ia-128
mp 286-287℃
1H-NMR(DMSO)δppm:1.31(s,9H),7.41(d,2H,J=8.7Hz),7.71(d,2H,J=8.4Hz),7.91(d,2H,J=8.7Hz),7.99(d,2H,J=8.7Hz),10.05(brs,1H),10.44(brs,1H).
Ia-129
mp 232-234℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.3-1.5(m,4H),1.8-2.0(m,4H),2.25(1H,m),3.07(m,1H),6.80(d,1H,J=9.0),7.37(d,1H,J=8.1),7.53(t,1H,J=8.1),7.75(t,1H,J=8.1),8.12(s,1H),10.16(s,1H).
Ia-130
mp 274-277℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.23-1.58(m,4H),1.81-2.03(m,4H),2.28(m,1H),3.07(m,1H),6.80(d,1H,J=8.4Hz),7.36(d-d,1H,J=0.9Hz,5.7Hz),7.43(d-d,1H,J=2.1Hz,8.7Hz),7.60(d,1H,J=5.4Hz),7.78(d,1H,J=8.7Hz),8.40(d,1H,1.8Hz),9.97(brs,1H).
Ia-131
mp 259-260℃
1H-NMR(DMSO)δppm:1.31(s,9H),7.40(d,1H,J=4.8Hz),7.41(d,2H,J=8.7Hz),7.66(d,1H,J=5.1Hz),7.67(d-d,1H,J=1.8Hz,8.7Hz),7.84(d,1H,J=9.0Hz),7.92(d,2H,J=8.7Hz),8.50(s,1H),10,03(brs,1H),10,27(brs 1H).
Ia-132
mp 265-266℃
1H-NMR(DMSO)δppm:1.17(d,6H,J=6.6Hz),1.31(s,9H),4.10(m,1H),7.35-7.46(m,3H),7.54(d,1H,J=7.5Hz),7.87-7.97(m,3H),8.15(brs,1H),8.20(d,1H,J=7.5Hz),10.03(brs,1H),10.25(brs,1H).
Ia-133
mp 249-250℃
1H-NMR(DMSO)δppm:1.31(s,9H),7.41(d,2H,J=8.7Hz),7.45(d,1H,J=5.4Hz),7.67(d-d,1H,J=1.8Hz,8.7Hz),7.76(d,1H,J=5.4Hz),7.92(d,2H,J=8.7Hz),7.95(d,1H,J=8.1Hz),8.39(d,1H,J=1.8Hz),10.02(brs,1H),10.23(brs,1H).
Ia-134
mp 305-306℃
1H-NMR(DMSO)δppm:1.25(m,2H),1.25(s,9H),1.52(m,2H),1.82(m,2H,),1.94(m,2H),2.13(m,1H),3.04(m,1H),6.00(d,1H,J=8.1),6.74(d,1H,J=8.4),7.3-7.5(m,6H),7.85(d,2H,J=7.5),8.31(d,1H,J=8.4).
Ia-135
mp 220-222℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.3-1.5(m,4H),1.8-2.0(m,4H),2.37(m,1H),3.03(m,1H),6.80(d,1H,J=8.7),7.04(m,1H),7.29(m,1H),7.79(m,1H),9.60(s,1H).
Ia-136
mp 263-264℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.3-1.5(m,4H),1.8-2.0(m,4H),2.20(m,1H),3.03(m,1H),6.80(d,1H,J=8.4),6.87(m,1H),7.31(m,2H),10.21(s,1H).
Ia-137
mp 260-262℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.3-1.5(m,4H),1.8-2.0(m,4H),2.30(m,1H),3.05(m,1H),6.80(d,1H,J=8.4),7.13(t,2H,J=8.1),7.31(m,1H),9.52(s,1H).
Ia-138
mp 270-273℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.3-1.5(m,4H),1.8-2.0(m,4H),2.12(m,1H),3.05(m,1H),6.79(d,1H,J=9.0),7.31(m,2H),7.80(m,1H),10.05(s,1H).
Ia-139
mp 267-270℃
1H-NMR(DMSO)δppm:1.30(s,9H),4.05(s,4H),6.04(s,2H),6.51(d,2H,J=8.7Hz),7.34(d,2H,J=8.4Hz),7.54(d,2H,J=8.4Hz),7.87(d,2H,J=8.4Hz),9.82(brs,1H),9.97(brs,1H).
Ia-140
mp227-229℃
1H-NMR(DMSO)δppm:1.22(d,6H,J=6.6Hz),1.20-1.57(m 4H),1.80-2.01(m,4H),2.27(m,1H),2.95-3.22(m,2H),6.99(d,1H,J=7.8Hz),7.65(d,2H,J=8.7Hz),7.80(d,2H,J=8.4Hz),10.18(brs,1H).
Ia-141
mp 205-207℃
1H-NMR(DMSO)δppm:1.22(d,6H,J=6.9Hz),1.20-1.55(m,4H),1.75-2.05(m,6H),2.21(m,1H),2.72-2.85(m,4H),2.93-3.20(m,2H),6.98(d,1H,J=8.1Hz),7.10(d,1H,J=8.1Hz),7.26(d-d,1H,J=2.1Hz,8.1Hz),7.51(s,1H),9.67(brs,1H).
Ia-142
mp 295-296℃
1H-NMR(DMSO)δppm:1-15(d,6H,J=6.6),1.27(s,9H),1.3-1.5(m,4H),1.8-2.0(m,4H),2.27(m,1H),3.05(m,1H),4.07(m,1H),6-80(d,1H,J=8.7),7.64(d,2H,J=8.7),7.79 (d,2H,J=8.7),8.06(d,1H,J=7.5),10.01(s,1H).
Ia-143
mp 146-147℃
1H-NMR(DMSO)δppm:1.26(s,9H),1.5-1.7(m,4H),2.36(t,2H,J=7.8),3.03(q,2H,J=6.3),6.89(t,1H,J=6.3),7.66(d,2H,J=8.4),7.80(d,2H,J=8.4),10.25(s,1H).
Ia-144
mp 138-140℃
1H-NMR(DMSO)δppm:1.21(d,6H,J=6.0),1.4-1.7(m,4H),2.37(t,2H,J=7.5),2.96(q,2H,J=6.3),3.14(m,1H),6.99(t,1H,J=5.4),7.66(d,2H,J=7.8),7.81(d,2H,J=7.8),10.26(s,1H).
