foerfarande foer framstaellning av 1,2,3,4,5,6 - hexahydro 2,6 - metano - 3 - bensazociner vilka verkar pao det centrala nervsystemet och vilka speciellt kan anvaendas saosom analgetika och saosom antagonister mot starka analgetika

摘要

1323491 2,6-Methano-4-benzazocines STERLING DRUG INC 3 June 1971 [4 June 1970] 18897/71 Heading C2C Novel 2,6-methano-3-benzazocines of the general formula wherein (a) YSP1/SP is a hydroxy, C 1- 22 alkanoyloxy, C 4-22 alkenoyloxy (one or two double bonds), Ar-C m H 2m -CO-O- (where m is 0, 1 or 2 and Ar is a phenyl group optionally substituted by 1-3 substituents selected from C 1-4 alkyl, C 1-4 alkoxy, trifluoromethyl, C 2-8 dialkylamino, halogen and C 1-6 alkanoylamino substituents), phenoxyacetoxy, naphthalenecarbonyloxy, pyridinecarbonyloxy, cycloalkyl- or fluorocycloalkyl-C m H 2m -CO-O- (optionally having one or more alkyl substituents on the ring and having a total of 4-10 C atoms, 3-7 of which are ring C atoms, m being 0, 1 or 2), C 2-7 alkylcarbonato, carboamoyloxy or C 2-9 monoordialkyl-carbamoyloxy group; YSP2/SP is a hydrogen atom or a C 1-6 alkyl or ArSP1/SP-C n H 2n -group (where n is 0, 1, 2, 3 or 4 and ArSP1/SP is a phenyl group optionally substituted by 1-3 substituents selected from C 1-4 alkyl, C 1-4 alkoxy and C 2-8 dialkylamino groups; or YSP1/SP and YSP2/SP together form an oxo group; Q is a C 3-8 alkyl, C 3-6 alkenyl, C 3-6 haloalkenyl (having 1-3 Cl, F and/or Br atoms attached to ethylenic C), C 2-6 cyanoalkyl, C 4-8 mono- or di-cyano-alkenyl, C 4-8 2,2-dialkoxyethyl, C 3-6 alkynyl, cycloalkyl- or fluoro-cycloalkyl- C n H 2n optionally having one or more alkyl substituents on the ring (where n is 0, 1, 2, 3 or 4 and there is a total of 3-10 C atoms, 3-7 of which are ring atoms), 2- or 3-cycloalkenyl optionally having one or more alkyl substituents on the ring (having 5 or 6 ring carbon atoms and a total of 5-8 carbon atoms) cycloalkenyl-C p H 2p - optionally having one or more alkyl substituents on the ring (where p is 1, 2, 3 or 4 and there is a total of 6-11 C atoms, 5 or 6 or them being in the ring) or ArSP2/SP-C p H 2p group (where p is 1, 2, 3 or 4 and ArSP2/SP is a phenyl group optionally substituted by amino, nitro, C 1-6 alkanoylamino, C 1-4 alkoxy, C 1-4 alkyl, halogen or trifluoromethyl substituents, provided that Q has no tertiary alpha-C atom; Z is a hydrogen atom or a hydroxy group or an acyloxy group as in the definition of YSP1/SP, and RSP1/SP and RSP2/SP are each a hydrogen atom or C 1-4 alkyl group; (b) YSP1/SP and YSP2/SP together form an oxo group, Z is a C 1-6 alkoxy, difluoromethoxy, trifluoromethoxy, benzyloxy or C 3-6 alkenyloxy group and Q, RSP1/SP and RSP2/SP are as defined under (a); (c) Q is a methyl or ethyl group, RSP2/SP is a C 1-4 alkyl group; Z is a hydrogen atom or a hydroxy, C 1-6 alkoxy, difluoromethoxy, trifluoromethoxy, benzyloxy or C 3-6 alkenyloxy group or an acyloxy group as in the definition of YSP1/SP under (a), and YSP1/SP, YSP2/SP and RSP1/SP are as defined under (a); (d) Q is a C 2-7 carbalkoxy, carbobenzyloxy or, when YSP1/SP and YSP2/SP together form an oxo group, a C 4-9 N-carbalkoxyaminoacetyl or N-carbobenzyloxyaminoacetyl group, YSP1/SP, YSP2/SP, RSP1/SP and RSP2/SP are as defined under (a) and Z is as defined under (c); (e) Q is a hydrogen atom, Z is as defined under (c) and YSP1/SP, YSP2/SP, RSP1/SP and RSP2/SP are as defined under (a); and (f) Q is a QSP1/SP-CO-group, where QSP1/SP is a C 1-7 alkyl, C 2-5 alkenyl, C 2-5 halo alkenyl (having 1-3 halogen atoms selected from Cl, F and Br attached to ethylenic C), C 2-5 alkynyl, cycloalkyl-C q H 2q - optionally having one or more alkyl substituents on the ring (where q is 0, 1, 2, or 3 and there is a total of 3-10 C atoms, 3-7 of which are in the ring) or ArSP2/SP-C q H 2q -group (where q is 0, 1, 2 or 3 and ArSP2/SP is a phenyl group optionally substituted by amino, nitro, C 1-6 alkanoylamino, C 1-4 alkoxy, C 1-4 alkyl, halogen or trifluoromethyl substituents, RSP1/SP and RSP2/SP are defined as under (a), YSP1/SP and YSP2/SP are defined as under (a) or, when an oxo group, may be in the form of the corresponding ketal, and Z is as defined under (c); and acid addition salts thereof are prepared (i) when Q is an optionally substituted alkyl, alkenyl, alkynyl or acyl group, by N-alkylation, -alkenylation, -alkynylation or -acylation of the corresponding compound in which Q is a hydrogen atom, (ii) when YSP1/SP and YSP2/SP together form an oxo group, by oxidation of the corresponding compound in which YSP1/SP and YSP2/SP are each a hydrogen atom; (iii) when YSP1/SP is a hydroxyl group and YSP2/SP is a hydrogen atom, by reduction of the product of (ii); (iv) when YSP1/SP is a hydroxyl group and YSP2/SP is other than a hydrogen atom, by reaction of the product of (ii) with a suitable Grignard reagent; and (v) by interconversions of substituents by esterification, hydrolysis or reduction; followed optionally by salification of the product. Novel 3,5-ethanonaphth[2,1-d]oxazol-2(3H)- ones of the general formula wherein YSP2/SP, RSP1/SP and RSP2/SP are as defined under (a) above and ZSP2/SP is defined as Z under (c) above, and acid addition salts thereof are prepared by reaction of a corresponding 2,6-methano-3- benzazocine of the first general formula above wherein YSP1/SP is a 1(eq)-hydroxy group and Q is a hydrogen atom with phosgene, or by heating the said 2,6-methano-3-benzazocine wherein YSP1/SP is a 1(eq)-hydroxy group and Q is a carbalkoxy group in the presence of an alkoxide, followed optionally by salification of the product. 2,6 - Methano - 3 - benzazocines of the first general formula above wherein YSP1/SP and YSP2/SP are each a hydrogen atom and the other symbols are as defined under (f) above are prepared by N-acylation of the corresponding compound in which Q is a hydrogen atom. Pharmaceutical compositions having central nervous system depressant activity comprise, as active ingedient, a 2,6-methano-3-benzazocine of the first general formula above wherein the symbols are defined as under (a), (b), (c) or (e), or an acid addition salt thereof, together with a suitable carrier and may be administered orally or parenterally.