TWI379832B - 8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists - Google Patents
8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists Download PDFInfo
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- TWI379832B TWI379832B TW096106339A TW96106339A TWI379832B TW I379832 B TWI379832 B TW I379832B TW 096106339 A TW096106339 A TW 096106339A TW 96106339 A TW96106339 A TW 96106339A TW I379832 B TWI379832 B TW I379832B
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- Prior art keywords
- ethyl
- azabicyclo
- bridge
- oct
- amino
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- 229940123257 Opioid receptor antagonist Drugs 0.000 title claims description 4
- 102000051367 mu Opioid Receptors Human genes 0.000 title description 14
- 108020001612 μ-opioid receptors Proteins 0.000 title description 14
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- MCBJGMPSAOWHPZ-UHFFFAOYSA-N sulfo trifluoromethanesulfonate Chemical compound OS(=O)(=O)OS(=O)(=O)C(F)(F)F MCBJGMPSAOWHPZ-UHFFFAOYSA-N 0.000 description 1
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- DNRQBQNOCHRZIZ-UHFFFAOYSA-N tert-butyl n-(cyclohexylmethyl)-n-(2-oxoethyl)carbamate Chemical compound CC(C)(C)OC(=O)N(CC=O)CC1CCCCC1 DNRQBQNOCHRZIZ-UHFFFAOYSA-N 0.000 description 1
- ZPKUIUGWAFVCMC-UHFFFAOYSA-N tert-butyl n-benzyl-n-(3-hydroxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)N(CCCO)CC1=CC=CC=C1 ZPKUIUGWAFVCMC-UHFFFAOYSA-N 0.000 description 1
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- VMJFLTWEWCSUOC-UHFFFAOYSA-J tetrasodium butanedioate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CCC([O-])=O.[O-]C(=O)CCC([O-])=O VMJFLTWEWCSUOC-UHFFFAOYSA-J 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- OKKJLVBELUTLKV-FIBGUPNXSA-N trideuteriomethanol Chemical compound [2H]C([2H])([2H])O OKKJLVBELUTLKV-FIBGUPNXSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000005591 trimellitate group Chemical group 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P1/10—Laxatives
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
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| MY145633A (en) * | 2006-03-01 | 2012-03-15 | Theravance Inc | 8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists |
| TWI409067B (zh) * | 2007-02-28 | 2013-09-21 | Theravance Inc | ８-氮雜雙環〔３．２．１〕辛烷化合物之結晶型 |
| TWI415850B (zh) * | 2007-07-20 | 2013-11-21 | Theravance Inc | 製備ｍｕ類鴉片受體拮抗劑之中間物的方法 |
| TWI423801B (zh) | 2007-08-27 | 2014-01-21 | Theravance Inc | 作為μ類鴉片受體拮抗劑之８－氮雜雙環〔３．２．１〕辛基－２－羥基苯甲醯胺化合物 |
| US7947710B2 (en) * | 2007-08-27 | 2011-05-24 | Theravance, Inc. | Disubstituted alkyl-8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists |
| EP2195313B1 (en) * | 2007-08-27 | 2014-04-02 | Theravance, Inc. | Heteroarylalkyl-8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists |
| ES2390195T3 (es) * | 2007-08-27 | 2012-11-07 | Theravance, Inc. | Compuestos de amidoalquil-8-azabiciclo(3,2,1)octano, como antagonistas del receptor opioide mu |
| WO2011035142A1 (en) * | 2009-09-18 | 2011-03-24 | Adolor Corporation | Use of opioid receptor antagonist for gastrointestinal tract disorders |
| US20120122928A1 (en) | 2010-08-11 | 2012-05-17 | Bayer Cropscience Ag | Heteroarylpiperidine and -Piperazine Derivatives as Fungicides |
| US8759527B2 (en) | 2010-08-25 | 2014-06-24 | Bayer Cropscience Ag | Heteroarylpiperidine and -piperazine derivatives as fungicides |