Ia-145
mp 134-136℃
1H-NMR(DMSO)δppm:1.26(s,9H),1.39(m,2H),1.4-1.7(m,4H),2.28(t,2H,J=7.2),2.79(m,4H),3.02(q,2H,J=7.2),6.88(t,1H,J=6.0),7.10(t,1H,J=6.0),7.51(s,1H),9.73(s,1H).
Ia-146
mp 135-137℃
1H-NMR(DMSO)δppm:1.20(d,6H,J=6.6),1.4-1.7(m,4H),1.99(m,2H),2.28(t,2H,J=7.2),2.79(m,4H),2.94(q,2H,J=6.3),3.13(m,1H),6.98(t,1H,J=6.9),7.10(d,2H,J=8.1),7.26(d,2H,J=8.1),7.51(s,1H),9.73(s,1H).
Ia-147
mp 206-207℃
1H-NMR(DMSO)δppm:1.29(s,9H),4.54(d,2H,J=5.7Hz),7.35(d,2H,J=9.0Hz),7.52(d,2H,J=7.8Hz),7.69(d,2H,J=8.1Hz),7.83(d,2H,J=8.7Hz),9.02(t,1H,J=5.7Hz),9.97(brs,1H).
Ia-148
mp 250-251℃
1H-NMR(DMSO)δppm:1.30(s,9H),7.18(t,2H,J=9.3Hz),7.40(d,2H,J=8.7Hz),7.76(d-d,2H,J=5.1Hz,9.3Hz),7.88(d,2H,J=9.0Hz),10.02(brs,1H),10.17(brs,1H).
Ia-149
mp 220-222℃
1H-NMR(DMSO)δppm:1.30(s,9H),3.74(s,3H),6.92(d,2H,J=9.0Hz),7.38(d,2H,J=9.0Hz),7.64(d,2H,J=9.0Hz),7.87(d,2H,J=9.0Hz),9.99(s,2H).
Ia-150
mp 264-266℃
1H-NMR(DMSO)δppm:1.31(s,9H),1.66-1.76(m,4H),2.57-2.66(m,2H),2,71-2.80(m,2H),6.98(m,1H),7.06-7.16(m,2H),7.38(d,2H,J=9.0Hz),7.90(d,2H,J=8.7Hz),9.60(s,1H),9.99(s,1H).
Ia-151
mp 235-236℃
1H-NMR(DMSO)δppm:1.03-1.39(m,5H),1.27(s,9H),1.55-1.87(m,5H),3.73(m,1H),7.31(d,2H,J=8.7Hz),7.76(d,2H,J=8.4Hz),8.01(d,1H,J=7.8Hz),9.90(s,1H).
Ia-152
mp 244-246℃
1H-NMR(DMSO)δppm:0.50-0.72(m,4H),1.27(s,9H),2.81(m,1H),7.31(d,2H,J=8.7Hz),7.73(d,2H,J=8.7Hz),8.30(d,1H,J=4.2Hz),9.91(brs,1H).
Ia-153
mp>300℃
1H-NMR(DMSO)δppm:1.06(m,6H),1.27(s,9H),1.2-1.5(m,4H),1.8-2.0(m,4H),2.25(m,1H),2.7(m,1H),3.05(m,1H),3.51(m,4H),4.30(m,1H),6.80(d,1H,J=8.4),7.34(d,2H,J=8.4),7.65(d,2H,J=8.4),10.01(s,1H).
Ia-154
mp 247-249℃
1H-NMR(DMSO)δppm:1.05(m,6H),1.27(s,9H),1.2-1.5(m,4H),1.8-2.0(m,4H),2.23 (m,1H),2.77(m,1H),3.05(m,1H),3.52(m,4H),4.83(m,1H),6.80(d,1H,J=9.0),7.03(d.1H,J=7.8),7.35(t,1H,J=7.8),7.59(d,1H,J=7.8),7.68(s,1H),9.96(s,1H).
Ia-155
mp 258-259℃
1H-NMR(DMSO)δppm:1.25(m,2H),1.50(m,2H),1.86(m,2H),1.99(m,2H),2.28(m,1H),2.93(s,3H),3.10(m,1H),7.02(d,1H,J=7.5),7.65(d,2H,J=8.4),7.80(d,2H,J=8.4).10.20(s,1H).
Ia-156
mp 250-253℃
1H-NMR(DMSO)δppm:1.28(m,2H),1.50(m,2H),1.82(m,2H),2.00(m,4H),2.22(m,1H),2.79(m,4H),2.92(s,3H),3.11(m,1H),7.01(d,1H,J=(1),7.26(d,1H,J=8.1),7.51(s1H),9.68(s,1H).
Ia-157
mp 259-262℃
1H-NMR(DMSO)δppm:1.13(d,6H,J=6.0),1.25(m,2H),1.50(m,2H),1.80(m,2H),1.95(m,2H),2.17(m,3H),2.92(s,3H),3.10(m,1H),3.70(m,2H),3.68(m,2H),6.86(d,2H J=9.3),7.00(d,1H,J=7.2),7.43(d,2H,J=9.3),9.58(s,1H).
Ia-158
mp 298-300℃
1H-NMR(DMSO)δppm:1.31(s,9H),7.30-7.50(m,5H),7.63-7,71(m,4H),7.87(d,2H,J=8.7Hz),7.91(d,2H,J=9.0Hz),10.03(brs,1H),10.22(brs,1H).
Ia-159
mp 278-281℃
1H-NMR(DMSO)δppm:0.74-1.87(m,20H),1.29(s,9H),3.76(m,1H),7.32(d,2H,J=8.4Hz),7.75(d,2H,J=8.7Hz),7.75(d,1H,J=8.7Hz),7.90(brs,1H).
Ia-160
mp 227-228℃
1H-NMR(DMSO)δppm:1.22-1.55(m,4H),1.27(s,9H),1.80-2.02(m,4H),2.23(m,1H),3.06(m,1H),6.78(d,1H,J=8.7Hz),7.45(t,1H,J=9.9Hz),7.82(m,1H),8.12(d-d,1H,J=2.4Hz,6.3Hz),10.17(brs,1H).
Ia-161
mp 259-260℃
1H-NMR(DMSO)δppm:1.22-1.54(m,4H),1.27(s,9H),1.78-2.01(m,4H),2.16(s,3H),2.21(m,1H),3.05(m,1H),6.77(d,1H,J=8.4Hz),7.12-7.21(m,2H),7.53(m,1H),9.90(brs,1H).
