CA2010011A1 - N-phenyl-n-(4-piperidinyl) amides useful as analgesics - Google Patents

N-phenyl-n-(4-piperidinyl) amides useful as analgesics

Info

Publication number
CA2010011A1
CA2010011A1 CA2010011A CA2010011A CA2010011A1 CA 2010011 A1 CA2010011 A1 CA 2010011A1 CA 2010011 A CA2010011 A CA 2010011A CA 2010011 A CA2010011 A CA 2010011A CA 2010011 A1 CA2010011 A1 CA 2010011A1
Authority
CA
Canada
Prior art keywords
lower alkyl
group
alkoxy
member selected
carbonyl
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
CA2010011A
Other languages
French (fr)
Other versions
CA2010011C (en
Inventor
Paul L. Feldman
Michael K. James
Marcus F. Brackeen
Michael Ross Johnson
Harry Jefferson Leighton
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Corp
Original Assignee
Paul L. Feldman
Michael K. James
Marcus F. Brackeen
Michael Ross Johnson
Harry Jefferson Leighton
Glaxo, Inc.
Glaxo Wellcome Inc.
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 Paul L. Feldman, Michael K. James, Marcus F. Brackeen, Michael Ross Johnson, Harry Jefferson Leighton, Glaxo, Inc., Glaxo Wellcome Inc. filed Critical Paul L. Feldman
Publication of CA2010011A1 publication Critical patent/CA2010011A1/en
Application granted granted Critical
Publication of CA2010011C publication Critical patent/CA2010011C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
    • C07D211/56—Nitrogen atoms
    • C07D211/58—Nitrogen atoms attached in position 4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids

Abstract

N-Phenyl-N-piperdinyl)amide derivatives are disclosed having the general formula (I).

(see fig.I) wherein:
X is a member selected from the group consisting of:
alkoxy-carbonyl-lower alkyl, lower alkyl-carbor-lyloxy-lower alkyl, alkenyloxy-carbonyl-lower alkyl, and (C1-2)alkoxy-(C1-2)alkoxy-carbonyl-lower alkyl.
Ar is a member selected from the group consisting of phenyl, mono-, di- and tri-substituted phenyl, wherein each subtitutuent is independently selected from the group consisting of halo, lower alkyl, lower alkoxy and trifluoromethyl;
R is a member selected from the group consisting of lower alkyl, and lower alkoxy-lower alkyl;
R1 is a member selected from the group consisting of hydrogen, lower alkoxy-carbonyl, and methoxymethyl; and R2 is a member selected from the group consisting of hydrogen and methyl;
and the diastereomeric and enantiomeric isomers thereof, and the acid addition salts of said compounds and isomers.

The compounds exhibit analgesic activity having relatively short durations of analgesic action. The invention embraces the compounds (I), pharmaceutical compositions of (I) and methods of providing analgesia with (I). Also included are certain novel intermediates for making (I).
CA002010011A 1989-02-15 1990-02-14 N-phenyl-n-(4-piperidinyl) amides useful as analgesics Expired - Fee Related CA2010011C (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US31131189A 1989-02-15 1989-02-15
US07/311,311 1989-02-15
US07/448,497 US5019583A (en) 1989-02-15 1989-12-11 N-phenyl-N-(4-piperidinyl)amides useful as analgesics
US07/448,497 1989-12-11

Publications (2)

Publication Number Publication Date
CA2010011A1 true CA2010011A1 (en) 1990-08-15
CA2010011C CA2010011C (en) 1997-12-02

Family

ID=26977841

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002010011A Expired - Fee Related CA2010011C (en) 1989-02-15 1990-02-14 N-phenyl-n-(4-piperidinyl) amides useful as analgesics

Country Status (22)

Country Link
US (1) US5019583A (en)
EP (1) EP0383579B1 (en)
JP (1) JP2895145B2 (en)
KR (1) KR0160979B1 (en)
AT (1) ATE140451T1 (en)
AU (1) AU636330B2 (en)
CA (1) CA2010011C (en)
CY (1) CY2002A (en)
CZ (1) CZ402591A3 (en)
DE (2) DE69027794T2 (en)
DK (1) DK0383579T3 (en)
ES (1) ES2088961T4 (en)
GR (1) GR3020719T3 (en)
HK (1) HK78297A (en)
IE (1) IE77156B1 (en)
LU (1) LU90011I2 (en)
MX (1) MX9203024A (en)
NL (1) NL960030I2 (en)
NZ (1) NZ232542A (en)
PT (1) PT93137B (en)
SG (1) SG47967A1 (en)
SK (1) SK402591A3 (en)