| EP2423210A1 (de) | 2010-08-25 | 2012-02-29 | Bayer CropScience AG | Heteroarylpiperidin- und -piperazinderivate als Fungizide |
| MX352731B (es) | 2010-10-27 | 2017-12-06 | Bayer Ip Gmbh | Derivados de heteroarilpiperidina y -piperazina como fungicidas. |
| JP5703009B2 (ja) * | 2010-12-16 | 2015-04-15 | 住友精化株式会社 | スルホン化合物、スルホン化合物の製造方法、および電気化学デバイス用電解液 |
| KR101848116B1 (ko) | 2011-02-01 | 2018-04-11 | 바이엘 인텔렉쳐 프로퍼티 게엠베하 | 살진균제로서의 헤테로아릴 피페리딘 및 헤테로아릴 피페라진 유도체 |
| IN2014CN01862A (enExample) | 2011-09-15 | 2015-05-29 | Bayer Ip Gmbh | |
| EP2921492B1 (de) | 2011-12-27 | 2017-09-06 | Bayer Intellectual Property GmbH | Heteroarylpiperidin- und -heteroarylpiperazinderivate |
| US9192570B2 (en) | 2013-12-20 | 2015-11-24 | AntiOP, Inc. | Intranasal naloxone compositions and methods of making and using same |
| PT3277278T (pt) | 2015-04-02 | 2020-04-16 | Theravance Biopharma R&D Ip Llc | Forma farmacêutica de combinação de um antagonista do recetor opioide mu e um agente opioide |
| SG11202007422QA (en) | 2018-02-05 | 2020-09-29 | Alkermes Inc | Compounds for the treatment of pain |
| EP4240740A4 (en) * | 2020-11-06 | 2024-12-11 | Actinogen Medical Limited | PROCESS FOR PREPARING HETEROCYCLIC METHANONE COMPOUNDS AND AZABICYCLO INTERMEDIATES THEREOF |
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| DE1067824B (de) * | 1954-10-20 | 1959-10-29 | Sandoz Ag | Verfahren zur Herstellung saeureamidartiger Tropanabkoemmlinge |
| 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 |
| UA58476C2 (uk) * | 1997-10-09 | 2003-08-15 | Санофі-Сентелябо | Похідні 8-азабіцикло[3.2.1]октан-3-метанаміну, фармацевтична композиція та лікарський засіб |
| US6900228B1 (en) | 1998-03-10 | 2005-05-31 | Research Triangle Institute | Opiate compounds, methods of making and methods of use |
| GB9810671D0 (en) | 1998-05-18 | 1998-07-15 | Pfizer Ltd | Anti-pruritic agents |
| TWI244481B (en) | 1998-12-23 | 2005-12-01 | Pfizer | 3-azabicyclo[3.1.0]hexane derivatives useful in therapy |
| GB9912410D0 (en) | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| US6469030B2 (en) | 1999-11-29 | 2002-10-22 | Adolor Corporation | Methods for the treatment and prevention of ileus |
| KR20030009376A (ko) | 2000-03-03 | 2003-01-29 | 오르토-맥네일 파마슈티칼, 인코퍼레이티드 | 3-(디아릴메틸렌)-8-아자비사이클로[3.2.1]옥탄 유도체 |
| US20030181447A1 (en) * | 2001-02-22 | 2003-09-25 | Boyd Robert E. | 3-(Diarylmethylene)-8-azabicyclo[3.2.1]octane derivatives |
| US20020025948A1 (en) | 2000-06-23 | 2002-02-28 | Banks Bernard Joseph | 3-azabicyclo[3.1.0]hexane derivatives useful in therapy |
| JP4009251B2 (ja) | 2001-10-09 | 2007-11-14 | 杏林製薬株式会社 | 新規な４−（２−フロイル）アミノピペリジン、その合成中間体、その製造方法および医薬としてのその用途 |
| GEP20084300B (en) | 2001-10-22 | 2008-02-11 | Pfizer Prod Inc | 3-azabicyclo (3.1.0) hexane derivatives as opioid receptor antagonists |
| US7381721B2 (en) | 2003-03-17 | 2008-06-03 | Adolor Corporation | Substituted piperidine compounds |
| US20040204453A1 (en) | 2003-04-14 | 2004-10-14 | Pfizer Inc | 4-Phenyl-piperidine compounds and their use as modulators of opioid receptors |
| JP3984281B2 (ja) * | 2003-04-14 | 2007-10-03 | ファイザー・プロダクツ・インク | ３−アザビシクロ〔３，２，１〕オクタン誘導体 |
| US7056930B2 (en) | 2003-04-14 | 2006-06-06 | Pfizer Inc. | 2-Azabicyclo[3.3.1]nonane derivatives |
| CA2522199A1 (en) | 2003-04-15 | 2004-10-28 | Pfizer Products Inc. | 3-benzhydrylidene-8-aza-bicyclo¬3.2.1|octane derivatives with opioid receptor activity |
| US6992090B2 (en) | 2003-06-16 | 2006-01-31 | Adolor Corporation | Substituted piperidine compounds and methods of their use |