Ia-162
mp 222-226℃
1H-NMR(DMSO)δppm:1.15(d,6H,J=6.3Hz),1.26(d,6H,J=6.9Hz),2.16-2.26(m,2H),3.31(m,1H),3.48-3.58(m,2H),3.63-3.76(m,2H),6.92(d,2H,J=9.0H),7.32(d,2H,J=8.7Hz),7.59(d,2H,9.0Hz),7.89(d,2H,J=9.0Hz),9.92(s,1H),10.13(brs,1H).
Ia-163
mp 197-200℃
1H-NMR(DMSO)δppm:1.26(d,6H,J=6.3Hz),1.95-2.09(m,2H),2.77-2.90(m,4H),3.32(m,1H),7.17(d,1H,J=8.1Hz),7.32(d,2H,J=8.7Hz),7.45(d-d,1H,J=1.8Hz,8.1Hz),7.64(brs,1H),7.90(d,2H,J=8.7Hz),9.99(brs,1H),10.13(brs,1H).
Ia-164
mp 145-247℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.3-2.0(m,16H),2.19(m,1H),3.05(m,1H),4.74(m,1H),6.79(d,1H,J=9.0),6.80(d,2H,J=9.0),7.47(d,2H,J=9.0),9.63(s,1H).
Ia-165
mp>300℃
1H-NMR(DMSO)δppm:1.03-2.02(m,18H),1.27(s,9H),2.26(m,1H),3.06(m,1H),3.73(m,1H),6.78(d,1H,J=8.7Hz),7.63(d,2H,J=9.0Hz),7.78(d,2H,J=8.7Hz),8.02(d,1H,J=8.1Hz),10.00(brs,1H).
Ia-166
mp 200-201℃
1H-NMR(DMSO)δppm:1.03-2.02(m,18H),1.27(s,9H),2.25(m,1H),3.06(m,1H),3.73(m,1H),6.78(d,1H,J=8.7Hz),7.33(t,1H,J=8.1Hz),7.46(d,1H,J=8.1Hz),7.76(m,1H),7.94(m,1H),8.14(d,1H,J=8.1Hz),9.92(brs,1H).
Ia-167
mp 282-285℃
1H-NMR(DMSO)δppm:1.22-1.57(m,4H),1.27(s,9H),1.87-2.03(m,4H),2.49(m,1H),3.07(m,1H),6.83(d,1H,J=8.7Hz),13.20(brs,1H).
Ia-168
mp 120-124℃
1H-NMR(DMSO)δppm:0.94-1.66(m,14H),1.27(s,9H),1.80-2.04(m,4H),2.25(m 1H),2.92(m,1H),3.06(m,1H),6.78(d,1H,J=8.7Hz),7.42-7.53(m,2H),7.63(d,1H,J=7.2Hz),7.73(m,1H),8.17(m,1H),10.11(brs,1H).
Ia-169
mp 256-257℃
1H-NMR(DMSO)δppm:0.93-1.20(m,5H),1.24-1.64(m,9H),1.27(s,9H),1.80-2.02(m,4H),2.27(m,1H),2.87(m,1H),3.06(m,1H),6.79(d,1H,J=9.0Hz),7.48(d,1H,J=7.2Hz),7.68-7.79(m,4H),10.17(brs,1H),
Ia-171
mp 242-244℃
1H-NMR(DMSO)δppm:1.27(m,12H),1.45(m,4H),1.90(m,4H),2.25(m,1H),3.07(m,1H),3.67(m,2H),6.77(d,1H,J=8.7),6.90(d,1H,J=7.8),7.31(t,1H,J=7.5),7.53(d,1H,J=7.8),7.59(s,1H),9.89(s,1H).
Ia-172
mp>310℃
1H-NMR(DMSO)δppm:1.27(m,12H),1.38(m,4H),1.84(m,2H),1.97(m,2H),2.25 (m,1H),3.07(m,1H),3.66(m,2H),6.81(d,1H,J=8.7),7.20(d,2H,J=6.7),7.61(d,2H,J=8.7),9.94(s,1H).
Ia-173
mp 279-281℃
1H-NMR(DMS0)δppm:1.27(s,9H),1.3-1.5(m,4H),1.83(m,6H),1.93(m,2H),2.21(m,1H),2.36(m,2H),3.05(m,1H),3.54(m,2H),6.79(d,1H,J=8.7),7.16(d,2H,J=9.0),7.56(d,2H,J=9.0),9.83(s,1H).
Ia-174
mp 258-262℃
1H-NMR(DMSO)δppm:0.29(m,2H),0.53(m,2H),1.20(m,1H),1.27(s,9H),1.3-1.5(m,4H),1.7-2.0(m,4H),2.20(m,1H),3.05(m,1H),3.75(d,2H,J=6.9),6.79(d,1H,J=9.0),6.83(d,2H,J=9.0),7.46(d,2H,J=9.0),9.64(s,1H).
Ia-175
mp 246-248℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.3-2.0(m,18H),2.19(m,1H),3.04(m,1H),4.23(m,1H),6.79(d,1H,J=8.7),6.84(d,2H,J=9.0),7.45(d,2H,J=9.0),9.64(s,1H).
Ia-176
mp 200-202℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.3-2.0(m,18H),2.21(m,1H),3.05(m,1H),4.23(m,1H),6.57(d,1H,J=6.9),6.80(d,1H,J=9.0),7.0-7.2(m,2H),7.28(s,1H),9.74(s,1H).
Ia-177
mp 266-268℃
1H-NMR(DMSO)δppm:1.22-1.56(m,4H),1.27(s,9H),1.79-2.02(m,4H),2.25(m,1H),3.05(m,1H),6.56(m,1H),6.77-6.84(m,2H),7.58-7.71(m,5H),9.92(brs,1H).
Ia-178
mp 223-224℃
1H-NMR(DMS0)δppm:1.26-1.54(m,4H),1.27(s,9H),1.81-2.02(m,4H),2.45(m,1H), 3.06(m,1H),6.80(d,1H,J=8.7Hz),8.15(d-d,1H,J=2.4Hz,9.0Hz),8.27(d,1H,J=9.0Hz),8.70(m,1H),10.85(brs,1H).
Ia-179
mp 224-227℃
1H-NMR(DMSO)δppm:1.24-1.56(m,4H),1.27(s,9H),1.80-2.03(m,4H),2.27(m,1H),3.06(m,1H),6.80(d,1H,J=8.7Hz),6.90(d,1H,J=1.8Hz),7.72-7.84(m,4H),8.60(d,1H,J=1.8Hz),10.09(brs,1H).
Ia-180
mp 226-227℃
1H-NMR(DMSO)δppm:0.92(d,6H,J=6.6Hz),1.26-1.55(m,4H),1.27(s,9H),1.80-2.03(m,4H),2.27(m,1H),3.05(m,1H),3.20(m,1H),6.80(d,1H,J=8.7Hz),7.42(d,1H,J=7.2Hz),7.67-7.79(m,4H),10.19(brs,1H).
