DE69427017T2 - Herstellung von 3,4,4-trisubstituiertem Piperidinyl-n-alkylcarboxylaten und Zwischenverbindungen, verwendbar als opioid Antagonisten - Google Patents

Herstellung von 3,4,4-trisubstituiertem Piperidinyl-n-alkylcarboxylaten und Zwischenverbindungen, verwendbar als opioid Antagonisten

Info

Publication number
DE69427017T2
DE69427017T2 DE69427017T DE69427017T DE69427017T2 DE 69427017 T2 DE69427017 T2 DE 69427017T2 DE 69427017 T DE69427017 T DE 69427017T DE 69427017 T DE69427017 T DE 69427017T DE 69427017 T2 DE69427017 T2 DE 69427017T2
Authority
DE
Germany
Prior art keywords
compound
acid
alkyl
compounds
crystalline
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.)
Expired - Lifetime
Application number
DE69427017T
Other languages
German (de)
English (en)
Other versions
DE69427017D1 (de
Inventor
Scott Alan Frank
Douglas Edward Prather
Jeffrey Alan Ward
John Arnold Werner
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.)
Eli Lilly and Co
Original Assignee
Eli Lilly and Co
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 Eli Lilly and Co filed Critical Eli Lilly and Co
Application granted granted Critical
Publication of DE69427017D1 publication Critical patent/DE69427017D1/de
Publication of DE69427017T2 publication Critical patent/DE69427017T2/de
Anticipated expiration legal-status Critical
Expired - Lifetime 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
    • C07D211/08—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
    • C07D211/18—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/34—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 substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
    • 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
    • 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
    • C07D211/18—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—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 substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—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 substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
DE69427017T 1993-12-08 1994-12-02 Herstellung von 3,4,4-trisubstituiertem Piperidinyl-n-alkylcarboxylaten und Zwischenverbindungen, verwendbar als opioid Antagonisten Expired - Lifetime DE69427017T2 (de)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US08/164,074 US5434171A (en) 1993-12-08 1993-12-08 Preparation of 3,4,4-trisubstituted-piperidinyl-N-alkylcarboxylates and intermediates

Publications (2)

Publication Number Publication Date
DE69427017D1 DE69427017D1 (de) 2001-05-10
DE69427017T2 true DE69427017T2 (de) 2001-09-06

Family

ID=22592858

Family Applications (1)

Application Number Title Priority Date Filing Date
DE69427017T Expired - Lifetime DE69427017T2 (de) 1993-12-08 1994-12-02 Herstellung von 3,4,4-trisubstituiertem Piperidinyl-n-alkylcarboxylaten und Zwischenverbindungen, verwendbar als opioid Antagonisten

Country Status (30)

Country Link
US (1) US5434171A (enExample)
EP (3) EP1607387A3 (enExample)
JP (2) JP3834075B2 (enExample)
KR (1) KR100356239B1 (enExample)
CN (2) CN1057294C (enExample)
AT (1) ATE200279T1 (enExample)
AU (1) AU681198B2 (enExample)
BR (1) BR9404842A (enExample)
CA (1) CA2137221C (enExample)
CO (1) CO4290427A1 (enExample)
CZ (1) CZ290559B6 (enExample)
DE (1) DE69427017T2 (enExample)
DK (1) DK0657428T3 (enExample)
ES (1) ES2155844T3 (enExample)
FI (2) FI106455B (enExample)
GR (1) GR3036136T3 (enExample)
HU (1) HUT71489A (enExample)
IL (1) IL111843A (enExample)
MY (1) MY121543A (enExample)
NO (1) NO302884B1 (enExample)
NZ (1) NZ270039A (enExample)
PE (1) PE41495A1 (enExample)
PL (1) PL181734B1 (enExample)
PT (1) PT657428E (enExample)
RU (1) RU2145958C1 (enExample)
SI (1) SI0657428T1 (enExample)
TW (1) TW290540B (enExample)
UA (1) UA52577C2 (enExample)
YU (2) YU49312B (enExample)
ZA (1) ZA949584B (enExample)

