WO2006078621B1 - 2-phenoxy-n- (1, 3 , 4-thiadizol-2-yl) pyridin-3-amine derivatives and related compounds as p2y1 receptor inhibitors for the treatment of thromboembolic disorders - Google Patents

2-phenoxy-n- (1, 3 , 4-thiadizol-2-yl) pyridin-3-amine derivatives and related compounds as p2y1 receptor inhibitors for the treatment of thromboembolic disorders

Info

Publication number
WO2006078621B1
WO2006078621B1 PCT/US2006/001535 US2006001535W WO2006078621B1 WO 2006078621 B1 WO2006078621 B1 WO 2006078621B1 US 2006001535 W US2006001535 W US 2006001535W WO 2006078621 B1 WO2006078621 B1 WO 2006078621B1
Authority
WO
WIPO (PCT)
Prior art keywords
substituted
alkyl
heterocycle
occurrence
phenyl
Prior art date
Application number
PCT/US2006/001535
Other languages
French (fr)
Other versions
WO2006078621A9 (en
WO2006078621A3 (en
WO2006078621A2 (en
Inventor
James C Sutton
Zulan Pi
Rejean Ruel
Heureux Alexandre L
Carl Thibeault
Patrick Y S Lam
Original Assignee
Bristol Myers Squibb Co
James C Sutton
Zulan Pi
Rejean Ruel
Heureux Alexandre L
Carl Thibeault
Patrick Y S Lam
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bristol Myers Squibb Co, James C Sutton, Zulan Pi, Rejean Ruel, Heureux Alexandre L, Carl Thibeault, Patrick Y S Lam filed Critical Bristol Myers Squibb Co
Priority to AU2006206611A priority Critical patent/AU2006206611A1/en
Priority to EP06733718A priority patent/EP1954696B1/en
Priority to JP2007552205A priority patent/JP2008527043A/en
Priority to AT06733718T priority patent/ATE499370T1/en
Priority to DE602006020327T priority patent/DE602006020327D1/en
Priority to MX2007008434A priority patent/MX2007008434A/en
Publication of WO2006078621A2 publication Critical patent/WO2006078621A2/en
Publication of WO2006078621A3 publication Critical patent/WO2006078621A3/en
Publication of WO2006078621B1 publication Critical patent/WO2006078621B1/en
Priority to NO20073665A priority patent/NO20073665L/en
Publication of WO2006078621A9 publication Critical patent/WO2006078621A9/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/38—Nitrogen atoms
    • C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Pyridine Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

The present invention provides novel heteroaryl compounds of formula (Ia) which are selective inhibitors of the human P2Y1 receptor. The invention also provides for various pharmaceutical compositions of the same and methods for treating diseases responsive to modulation of P2Y1 receptor activity. (Ia) or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein: ring A is a 5- to 6-membered heteroaryl comprising: carbon atoms and 1-4 ringheteroatoms selected from N, NR11, S(O)p, and O, wherein said heteroaryl is substituted with 0-4 R1; ring B is phenyl substituted with 0-4 R7, pyridyl substituted with 0-3 R7, or thienyi substituted with 0-2 R7; X is NH or NMe; Y is O or S; R5 is a -(CRfRf)n-C3-10 carbocycle substituted with 1-4 R5a, or a -(CRfRf)n-5- to 10-membered heterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, NR11, O, and S(O)p, wherein said heterocycle is substituted with 0-4 R5a; the other substituents and variables are defined in the claims.

