ZA200502174B - N-substituted hydromorphones and the use thereof - Google Patents

N-substituted hydromorphones and the use thereof Download PDF

Info

Publication number: ZA200502174B
Authority: ZA; South Africa
Prior art keywords: compound; pain; mammal; compounds; treating
Prior art date: 2002-09-25

Application number

ZA200502174A

Other languages

English (en)

Inventor

Donald J Kyle

Original Assignee

Euro Celtique Sa

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.)

2002-09-25

Filing date

2005-03-15

Publication date

2006-05-31

2005-03-15 Application filed by Euro Celtique Sa filed Critical Euro Celtique Sa

2006-05-31 Publication of ZA200502174B publication Critical patent/ZA200502174B/en

Links

WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical class O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 title claims description 15
150000001875 compounds Chemical class 0.000 claims description 78
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239000008194 pharmaceutical composition Substances 0.000 claims description 7
125000000217 alkyl group Chemical group 0.000 claims description 6
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239000003814 drug Substances 0.000 claims description 5
208000035475 disorder Diseases 0.000 claims description 4
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INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
- C07D489/04—Salts; Organic complexes
- 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
- A61P1/12—Antidiarrhoeals
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- C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone

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ZA200502174A 2002-09-25 2005-03-15 N-substituted hydromorphones and the use thereof ZA200502174B (en)

Applications Claiming Priority (1)

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US41325402P	2002-09-25	2002-09-25

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ZA200502174B true ZA200502174B (en)	2006-05-31

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ZA200502174A ZA200502174B (en)	2002-09-25	2005-03-15	N-substituted hydromorphones and the use thereof

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US (1)	US6825205B2 (ja)
EP (2)	EP1803724A1 (ja)
JP (2)	JP4806190B2 (ja)
KR (1)	KR20050074462A (ja)
CN (1)	CN100387600C (ja)
AT (1)	ATE360633T1 (ja)
AU (1)	AU2003272642B2 (ja)
BR (1)	BR0314488A (ja)
CA (1)	CA2500118C (ja)
CY (1)	CY1106697T1 (ja)
DE (1)	DE60313478T2 (ja)
DK (1)	DK1543010T3 (ja)
ES (1)	ES2286461T3 (ja)
HK (1)	HK1080456A1 (ja)
MX (1)	MXPA05003104A (ja)
NZ (1)	NZ538726A (ja)
PT (1)	PT1543010E (ja)
WO (1)	WO2004029059A1 (ja)
ZA (1)	ZA200502174B (ja)

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20040202717A1 (en)	2003-04-08	2004-10-14	Mehta Atul M.	Abuse-resistant oral dosage forms and method of use thereof
US20070185145A1 (en) *	2006-02-03	2007-08-09	Royds Robert B	Pharmaceutical composition containing a central opioid agonist, a central opioid antagonist, and a peripheral opioid antagonist, and method for making the same
AU2007297827B2 (en)	2006-09-20	2012-09-20	Mallinckrodt Llc	Preparation of substituted morphinan-6-ones and salts and intermediates thereof
CA2670342A1 (en) *	2006-11-22	2008-06-12	Progenics Pharmaceuticals, Inc.	N-oxides of 4,5-epoxy-morphinanium analogs
JP2010510329A (ja) *	2006-11-22	2010-04-02	プロジェニックスファーマスーティカルスインコーポレーテッド	７，８−飽和−４，５−エポキシ−モルフィナニウム類似体
EP2137189B1 (en) *	2007-03-06	2015-05-06	Mallinckrodt LLC	Process for the preparation of quaternary n-alkyl morphinan alkaloid salts
US9040726B2 (en)	2007-03-06	2015-05-26	Mallinckrodt Llc	Process for the preparation of quaternary N-alkyl morphinan alkaloid salts
MX2010001371A (es) *	2007-08-09	2010-03-10	Rensselaer Polytech Inst	Carboxamidas opioides cuaternarias.
JP2011500686A (ja) *	2007-10-18	2011-01-06	アイコバイオテクノロジー	オピオイドと中性アンタゴニストを用いる組合せ鎮痛剤
US8748448B2 (en)	2007-10-18	2014-06-10	Aiko Biotechnology	Combination analgesic employing opioid agonist and neutral antagonist
US20110112129A2 (en) *	2007-11-26	2011-05-12	Pharmacofore, Inc.	Peripheral Phenolic Opioid Antagonist
EP2285780B1 (en)	2008-05-27	2015-08-26	Mallinckrodt LLC	Processes and compounds for the preparation of normorphinans
WO2010028004A2 (en)	2008-09-03	2010-03-11	Mallinckrodt Inc.	Substituted berbines and processes for their synthesis
EA201390422A1 (ru)	2010-09-21	2014-01-30	Пердью Фарма Л.П.	Бупренорфиновые аналоги
CA2890655A1 (en)	2012-11-09	2014-05-15	Purdue Pharma L.P.	Benzomorphan analogs and the use thereof
EP2951160B1 (en)	2013-01-31	2019-04-24	Purdue Pharma LP	Benzomorphan analogs and the use thereof
US8969358B2 (en)	2013-03-15	2015-03-03	Purdue Pharma L.P.	Buprenorphine analogs
US9862726B2 (en)	2013-12-26	2018-01-09	Purdue Pharma L.P.	Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans
JP6353543B2 (ja)	2013-12-26	2018-07-04	パーデュー、ファーマ、リミテッド、パートナーシップ	環縮小モルフィナン及びその使用
WO2015097548A1 (en)	2013-12-26	2015-07-02	Purdue Pharma L.P.	7-beta-alkyl analogs of orvinols
WO2015097547A1 (en)	2013-12-26	2015-07-02	Purdue Pharma L.P.	10-substituted morphinan hydantoins
US10550088B2 (en)	2013-12-27	2020-02-04	Purdue Pharma L.P.	6-substituted and 7-substituted morphinan analogs and the use thereof
EP3148535A4 (en)	2014-05-27	2017-11-29	Purdue Pharma LP	Spirocyclic morphinans and use thereof
MA40171A (fr)	2014-06-13	2017-04-19	Purdue Pharma Lp	Dérivés d'azamophinan et leur utilisation
MA41125A (fr)	2014-12-05	2017-10-10	Purdue Pharma Lp	Dérivés de 6.7-cyclomorphinane et leur utilisation
US10745402B2 (en)	2017-01-02	2020-08-18	Purdue Pharma L.P.	Morphinan derivatives and use thereof