Ia-181
mp 191-192℃
1H-NMR(DMSO)δppm:0.95(d,6H,J=6.6Hz),1.26-1.55(m,4H),1.27(s,9H),1.80-2.03(m,4H),2.25(m,1H),3.06(m,1H),3.23(m,1H),6.80(d,1H,J=8.4Hz),7.41-7.53(m,2H),7.58(d,1H,J=7.2Hz),7.73(m,1H),8.18(m,1H),10.13(brs,1H).
Ia-182
mp 192-193℃
1H-NMR(DMSO)δppm:0.30(m,2H),0.55(m,2H),1.2-1.5(m,5H),1.27(s,1H),1.8-2.0(m,4H),2.20(m,1H),3.04(m,1H),3.75(d,2H,J=6.9),6.58(m,1H),6.79(d,1H,J=8.7),7.0-7.2(m,2H),7.31(s,1H),9.76(s,1H).
Ia-183
mp>310℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.3-1.5(m,4H),1.82(m,2H),1.97(m,2H),2.04(m,2H),2.39(m,1H),2.46(t,2H,J=7.8),3.07(m,1H),3.79(t,2H,J=7.5),6.79(d,1H,J=8.7),7.56(m,4H),9.80(s,1H).
Ia-184
mp 281-283℃
1H-NMR(DMSO)δppm:1.24-1.57(m,4H),1.27(s,9H),1.80-2.04(m,4H),2.27(m,1H),3.06(m,1H),6.80(d,1H,J=9,0Hz),7.33(s,1H),7.75(d,2H,J=9.3Hz),7.91(d,2H,J=8.7Hz),8.16(s,1H),10.09(brs,1H).
Ia-185
mp 226-227℃
1H-NMR(DMSO)δppm:1.24-1.58(m,10H),1.27(s,9H),1.81-2.02(m,4H),2.28(m,1H),2.78-2.88(m,4H),3.06(m,1H),6.80(d,1H,J=8.7Hz),7.64(d,2H,J=8.7Hz),7.82(d,2H,J=8.7Hz),10.25(brs,1H).
Ia-186
mp 148-150℃
1H-NMR(DMSO)δppm:1.25-1.60(m,10H),1.27(s,9H),1.82-2.03(m,4H),2.24(m,1H),2.82-2.92(m,4H),3.06(m,1H),6.79(d,1H,J=8.4Hz),7.36(m,1H),7.55(t,1H,J=7.8Hz),7.84(m,1H),8.06(m,1H),10.18(brs,1H).
Ia-187
mp>310℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.36(s,9H),1.43(m,4H),1.85(m,2H),1.93(m,2H),2.27(m,1H),3.06(m,1H),6.80(d,1H,J=8.7),7.58(s,1H),7.62(d,2H),7.75(d,2H,J=9.0),10.00(s,1H).
Ia-188
mp 285-292℃
1H-NMR(DMSO)δppm:0.85(t,3H,J=7.5),1.11(d,3H,J=6.3),1.26(s,9H),13-1.6(m,6H),1.85(m,2H),1.95(m,2H),2.27(m,1H),3.06(m,1H),3.90(m,1H),6.80(d,1H,J=8.4),7.64(d,2H,J=8.7),7.79(d,2H,J=8.7),7.99(d,1H,J=8.1),10.02(s,1H)
Ia-189
mp 278-281℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.2-2.0(m,17H),2.03(m,2H),3.03(m,1H),6.79(d,1H,J=8.4),7.1-7.3(m,3H),7.94(s,1H),9.78(m,2H).
Ia-190
mp>310℃
1H-NMR(DMSO)δppm:1.1-2.0(m,17H),1.27(s,9H),2.25(m,2H),3.03(m,1H),6.79(d,1H,J=8.7),7.48(m,4H),9.71(m,2H),
Ia-191
mp 275-277℃
1H-NMR(DMSO)δppm:1.16(d,6H,J=6.6Hz),1.31(s,9H),4.09(m,1H),7.41(d,2H,J=8.7Hz),7.84(s,4H),7.90(d,2H,J=9.0Hz),8.11(d,1H,J=7.5Hz),10.04(brs,1H),10.30(brs,1H).
Ia-192
mp 204-205℃
1H-NMR(DMSO)δppm:1.15(d,6H,J=6.6Hz),1.20-1.56(m,4H),1.22(d,6H,J=6.6Hz),1.78-2.00(m,4H),2.25(m,1H),2.98-3.22(m,2H),4.06(m,1H),6.99(d,1H,J=8.1Hz),7.34(t,1H,J=8.1Hz),7.46(d,1H,J=7.8Hz),7.75(m 1H),7.96(m,1H),8.17(d,1H,J=8.7Hz),9.94(brs,1H).
Ia-193
mp 285-286℃
1H-NMR(DMSO)δppm:1.15(d,6H,J=6.6Hz),1.20-1.56(m,4H),1.22(d,6H,J=6.9Hz),1.79-2.00(m,4H),2.26(m,1H),2.97-3.20(m,2H),4.07(m,1H),6.99(d,1H,J=7.8Hz),7.64(d,2H,J=8.7Hz),7.79(d,2H,J=8.7Hz),8.06(d,1H,J=7.5Hz),10.02(brs,1H).
Ia-194
mp 248-250℃
1H-NMR(DMSO)δppm:1.22-1.57(m,4H),1.22(d,6H,J=6.6Hz),1.78-2.00(m,4H),2.25(m,1H),2.98-3.22(m,2H),6.56(m,1H),6.82(d,1H,J=3.3Hz),6.99(d,1H,J=7.8 Hz),7.58-7.71(m,5H),9.92(brs,1H).
Ia-195
mp 271-275℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.28-1.56(m,4H),1.80-2.02(m,4H),2.25(m,1H),3.06(m,1H),6.80(d,1H,J=9.0Hz),7.57(s,1H),7.62-7.74(m,4H),8.39(s,1H),9.99(brs,1H).
Ia-196
mp 226-228℃
1H-NMR(CDCl3)δppm:0.30(m,2H),1.23(d,6H,J=6.9),1.2-2.0(m,4H),2.20(m,1H),3.10(m,2H),3.76(d,2H,J=6.9),6.83(d,2H,J=8.7),6.99(d,1H,J=8.1),7.46(d,2H,J=8.7),9.65(s,1H).