Claims

received by the International Bureau on 29 Aug 2006 (29.08.06)What is claimed is:
1. A compound of Formula (Ia):
Figure imgf000003_0001
(Ia) or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein: ring A is selected from:
Figure imgf000003_0002
alternatively, ring A is substituted with 0-3 R1 and is selected from:
Figure imgf000003_0003
. ring B is phenyl substituted with 0-4 R7, pyridyl substituted with 0-3 R7, or thienyl substituted with 0-2 R7;
X is NH;
Y is O;
R1, Rla, Rlb, Rlc, Rld, and Rle are, independently at each occurrence, C i-6 alkyl substituted with 0-2 Ra, C2-6 alkenyl substituted with 0-2 Ra, C2-6 alkynyl substituted with 0-2 Ra, Br, CN5 CF3, -CF2CF3, -C(NH2)=N(OH), C(O)RC, - CH(=NOH), -C(O)ORC, NR12R13, -C(O)NR12RlS,
295 -CON(Me)(CH2)2θH, -CO-morpholin-4-yl, -SQ2-morpholin-4-yl, -S(O)pNR12R13, -(CH2)rC3-6 cycloalkyl substituted with 0-2 Rb, -(CH2)r-adamantyl substituted with 0-2 Rb, -(CH2)r-phenyl substituted with 0-4 Rb, - (CH2)rnaphthyl substituted with 0-4 Rb, -(CH2)r-3- to 10-membered heterocycle substituted with 0-4 Rb, wherein said heterocycle is selected from: aziridinyl, azetidinyl, pyrrolidinyl, furanyl, imidazolyl, oxadiazolyl, thienyl, pyrrolyl, isoxazolyl, triazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, piperdinyl, morpholinyl, piperazinyl, 1,3-benzodioxolyl, benzothienyl, isoindolinyl,
1,4-diazacycloheptanyl, tetrahydroisoquinolyl, and
Figure imgf000004_0001
; alternatively, R1 a and Rlb or R1 d and R1 e are combined with the carbon atoms to which they attached, form a 5- to 6-membered carbocycle or heterocycle comprising: carbon atoms and 0-3 additional heteroatoms selected from N, NR1 1, O, and S(O)p, 0-2 carbonyl, and 0-1 additional double bond, wherein said carbocycle and heterocycle are substituted with 0-3 Rb; alternatively, two R1S are combined with the carbon atoms to which they attached, form a 5- to 7-membered carbocycle or heterocycle comprising: carbon atoms and 0-3 additional heteroatoms selected from N, NR11, O, and S(O)p, 0-2 carbonyls, and 0-2 double bond, wherein said carbocycle or heterocycle is substituted with 0-4 Rb;
R5 is phenyl substituted with 1-4 R5a or pyridyl substituted with 1-4 R5a;
R5a is, independently at each occurrence, F, Cl, Br, I, -(CR1Ri)1-ORc, SRC, CN, NO2, CF3, -CF2CF3, OCF3, -OCF2CF2H, -OCF2CF3, -NR12R13, -C(O)RC, -C(O)ORC, -C(O)NR12R13, -NR^C(O)Rd -S(O)pNR12R13, -S(O)Rd, -S(O)2Rd, -Si(Me)3, Si(Ct-4 alkyl)3, Cμ4 haloalkyl, C1-4 haloalkyloxy-, C 1.4 alkyloxy-, Ci_4 alkylthio-, C1.4 alkyl-C(O)-, C1.4 alkyl-O-C(O)-, C1.4 alkyl-C(O)NH-, C1-8 alkyl substituted with 0-2 Ra, C2_s alkenyl substituted with 0-2 Ra, C2-8 alkynyl substituted with 0-2 Ra, -(CRfRf)rC3.io carbocycle substituted with 0-3 Re, or -(CRfRf)r-5- to lQ-membered heterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, NR1I, O, and S(O)p, wherein said heterocycle is substituted with 0-3 Re; alternatively, two R5a groups, together with the atoms to which they are attached, form a 5- to 7-membered carbocyclic or heterocyclic ring comprising: carbon atoms and 0-2 heteroatoms selected from N, NR11, O, and S(O)p, 0-1 carbonyl and 0-3 double bonds, wherein said carbocyclic or heterocyclic ring is substituted , with 0-3 Re;
R7 is, independently at each occurrence, H, F, Cl3 Br, I, OCF3, CF3, ORC, SRC, CN, NO2, -NR12R13, -C(O)RC, -C(O)ORC, -C(O)NR12R13, -NR14C(O)Rd -S(O)pNR12R13, -S(O)Rd, -S(O)2Rd, C1-8 alkyl substituted with 0-2 Ra, C2.8 alkenyl substituted with 0-2 Ra, C2-8 alkynyl substituted with 0-2 Ra, -(CRfRf)r-C3-io carbocycle substituted with 0-3 Rb, or -(CRfR^)r-5- to 10-membered heterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, NR7b, O, and S(O)p, wherein said heterocycle is substituted with 0-3 Rb; alternatively, two R7S can form a 5- to 7-membered carbocyclic or heterocyclic ring comprising: carbon atoms and 0-3 ring heteroatoms selected from O, N, NR7b, and S(O)p, wherein said carbocyclic or heterocyclic ring is substituted with 0-3 R7c;
R7b is, independently at each occurrence, H, C 1.4 alkyl, (C 1.4 alkyl)C(O)-, phenyl-C(O)-, benzyl-C(O)-, benzyl-S(O)2-, (Ci_4 alkyl)NHC(O)-, (C M alkyl)2NC(O)-, phenyl-NHC(O)-, benzyl-NHC(O)-, (Cμ4 alkyl)-S(O)2-, phenyl-S(O)2-, phenyl substituted with 0-3 Rb, or benzyl substituted with 0-3 Rb;
R7c is, independently at each occurrence, H, F, Cl, Br5 1, OCF3, CF3, ORC, SRc5 CN, NO2, -NR12R13, -C(O)Rc, -C(O)ORC, -C(O)NR12R13, -NR14C(O)Rd -S(O)pNR12R13, -S(O)Rd, -S(O)2Rd, C1-4 alkyl, phenyl substituted with 0-3 Rb, or benzyl substituted with 0-3 Rb;
297 R11 is, independently at each occurrence, H, Cj -6 alkyl substituted with 1-5 fluorine, -(CRfRf)rC(O)NR12R13, C1-8 alkyl substituted with 0-2 Ra, C2-8 alkenyl substituted with 0-2 Ra, C2-8 alkynyl substituted with 0-2 Ra, (Ci-6 alkyl)C(O)-, (C3-6 cycloalkyl)Ci.3 alkyl-C(O)-, (C3.6 cycloalkyl)C(O)-, phenyl-C(O)-, benzyl-C(O)-, (Ci_6 alkyl)NHC(O)-, (Ci_6 alkyl)2NC(O)-, phenyl-NHC(O)-, benzyl-NHC(O)-, (phenyl)(Ci_6 alkyl)NC(O)-, (benzyl)(Ci.6 alkyl)NC(O)-, (Ci_6 alkyl)-S(O)2-, phenyl-S(O)2-, benzyl-S(O)2-, -(CR^R.f)r-C3-io carbocycle, or -(CRfRf)r-5- to 10-membered lieterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, NRf, O, and S(O)p; wherein said phenyl, benzyl, carbocycle, and heterocycle are substituted with 0-3 Rb;
R12 is, independently at each occurrence, H, C]_6 alkyl substituted with 1-5 fluorine, -(CRfRf)1C(O)NR1Rf Cμ6 alkyl, (Cμ6 alkyl)C(O)-, (Cμ4 alkyl)OC(O)-, (C6-I0 aryl)-CH2-OC(O)-, (C6-I0 aryl)-CH2-C(O)-,
(Ci-4 EIlCyI)-C(O)O-(CL4 alkyl)-OC(O)-, (C6_i0 aryl)-C(O)O-(Ci-4 alkyl)-OC(O)-, (Ci-6 alkyl)-NHC(O)-, (C6-I0 aryl)-NHC(O)-, (5- to 10-membered heteroaryl)-NHC(O)-,
(5- to 10-membered heteroaryl)-CH2-OC(O)-, (5- to 10-membered heteroaryl)-C(O)-, (C6-I0 aryl)-(C0-4 alkyl)-C(O)-, (Cw alkyl)-S(O)2-, (C6-I0 aryl)-S(O)2-, (5- to 10-membered heteroaryl)-S(O)2-, or (C6-I0 aryl)-(Ci_4 alkyl)-S(0)2-, -(CRfRf)n-(C6-IO aryl), -(CRfRf)n- 5- to 10-membered heterocycle; wherein said alkyl, phenyl and aryl are substituted with 0-2 RS; said 5- to 10-membered heteroaryl is substituted with with 0-2 RS and comprises: carbon atoms and 1-4 heteroatoms selected from N, NRf, O, and S(O)p; said 5- to 10-membered heterocycle is substituted with with 0-2 RS and comprises: carbon atoms and 1-4 heteroatoms selected from N, NRf, O, and S(O)p;
R13 is, independently at each occurrence, H, Cμ6 alkyl, or -(CH2)n-phenyl; alternatively, R12 and R13, when attached to the same nitrogen, combine to form a 5- to 10-membered heterocyclic ring comprising: carbon atoms and 1-2 additional heteroatoms selected from N, NRf O, and S(O)p;
