ES307301A1 - Benzomorphans and process for their preparation - Google Patents

Benzomorphans and process for their preparation

Info

Publication number
ES307301A1
ES307301A1 ES0307301A ES307301A ES307301A1 ES 307301 A1 ES307301 A1 ES 307301A1 ES 0307301 A ES0307301 A ES 0307301A ES 307301 A ES307301 A ES 307301A ES 307301 A1 ES307301 A1 ES 307301A1
Authority
ES
Spain
Prior art keywords
benzomorphan
methyl
hydrogen
phenyl
methoxybenzyl
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
ES0307301A
Other languages
Spanish (es)
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.)
Novartis AG
Original Assignee
JR Geigy AG
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 JR Geigy AG filed Critical JR Geigy AG
Publication of ES307301A1 publication Critical patent/ES307301A1/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • 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
    • C07D211/68—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 one double bond between ring members or between a ring member and a non-ring member
    • C07D211/70—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 one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • 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
    • C07D211/80—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 two double bonds between ring members or between ring members and non-ring members
    • C07D211/82—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • 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
    • C07D221/26—Benzomorphans

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Discharge Lamp (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

The invention comprises compounds of formula <FORM:1077711/C2/1> wherein X is oxygen or sulphur, R1 is hydrogen, hydroxy or C1- 6 alkoxy or alkanoyloxy, R2 is C1- 6 alkyl, b -methoxyethyl or phenyl optionally substituted by a halogen atom or a hydroxy or C1- 9 alkoxy group, R3 is hydrogen or a C1- 3 alkyl group, R4 is hydrogen, or a C1- 5 alkyl, C2- 5 alkenyl, phenyl, chlorophenyl, bromophenyl or C7- 8 phenyl-alkyl group, R5 is hydrogen or a C1- 6 alkyl group, or the group -NR4R5 forms a saturated heterocycle having up to 7 carbon atoms in which the nitrogen atom is the only hetero-atom or a morpholino group, acid addition salts thereof, and their preparation by (a) reaction of an N-unsubstituted benzomorphan, in the presence of an acid-binding agent, with phosgene and an amine HNR4R5 or with a compound HalCONR4R5, or with an isocyanate of formula R4-N=C=X or (VII) M\sJ \sKN=C=O wherein M is an alkali metal, (b) reaction of an N-cyano-benzomorphan with water or hydrogen sulphide, the former optionally under oxidative conditions, (c) reaction of an N-unsubstituted or N-alkyl-benzomorphan with a compound of formula Hal-COOR6, wherein R6 is a C1- 6 alkyl group, to form an N-alkoxycarbonyl-benzomorphan and treating this with an alkali metal amide, (d) O-alkylation, O-acylation or ether or ester hydrolysis, (e) conversion of a carbamyl group to a thiocarbamyl group, or (f) optical resolution by formation of optically active salts, followed by regeneration of the base. N - Cyano - benzomorphan starting materials are prepared by cyclization of a compound of formula <FORM:1077711/C2/2> in the presence of a Lewis acid to form an N-methyl-benzomorphan which may be optically resolved by formation of an optically active salt, followed by regeneration of the base, acylating any free hydroxy groups, and reacting the product with cyanogen bromide. 21 - Methoxy - 5 - phenyl - 6,7 - benzomorphan hydrochloride is prepared by treatment of 21-hydroxy - 5 - phenyl - 6,7 - benzomorphan with ethereal diazomethane, followed by hydrochloric acid. 1 - Methyl - 2 - (p - methoxybenzyl) - 4 - (p-chlorophenyl) - 1,2,5,6 - tetrahydropyridine hydrobromide is prepared by reaction of 4-(p-chlorophenyl) - 1,2,5,6 - tetrahydropyridine with formaldehyde and formic acid to form the N-methyl derivative, treatment of this with p-methoxybenzyl chloride to form the N-methyl - N - (p - methoxybenzyl) compound, and treating this with phenyl lithium and hydrogen bromide. 1 - Methyl - 1 - (p - methoxybenzyl) - 4 - (p-hydroxyphenyl) - 1,2,5,6 - tetrahydropyridine hydrobromide is prepared by reaction of 1-methyl-4-piperidone with phenol and hydrogen chloride to form 1-methyl-4-(p-hydroxyphenyl)-1,2,5,6 -tetrahydropyridine, reacting this with p-methoxybenzyl chloride to form the N-methyl-N-(p-methoxybenzyl)-compound, and treating this with potassium amide in liquid ammonia. The compounds of the invention have analgesic, anti-tussive and morphine-antagonistic activity and may be used in pharmaceutical compositions in combination with a carrier, for example in forms suitable for oral or parenteral administration.
ES0307301A 1963-12-20 1964-12-19 Benzomorphans and process for their preparation Expired ES307301A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US33229663A 1963-12-20 1963-12-20