Ia-197
mp 173-175℃
1H-NMR(DMSO)δppm:0.31(m,2H),0.56(m,2H),1.22(d,6H,J=6.6),1.2-1.5(m,4H),1.8-2.0(m,4H),2.22(m,1H),3.10(m,1H),3.76(d,1H,J=7.2),6.58(d,1H,J=8.1),7.0-7.2(m,2H),7.32(s,1H),9.78(s,1H).
Ia-198
mp 233-235℃
1H-NMR(DMSO)δppm:1.25(d,6H,J=6.9),1.2-2.0(m,16H),2.19(m,1H),3.10(m,2H),4.73(m,1H),6.80(d,2H,J=8.7),6.98(d,1H,J=7.8),7.45(d,2H,J=8.7),9.63(s,1H).
Ia-199
mp 185-186℃
1H-NMR(DMSO)δppm:1.22(d,6H,J=6.9),1.2-2.0(m,16H),2.22(m,1H),3.10(m,2H),4.73(m,1H),6.54(m,1H),7.0-7.2(m,2H),7.3(s,1H),9.75(s,1H).
Ia-200
mp 235-237℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.3-1.6(m,6H),1.8-2.0(m,6H),2.20(m,1H), 3.05(m,1H),3.45(m,2H),3.82(m,2H),4.47(m,1H),6.79(d,1H,J=9.0),6.89(d,2H,J=9.0),7.47(d,2H,J=9.0),9.66(s,1H).
Ia-201
mp 300-301℃
1H-NMR(DMSO)δppm:1.15(d,6H,J=6.6Hz),1.26-1.56(m,4H),1.27(s,9H),1.82-2.03(m,4H),2.23(s,3H),2.37(m,1H),3.06(m,1H),4.07(m,1H),6.81(d,1H,J=8.7Hz),7.52(d,1H,J=8.4Hz),7.62(d,1H,J=8.4Hz),7.68(s,1H),8.09(d,1H,J=7.5Hz),9.22(brs,1H),
Ia-202
mp 269-270℃
1H-NMR(DMSO)δppm:1.25-1.26(m,4H),1.27(s,9H),1.80-2.03(m,4H),2.25(m,1H),3.07(m,1H),6.80(d,1H,J=8.4Hz),7.11(m,1H),7.42(d,1H,J=3.6Hz),7.48(m,1H),7.58(d,2H,J=8.7Hz),7.64(d,2H,J=8.4Hz),9.92(brs,1H).
Ia-203
mp 271-273℃
1H-NMR(DMSO)δppm:1.14-1.54(m,9H),1.26(s,9H),1.63-1.88(m,7H),1.89-2.01(m,2H),2.21(m,1H),2.42(m,1H),3.04(m,1H),6.79(d,1H,J=9.0Hz),7.11(d,2H,J=8.4Hz),7.47(d,2H,J=8.1Hz),9.70(brs,1H).
Ia-204
mp 250-251℃
1H-NMR(DMSO)δppm:1.22-1.39(m,2H),1.22(d,6H,J=6.6Hz),1.40-1.57(m 2H),1.80-2.01(m,4H),2.28(m,1H),2.98-3.21(m,2H),7.00(d,1H,J=7.8Hz),7.34(s,1H),7.75(d,2H,J=9.0Hz),7.91(d,2H,J=8.7Hz),8.17(s,1H),10.10(brs,1H).
Ia-205
mp 239-240℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.2-1.5(m,4H),1.8-2.0(m,5H),2.08(m,2H),3.05(m,1H),3.80(m,4H),4.95(m,1H),6.79(d,1H,J=8.7),6.83(d,2H,J=8.7),7.48(d, 2H,J=8.7),9.66(s,1H).
Ia-206
mp 236-238℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.2-1.7(m,8H),1.8-2.0(m,6H),2.18(m,1H),3.04(m,1H),3.3-3.6(m,2H),3.85(m,3H),6.80(d,1H,J=9.0),6.84(d,2H,J=9.0),7.47(d,2H,J=9.0),9.65(s,1H).
Ia-207
mp 224-226℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.2-1.5(m,4H),1.8-2.0(m,4H),2.24(m,1H),2.39(m,2H),3.06(m,1H),3.50(t,2H,J=7.5),3.70(t,2H,J=6.3),6.78(d,1H,J=6.6),6.83(m,1H),7.25(m,1H),7.27(m,1H),7.54(s,1H),9.61(s,1H).
Ia-208
mp 275-277℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.3-1.5(m,4H),1.8-2.0(m,4H),2.22(m,1H),2.38(m,2H),3.07(m,1H),3.47(t,2H,J=6.9),3.69(t,2H,J=6.6),6.80(d,1H,J=8.7),7.14(d,2H,J=8.4),7.58(d,2H,J=8.4),9.83(s,1H).
Ia-209
mp 214-215℃
1H-NMR(DMSO)δppm:1.26-1.56(m,4H),1.27(s,9H),1.80-2.03(m,4H),2.25(m,1H),3.06(m,1H),6.59(m,1H),6.81(d,1H,J=8.4Hz),6.86(d,1H,J=2.7Hz),7.28-7.40(m,2H),7.47(m,1H),7.75(s,1H),8.01(s,1H),9.91(brs,1H).
Ia-210
mp 272-275℃
1H-NMR(DMSO)δppm:1.31(s,9H),6.59(m,1H),6.87(d,1H,J=3.3Hz),7.41(d,2H,J=8.7Hz),7.68(d,2H,J=8.7Hz),7.72(m,1H),7.83(d,2H,J=8.7Hz),7.90(d,2H,J=8.7Hz),10.03(brs,1H),10.22(brs,1H).
Ia-211
mp 251-255℃
1H-NMR(DMSO)δppm:1.31(s,9H),7.36(s,1H),7.41(d,2H,J=8.4Hz),7.91(d,2H,J=8.4Hz),7.92-8.00(m,4H),8.19(s,1H),10.06(brs,1H),10.38(brs,1H).
Ia-212
mp 241-244℃
1H-NMR(DMSO)δppm:1.30(s,9H),1.50-1.78(m,6H),1.81-1.97(m,2H),4.78(m,1H),6.87(d,2H,J=9.0Hz),7.38(d,2H,J=8.7Hz),7.61(d,2H,J=9.0Hz),7.87(d,2H,J=8.7Hz),9.97(brs,1H),9.99(brs,1H).
