GB1412129A - N-substituted-14-hydroxy-3-substituted morphinane derivatives - Google Patents

N-substituted-14-hydroxy-3-substituted morphinane derivatives

Info

Publication number
GB1412129A
GB1412129A GB4161972A GB4161972A GB1412129A GB 1412129 A GB1412129 A GB 1412129A GB 4161972 A GB4161972 A GB 4161972A GB 4161972 A GB4161972 A GB 4161972A GB 1412129 A GB1412129 A GB 1412129A
Authority
GB
United Kingdom
Prior art keywords
hydroxy
methoxy
morphinan
methoxymorphinan
alkyl
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
Application number
GB4161972A
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.)
Bristol Myers Co
Original Assignee
Bristol Myers 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 Bristol Myers Co filed Critical Bristol Myers Co
Publication of GB1412129A publication Critical patent/GB1412129A/en
Expired legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
    • C07D303/02—Compounds containing oxirane rings
    • C07D303/36—Compounds containing oxirane rings with hydrocarbon radicals, substituted by nitrogen atoms
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/22—Bridged ring systems
    • C07D221/28—Morphinans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/22—Ortho- or ortho- and peri-condensed systems containing three rings containing only six-membered rings
    • C07C2603/26—Phenanthrenes; Hydrogenated phenanthrenes

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pain & Pain Management (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

1412129 Morphinane derivatives BRISTOL MYERS CO 7 Sept 1972 [8 Sept 1971 13 Jan 1972] 41619/72 Heading C2C [Also in Division A5] The invention comprises compounds of the formula (XXXX) wherein R<SP>1</SP> is -CH 2 -C # CH, or C 3-7 alkenyl in which R<SP>4</SP> is H or CH 3 , R<SP>2</SP> is H, C 1-6 alkyl, C 2-6 acyl CH 3 .C(CH 3 ) 2 .COCH 3 OCH 2 - or and R is H, C 2-6 acyl, trichloroacetyl or cinnamoyl. Compounds XXXX where R<SP>2</SP> and R are H can be obtained by treating a compound XXXX (where R is H, R 3 is C 1-7 alkyl, and R<SP>1</SP> is H, with an alkylating or acylating agent W-(Z)-X, where W is -C # CH, -CH = CH 2 , -CH = C(CH 3 ) 2 and C 2-6 alkenyl, Z is -CO- or -CH 2 -, X is Cl, Br or I, in an inert organic solvent in the presence of a tert. amine to form a compound XXXX (R is H, R 2 is alkyl, R<SP>1</SP> is -(Z)-W), treating the product with LiAlH 4 when Z is -CO- and cleaving the ether R<SP>2</SP>O- using HBr, BBr 3 or pyridine.HCl. Compounds in which R<SP>1</SP> is -CH 2 C # CH, -CH 2 -CH = CH 2 , -CH 2 -CH = C(CH 3 ) 2 , -CH 2 -CH = CH-Cl or C 3-7 alkenyl, are obtained by treating or compound XXXX (where R and R<SP>1</SP> are H, R 2 is alkyl) with R<SP>1</SP>-X, where X is Cl, Br or I, in an inert organic solvent in the presence of a tert. amine, and cleaving the ether as above. A further preparation comprises reacting a compound of Formula XXXXIIb where R<SP>2</SP> is C 1-7 alkyl with W-(Z)-X (where