298 R14 is, independently at each occurrence, H, Ci-6 alkyl substituted with 0-2 R14a, C2-6 alkenyl substituted with 0-2 R14a, C2-6 alkynyl substituted with 0-2 R14a, -(CH2)r-C3_io carbocycle substituted with 0-3 RS3 or -(CH2)r-5- to 10-membered heterocycle comprising: carbon atoms and 1-4 heteroatonis selected from N, NRf O, and S(O)p, wherein said heterocycle is substituted with 0-3 RS;
R14a is, independently at each occurrence, H, C 1-4 alkyl, ORf, Cl5 F, Br, I, =0, CF3, CN, NO2, NR12R1S, -C(O)Rf, -C(O)ORf -C(O)NR12R13, or -S(O)pRf;
Ra is, independently at each occurrence, H, F, OCF3, CF3, -(CRfRf)rORc, -(CRfRf)rSRc, CN,
Figure imgf000007_0001
-(CRfRf)rC(O)Rc, -(CRfRf)rC(O)ORc, -(CRfRf)AO)NR12R13, -(CRfRfJrNRl4C(O)Rd -(CRfRf)1-S(O)PNR12R13, -(CRfRf)r S(O)Rd, -(CRfRf)rS(O)2Rd, C1-4 alkyl substituted with 1-5 fluorine, -(CH2VC3-IO carbocycle substituted with 0-3 Re, or -(CH2)r-5- to 10-membered heterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, NRf O, and S(O)p, wherein said heterocycle is substituted with 0-3 Re;
Rb is, independently at each occurrence, H, =0, F, Cl, Br, I, -(CH2)r-ORc, SRc, CN, NO2, CF3, OCF3, -(CRfRf)rNR12R13, -C(O)RC, -(CH2)rC(0)0Rc, -(CH2VC(O)NRl2R13, -NRl4C(O)Rd, -S(O)pNR12R13, -S(O)Rd, -S(O)2Rd, Ci-4 haloalkyl, C1.4 haloalkyloxy-, C1^ alkyl substituted with 0-2 Ra, C2-6 alkenyl substituted with 0-2 Ra, C2-6 alkynyl substituted with 0-2 Ra, -(CH2)r-C3.io carbocycle substituted with 0-3 Re, or -(CH2)r-5- to 10-membered heterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, NRf, O5 and S(O)p, wherein said heterocycle is substituted with 0-3 Re;
Rc is, independently at each occurrence, H, -OP(O)(OEt)2, Cj.g alkyl substituted with 0-2 Re, C2-8 alkenyl substituted with 0-2 Re, C2-8 alkynyl substituted with 0-2 Re, -(CRfRf)r-C3-8 cycloalkyl substituted with 0-2 Re, -(CRfRf)r-C6-io aryl substituted with 0-2 Re, or -(CRfRf)r-5- to 10-membered heterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, NRf, O, and S(O)p, wherein said heterocycle is substituted with 0-2 Re;
Rd is, independently at each occurrence, CF3, OH, C1-4 alkoxy, C 1-6 alkyl,
299 -(CH2)r-C3-io carbocycle substituted with 0-2 Re, or -(CH2)r-5- to 10- membered lieterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, NRf O5 and S(O)p, wherein said heterocycle is substituted with 0-2 Re;
Re is, independently at each occurrence, H, =O, -(CH2)r-ORf, F, Cl, Br, I, CN, NO2, -(CH2VNR12R13, -C(O)Rf, -(CH2)r-C(O)ORf, -NR14C(O)Rf, -(CH2)r-C(O)NR12R13, -SO2NR12R13, -NR14SO2NR12R13, -NR14SO2-Ci_4 alkyl, -NR14SO2CF3, -NR14SO2-phenyl, -S(O)2CF3, -S(O)p-Ci.4 alkyl, -S(O)p-phenyl, -(CF2^CF3, Si(Ci_4 alkyl)3, Cμs alkyl substituted with 0-2 Rg, C2_s alkenyl substituted with 0-2 RS, C2-8 alkynyl substituted with 0-2 RS5 -(CH2)r-C3-8 cycloalkyl substituted with 0-2 R8, -(CH2)r-C6-io aryl substituted with 0-2 RS, or -(CH2)r-5- to 10-membered heterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, NRf, O, and S(O)p, wherein said heterocycle is substituted with 0-2 RS; alternatively, two Re groups, together with the atoms to which they are attached, form a 5- to 7-membered carbocyclic or heterocyclic ring comprising: carbon atoms and 0-2 heteroatoms selected from N, NRf, O, and S(O)p, 0-1 carbonyl and 0-3 double bonds, wherein said carbocyclic or heterocyclic ring is substituted with 0-3 RS;
Rf is, independently at each occurrence, H, F, Cj.g alkyl, or ~(CH2)n-phenyl;
Rg is, independently at each occurrence, H, =0, ORf, F, Cl, Br, I, CN, NO2, -NRfRf, -C(O)Rf -C(O)ORf -NRfC(O)Rf -C(O)NRfRf -SO2NRfRf, -NRfSO2NRfRf, ~NRfSO2-Ci_4 alkyl, -NRfSO2CF3, -NRfSO2-phenyl, -S(O)2CF3, -S(O)p-Ci_4 alkyl, -S(O)p-phenyl, -(CF2)rCF3, Ci_6 alkyl, C2.6 alkenyl, or C2.6 alkynyl;
Rh is, independently at each occurrence, Cμg alkyl substituted with 0-2 Rg, or -(CH2)n-phenyl substituted with 0-2 Rg, or -(CH2)n-5- to 10-membered heterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, NRf, O, and S(O)p, wherein said heterocycle is substituted with 0-2 Rg;
Ri is, independently at each occurrence, H, Cj .5 alkyl substituted with 0-2 Rg,
300 -(CH2)n-phenyl substituted with 0-2 Rg, or -(CH2)n-5- to lQ-membered heterocycle comprising: carbon atoms and 1-4 lieteroatoms selected from N, NRf, O, and S(O)p, wherein said heterocycle is substituted with 0-2 R§; n, at each occurrence, is selected from 0, 1, 2, 3, and 4; p, at each occurrence, is selected from 0, 1, and 2; and r, at each occurrence, is selected from 0, 1, 2, 3, and 4; provided that: when Y is O, ring B is phenylene substituted with Cl, R5 is pyridyl, then ring A is other than trizolyl substituted with CO2H.
2. A compound according to Claim 1, wherein: ring B is
Figure imgf000009_0001
R7, R7a, R7b, and R7c are, independently at each occurrence, H, Me, Cl, Br, CN, OMe, SMe, NHMe, NH2, NMe2, or -NH(4-OMe-Ph);
R8 and R8b are, independently at each occurrence, H, Me, Cl, Br5 CN, NMe2, or -N(Me)(4-OMe-Ph); and
R5 is phenyl substituted with 1-4 R5a.
3. A compound according to Claim 1 , wherein:
r
Figure imgf000009_0002
ing B is
4. A compound according to Claim I5 wherein:
301
Figure imgf000010_0001
5. A compound of Formula (II):
Figure imgf000010_0002
(H)
302
PCT/US2006/001535 2005-01-19 2006-01-17 2-phenoxy-n- (1, 3 , 4-thiadizol-2-yl) pyridin-3-amine derivatives and related compounds as p2y1 receptor inhibitors for the treatment of thromboembolic disorders WO2006078621A2 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
AU2006206611A AU2006206611A1 (en) 2005-01-19 2006-01-17 2-phenoxy-N- (1, 3 , 4-thiadizol-2-yl) pyridin-3-amine derivatives and related compounds as P2Y1 receptor inhibitors for the treatment of thromboembolic disorders
EP06733718A EP1954696B1 (en) 2005-01-19 2006-01-17 2-phenoxy-n-(1,3,4-thiadizol-2-yl)pyridin-3-amine derivatives and related compounds as p2y1 receptor inhibitors for the treatment of thromboembolic disorders
JP2007552205A JP2008527043A (en) 2005-01-19 2006-01-17 2-phenoxy-N- (1,3,4-thiadiazol-2-yl) pyridin-3-amine derivatives and related compounds as P2Y1 receptor inhibitors for the treatment of thromboembolic disorders
AT06733718T ATE499370T1 (en) 2005-01-19 2006-01-17 2-PHENOXY-N-(1,3,4-THIADIZOL-2-YL)PYRIDINE-3-AMINE DERIVATIVES AND RELATED COMPOUNDS AS P2Y1 RECEPTOR INHIBITORS FOR THE TREATMENT OF THROMBOEMBOLIC DISEASES
DE602006020327T DE602006020327D1 (en) 2005-01-19 2006-01-17 2-PHENOXY-N- (1,3,4-THIADIZOL-2-YL) PYRIDINE-3-AMINDER INHIBITOR FOR THE TREATMENT OF THROMBOEMBOLIC ILLNESSES
MX2007008434A MX2007008434A (en) 2005-01-19 2006-01-17 2-phenoxy-n- (1, 3 , 4-thiadizol-2-yl) pyridin-3-amine derivatives and related compounds as p2y1 receptor inhibitors for the treatment of thromboembolic disorders.
NO20073665A NO20073665L (en) 2005-01-19 2007-07-17 2-Phenoxy-N- (1,3,4-thiadizol-2-yl) pyridine-3-amine derivatives and related compounds as P2Y1 receptor inhibitors for the treatment of thromboembolic disorders