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HN1999000149A (es) * 1998-09-09 2000-01-12 Pfizer Prod Inc Derivados de 4,4-biarilpiperidina
GB9912410D0 (en) 1999-05-28 1999-07-28 Pfizer Ltd Compounds useful in therapy
GB9912415D0 (en) 1999-05-28 1999-07-28 Pfizer Ltd Compounds useful in therapy
GB9912416D0 (en) 1999-05-28 1999-07-28 Pfizer Ltd Compounds useful in therapy
GB9912417D0 (en) 1999-05-28 1999-07-28 Pfizer Ltd Compounds useful in therapy
GB9912411D0 (en) 1999-05-28 1999-07-28 Pfizer Ltd Compounds useful in therapy
GB9912413D0 (en) 1999-05-28 1999-07-28 Pfizer Ltd Compounds useful in therapy
US6451806B2 (en) 1999-09-29 2002-09-17 Adolor Corporation Methods and compositions involving opioids and antagonists thereof
US6469030B2 (en) 1999-11-29 2002-10-22 Adolor Corporation Methods for the treatment and prevention of ileus
EP1404323B1 (en) * 2001-06-05 2009-10-28 The University of Chicago Use of methylnaltrexone to treat immune suppression
US20030068829A1 (en) * 2001-06-25 2003-04-10 Symyx Technologies, Inc. High throughput crystallographic screening of materials
JP4814488B2 (ja) * 2001-10-18 2011-11-16 ネクター セラピューティックス 重合体共役物オピオイドアンタゴニスト
US6794510B2 (en) * 2002-08-08 2004-09-21 Adolor Corporation Processes for the preparation of peripheral opioid antagonist compounds and intermediates thereto
US7381721B2 (en) * 2003-03-17 2008-06-03 Adolor Corporation Substituted piperidine compounds
DK1615646T4 (da) 2003-04-08 2022-10-10 Progenics Pharm Inc Farmaceutiske formuleringer, der indeholder methylnaltrexon
EP1617846A1 (en) * 2003-04-08 2006-01-25 Progenics Pharmaceuticals, Inc. The use of peripheral opiois antagonists, especially methylnaltrexone to treat irritable bowel syndrome
US6992090B2 (en) * 2003-06-16 2006-01-31 Adolor Corporation Substituted piperidine compounds and methods of their use
FR2861304B1 (fr) * 2003-10-23 2008-07-18 Univ Grenoble 1 Modulateurs des canaux cftr
US20050148630A1 (en) * 2003-12-02 2005-07-07 Carpenter Randall L. Methods of preventing and treating non-opioid induced gastrointestinal dysfunction
US8946262B2 (en) * 2003-12-04 2015-02-03 Adolor Corporation Methods of preventing and treating gastrointestinal dysfunction
US20060182692A1 (en) * 2003-12-16 2006-08-17 Fishburn C S Chemically modified small molecules
WO2005058367A2 (en) * 2003-12-16 2005-06-30 Nektar Therapeutics Al, Corporation Pegylated small molecules
US7087749B2 (en) * 2004-03-11 2006-08-08 Adolor Corporation Substituted piperidine compounds and methods of their use
US20050240177A1 (en) * 2004-04-26 2005-10-27 Packaging Service Corporation Of Kentucky Electrosurgical forceps
US7700626B2 (en) * 2004-06-04 2010-04-20 Adolor Corporation Compositions containing opioid antagonists
US8039456B2 (en) 2004-08-12 2011-10-18 Helsinn Therapeutics (U.S.), Inc. Method of stimulating the motility of the gastrointestinal system using ipamorelin
AU2005272598B2 (en) * 2004-08-12 2011-11-17 Helsinn Therapeutics (U.S.), Inc. Method of stimulating the motility of the gastrointestinal system using growth hormone secretagogues
US20060063792A1 (en) * 2004-09-17 2006-03-23 Adolor Corporation Substituted morphinans and methods of their use
US20060211733A1 (en) * 2005-03-04 2006-09-21 Adolor Corporation Methods of preventing and treating opioid bowel dysfunction
US9662325B2 (en) 2005-03-07 2017-05-30 The University Of Chicago Use of opioid antagonists to attenuate endothelial cell proliferation and migration
CN104248763A (zh) * 2005-03-07 2014-12-31 芝加哥大学 阿片样物质拮抗剂用于减少内皮细胞增殖和迁移的用途
US8524731B2 (en) 2005-03-07 2013-09-03 The University Of Chicago Use of opioid antagonists to attenuate endothelial cell proliferation and migration
US8518962B2 (en) 2005-03-07 2013-08-27 The University Of Chicago Use of opioid antagonists
AR057035A1 (es) 2005-05-25 2007-11-14 Progenics Pharm Inc SíNTESIS DE (R)-N-METILNALTREXONA, COMPOSICIONES FARMACÉUTICAS Y USOS
AR057325A1 (es) 2005-05-25 2007-11-28 Progenics Pharm Inc Sintesis de (s)-n-metilnaltrexona, composiciones farmaceuticas y usos
CN101262867A (zh) * 2005-07-01 2008-09-10 叶林发现公司 用于治疗肥胖的mao-b抑制剂
US7914776B2 (en) * 2005-10-07 2011-03-29 Adolor Corporation Solid dispersions of opioid antagonists
US20070092576A1 (en) * 2005-10-20 2007-04-26 Adolor Corporation Compositions containing opioid antagonists
US7538110B2 (en) 2005-10-27 2009-05-26 Adolor Corporation Opioid antagonists
CN100383121C (zh) * 2006-03-07 2008-04-23 天津泰普药品科技发展有限公司 阿韦苄酯化合物及其制备方法和以该化合物制备阿韦莫哌的工艺
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US8546418B2 (en) 2007-03-29 2013-10-01 Progenics Pharmaceuticals, Inc. Peripheral opioid receptor antagonists and uses thereof
JP5469593B2 (ja) 2007-03-29 2014-04-16 ワイス・エルエルシー 末梢性オピオイド受容体アンタゴニストおよびその使用
CA2945356C (en) 2007-03-29 2021-03-23 Progenics Pharmaceuticals, Inc. (r)-n-methylnaltrexone bromide and pharmaceutical compostitions therof useful as peripheral .mu. opioid receptor antagonist
CN101959892B (zh) 2008-02-06 2014-01-08 普罗热尼奇制药公司 (r),(r)-2,2’-二-甲基纳曲酮的制备和用途
AU2009225434B2 (en) 2008-03-21 2014-05-22 The University Of Chicago Treatment with opioid antagonists and mTOR inhibitors
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CA2676881C (en) 2008-09-30 2017-04-25 Wyeth Peripheral opioid receptor antagonists and uses thereof
CN101429154B (zh) * 2008-11-14 2011-01-05 天津泰普药品科技发展有限公司 无水阿维莫泮及其药物组合物
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CN103360302B (zh) * 2012-03-29 2015-08-26 北大方正集团有限公司 阿维莫泮的纯化方法
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US5136040A (en) * 1991-02-26 1992-08-04 Eli Lilly And Company Preparation of substituted tetrahydropyridines
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US5159081A (en) * 1991-03-29 1992-10-27 Eli Lilly And Company Intermediates of peripherally selective n-carbonyl-3,4,4-trisubstituted piperidine opioid antagonists