Publications (1)

Publication Number Publication Date
ES307301A1 true ES307301A1 (en) 1965-05-16

Family

ID=23297612

Family Applications (4)

Application Number Title Priority Date Filing Date
ES0307301A Expired ES307301A1 (en) 1963-12-20 1964-12-19 Benzomorphans and process for their preparation
ES0307300A Expired ES307300A1 (en) 1963-12-20 1964-12-19 Procedure for the preparation of new substitute 6,7-benzomorphanes. (Machine-translation by Google Translate, not legally binding)
ES0307299A Expired ES307299A1 (en) 1963-12-20 1964-12-19 Procedure for the preparation of substitute 6,7-benzomorphanes. (Machine-translation by Google Translate, not legally binding)
ES0307302A Expired ES307302A1 (en) 1963-12-20 1964-12-19 Procedure for preparing new substituteed 6,7-benzomorphanes. (Machine-translation by Google Translate, not legally binding)

Family Applications After (3)

Application Number Title Priority Date Filing Date
ES0307300A Expired ES307300A1 (en) 1963-12-20 1964-12-19 Procedure for the preparation of new substitute 6,7-benzomorphanes. (Machine-translation by Google Translate, not legally binding)
ES0307299A Expired ES307299A1 (en) 1963-12-20 1964-12-19 Procedure for the preparation of substitute 6,7-benzomorphanes. (Machine-translation by Google Translate, not legally binding)
ES0307302A Expired ES307302A1 (en) 1963-12-20 1964-12-19 Procedure for preparing new substituteed 6,7-benzomorphanes. (Machine-translation by Google Translate, not legally binding)

Country Status (12)