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US64528505P 2005-01-19 2005-01-19
US60/645,285 2005-01-19
US74931705P 2005-12-09 2005-12-09
US60/749,317 2005-12-09

Publications (4)

Publication Number Publication Date
WO2006078621A2 WO2006078621A2 (en) 2006-07-27
WO2006078621A3 WO2006078621A3 (en) 2006-10-05
WO2006078621B1 true WO2006078621B1 (en) 2006-10-26
WO2006078621A9 WO2006078621A9 (en) 2008-06-19

Family

ID=36579581

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2006/001535 WO2006078621A2 (en) 2005-01-19 2006-01-17 2-phenoxy-n- (1, 3 , 4-thiadizol-2-yl) pyridin-3-amine derivatives and related compounds as p2y1 receptor inhibitors for the treatment of thromboembolic disorders

Country Status (13)

Country Link
US (2) US7645778B2 (en)
EP (1) EP1954696B1 (en)
JP (1) JP2008527043A (en)
KR (1) KR20070100894A (en)
AR (1) AR053011A1 (en)
AT (1) ATE499370T1 (en)
AU (1) AU2006206611A1 (en)
DE (1) DE602006020327D1 (en)
MX (1) MX2007008434A (en)
NO (1) NO20073665L (en)
PE (1) PE20061120A1 (en)
TW (1) TW200638934A (en)
WO (1) WO2006078621A2 (en)