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3536809A (en)	1969-02-17	1970-10-27	Alza Corp	Medication method
US3598123A (en)	1969-04-01	1971-08-10	Alza Corp	Bandage for administering drugs
US3845770A (en)	1972-06-05	1974-11-05	Alza Corp	Osmatic dispensing device for releasing beneficial agent
US3916899A (en)	1973-04-25	1975-11-04	Alza Corp	Osmotic dispensing device with maximum and minimum sizes for the passageway
US4008719A (en)	1976-02-02	1977-02-22	Alza Corporation	Osmotic system having laminar arrangement for programming delivery of active agent
US4176186A (en) *	1978-07-28	1979-11-27	Boehringer Ingelheim Gmbh	Quaternary derivatives of noroxymorphone which relieve intestinal immobility
IE58110B1 (en)	1984-10-30	1993-07-14	Elan Corp Plc	Controlled release powder and process for its preparation
EP0306575B1 (en) *	1987-09-10	1992-07-29	The University Of Chicago	Quaternary derivatives of noroxymorphone which relieve nausea and emesis
US5073543A (en)	1988-07-21	1991-12-17	G. D. Searle & Co.	Controlled release formulations of trophic factors in ganglioside-lipsome vehicle
IT1229203B (it)	1989-03-22	1991-07-25	Bioresearch Spa	Impiego di acido 5 metiltetraidrofolico, di acido 5 formiltetraidrofolico e dei loro sali farmaceuticamente accettabili per la preparazione di composizioni farmaceutiche in forma a rilascio controllato attive nella terapia dei disturbi mentali organici e composizioni farmaceutiche relative.
US5120548A (en)	1989-11-07	1992-06-09	Merck & Co., Inc.	Swelling modulated polymeric drug delivery device
US5733566A (en)	1990-05-15	1998-03-31	Alkermes Controlled Therapeutics Inc. Ii	Controlled release of antiparasitic agents in animals
US5698155A (en)	1991-05-31	1997-12-16	Gs Technologies, Inc.	Method for the manufacture of pharmaceutical cellulose capsules
US5968551A (en)	1991-12-24	1999-10-19	Purdue Pharma L.P.	Orally administrable opioid formulations having extended duration of effect
US5580578A (en)	1992-01-27	1996-12-03	Euro-Celtique, S.A.	Controlled release formulations coated with aqueous dispersions of acrylic polymers
US5591767A (en)	1993-01-25	1997-01-07	Pharmetrix Corporation	Liquid reservoir transdermal patch for the administration of ketorolac
IT1270594B (it)	1994-07-07	1997-05-07	Recordati Chem Pharm	Composizione farmaceutica a rilascio controllato di moguisteina in sospensione liquida
ATE359076T1 (de) *	1996-11-25	2007-05-15	Toray Industries	Mittel gegen juckreiz
WO2001014382A1 (fr) *	1999-08-23	2001-03-01	Toray Industries, Inc.	Analgesiques contenant des derives sel d'ammonium quaternaire comme principe actif