W is R 4 -substituted-cyclopropyl or cyclobutyl or 1-methylcyclopropyl), epoxidizing the product and reacting the epoxide with LiAlH 4 to form a compound XXXX (where R is H, R<SP>2</SP> is alkyl and R<SP>1</SP> is -CH 2 W), and optionally acylating the 14- hydroxy group and/or cleaving the ether group R<SP>2</SP>O-. Preparation of the following series of intermediates and products is also described: 3,4- dihydro - 7 - methoxy - 2,2 - tetramethylene- 1(2H) - naphthalenone; 1 - hydroxy - 7 - methoxy - 1,2,3,4 - tetrahydro - 2,2 - tetramethylene- 1 -naphthaleneacetonitrile; 1-(2-amino)-7-methoxy - 1,2,3,4 - tetrahydro - 2,2 - tetramethylene- 1 - naphthol; 4a - (2 - aminoethyl) - 1,2,3,4,4a,9- hexahydro - 6 - methoxyphenanthrene; 4a- [2 - (ethoxycarbonylamino)ethyl] - 1,2,3,4,4a,9- hexahydro - 6 - methoxyphenanthrene; 10,10a- α - epoxy - 4a - [2 - (ethoxycarbonylamino)- ethyl] 1,2,3;4,4a9,10,10a - octahydro - 6 - methoxyphenanthrene; N - ethoxy - carbonyl- 14 - hydroxy - 3 - methoxyisomorphinan; 14- hydroxy - 3 - methoxy - N - methylisomorphinan; N-ethoxycarbonyl-3-methoxy-#<SP>8</SP>-morphinan; 8,14# - epoxy - N - ethoxycarbonyl- 3 - methoxymorphinan (mixed isomers); N- ethoxycarbonyl - 14 - hydroxy - 3 - methoxymorphinan; 14-hydroxy-3-methoxy-N-methylmorphinan; 3,14 - dihydroxy - N - methyl morphinan; 3 - methoxy - #<SP>8,14</SP> - morphinan; N - cyclopropylcarbonyl - 3 - methoxy - #<SP>8,14</SP>- morphinan; N - cyclopropylcarbonyl - 8,14- epoxy - 3 - methoxymorphinan; N - cyclopropylmethyl - 14 - hydroxy - 3 - methoxymorphinan; 3,14 - dihydroxy - N - cyclopropylmethylmorphinan; 3 - methoxy - N - trifluoroacetyl- #<SP>8,14</SP> - morphinan; 8,14 - epoxy - 3 - methoxy- N - trifluoroacetylmorphinan; 8,14 - epoxy - 3 - methoxy morphinan; 14 - hydroxy- 3-methoxymorphinan; 3,14-dihydroxy-morphinan; N - cyclobutylcarbonyl - 14, - hydroxy- 3 - methoxymorphinan; N - cyclobutylmethyl- 14 - hydroxy - 3 - methoxy - morphinan; N- cyclobutylmethyl - 3,14 - dihydroxymorphinan; N - allyl - 14 - hydroxy - 3 - methoxymorphinan; N - allyl - 3,14 - dihydroxymorphinan; N- dimethyl - allyl - 14 - hydroxy - 3 - methoxymorphinan; N - dimethylallyl - 3,14 - dihydroxymorphinan; N - 2<SP>1</SP>- methylallyl - 14 - hydroxy - 3 - methoxy - morphinan; N - 2 - methylallyl-3,14-dihydroxy morphinan; N-cyclopropylmethyl - 3 - acetoxy - 4 - hydroxymorphinan; N - cyclopropylmethyl - 3 - isonicotinolyoxy- 14 - hydroxymorphinan; N - cyclobutylmethyl - 14 - hydroxy - 3 - methoxymethyloxymorphinan; N - cyclobutylmethyl - 3,14 - diacetoxy - morphinan; N - cyclobutylmethyl- 14 - acetoxy 3 - hydroxymorphinan; d and lisomers of 3,14-dihydroxy-N-cyclopropylmethylmorphinan.
GB4161972A 1971-09-08 1972-09-07 N-substituted-14-hydroxy-3-substituted morphinane derivatives Expired GB1412129A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US17883771A 1971-09-08 1971-09-08
US00217633A US3819635A (en) 1971-09-08 1972-01-13 14-hydroxymorphinan derivatives