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7470712B2 (en) * 2004-01-21 2008-12-30 Bristol-Myers Squibb Company Amino-benzazoles as P2Y1 receptor inhibitors
US7388021B2 (en) * 2004-05-12 2008-06-17 Bristol Myers Squibb Company Urea antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions
US7550499B2 (en) 2004-05-12 2009-06-23 Bristol-Myers Squibb Company Urea antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions
ES2352796T3 (en) * 2005-06-27 2011-02-23 Bristol-Myers Squibb Company CYCLIC ANTAGONISTS UNITED TO C OF THE P2Y1 RECEIVER USEFUL IN THE TREATMENT OF THROMBOTHIC AFFECTIONS.
KR20080027890A (en) 2005-06-27 2008-03-28 브리스톨-마이어스 스큅 컴퍼니 N-linked heterocyclic antagonists of p2y1 receptor useful in the treatment of thrombotic conditions
ATE502924T1 (en) * 2005-06-27 2011-04-15 Bristol Myers Squibb Co LINEAR UREA MIMETIC ANTAGONISTS OF THE P2Y1 RECEPTOR FOR THE TREATMENT OF THROMBOSIS
WO2007002634A1 (en) * 2005-06-27 2007-01-04 Bristol-Myers Squibb Company Carbocycle and heterocycle antagonists of p2y1 receptor useful in the treatment of thrombotic conditions
CN101273022A (en) * 2005-07-04 2008-09-24 雷迪博士实验室有限公司 Thiazoles derivatives as AMPK activator
JP2009526868A (en) * 2006-02-15 2009-07-23 アボット・ラボラトリーズ Novel acetyl-CoA carboxylase (ACC) inhibitors and their use in diabetes, obesity and metabolic syndrome
WO2007118149A2 (en) * 2006-04-07 2007-10-18 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical Lollege Thiazole and thiophene analogues, and their use in treating autoimmune diseases and cancers
TW200811164A (en) * 2006-05-12 2008-03-01 Jerini Ag New heterocyclic compounds for the inhibition of integrins and use thereof
US7960569B2 (en) * 2006-10-17 2011-06-14 Bristol-Myers Squibb Company Indole antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions
JP4941971B2 (en) * 2007-01-29 2012-05-30 独立行政法人産業技術総合研究所 Process for producing alkylthio-substituted nitrogen-containing heterocyclic compound
RU2532135C2 (en) * 2007-02-22 2014-10-27 Зингента Партисипейшнс Аг Iminopyridine derivatives and use thereof as microbiocides
JP5527923B2 (en) * 2007-03-28 2014-06-25 公益財団法人相模中央化学研究所 Heterocyclic compound having perfluoroalkyl group and method for producing the same
JP5385895B2 (en) 2007-04-10 2014-01-08 ブリストル−マイヤーズ スクイブ カンパニー Thiazolyl compounds useful as kinase inhibitors
NZ583538A (en) 2007-09-21 2012-06-29 Array Biopharma Inc Pyridin-2-yl-amino-1,2,4 -thiadiazole derivatives as glucokinase activators for the treatment of diabetes mellitus
PT2195312E (en) 2007-10-09 2013-02-20 Merck Patent Gmbh Pyridine derivatives useful as glucokinase activators
JO2784B1 (en) * 2007-10-18 2014-03-15 شركة جانسين فارماسوتيكا ان. في 1,3,5-trisubstitued triazole derivative
JP2011500625A (en) * 2007-10-18 2011-01-06 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ Tri-substituted 1,2,4-triazole
WO2010012793A1 (en) * 2008-08-01 2010-02-04 Bayer Cropscience Sa Fungicide aminothiazole derivatives
ES2779001T3 (en) 2008-12-03 2020-08-13 Scripps Research Inst Stem cell cultures
US9138309B2 (en) 2010-02-05 2015-09-22 Allergan, Inc. Porous materials, methods of making and uses
AR081331A1 (en) 2010-04-23 2012-08-08 Cytokinetics Inc AMINO- PYRIMIDINES COMPOSITIONS OF THE SAME AND METHODS FOR THE USE OF THE SAME
EP2560488B1 (en) 2010-04-23 2015-10-28 Cytokinetics, Inc. Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use
AR081626A1 (en) 2010-04-23 2012-10-10 Cytokinetics Inc AMINO-PYRIDAZINIC COMPOUNDS, PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM AND USE OF THE SAME TO TREAT CARDIAC AND SKELETIC MUSCULAR DISORDERS
ES2609837T3 (en) * 2010-08-10 2017-04-24 Octeta Therapeutics, Llc New synthesis of thiazolidinedione compounds
US8759380B2 (en) 2011-04-22 2014-06-24 Cytokinetics, Inc. Certain heterocycles, compositions thereof, and methods for their use
AU2013348167A1 (en) 2012-11-20 2015-05-28 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of indoleamine 2,3-dioxygenase
CA2930712A1 (en) * 2013-11-14 2015-05-21 Scynexis Inc. Antiparasitic compounds
BR112018004447A2 (en) 2015-09-18 2018-09-25 Kaken Pharmaceutical Co., Ltd. Medicine containing a beer reel derivative and it
DE102018113646B4 (en) 2018-06-07 2021-06-24 Helmholtz-Zentrum Dresden - Rossendorf E.V. 2-Phenoxypyridin-3-amine derivatives and their use
CA3102381A1 (en) 2018-06-15 2019-12-19 Handa Oncology, Llc Kinase inhibitor salts and compositions thereof
EP4094762A1 (en) 2021-05-25 2022-11-30 UCL Business Ltd Treatment of neurological indications
EP4095134A1 (en) 2021-05-25 2022-11-30 UCL Business Ltd Polycyclic compounds for the treatment of neurological indications