2003
- 2003-09-24 AT AT03754837T patent/ATE360633T1/de active
- 2003-09-24 EP EP07007240A patent/EP1803724A1/en not_active Withdrawn
- 2003-09-24 CA CA2500118A patent/CA2500118C/en not_active Expired - Fee Related
- 2003-09-24 EP EP03754837A patent/EP1543010B1/en not_active Expired - Lifetime
- 2003-09-24 KR KR1020057005255A patent/KR20050074462A/ko not_active Application Discontinuation
- 2003-09-24 JP JP2004540164A patent/JP4806190B2/ja not_active Expired - Fee Related
- 2003-09-24 PT PT03754837T patent/PT1543010E/pt unknown
- 2003-09-24 NZ NZ538726A patent/NZ538726A/en not_active IP Right Cessation
- 2003-09-24 AU AU2003272642A patent/AU2003272642B2/en not_active Ceased
- 2003-09-24 CN CNB038229587A patent/CN100387600C/zh not_active Expired - Fee Related
- 2003-09-24 DE DE60313478T patent/DE60313478T2/de not_active Expired - Lifetime
- 2003-09-24 WO PCT/US2003/029876 patent/WO2004029059A1/en active IP Right Grant
- 2003-09-24 US US10/668,326 patent/US6825205B2/en not_active Expired - Lifetime
- 2003-09-24 ES ES03754837T patent/ES2286461T3/es not_active Expired - Lifetime
- 2003-09-24 DK DK03754837T patent/DK1543010T3/da active
- 2003-09-24 MX MXPA05003104A patent/MXPA05003104A/es active IP Right Grant
- 2003-09-24 BR BR0314488-7A patent/BR0314488A/pt not_active IP Right Cessation
2005
- 2005-03-15 ZA ZA200502174A patent/ZA200502174B/en unknown
- 2005-12-22 HK HK05111890A patent/HK1080456A1/xx not_active IP Right Cessation
2007
- 2007-07-03 CY CY20071100881T patent/CY1106697T1/el unknown
2010
- 2010-10-28 JP JP2010242645A patent/JP2011042681A/ja not_active Withdrawn

Also Published As

Publication number	Publication date
US20040067973A1 (en)	2004-04-08
DE60313478D1 (de)	2007-06-06
DK1543010T3 (da)	2007-09-17
NZ538726A (en)	2006-11-30
CY1106697T1 (el)	2012-05-23
AU2003272642B2 (en)	2009-07-09
KR20050074462A (ko)	2005-07-18
AU2003272642A1 (en)	2004-04-19
JP4806190B2 (ja)	2011-11-02
DE60313478T2 (de)	2008-01-03
JP2006503850A (ja)	2006-02-02
WO2004029059A1 (en)	2004-04-08
JP2011042681A (ja)	2011-03-03
BR0314488A (pt)	2005-08-02
EP1543010B1 (en)	2007-04-25
ES2286461T3 (es)	2007-12-01
CN100387600C (zh)	2008-05-14
HK1080456A1 (en)	2006-04-28
CA2500118A1 (en)	2004-04-08
EP1543010A1 (en)	2005-06-22
MXPA05003104A (es)	2005-05-27
CN1684967A (zh)	2005-10-19
CA2500118C (en)	2011-04-12
EP1803724A1 (en)	2007-07-04
ATE360633T1 (de)	2007-05-15
US6825205B2 (en)	2004-11-30
PT1543010E (pt)	2007-07-26

Publication	Publication Date	Title
AU2003272642B2 (en)	2009-07-09	N-substituted hydromorphones and the use thereof
CN102718710B (zh)	2014-11-05	***烷化合物
RU2303597C1 (ru)	2007-07-27	Фармацевтическая композиция, способы ее получения и применения
US20070105884A1 (en)	2007-05-10	Opiate analogs selective for the delta-opioid receptor
EP1456212B1 (de)	2006-12-06	6-aminomorphinanderivate, herstellungsverfahren dafür und deren verwendung
WO2001013909A2 (en)	2001-03-01	Compositions and methods for treating opiate intolerance
SK61398A3 (en)	1998-09-09	Use of epinastine in the treatment of pain
EP2986612B1 (en)	2017-06-07	Deuterated morphine derivatives
CN102993213A (zh)	2013-03-27	有机化合物
US20150164835A1 (en)	2015-06-18	Opioid Salts with Release Properties and Characteristics Useful for Abuse Deterrent Drug Product Formulations
WO2023163969A2 (en)	2023-08-31	Naltrexamine derivatives bearing 5-member heterocyclic ring systems as opioid receptor modulators
CZ298398A3 (cs)	1999-06-16	Farmaceutický přípravek
US6284769B1 (en)	2001-09-04	Nonpeptide kappa opioid receptor antagonists
EP0324212B1 (en)	1993-08-04	Glucuronic acid derivatives of opioid antagonists
US8609682B2 (en)	2013-12-17	Analgesic agents
RU2761219C2 (ru)	2021-12-06	Терапевтическое средство от расстройств, связанных с употреблением алкоголя
WO1993021188A1 (en)	1993-10-28	Delta opioid receptor-selective benzylidene-substituted morphinans for the treatment of alcohol abuse