Country Link
AT (4) AT249277B (en)
BE (2) BE657405A (en)
CH (7) CH449640A (en)
DE (2) DE1445854A1 (en)
DK (4) DK108497C (en)
ES (4) ES307301A1 (en)
FR (2) FR4346M (en)
GB (2) GB1092394A (en)
IL (2) IL22643A (en)
NL (3) NL6414820A (en)
NO (2) NO119274B (en)
SE (2) SE322779B (en)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7923454B2 (en) 2002-05-17 2011-04-12 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
WO2003097608A2 (en) 2002-05-17 2003-11-27 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
US8835426B2 (en) 2007-02-26 2014-09-16 Vitae Pharmaceuticals, Inc. Cyclic urea and carbamate inhibitors of 11β-hydroxysteroid dehydrogenase 1
EP2183228B1 (en) 2007-07-26 2014-08-20 Vitae Pharmaceuticals, Inc. CYCLIC INHIBITORS OF 11ß -HYDROXYSTERIOD DEHYDROGENASE 1
AR069207A1 (en) 2007-11-07 2010-01-06 Vitae Pharmaceuticals Inc CYCLIC UREAS AS INHIBITORS OF THE 11 BETA - HIDROXI-ESTEROIDE DESHIDROGENASA 1
WO2009063061A2 (en) 2007-11-16 2009-05-22 Boehringer Ingelheim International Gmbh Aryl- and heteroarylcarbonyl derivatives of benzomorphanes and related scaffolds, medicaments containing such compounds and their use
CA2708303A1 (en) 2007-12-11 2009-06-18 Vitae Pharmaceuticals, Inc. Cyclic urea inhibitors of 11.beta.-hydroxysteroid dehydrogenase 1
TW200934490A (en) 2008-01-07 2009-08-16 Vitae Pharmaceuticals Inc Lactam inhibitors of 11 &abgr;-hydroxysteroid dehydrogenase 1
JP5490020B2 (en) 2008-01-24 2014-05-14 ヴァイティー ファーマシューティカルズ，インコーポレイテッド Cyclic carbazate and semicarbazide inhibitors of 11β-hydroxysteroid dehydrogenase 1
WO2009102428A2 (en) 2008-02-11 2009-08-20 Vitae Pharmaceuticals, Inc. 1,3-OXAZEPAN-2-ONE AND 1,3-DIAZEPAN-2-ONE INHIBITORS OF 11β -HYDROXYSTEROID DEHYDROGENASE 1
EP2245014B1 (en) * 2008-02-12 2011-11-02 Boehringer Ingelheim International GmbH Urea derivatives of benzomorphanes and related scaffolds, medicaments containing such compounds and their use
WO2009102460A2 (en) 2008-02-15 2009-08-20 Vitae Pharmaceuticals, Inc. Inhibitors of 11beta-hydroxysteroid dehydrogenase 1
JP5301563B2 (en) 2008-05-01 2013-09-25 ヴァイティー ファーマシューティカルズ，インコーポレイテッド Cyclic inhibitor of 11β-hydroxysteroid dehydrogenase 1
CA2723039A1 (en) 2008-05-01 2009-11-05 Vitae Pharmaceuticals, Inc. Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1
EP2291373B1 (en) 2008-05-01 2013-09-11 Vitae Pharmaceuticals, Inc. Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1
EP2291370B1 (en) 2008-05-01 2013-11-27 Vitae Pharmaceuticals, Inc. Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1
CA2724214A1 (en) 2008-05-13 2009-11-19 Boehringer Ingelheim International Gmbh Alicyclic carboxylic acid derivatives of benzomorphans and related scaffolds, medicaments containing such compounds and their use
TW201016691A (en) 2008-07-25 2010-05-01 Boehringer Ingelheim Int Inhibitors of 11beta-hydroxysteroid dehydrogenase 1
NZ590495A (en) 2008-07-25 2012-10-26 Vitae Pharmaceuticals Inc Dihydropyridin-phenyl-3-oxazinan-2-ones as inhibitors of 11beta-hydroxysteroid dehydrogenase 1
CA2738453C (en) 2008-10-23 2017-07-04 Boehringer Ingelheim International Gmbh Urea derivatives of substituted nortropanes, medicaments containing such compounds and their use
CA2744946A1 (en) 2009-02-04 2010-08-12 Boehringer Ingelheim International Gmbh Cyclic inhibitors of 11.beta.-hydroxysteroid dehydrogenase 1
UA109255C2 (en) 2009-04-30 2015-08-10 Берінгер Інгельхайм Інтернешнл Гмбх Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1
US8703765B2 (en) 2009-06-02 2014-04-22 Boehringer Ingelheim International Gmbh Cyclic inhibitors of 11β-hydroxysteroid dehydrogenase 1
WO2011011123A1 (en) 2009-06-11 2011-01-27 Vitae Pharmaceuticals, Inc. Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 based on the 1,3 -oxazinan- 2 -one structure
EP2448928B1 (en) 2009-07-01 2014-08-13 Vitae Pharmaceuticals, Inc. Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1
TWI531571B (en) 2009-11-06 2016-05-01 維它藥物公司 Aryl-and heteroarylcarbonyl derivatives of hexahydroindenopyridine and octahydrobenzoquinoline
US8933072B2 (en) 2010-06-16 2015-01-13 Vitae Pharmaceuticals, Inc. Substituted 5-,6- and 7-membered heterocycles, medicaments containing such compounds, and their use
JP5813106B2 (en) 2010-06-25 2015-11-17 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Azaspirohexanone as an inhibitor of 11-β-HSD1 for the treatment of metabolic disorders
CA2813671A1 (en) 2010-11-02 2012-05-10 Boehringer Ingelheim International Gmbh Pharmaceutical combinations for the treatment of metabolic disorders
TWI537258B (en) 2010-11-05 2016-06-11 百靈佳殷格翰國際股份有限公司 Aryl-and heteroarylcarbonyl derivatives of hexahydroindenopyridine and octahydrobenzoquinoline
US8735585B2 (en) 2011-08-17 2014-05-27 Boehringer Ingelheim International Gmbh Indenopyridine derivatives

Also Published As

Publication number Publication date
DK108495C (en) 1967-12-27
AT249277B (en) 1966-09-12
CH449640A (en) 1968-01-15
NL127995C (en)
IL22642A (en) 1968-07-25
CH449643A (en) 1968-01-15
CH449641A (en) 1968-01-15
FR4346M (en) 1966-08-16
SE322779B (en) 1970-04-20
NL6414821A (en) 1965-06-21
FR4345M (en) 1966-08-16
IL22643A (en) 1968-07-25
NO119273B (en) 1970-04-27
DK108497C (en) 1967-12-27
SE305657B (en) 1968-11-04
DK108496C (en) 1967-12-27
GB1077711A (en) 1967-08-02
DE1445853A1 (en) 1968-12-05
NL6414820A (en) 1965-06-21
AT253687B (en) 1967-04-25
AT249276B (en) 1966-09-12
ES307300A1 (en) 1965-05-01
CH449639A (en) 1968-01-15
AT261126B (en) 1968-04-10
NO119274B (en) 1970-04-27
BE657405A (en) 1965-06-21
CH448118A (en) 1967-12-15
CH446371A (en) 1967-11-15
DK106552C (en) 1967-02-20
CH449642A (en) 1968-01-15
ES307302A1 (en) 1965-05-16
DE1445854A1 (en) 1968-12-05
ES307299A1 (en) 1965-05-16
GB1092394A (en) 1967-11-22
BE657406A (en) 1965-06-21

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