Family Cites Families (93)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3118888A (en) 1964-01-21 Acylated s-triazines and process for their preparation
NL280954A (en) 1961-07-14
US4179563A (en) 1978-05-19 1979-12-18 Warner-Lambert Company 3-Aryloxy-substituted-aminopyridines and methods for their production
US4186199A (en) 1978-11-02 1980-01-29 American Hoechst Corporation Indolo-,1,2-dihydroindolo-, and 1,2,6,7-tetrahydroindolo [1,7-ab][1,5] benzodiazepines
DE3065190D1 (en) 1979-11-05 1983-11-10 Beecham Group Plc Enzyme derivatives, and their preparation
JPS56166180A (en) 1980-05-28 1981-12-21 Chugai Pharmaceut Co Ltd Dibenzoxazepine derivative and its preparation
JPS56167649A (en) 1980-05-30 1981-12-23 Chugai Pharmaceut Co Ltd Diphenyl ether derivative
US4663453A (en) 1983-05-18 1987-05-05 Hoechst-Roussel Pharmaceuticals Inc. Benzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepines having dopamine receptor activity
US4761411A (en) 1983-05-18 1988-08-02 Hoechst-Roussel Pharmaceuticals Inc. Dihydrobenzopyrrolobenzodiazepines useful for treating pyschoses
JPS62280847A (en) 1986-05-30 1987-12-05 Konica Corp Silver halide photographic sensitive material containing new magnenta coupler
US4840947A (en) 1986-10-14 1989-06-20 Hoechst-Roussel Pharmaceuticals, Inc. Antiinflammatory and analgesic piperidin-4-yl-tetracyclic benzodiazepines and use thereas
JP2577222B2 (en) 1987-04-10 1997-01-29 興和株式会社 New substituted anilide derivatives
JPH0339740A (en) 1989-07-06 1991-02-20 Konica Corp Transfer type heatdevelopable color photosensitive material
JP2951434B2 (en) 1991-04-18 1999-09-20 三菱製紙株式会社 Electrophotographic photoreceptor
NZ264063A (en) 1993-08-13 1995-11-27 Nihon Nohyaku Co Ltd N-(2-phenylpyrid-3-yl)- and n-(4-phenylpyrimidin-5-yl)-n'-phenylurea derivatives and pharmaceutical compositions
JP3395285B2 (en) 1993-10-06 2003-04-07 日本製紙株式会社 Thermal recording medium
US5547966A (en) 1993-10-07 1996-08-20 Bristol-Myers Squibb Company Aryl urea and related compounds
US5612359A (en) 1994-08-26 1997-03-18 Bristol-Myers Squibb Company Substituted biphenyl isoxazole sulfonamides
DE4443641A1 (en) 1994-12-08 1996-06-13 Bayer Ag Substituted carboxamides
WO1996025157A1 (en) 1995-02-17 1996-08-22 Smithkline Beecham Corporation Il-8 receptor antagonists
KR19980703048A (en) 1995-03-20 1998-09-05 피터쥐.스트링거 5-substituted-3- (1,2,3,6-tetrahydropyridin-4-yl) - and 3- (piperidin-4-yl) -1H- indole: A novel 5-HT1F agonist
JP4009681B2 (en) 1995-11-07 2007-11-21 キリンファーマ株式会社 Quinoline derivatives and quinazoline derivatives that inhibit platelet-derived growth factor receptor autophosphorylation and pharmaceutical compositions containing them
KR20000004963A (en) 1996-03-25 2000-01-25 피터 지. 스트링거 TETRAHYDRO-BetA-cARBOLINE COMPOUNDS
AU5584698A (en) 1996-10-30 1998-05-22 University Of North Carolina At Chapel Hill, The P2y receptor antagonists
US6020357A (en) 1996-12-23 2000-02-01 Dupont Pharmaceuticals Company Nitrogen containing heteroaromatics as factor Xa inhibitors
US6187797B1 (en) 1996-12-23 2001-02-13 Dupont Pharmaceuticals Company Phenyl-isoxazoles as factor XA Inhibitors
TW536540B (en) 1997-01-30 2003-06-11 Bristol Myers Squibb Co Endothelin antagonists: N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide and N-(4,5-dimethyl-3-isoxazolyl)-2'-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4'-(2-oxazolyl)[1,1'-biphe
US5858289A (en) 1997-02-24 1999-01-12 Global Consulting, Inc. Process for preparing compressed shape of ceramic fiber
ZA985247B (en) 1997-06-19 1999-12-17 Du Pont Merck Pharma Guanidine mimics as factor Xa inhibitors.
US6022884A (en) 1997-11-07 2000-02-08 Amgen Inc. Substituted pyridine compounds and methods of use
EP1037632B1 (en) 1997-11-10 2006-01-11 Bristol-Myers Squibb Company Benzothiazole protein tyrosine kinase inhibitors
JP2002508366A (en) 1997-12-12 2002-03-19 スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー Quinoline piperazine and quinoline piperidine derivatives, methods for their preparation, and their use as complex 5-HT1A, 5-HT1B and 5-HT1D receptor antagonists
DE1042305T1 (en) 1997-12-22 2001-04-19 Bayer Ag INHIBITION OF p38 KINASE USING SYMMETRIC AND ASYMMETRIC DIPHENYL UREAS
US7517880B2 (en) 1997-12-22 2009-04-14 Bayer Pharmaceuticals Corporation Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas
US6329395B1 (en) 1998-06-08 2001-12-11 Schering Corporation Neuropeptide Y5 receptor antagonists
DE69940063D1 (en) 1998-07-06 2009-01-22 Bristol Myers Squibb Co BIPHENYLSULFONAMIDE AS A DOUBLE-ACTIVE RECEPTOR ANTAGONIST OF ANGIOTENSIN AND ENDOTHELIN
TR200101028T2 (en) 1998-10-06 2001-08-21 Dainippon Pharmaceutical Co., Ltd. 2,3-Substituted pyridine derivative, the process used in its preparation, the pharmaceutical composition and intermediate containing it
EP1123918B1 (en) 1998-10-20 2005-03-09 Takeda Pharmaceutical Company Limited Aromatic amine derivatives, process for the preparation thereof and agents containing the same
GB9823873D0 (en) 1998-10-30 1998-12-30 Pharmacia & Upjohn Spa 2-ureido-thiazole derivatives,process for their preparation,and their use as antitumour agents
GB9828511D0 (en) 1998-12-24 1999-02-17 Zeneca Ltd Chemical compounds
US6358945B1 (en) 1999-03-12 2002-03-19 Boehringer Ingelheim Pharmaceuticals, Inc. Compounds useful as anti-inflammatory agents
US6548529B1 (en) 1999-04-05 2003-04-15 Bristol-Myers Squibb Company Heterocyclic containing biphenyl aP2 inhibitors and method
PL215901B1 (en) * 1999-04-15 2014-02-28 Bristol Myers Squibb Co Cyclic protein tyrosine kinase inhibitors
AU5546000A (en) 1999-06-14 2001-01-02 Protherics Molecular Design Limited Compounds
CO5200760A1 (en) 1999-06-16 2002-09-27 Smithkline Beecham Corp RECEIVER ANTAGONISTS OF IL-8 CEPTOR IL-8
JP2001089412A (en) 1999-09-22 2001-04-03 Otsuka Pharmaceut Co Ltd Benzene derivative or its pharmaceutically acceptable salt
WO2001023358A1 (en) 1999-09-27 2001-04-05 Sagami Chemical Research Center Pyrazole derivatives, intermediates for the preparation thereof, processes for the preparation of both and herbicides containing the derivatives as the active ingredient