Ia-213
mp 283-286℃
1H-NMR(DMSO)δppm:1.31(s,9H),7.12(d-d,1H,J=3.6Hz,5.1Hz),7.41(d,2H,J=9.0Hz),7.46(m,1H),7.50(d-d,1H,J=1.2Hz,5.1Hz),7.64(d,2H,J=8.7Hz),7.82(d,2H,J=8.7Hz),7.90(d,2H,J=9.3Hz),10.03(brs,1H),10.22(brs,1H).
Ia-216
mp 224-225℃
1H-NMR(CDCl3)δppm:1.22(d,6H,J=6.9),1.2-1.5(m,4H),1.8-2.0(m,4H),2.45(m,1H),3.12(m,2H),6.99(d,1H,J=8.1),8.15(m,1H),8.27(d,1H,J=9.0),8.69(s,1H),10.86(s,1H).
Ia-219
mp270-272℃
1H-NMR(DMSO)δppm:1.28(s,9H),1.34-1.51(m,2H),1.80-1.92(m,2H),2.83-2.97(m,2H),3.32(m,1H),3.99-4.12(m 2H),6.92(d,1H,J=8.7Hz),7.57(d,2H,J=8.7Hz),7.68(d,2H,J=9.0Hz),8.90(brs,1H).
Ia-220
mp 187-189℃
1H-NMR(DMSO)δppm:1.28(s,9H),1.31-1.51(m,2H),1.78-1.90(m,2H),2.78-2.93(m,2H),8.30(m,1H),3.97-4.09(m,2H),6.90(d,1H,J=8.7Hz),7.06(t,2H,J=9.0Hz),7.44 (d-d,2H,J=4.8Hz,9.0Hz),8.53(brs,1H).
Ia-221
mp 260-262℃
1H-NMR(DMSO)δppm:1.12-1.50(m,7H),1.28(s,9H),1.63-1.90(m,7H),2.40(m,1H),2.76-2.91(m,2H),3.28(m,1H),3.96-4.09(m,2H),6.90(d,1H,J=8.7Hz),7.06(d,2H,J=8.4Hz),7.32(d,2H,J=8.4Hz),8.40(brs,1H).
Ia-222
mp 265-267℃
1H-NMR(DMSO)δppm:1.23(d,6H,J=6.6Hz),1.31-1.48(m,2H),1.77-1.90(m,2H),2.84-2.98(m,2H),3.16(m,1H),3.33(m,1H),3.96-4.10(m,2H),7.11(d,1H,J=7.8Hz),7.57(d,2H,J=8.7Hz),7.67(d,2H,J=8.4Hz),8.90(brs,1H).
Ia-223
mp 183-186℃
1H-NMR(DMSO)δppm:1.23(d,6H,J=6.9Hz),1.28-1.47(m,2H),1.76-1.88(m,2H),2.80-3.16(m,2H),3.16(m,1H),3.32(m,1H),3.94-4.07(m,2H),7.00-7.14(m,3H),7.44(d-d,2H,J=4.8Hz,9.0Hz),8.53(brs,1H).
Ia-224
mp 232-234℃
1H-NMR(DMSO)δppm:1.12-1.46(m,7H),1.23(d,6H,J=6.6Hz),1.63-1.87(m,7H),2.40(m,1H),2.78-2.93(m,2H),3.15(m,1H),3.31(m,1H),3.94-4.07(m,2H),7.06(d,2H,J=8.4Hz),7.09(d,1H,J=8.1Hz),7.32(d,2H,J=8.4Hz),8.39(brs,1H).
Ia-225
mp 222-224℃
1H-NMR(DMSO)δppm:1.28(s,9H),1.30-1.61(m,4H),1.77-1.98(m,4H),2.66-2.90(m,2H),3.28(m,1H),3.40-3.50(m,2H),3.79-3.88(m,2H),3.96-4.08(m,2H),4.44(m,1H),6.85(d,2H,J=9.0Hz),6.91(d,1H,J=9.0Hz),7.31(d,2H,J=9.3Hz),8.34(brs,1H).
Ia-226
mp 194-195℃
1H-NMR(CDCl3/DMSO)δppm:1.39(d,6H,J=7.2Hz),1.66(五重峰,2H,J=6.8Hz),1.87(五重峰,2H,J=7.7Hz),2.47(t,2H,J=7.5Hz),3.11-3.22(m,1H),3.21(t,2H,J=6.2Hz),5.00(brs,1H),7.35-7.56(m,5H),7.86(d,1H,J=8.4Hz),8.05(dd,1H,J=1.8,8.1Hz),8.20(d,1H,J=1.8Hz),9.24(s,1H).
Ia-227
mp>300℃
1H-NMR(DMSO)δppm:1.22(d,6H,J=6.3Hz),1.20-1.40(m,4H),1.74-2.10(m,4H),2.20-2.40(m,1H),2.39(s,3H),3.00-3.30(m,2H),6.25(s,1H),6.99(brs,1H),7.43-7.57(m,1H),7.71(d,1H,J=8.1Hz),7.76(s,1H),10.27(s,1H).
Ia-228
mp 168-169℃
1H-NMR(DMSO)δppm:1.26(s,9H),1.49(五重峰,2H,J=7.5Hz),1.64(五重峰,2H,J=7.4Hz),2.38(t,2H,J=7.2Hz),2.40(s,3H),3.04(q,2H,J=6.5Hz),6.25(s,1H),6.89(t,1H,J=6.0Hz),7.48(dd,1H,J=1.8,8.4Hz),7.71(d,1H,J=8.4Hz),7.77(d,1H,J=1.8Hz),10.33(s,1H).
Ia-229
mp 174-175℃
1H-NMR(DMSO)δppm:1.21(d,6H,J=6.6Hz),1.42-1.56(m,2H),1.56-1.70(m,2H),2.33-2.42(m,2H),2.40(s,3H),2.90-3.02(m,2H),3.14(七重峰,1H,J=6.5Hz),6.26(s,1H),6.99(brs,1H),7.48(d,1H,J=8.4Hz),7.71(d,1H,J=8.7Hz),7.77(s,1H),10.33(s,1H).
Ia-230
mp 194-195℃
1H-NMR(DMSO)δppm:0.86(d,6H,J=6.9Hz),1.25-1.65(m,4H),1.27(s,9H),1.81-2.05(m,5H),2.23-2.35(m,1H),2.99-3.15(m,1H),3.36(d,2H,J=7.2Hz),6.80(d,1H,J=8.4Hz),7.80(d,1H,J=8.4Hz),7.87(d,1H,J=8.4Hz),8.19(s,1H),10.44(s,1H).