Families Citing this family (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5130321A (en) * 1990-12-18 1992-07-14 Glaxo Inc. Analgesic n-phenyl-n-(3-or 1-3-me-4-piperidinyl)amides
US5214148A (en) * 1990-12-18 1993-05-25 Glaxo Inc. Analgesic N-phenyl-N-(3-OR1 -3-ME-4-piperidinyl)amides
GB9316863D0 (en) * 1993-08-13 1993-09-29 Glaxo Group Ltd Chemical process
US5466700A (en) * 1993-08-30 1995-11-14 Glaxo Wellcome Inc. Anesthetic use of N-phenyl-N-(4-piperidinyl)amides
US5866591A (en) * 1996-09-11 1999-02-02 Glaxo Wellcome Inc. Stable formulations of remifentanil
DK1049676T3 (en) * 1997-12-24 2006-01-16 Ortho Mcneil Pharm Inc 4- [Aryl (piperidin-4-yl)] aminobenzamides which bind to the delta opioid receptor
US6858018B1 (en) * 1998-09-28 2005-02-22 Vyteris, Inc. Iontophoretic devices
US6436959B1 (en) 1998-12-23 2002-08-20 Ortho-Mcneil Pharmaceutical, Inc. 4-[aryl(piperidin-4-yl)]aminobenzamides
US7074935B2 (en) 1999-12-06 2006-07-11 Mallinckrodt Inc. Methods for the syntheses of alfentanil, sufentanil and remifentanil
WO2001068604A2 (en) 2000-03-14 2001-09-20 Sepracor, Inc. 3-substituted piperidines comprising urea functionality, and methods of use thereof
CA2417727C (en) 2000-07-31 2009-09-01 Nycomed Danmark A/S Fentanyl composition for nasal administration
EP1414798A2 (en) 2001-04-03 2004-05-06 Aryx Therapeutics Ultrashort-acting opioids for transdermal application
JP2005516926A (en) * 2001-12-17 2005-06-09 アリックス セラピューティクス Analgesic delivery system and method of use
JPWO2005030722A1 (en) * 2003-09-29 2006-12-07 日本ケミファ株式会社 N-substituted-N- (4-piperidinyl) amide derivatives
CN1960974A (en) 2004-06-18 2007-05-09 神经研究公司 Alkyl substituted piperidine derivatives and their use as monoamine neurotransmitter re-uptake inhibitors
WO2006030931A1 (en) * 2004-09-14 2006-03-23 Nippon Chemiphar Co., Ltd. N-substituted n-(4-piperidinyl)amide derivative
WO2007061555A1 (en) * 2005-11-17 2007-05-31 Mallinckrodt Inc. Process for synthesizing remifentanil
AU2007208438A1 (en) * 2006-01-24 2007-08-02 Mallinckrodt Inc. Process for synthesizing remifentanil
CN101379032A (en) * 2006-02-03 2009-03-04 马林克罗特公司 Crystalline form of remifentanil hydrochloride
EP1867635A1 (en) * 2006-06-15 2007-12-19 Kern Pharma, S.L. Process for preparing remifentanil, intermediates thereof, use of said intermediates and processes for their preparation
CN104059072B (en) 2006-07-10 2016-06-22 Paion英国有限公司 Fugitive benzodiazepine * salt and polymorphic thereof
GB0613693D0 (en) * 2006-07-10 2006-08-16 Cenes Ltd Benzodiazepine salts (3)
US20100099880A1 (en) * 2006-10-05 2010-04-22 Brian Cheng Alternate Process for Remifentanil Preparation
WO2008066708A2 (en) * 2006-11-29 2008-06-05 Mallinckrodt Inc. New process for remifentanil synthesis
RU2540116C2 (en) * 2008-03-31 2015-02-10 Дзе Дженерал Хоспитал Корпорейшн Etomidate analogues with improved pharmacokinetic and pharmacodynamic properties
JP2011526257A (en) * 2008-07-03 2011-10-06 シラグ アーゲー Process for producing N-phenyl-N- (4-piperidinyl) amide salt
US8299258B2 (en) * 2008-11-04 2012-10-30 Cambrex Charles City Method of making piperidine derivatives
WO2011005969A2 (en) 2009-07-10 2011-01-13 The General Hospital Corporation Etomidate analogues that do not inhibit adrenocortical steroid synthesis
EP2450039A1 (en) 2010-11-08 2012-05-09 PAION UK Ltd. Dosing regimen for sedation with CNS 7056 (Remimazolam)
JP6196986B2 (en) 2012-01-13 2017-09-13 ザ ジェネラル ホスピタル コーポレイション Anesthetic compounds and related methods of use
BR112015007647A2 (en) 2012-10-08 2017-07-04 Auckland Uniservices Ltd ketamine derivatives
AR094963A1 (en) 2013-03-04 2015-09-09 Ono Pharmaceutical Co EXCELLENT OXIDATION REACTION IN THE CONVERSION INDEX
CN103728403B (en) * 2013-08-30 2015-10-07 宜昌人福药业有限责任公司 The detection method of related substance in a kind of remifentanil hydrochloride bulk drug
PT3199523T (en) 2016-01-29 2018-11-14 Bioka S R O The new process for producing n-phenyl-n-(4-piperidinyl) amide derivatives such as remifentanil and carfentanil
PL3643704T3 (en) 2018-10-26 2021-06-14 Hameln Pharma Gmbh New intermediates for the preparation of remifentanil hydrochloride
GB202010168D0 (en) * 2020-07-02 2020-08-19 Johnson Matthey Plc Process for preparing remifentanil hydrochloride
CN114262320A (en) * 2021-12-28 2022-04-01 宜昌人福药业有限责任公司 Synthesis method for preparing anilinopiperidine drugs by using continuous flow microchannel reactor