MY125533A (en) 1999-12-06 2006-08-30 Bristol Myers Squibb Co Heterocyclic dihydropyrimidine compounds
DE19962924A1 (en) 1999-12-24 2001-07-05 Bayer Ag Substituted oxazolidinones and their use
ATE336492T1 (en) 2000-01-14 2006-09-15 Us Gov Health & Human Serv METHONOCARBACYCLOALKYLANALOGUES OF NUCLEOSIDES
EP1254136A4 (en) 2000-01-29 2005-06-01 Lg Chem Investment Ltd FACTOR Xa INHIBITORS WITH ARYL-AMIDINES AND DERIVATIVES, AND PRODRUGS THEREOF
US6906063B2 (en) 2000-02-04 2005-06-14 Portola Pharmaceuticals, Inc. Platelet ADP receptor inhibitors
IL151045A0 (en) 2000-02-07 2003-04-10 Abbott Gmbh & Co Kg 2-benzothiazolyl urea derivatives and their use as protein kinase inhibitors
AU2000240570A1 (en) 2000-03-29 2001-10-08 Knoll Gesellschaft Mit Beschraenkter Haftung Pyrrolopyrimidines as tyrosine kinase inhibitors
US6586453B2 (en) 2000-04-03 2003-07-01 3-Dimensional Pharmaceuticals, Inc. Substituted thiazoles and the use thereof as inhibitors of plasminogen activator inhibitor-1
AR035216A1 (en) 2000-12-01 2004-05-05 Astrazeneca Ab MANDELIC ACID DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE DERIVATIVES, USE OF THESE DERIVATIVES FOR THE MANUFACTURE OF MEDICINES, TREATMENT METHODS, PROCESSES FOR THE PREPARATION OF THESE DERIVATIVES, AND INTERMEDIARY COMPOUNDS
ATE322246T1 (en) 2001-01-31 2006-04-15 P & G Clairol Inc NEW COUPLING AGENT FOR OXIDATIVE HAIR DYEING
WO2002064211A1 (en) 2001-02-09 2002-08-22 Merck & Co., Inc. Thrombin inhibitors
AU2002305260A1 (en) 2001-04-27 2002-11-11 Vertex Pharmaceuticals Incorporated Pyrazole derived kinase inhibitors
WO2002090352A2 (en) 2001-05-08 2002-11-14 Schering Aktiengesellschaft Selective anthranilamide pyridine amides as inhibitors of vegfr-2 and vegfr-3
WO2003007955A2 (en) 2001-07-20 2003-01-30 Cancer Research Technology Limited Biphenyl apurinic/apyrimidinic site endonuclease inhibitors to treat cancer
US20040259875A1 (en) 2001-07-31 2004-12-23 Takeshi Yura Amine derivatives
IL159926A0 (en) 2001-08-06 2004-06-20 Pharmacia Italia Spa Aminoisoxazole derivatives active as kinase inhibitors
AU2002341693B2 (en) 2001-09-21 2008-05-29 Bristol-Myers Squibb Holdings Ireland Unlimited Company Lactam-containing compounds and derivatives thereof as factor Xa inhibitors
US20050009815A1 (en) 2001-11-27 2005-01-13 Devita Robert J. 4-Aminoquinoline compounds
JP2003192587A (en) 2001-12-26 2003-07-09 Bayer Ag Urea derivative
WO2003055848A2 (en) 2001-12-26 2003-07-10 Bayer Healthcare Ag Urea derivatives as vr1- antagonists
AU2003210969A1 (en) 2002-02-11 2003-09-04 Bayer Corporation Aryl ureas with raf kinase and angiogenesis inhibiting activity
AU2003209116A1 (en) 2002-02-11 2003-09-04 Bayer Pharmaceuticals Corporation Aryl ureas with angiogenesis inhibiting activity
US20030216396A1 (en) 2002-02-11 2003-11-20 Bayer Corporation Pyridine, quinoline, and isoquinoline N-oxides as kinase inhibitors
DE10213228A1 (en) 2002-03-25 2003-10-16 Bayer Ag Cyclopentene derivatives
CA2485429A1 (en) 2002-05-06 2004-07-15 Vertex Pharmaceuticals Incorporated Thiadiazoles or oxadiazoles and their use as inhibitors of jak protein kinase
BR0312023A (en) 2002-06-27 2005-03-22 Novo Nordisk As Compound, glucose kinase activating compound, method for preventing hypoglycemia, use of a compound, and pharmaceutical composition
IL166040A0 (en) 2002-08-01 2006-01-15 Neurosearch As Compounds useful for the treatment of diseases responsive to antiangiogenetic therapy
CN100497302C (en) 2002-09-05 2009-06-10 神经研究公司 Diarylurea derivatives and their use as chloride channel blockers
EP1402888A1 (en) 2002-09-18 2004-03-31 Jerini AG The use of substituted carbocyclic compounds as rotamases inhibitors
US20040209930A1 (en) 2002-10-02 2004-10-21 Carboni Joan M. Synergistic methods and compositions for treating cancer
AU2003280308A1 (en) 2002-11-21 2004-06-15 Neurosearch A/S Aryl ureido derivatives and their medical use
WO2004054617A1 (en) * 2002-12-13 2004-07-01 Kyowa Hakko Kogyo Co., Ltd. Preventives and/or remedies for central diseases
US7056889B2 (en) * 2002-12-16 2006-06-06 Kimberly-Clark, Worldwide, Inc. Compounds that bind P2Y2 or P2Y1 receptors
TWM252710U (en) 2003-07-18 2004-12-11 Huei-Chiun Shiu Annealing equipment
WO2005012221A1 (en) 2003-08-04 2005-02-10 Ono Pharmaceutical Co., Ltd. Diphenyl ether compound, process for producing the same, and use
US20050256161A1 (en) 2003-08-13 2005-11-17 Tempest Paul A Melanin concentrating hormone receptor antagonists
ES2711313T3 (en) 2003-12-26 2019-05-03 Masatoshi Hagiwara Method of regulating the phosphorylation of the SR protein and antiviral agents that comprise the regulator of the activity of the SR protein as an active ingredient
US7470712B2 (en) 2004-01-21 2008-12-30 Bristol-Myers Squibb Company Amino-benzazoles as P2Y1 receptor inhibitors
US7388021B2 (en) 2004-05-12 2008-06-17 Bristol Myers Squibb Company Urea antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions
US7550499B2 (en) 2004-05-12 2009-06-23 Bristol-Myers Squibb Company Urea antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions
JP4319958B2 (en) 2004-09-15 2009-08-26 株式会社グリーンセイジュ Distilled water production system
WO2007002634A1 (en) 2005-06-27 2007-01-04 Bristol-Myers Squibb Company Carbocycle and heterocycle antagonists of p2y1 receptor useful in the treatment of thrombotic conditions
ATE502924T1 (en) 2005-06-27 2011-04-15 Bristol Myers Squibb Co LINEAR UREA MIMETIC ANTAGONISTS OF THE P2Y1 RECEPTOR FOR THE TREATMENT OF THROMBOSIS
KR20080027890A (en) 2005-06-27 2008-03-28 브리스톨-마이어스 스큅 컴퍼니 N-linked heterocyclic antagonists of p2y1 receptor useful in the treatment of thrombotic conditions
ES2352796T3 (en) 2005-06-27 2011-02-23 Bristol-Myers Squibb Company CYCLIC ANTAGONISTS UNITED TO C OF THE P2Y1 RECEIVER USEFUL IN THE TREATMENT OF THROMBOTHIC AFFECTIONS.
US7960569B2 (en) * 2006-10-17 2011-06-14 Bristol-Myers Squibb Company Indole antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions

Also Published As

Publication number Publication date
NO20073665L (en) 2007-10-18
PE20061120A1 (en) 2006-10-13
US20060173002A1 (en) 2006-08-03
WO2006078621A9 (en) 2008-06-19
AU2006206611A1 (en) 2006-07-27
AR053011A1 (en) 2007-04-18
US7645778B2 (en) 2010-01-12
TW200638934A (en) 2006-11-16
KR20070100894A (en) 2007-10-12
WO2006078621A3 (en) 2006-10-05
ATE499370T1 (en) 2011-03-15
US20100093689A1 (en) 2010-04-15
DE602006020327D1 (en) 2011-04-07
EP1954696A2 (en) 2008-08-13
MX2007008434A (en) 2007-07-25
WO2006078621A2 (en) 2006-07-27
EP1954696B1 (en) 2011-02-23
JP2008527043A (en) 2008-07-24
US8273772B2 (en) 2012-09-25

Similar Documents

Publication Publication Date Title
WO2006078621B1 (en) 2-phenoxy-n- (1, 3 , 4-thiadizol-2-yl) pyridin-3-amine derivatives and related compounds as p2y1 receptor inhibitors for the treatment of thromboembolic disorders
EA200500304A1 (en) DERIVATIVES 3- (SULPHONAMIDOETHYL) INDOL, INTENDED TO BE USED AS MIMETIC GLYCOCORTICOIDS IN THE TREATMENT OF INFLAMMATORY, ALLERGIC AND PROLIFERATIVE DISEASES
US20070197537A1 (en) Heterobicyclic thiophene compounds and methods of use
JP6678679B2 (en) Ataxia-telangiectasia and Rad3-related (ATR) protein kinase inhibitors
JP2018520195A5 (en)
JP2012512886A5 (en)
RU2005123394A (en) DIAMINE DERIVATIVES
JP2015522650A5 (en)
JP2006524222A5 (en)
NO20072371L (en) Kinuclidine derivatives and their use as muscarinic M3 receptor antagonists
NO20075169L (en) New imidazo (1,5-A) ornamental derivatives, process for preparation and pharmaceutical compositions containing the same.
BRPI0608216A2 (en) therapeutic agent for a tumor, method for treating a tumor, and use of a benzoyl compound, a prodrug thereof or a pharmaceutically acceptable salt thereof
NO20073926L (en) Pyrazole compounds that modulate activity of CDK, GSK and aurorakinases
BRPI0411365A (en) aminopyridine derivatives
EA200601350A1 (en) NITROGEN-CONTAINING HETEROCYCLIC DERIVATIVES AND THEIR PHARMACEUTICAL APPLICATIONS
JP2016507581A5 (en)
JP2014532716A5 (en)
CN107151250B (en) Pyrimidine seven-membered ring compound, preparation method thereof, medicinal composition and application thereof
JP2015504076A5 (en)
DE60206911D1 (en) IMIDAZOLE-2-CARBOXYLAMIDE DERIVATIVES AS RAF KINASE INHIBITORS
JP2016507502A5 (en)
ES2298853T3 (en) AROILFURANS AND AROILTIOPHENES APPROPRIATE FOR THE TREATMENT OF CANCER.
EP2205088A4 (en) Naphthalene-based inhibitors of anti-apoptotic proteins
PT509398E (en) QUINOXALINES PROCESS FOR THEIR PREPARATION AND ITS UTILIZATION
AU2016324158B2 (en) PCNA inhibitors

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200680008886.8

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 12007501444

Country of ref document: PH

WWE Wipo information: entry into national phase

Ref document number: MX/a/2007/008434

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 2006206611

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2007552205

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 5767/DELNP/2007

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 2006733718

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2006206611

Country of ref document: AU

Date of ref document: 20060117

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 1020077018794

Country of ref document: KR