Ia-231
mp 221-222℃
1H-NMR(DMSO)δppm:0.86(d,6H,J=6.9Hz),1.22-1.40(m,2H),1.23(d,6H,J=6.9Hz),1.40-1.58(m,2H),1.82-2.04(m,5H),2.22-2.37(m,1H),3.00-3.16(m,1H),3.15(七重峰,1H,J=6.6Hz),3.36(d,2H,J=7.5Hz),6.99(d,1H,J=7.5Hz),7.80(d,1H,J=8.4Hz),7.86(d,1H,J=8.4Hz),8.19(s,1H),10.45(s,1H).
Ia-232
mp 196-197℃
1H-NMR(CDCl3)δppm:0.93(d,6H,J=6.6Hz),1.42(s,1H),1.60-1.70(m,2H),1.88(五重峰,2H,J=7.4Hz),2.02-2.20(m,1H),2.46(t,2H,J=7.7Hz),3.29(q,2H,J=6.1Hz),3.48(d,2H,J=7.8Hz),4.26(t,1H,J=6.0Hz),7.76(d,1H,J=8.1Hz),7.90(dd,1H,J=1.8,8.1Hz),8.07(d,1H,J=1.5Hz),8.39(s,1H).
Ia-233
p.151-152℃
1H-NMR(CDCl3)δppm:0.93(d,6H,J=6.6Hz),1.40(d,6H,J=6.6Hz),1.62-1.69(m,2H),1.88(五重峰,2H,J=7.3Hz),2.03-2.16(m,1H),2.47(t,2H,J=7.5Hz),3.21(七重峰,1H,J=6.8Hz),3.23(q,2H,J=6.3Hz),3.48(d,2H,J=7.5Hz),4.43(t,1H,J=6.0Hz),7.76(d,1H,J=8.4Hz),7.91(dd,1H,J=1.8,8.4Hz),8.06(d,1H,J=1.8Hz),8.36(s,1H).
Ia-234
mp 219-220℃
1H-NMR(DMSO-d6)δppm:1.28(s,9H),1.30-1.50(m,2H),1.74-1.88(m,2H),2.83(t,2H,J=11.1Hz),3.20-3.32(m,1H),3.94-4.07(m,2H),5.94(s,2H),6.77(d,1H,J=8.8Hz),6.82(dd,1H,J=1.8,6.7Hz),6.89(d,1H,J=8.7Hz),7.11(d,1H,J=1.8Hz),8.38(s,1H).
Ia-235
mp 280-282℃
1H-NMR(DMSO-d6)δppm:1.27(s,9H),1.26-1.57(m,4H),1.86-2.03(m,4H),2.38-2.50(m,1H),3.00-3.14(m,1H),6.81(d,1H,J=8.4Hz),7.29(t,1H,J=8.4Hz),7.43(t,1H,J=7.5Hz),7.73(d,1H,J=8.4Hz),7.96(d,1H,J=7.5Hz),12.27(s,1H).
Ia-237
mp 204-205℃
1H-NMR(DMSO)δppm:1.23(d,6H,J=6.6Hz),1.29-1.61(m,4H),1.75-1.98(m,4H),2.78-2.92(m,2H),3.15(m,1H),3.29(m,1H),3.38-3.51(m,2H),3.78-3.89(m,2H),3.94-4.06(m,2H),4.44(m,1H),6.85(d,2H,J=9.0Hz),7.10(d,1H,J=7.8Hz),7.31(d,2H,J=9.3Hz),8.34(brs,1H).
Ia-238
mp 128-130℃
1H-NMR(DMSO)δppm:1.26(s,9H),1.41-1.53(m,2H),1.55-1.68(m,2H),2.44(t,2H,J=7.2Hz),2.98-3.07(m,2H),6.90(t,1H,J=6.0Hz),8.16(d-d,1H,J=2.1Hz,8.7Hz),8.29(d,1H,J=8.7Hz),8.70(m,1H),10.91(brs,1H).
Ia-239
mp 256-258℃
1H-NMR(DMSO)δppm:1.26-1.53(m,4H),1.26(s,9H),1.76-2.00(m,4H),2.23(s,3H),2.39(m,1H),3.04(m,1H),6.80(d,1H,J=8.7Hz),7.57(d-d,1H,J=2.4Hz,8.4Hz),7.97(d,1H,J=8.4Hz),8.12(m,1H),10.26(brs,1H).
Ia-240
mp 288-290℃
1H-NMR(DMSO)δppm:1.26-1.53(m,4H),1.27(s,9H),1.78-1.90(m,4H),2.40(m,1H),3.04(m,1H),6.81(d,1H,J=8.7Hz),7.07(m,1H),7.75(m,1H),8.07(d,1H,J=8.4Hz),8.29(m,1H),10.36(brs,1H).
Ia-241
mp 249-250℃
1H-NMR(DMSO)δppm:1.28(s,9H),1.34-1.50(m,2H),1.79-1.90(m,2H),2.74-2.98(m,2H),3.32(m,1H),4.02-4.14(m,2H),6.91(d,1H,J=8.4Hz),7.94(d,1H,J=9.0Hz),8.04(d-d,1H,J=2.1Hz,9.0Hz),8.60(s,1H),9.76(brs,1H).
Ia-242
mp 250-252℃
1H-NMR(DMSO)δppm:1.24(s,9H),1.27(s,9H),1.24-1.54(m,4H),1.76-1.88(m,2H),1.90-2.01(m,2H),2.21(m,1H),3.05(m,1H),6.79(d,1H,J=8.7Hz),6.88(d,2H,J=9.0Hz),7.48(d,2H,J=9.0Hz),9.72(brs,1H).
mp 250-252℃
1H-NMR(DMSO)δppm:1.15(d,6H,J=6.6Hz),1.28(s,9H),1.35-1.52(m,2H),1.78-1.92(m,2H),2.20(s,3H),2.81-2.96(m,2H),3.33(m,1H),3.96-4.16(m,3H),6.92(d,1H,J=8.7Hz),7.27(d,1H,J=8.1Hz),7.60(m,1H),7.66(m,1H),8.06(d,1H,J=7.8Hz),8.14(brs,1H).
Ia-244
mp 211-213℃
1H-NMR(DMSO)δppm:1.29(s,9H),1.35-1.52(m,2H),1.81-1.93(m,2H),2.83-2.97(m,2H),3.32(m,1H),4.03-4.14(m,2H),6.93(d,1H,J=8.7Hz),7.55(d-d,1H,J=2.1Hz,9.0Hz),7.94(d,1H,J=9.0Hz),8.29(d,1H,J=1.8Hz),8.78(brs,1H),9.19(s,1H).