Also Published As

Publication number Publication date
UA52577C2 (uk) 2003-01-15
ZA949584B (en) 1996-06-03
YU70294A (sh) 1997-07-31
BR9404842A (pt) 1995-08-08
HK1013826A1 (en) 1999-09-10
EP0657428A1 (en) 1995-06-14
HUT71489A (en) 1995-11-28
AU7917094A (en) 1995-06-15
AU681198B2 (en) 1997-08-21
NO302884B1 (no) 1998-05-04
CA2137221C (en) 2011-02-22
CN1111239A (zh) 1995-11-08
FI945703L (fi) 1995-06-09
KR100356239B1 (ko) 2002-12-26
PE41495A1 (es) 1995-11-28
GR3036136T3 (en) 2001-09-28
EP1607387A2 (en) 2005-12-21
CO4290427A1 (es) 1996-04-17
PT657428E (pt) 2001-07-31
MY121543A (en) 2006-02-28
NO944644D0 (no) 1994-12-02
FI20000353L (fi) 2000-02-17
RU94042903A (ru) 1996-10-27
ATE200279T1 (de) 2001-04-15
DK0657428T3 (da) 2001-05-07
EP1607387A3 (en) 2007-01-03
CN1057294C (zh) 2000-10-11
CA2137221A1 (en) 1995-06-09
ES2155844T3 (es) 2001-06-01
CN1121387C (zh) 2003-09-17
FI106860B (fi) 2001-04-30
HU9403466D0 (en) 1995-02-28
JP2006070042A (ja) 2006-03-16
JP3834075B2 (ja) 2006-10-18
KR950017957A (ko) 1995-07-22
JPH07215937A (ja) 1995-08-15
EP0657428B1 (en) 2001-04-04
PL306068A1 (en) 1995-06-12
NZ270039A (en) 1996-08-27
CN1223257A (zh) 1999-07-21
NO944644L (no) 1995-06-09
US5434171A (en) 1995-07-18
SI0657428T1 (en) 2001-08-31
YU49312B (sh) 2005-06-10
CZ290559B6 (cs) 2002-08-14
EP0984004A3 (en) 2003-10-15
CZ299294A3 (en) 1995-10-18
IL111843A0 (en) 1995-03-15
TW290540B (enExample) 1996-11-11
FI106455B (fi) 2001-02-15
IL111843A (en) 2000-02-29
PL181734B1 (pl) 2001-09-28
EP0984004A2 (en) 2000-03-08
FI945703A0 (fi) 1994-12-02
DE69427017D1 (de) 2001-05-10
YU82304A (sh) 2006-03-03
RU2145958C1 (ru) 2000-02-27

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Legal Events

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8364 No opposition during term of opposition
8328 Change in the person/name/address of the agent

Representative=s name: KROHER, STROBEL RECHTS- UND PATENTANWAELTE, 80336

8328 Change in the person/name/address of the agent

Representative=s name: DR. SCHOEN & PARTNER, 80336 MUENCHEN