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NL135583C (en) * 1961-10-10
US3655675A (en) * 1968-09-09 1972-04-11 Sterling Drug Inc N-(n-heteryl)-acylanilides
US3998834A (en) * 1975-03-14 1976-12-21 Janssen Pharmaceutica N.V. N-(4-piperidinyl)-n-phenylamides and -carbamates
US4179569A (en) * 1975-03-14 1979-12-18 Janssen Pharmaceutica N.V. N-(4-piperidinyl)-N-phenylamides
US4167574A (en) * 1978-03-13 1979-09-11 Janssen Pharmaceutica, N.V. N-phenyl-N-(4-piperidinyl)amides
US4584303A (en) * 1984-04-09 1986-04-22 The Boc Group, Inc. N-aryl-N-(4-piperidinyl)amides and pharmaceutical compositions and method employing such compounds
US4801721A (en) * 1984-08-16 1989-01-31 Ryan James W Stereospecific synthesis of carboxyalkyl peptides
CA1317940C (en) * 1987-09-25 1993-05-18 Georges H. P. Van Daele Substituted n-(1-alkyl-3-hydroxy-4-piperidinyl)benzamides

Also Published As

Publication number Publication date
DE19675028I2 (en) 2002-11-07
SG47967A1 (en) 1998-04-17
IE77156B1 (en) 1997-12-03
HK78297A (en) 1997-06-20
DE69027794D1 (en) 1996-08-22
NL960030I1 (en) 1997-02-03
DK0383579T3 (en) 1996-10-14
US5019583A (en) 1991-05-28
PT93137A (en) 1990-08-31
JP2895145B2 (en) 1999-05-24
ATE140451T1 (en) 1996-08-15
SK402591A3 (en) 2000-09-12
AU4973190A (en) 1990-08-23
CY2002A (en) 1997-12-05
CA2010011C (en) 1997-12-02
IE900532L (en) 1990-08-15
KR0160979B1 (en) 1998-12-01
PT93137B (en) 1996-02-29
ES2088961T3 (en) 1996-10-01
AU636330B2 (en) 1993-04-29
GR3020719T3 (en) 1996-11-30
NL960030I2 (en) 1997-05-01
DE69027794T2 (en) 1997-01-02
ES2088961T4 (en) 1996-12-01
JPH02300167A (en) 1990-12-12
EP0383579A1 (en) 1990-08-22
MX9203024A (en) 1992-07-01
LU90011I2 (en) 1997-03-11
EP0383579B1 (en) 1996-07-17
KR900012906A (en) 1990-09-03
CZ402591A3 (en) 1993-04-14
NZ232542A (en) 1992-06-25

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