Ia-245
mp196-197℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.2-1.6(m,6H),1.8-2.0(m,6H),2.23(m,1H),3.05(m,1H),3.73(m,4h),4.99(s,1H),6.79(d,1H,J=8.7),7.13(d,1H,J=6.8),7.22(t,1H,J=6.8),7.49(d,1H,J=6.8),7.72(s,1H),9.78(s,1H).
Ia-246
mp 242-244℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.2-1.5(m,4H),1.65(m,4H),1.8-2.0(m,4H),2.23(m,1H),2.71(m,1H),3.06(m,1H),3.43(m,2H),3.93(m,2H),6.79(d,1H,J=8.7),6.91(d,1H,J=8.7),7.20(t,1H,J=7.5),7.40(d,1H,J=7.5),7.53(s,1H),9.76(s,1H).
Ia-247
mp 242-245℃
1H-NMR(DMSO)δppm:1.27(s,9H),1.2-1.6(m,6H),1.8-2.0(m,6H),2.23(m,1H),3.05(m,1H),3.74(m,4H),4.94(brs,1H),6.79(d,1h,J=8.7),7.38(d,1H,J=8.7),7.52(d,1H,J=8.7),9.76(s,1H)
Ia-248
mp 272-274℃
1H-NMR(CDCl3)δppm:1.27(s,9H),1.2-1.5(m,4H),1.62(m,4H),1.8-2.0(m,4H),2.22(m,1H),2.68(m,1H),3.05(m,1H),3.41(m,2H),3.92(m,2H),6.79(d,1H,J=9.0),7.15(d,2H,J=8.7),7.50(d,2H,J=8.7),9.73(s,1H).
Ia-249mp 174-176℃
Ia-250mp 255-257℃
Ia-252mp 249-251℃
Ia-253mp 120-121℃
Ia-254mp 236-237℃
Ia-255mp 172-174℃
Ia-256mp 257-259℃
Ia-257mp 179-180℃
Ia-258mp 227-229℃
Ia-259mp 135-136℃
实验1对NPY Y5受体的亲和性
将编码人体NPY Y5受体的cDNA序列(WO96/16542)克隆于表达载体pME18S中(Takebe等,Mol.Cell.Biol.8,8957)。根据指导方案,采用脂质转染胺试剂(商标,Gico BRL Co.,Ltd.),将得到的表达载体转染至宿主CHO细胞中,得到稳定表达NPY Y5受体的细胞。
在25℃下,在试验缓冲液(含有0.1%牛血清清蛋白的20mMHEPES-Hanks缓冲液,pH7.4)中,将由以上表达NPY Y5受体的CHO细胞制备的膜、本发明化合物以及30,000cpm[125I]肽YY(终浓度60pM:Amersham)孵育2小时,然后采用用聚乙烯亚胺处理过的玻璃 滤器GF/C过滤该混合液。将该玻璃滤器用50mM Tris-HCl缓冲液(pH7.4)洗涤,用伽玛计数器测定滤器上的放射性。在200nM肽YY存在下,测定非特异性结合。计算试验化合物对特异肽YY结合的50%抑制浓度(IC50值)(Inui,A.等,Endocrinology 131,2090-2096(1992))。结果见表1和2。
本发明化合物抑制肽YY(NPY同系物)与NPY Y5受体的结合。换言之,本发明化合物显示对NPY Y5受体具有亲和性。
实验2cAMP在CHO细胞中产生抑制活性
在37℃、在2.5mM异丁基甲基黄嘌呤(SIGMA)存在下,将表达人体NPY Y5受体的CHO细胞孵育20分钟,然后加入本发明化合物,孵育5分钟。然后,向该细胞中加入50nM NPY和10μM毛喉素(SIGMA),孵育30分钟。加入1N HCl终止该反应,然后用EIA试剂盒(Amersham LIFE SCIENCE)测定上清液中cAMP的量。将NPY对毛喉素刺激的cAMP的抑制活性当作100%,计算本发明化合物对NPY活性的50%抑制浓度(IC50值)。结果见表1-4。
表1
表2
表3
表4
如表1-4中所示,本发明化合物具有NPY Y5受体拮抗活性。
实验3
根据实验1类似的途径,采用由Y1-表达细胞(人体成神经细胞瘤,SK-N-MC)制备的膜和由Y2-表达细胞(人体成神经细胞瘤,SMS-KAN)制备的膜进行本实验,以便测定对NPY Y1受体和NPY Y2受体的亲和力。
I-27、I-32、I-41、I-45、1-46、I-47、I-48、I-49、I-59、I-61、I-63、I-64、I-66、I-69、I-72、I-152、I-154、I-204、I-205、I-212、Ia-3、Ia-5、Ia-6、Ia-12、Ia-16、Ia-17、Ia-20、Ia-21、Ia-22、Ia-26、Ia-28、Ia-29、Ia-30、Ia-31、Ia-32、Ia-33、Ia-37、Ia-39、Ia-40、Ia-50、Ia-51、Ia-54、Ia-62、Ia-67、Ia-124、Ia-126、Ia-139、Ia-140、Ia-142、Ia-178、Ia-199和Ia-200对NPY Y1和NPY Y2受体的结合IC50值为100,000nM或者更高,各化合物对NPY Y5受体具有选择性。
制剂实施例1 片剂
化合物(I-1) 15mg
淀粉 15mg
乳糖 15mg
微晶纤维素 19mg
聚乙烯醇 3mg
蒸馏水 30ml
硬脂酸钙 3mg
除硬脂酸钙外,将以上所有组分混合均匀后,将混合物粉碎,制粒,干燥得到适当大小的颗粒。向颗粒中加入硬脂酸钙,经压模制成片。
制剂实施例2胶囊剂
化合物(I-2) 10mg
硬脂酸镁 10mg
乳糖 80mg
将以上所有组分混合,制成粉末或颗粒,然后填充入胶囊中。
制剂实施例3颗粒剂
化合物(I-3) 30g
乳糖 265g
硬脂酸镁 5g
将以上所有组分混合均匀,经压模,然后粉碎,制粒,过筛制备适当体积的颗粒。
工业适用性
如以上实验中所示,本发明化合物具有NPY Y5受体拮抗活性。因此,本发明化合物可用作抗肥胖剂和减食欲剂。
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103649059A (zh) * | 2011-04-27 | 2014-03-19 | 盐野义制药株式会社 | 具有npy y5受体拮抗作用的五元环芳香族杂环衍生物 |
CN103649059B (zh) * | 2011-04-27 | 2016-10-26 | 盐野义制药株式会社 | 具有npy y5受体拮抗作用的五元环芳香族杂环衍生物 |
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