Publications (1)

Publication Number Publication Date
GB1412129A true GB1412129A (en) 1975-10-29

Family

ID=26874723

Family Applications (2)

Application Number Title Priority Date Filing Date
GB4161972A Expired GB1412129A (en) 1971-09-08 1972-09-07 N-substituted-14-hydroxy-3-substituted morphinane derivatives
GB1057175A Expired GB1412130A (en) 1971-09-08 1972-09-07 3-substituted-morphinan derivatives

Family Applications After (1)

Application Number Title Priority Date Filing Date
GB1057175A Expired GB1412130A (en) 1971-09-08 1972-09-07 3-substituted-morphinan derivatives

Country Status (19)

Country Link
US (1) US3819635A (en)
JP (1) JPS5310596B2 (en)
AU (1) AU470102B2 (en)
BE (1) BE788478A (en)
CA (1) CA999578A (en)
CH (1) CH590845A5 (en)
CY (1) CY980A (en)
DD (1) DD100255A5 (en)
DE (3) DE2265256C2 (en)
DK (1) DK141624B (en)
FR (1) FR2154481B1 (en)
GB (2) GB1412129A (en)
HK (1) HK2679A (en)
IE (2) IE36687B1 (en)
KE (1) KE2911A (en)
MY (1) MY7900027A (en)
NL (1) NL162072C (en)
SE (2) SE398877B (en)
YU (1) YU45099B (en)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3910920A (en) * 1973-11-07 1975-10-07 Bristol Myers Co 3,14,17-Substituted-6,7-tetramethylenemorphinans
US3980641A (en) * 1975-07-31 1976-09-14 Bristol-Myers Company Process for the preparation of 14-hydroxymorphinans
US4017497A (en) * 1975-11-18 1977-04-12 Bristol-Myers Company Process for the preparation of 14-hydroxymorphinan derivatives
US4058531A (en) * 1976-03-23 1977-11-15 Bristol-Myers Company Process for the preparation of 14-hydroxymorphinan derivatives
JPS52136176A (en) * 1976-03-23 1977-11-14 Bristol Myers Co Method of improving 144hydroxymorphinan derivatives
US4139534A (en) * 1977-02-17 1979-02-13 Bristol-Myers Company Process for the preparation of 14-hydroxymorphinan derivatives
US4052389A (en) * 1976-03-23 1977-10-04 Bristol-Myers Company Derivatives of 9,10-dihydroxy-1-(p-alkoxybenzyl)-perhydroisoquinoline oxazine-3-one
GB1587831A (en) * 1977-03-23 1981-04-08 Reckitt & Colmann Prod Ltd Morphine derivatives
GB1593191A (en) * 1977-03-23 1981-07-15 Reckitt & Colmann Prod Ltd Derivatives of morphine
US4115389A (en) * 1977-05-02 1978-09-19 Bristol-Myers Company Process of N-demethylating (-)-1-(p-methoxybenzyl)-2-methyl-1,2,3,4,5,6,7,8-octahydroisoquinoline
US4338320A (en) * 1978-11-15 1982-07-06 The Board Of Regents Of The University Of Nebraska Esters of 6'-hydroxycinchonine, and a method of treating arrythmia with them
US4228285A (en) * 1979-02-28 1980-10-14 Bristol-Myers Company 14-Hydroxy-6-oxamorphinans and 14-hydroxy-6-oxaisomorphinans
US4272540A (en) * 1979-04-24 1981-06-09 Sisa, Incorporated 14-Methoxymorphinan-6-one compounds and therapeutic methods of treating pain and drug dependence with them
US4322427A (en) * 1981-04-16 1982-03-30 Bristol-Myers Company Analgetic compositions and methods of use
EP0661283B1 (en) * 1993-07-19 1998-10-21 Toray Industries, Inc. Brain cell protective
CA2143864C (en) * 1993-07-23 2006-01-24 Hiroshi Nagase Morphinan derivatives and pharmaceutical use thereof
CZ281174B6 (en) * 1993-08-13 1996-07-17 Galena, A.S. Process for preparing 3,14beta-dihydroxy-17-normorphinan
ATE265846T1 (en) 1998-02-25 2004-05-15 Abbott Lab SUSTAINED RELEASE FORMULATIONS CONTAINING BUTORPHANOL
US20040167164A1 (en) * 1998-05-05 2004-08-26 Jose Pozuelo Compositions and methods for treating particular chemical addictions and mental illnesses
US7501433B2 (en) * 2002-05-17 2009-03-10 Jenken Biosciences, Inc. Opioid and opioid-like compounds and uses thereof
EP2987788A1 (en) 2002-05-17 2016-02-24 Taiwanj Pharmaceuticals Co., Ltd. Opioid and opioid-like compounds and uses thereof
US7923454B2 (en) 2002-05-17 2011-04-12 Jenken Biosciences, Inc. Opioid and opioid-like compounds and uses thereof
US8017622B2 (en) 2003-05-16 2011-09-13 Jenken Biosciences, Inc. Opioid and opioid-like compounds and uses thereof
CN103073496B (en) * 2013-02-18 2015-08-26 苏州立新制药有限公司 The preparation method of Dextromethorphane Hbr
KR102102513B1 (en) 2014-10-14 2020-04-20 히사미쓰 세이야꾸 가부시키가이샤 Adhesive patch

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3166559A (en) * 1965-01-19 J-lower alkoxy-x-phenyloxy-ix-hydroxy-
GB1028407A (en) * 1962-04-06 1966-05-04 Shionogi & Co Improvements in or relating to morphinan derivatives and their preparation
FR1362540A (en) * 1963-04-05 1964-06-05 Shionogi & Co Substituted n derivatives of morphinan and their production

Also Published As

Publication number Publication date
DE2265255C2 (en) 1986-06-05
NL7212176A (en) 1973-03-12
IE36688B1 (en) 1977-02-02
SE403286B (en) 1978-08-07
FR2154481A1 (en) 1973-05-11
IE36687L (en) 1973-03-08
DE2265256C2 (en) 1985-10-24
HK2679A (en) 1979-01-19
CY980A (en) 1979-03-23
NL162072C (en) 1980-04-15
DE2243961C2 (en) 1988-07-21
SE7506292L (en) 1975-06-02
AU470102B2 (en) 1976-03-04
SE398877B (en) 1978-01-23
CA999578A (en) 1976-11-09
NL162072B (en) 1979-11-15
DE2265255A1 (en) 1977-01-27
KE2911A (en) 1979-01-26
DE2243961A1 (en) 1973-04-05
US3819635A (en) 1974-06-25
DD100255A5 (en) 1973-09-12
YU45099B (en) 1992-07-20
DK141624B (en) 1980-05-12
IE36687B1 (en) 1977-02-02
DE2265256A1 (en) 1977-01-27
JPS5310596B2 (en) 1978-04-14
FR2154481B1 (en) 1976-04-23
MY7900027A (en) 1979-12-31
AU4622872A (en) 1974-03-07
CH590845A5 (en) 1977-08-31
GB1412130A (en) 1975-10-29
JPS4834864A (en) 1973-05-22
DK141624C (en) 1980-10-13
YU227772A (en) 1982-02-28
BE788478A (en) 1973-03-06

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Legal Events

Date Code Title Description
PS Patent sealed [section 19, patents act 1949]
PE20 Patent expired after termination of 20 years