| EP1737853A1 (en) | 2004-02-03 | 2007-01-03 | Janssen Pharmaceutica N.V. | 3-(diheteroarylmethylene)-8-azabicyclo¬3.2.1|octane and 3-((aryl)(heteroaryl)methylene)-8-azabicyclo¬3.2.1|octane derivatives |
| US7087749B2 (en) | 2004-03-11 | 2006-08-08 | Adolor Corporation | Substituted piperidine compounds and methods of their use |
| US7538110B2 (en) | 2005-10-27 | 2009-05-26 | Adolor Corporation | Opioid antagonists |
| MY145633A (en) | 2006-03-01 | 2012-03-15 | Theravance Inc | 8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists |
| MX2009004965A (es) | 2006-11-07 | 2009-06-05 | Nektar Therapeutics Al Corp | Formas de dosificacion y co-administracion de un agonista de opioides y un antagonista de opioides. |
| TWI409067B (zh) | 2007-02-28 | 2013-09-21 | Theravance Inc | ８-氮雜雙環〔３．２．１〕辛烷化合物之結晶型 |
| TWI415850B (zh) * | 2007-07-20 | 2013-11-21 | Theravance Inc | 製備ｍｕ類鴉片受體拮抗劑之中間物的方法 |
| EP2195313B1 (en) * | 2007-08-27 | 2014-04-02 | Theravance, Inc. | Heteroarylalkyl-8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists |
| US7947710B2 (en) * | 2007-08-27 | 2011-05-24 | Theravance, Inc. | Disubstituted alkyl-8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists |
| TWI423801B (zh) * | 2007-08-27 | 2014-01-21 | Theravance Inc | 作為μ類鴉片受體拮抗劑之８－氮雜雙環〔３．２．１〕辛基－２－羥基苯甲醯胺化合物 |
| ES2390195T3 (es) | 2007-08-27 | 2012-11-07 | Theravance, Inc. | Compuestos de amidoalquil-8-azabiciclo(3,2,1)octano, como antagonistas del receptor opioide mu |
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2007
- 2007-02-07 MY MYPI20070176A patent/MY145633A/en unknown
- 2007-02-26 TW TW096106339A patent/TWI379832B/zh active
- 2007-02-28 BR BRPI0708490A patent/BRPI0708490B8/pt not_active IP Right Cessation
- 2007-02-28 EP EP07752111A patent/EP2001876B1/en active Active
- 2007-02-28 SI SI200730691T patent/SI2001876T1/sl unknown
- 2007-02-28 AT AT07752111T patent/ATE509928T1/de active
- 2007-02-28 PL PL07752111T patent/PL2001876T3/pl unknown
- 2007-02-28 KR KR1020087024027A patent/KR101376479B1/ko active Active
- 2007-02-28 AR ARP070100835A patent/AR059690A1/es active IP Right Grant
- 2007-02-28 US US11/711,961 patent/US7622508B2/en active Active
- 2007-02-28 WO PCT/US2007/005388 patent/WO2007103187A2/en not_active Ceased
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- 2007-02-28 JP JP2008557405A patent/JP5086280B2/ja active Active
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- 2007-02-28 PE PE2007000212A patent/PE20071311A1/es active IP Right Grant
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2008
- 2008-08-26 IL IL193690A patent/IL193690A/en active IP Right Grant
- 2008-09-17 MA MA31246A patent/MA30284B1/fr unknown
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2009
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2011
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2012
- 2012-06-20 US US13/527,942 patent/US8664242B2/en active Active
- 2012-08-01 JP JP2012171119A patent/JP2012211193A/ja not_active Withdrawn
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2014
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2015
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2017
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2018
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2019
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2022
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