IE36688B1 - 3-substituted-morphinan derivatives - Google Patents

3-substituted-morphinan derivatives

Info

Publication number
IE36688B1
IE36688B1 IE103/76A IE10372A IE36688B1 IE 36688 B1 IE36688 B1 IE 36688B1 IE 103/76 A IE103/76 A IE 103/76A IE 10372 A IE10372 A IE 10372A IE 36688 B1 IE36688 B1 IE 36688B1
Authority
IE
Ireland
Prior art keywords
hydroxy
methoxy
morphinan
methoxymorphinan
alkyl
Prior art date
Application number
IE103/76A
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 IE36688B1 publication Critical patent/IE36688B1/en

Links

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

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. [GB1412129A]
IE103/76A 1971-09-08 1972-09-06 3-substituted-morphinan derivatives IE36688B1 (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
IE36688B1 true IE36688B1 (en) 1977-02-02

Family

ID=26874723

Family Applications (2)

Application Number Title Priority Date Filing Date
IE103/76A IE36688B1 (en) 1971-09-08 1972-09-06 3-substituted-morphinan derivatives
IE1213/72A IE36687B1 (en) 1971-09-08 1972-09-06 N-substituted-14-hydroxy-3-substituted morphinan derivatives

Family Applications After (1)

Application Number Title Priority Date Filing Date
IE1213/72A IE36687B1 (en) 1971-09-08 1972-09-06 N-substituted-14-hydroxy-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) DE2243961A1 (en)
DK (1) DK141624B (en)
FR (1) FR2154481B1 (en)
GB (2) GB1412129A (en)
HK (1) HK2679A (en)
IE (2) IE36688B1 (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
US4052389A (en) * 1976-03-23 1977-10-04 Bristol-Myers Company Derivatives of 9,10-dihydroxy-1-(p-alkoxybenzyl)-perhydroisoquinoline oxazine-3-one
US4139534A (en) * 1977-02-17 1979-02-13 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
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
WO1995003307A1 (en) * 1993-07-19 1995-02-02 Toray Industries, Inc. Brain cell protective
JP3843456B2 (en) * 1993-07-23 2006-11-08 東レ株式会社 Morphinan derivatives and pharmaceutical applications
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
US7923454B2 (en) 2002-05-17 2011-04-12 Jenken Biosciences, Inc. Opioid and opioid-like compounds and uses thereof
WO2003097608A2 (en) 2002-05-17 2003-11-27 Jenken Biosciences, Inc. Opioid and opioid-like compounds and uses thereof
US7501433B2 (en) * 2002-05-17 2009-03-10 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
EP3207923B1 (en) 2014-10-14 2019-09-04 Hisamitsu Pharmaceutical Co., Inc. 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
YU227772A (en) 1982-02-28
YU45099B (en) 1992-07-20
AU4622872A (en) 1974-03-07
SE403286B (en) 1978-08-07
DE2265255C2 (en) 1986-06-05
BE788478A (en) 1973-03-06
NL162072C (en) 1980-04-15
NL162072B (en) 1979-11-15
DE2243961C2 (en) 1988-07-21
JPS5310596B2 (en) 1978-04-14
DE2265256A1 (en) 1977-01-27
DE2265255A1 (en) 1977-01-27
FR2154481B1 (en) 1976-04-23
MY7900027A (en) 1979-12-31
DD100255A5 (en) 1973-09-12
JPS4834864A (en) 1973-05-22
DE2243961A1 (en) 1973-04-05
AU470102B2 (en) 1976-03-04
SE398877B (en) 1978-01-23
CH590845A5 (en) 1977-08-31
DK141624B (en) 1980-05-12
GB1412129A (en) 1975-10-29
KE2911A (en) 1979-01-26
GB1412130A (en) 1975-10-29
DE2265256C2 (en) 1985-10-24
CY980A (en) 1979-03-23
HK2679A (en) 1979-01-19
DK141624C (en) 1980-10-13
NL7212176A (en) 1973-03-12
CA999578A (en) 1976-11-09
US3819635A (en) 1974-06-25
SE7506292L (en) 1975-06-02
FR2154481A1 (en) 1973-05-11
IE36687B1 (en) 1977-02-02
IE36687L (en) 1973-03-08

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