Sumitomo Chemical Company, Limited

Kenji Kobayashi

Hisao Yamamoto

Toshio Atsumi

Yoshiaki Takebayashi

Shigeho Inaba

Toshitsugu Fukumaru

Hiroyuki Mizote

Michio Kimura

Takeshi Nakajima

Novel 2-substituted 6,7-benzomorphan derivatives of the formula: ##SPC1## And acid addition salts thereof, which are useful as non-addicting analgesics, pain relieving agents and antitussives and can be prepared by reacting 6,7-benzomorphan derivatives of the formula: ##SPC2## With the reactive derivatives of alcohols of the formula: ##EQU1## [wherein R is a hydrogen atom, a hydroxyl group, an alkoxy group or an alkanoyloxy group; R.sub.1 is a hydrogen atom, an alkyl group, an alkoxyalkyl group or a substituted or unsubstituted aryl group; R.sub.3 is a hydrogen atom or a hydroxyl group; R.sub.4 is a hydrogen atom, an alkyl group or a substituted or unsubstituted aryl group, or R.sub.3 and R.sub.4 may form an alkylidene group or a carbonyl group together with the carbon atom to which these substituents are bonded; R.sub.2, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9 and R.sub.10 are each a hydrogen atom or an alkyl group; A is an alkylene group; and m is an integer of 0 to 2].

Novel 2-substituted 6,7-benzomorphan derivatives and salts thereof in

An analgesic composition comprising an analgesically effective amount of at least one 6,7-benzomorphan derivative of the formula: ##SPC1## Wherein R is a hydrogen atom, a hydroxyl group, a C.sup.1 - C.sup.3 alkoxy group or a C.sup.1 - C.sup.8 alkanoyloxy group; R.sub.1 is a hydrogen atom, a C.sup.1 - C.sup.5 alkyl group, a phenyl group, a halophenyl group, an alkylphenyl group wherein the alkyl moiety has 1 to 3 carbon atoms, an alkoxyphenyl group wherein the alkoxy moiety has 1 to 3 carbon atoms, a trifluoromethylphenyl group, an alkylthiophenyl group wherein the alkylthio moiety has 1 to 3 carbon atoms or a group of the formula (C.sub.m H.sub.2m.sub.-p.sub.+1) - (R.sub.9).sub.p wherein m is an integer of 1 - 6, p is an integer of 1 - 2 and R.sub.9 is a C.sup.1 - C.sup.3 alkoxy group; R.sub. 2 is a hydrogen atom or a C.sup.1 - C.sup.3 alkyl group; R.sub.3 is a hydrogen atom, a C.sup.1 - C.sup.3 alkyl group, a phenyl group or an alkoxyphenyl group wherein the alkoxy moiety has 1 to 3 carbon atoms; R.sub.4 is a hydrogen atom or a hydroxyl group, or R.sub.3 and R.sub.4 may form a C.sup.1 - C.sup.3 alkylidene group or a carbonyl group together with a carbon atom to which these substituents are bonded; R.sub.5 is a hydrogen atom or C.sup.1 - C.sup.3 alkyl group; R.sub.6 is a hydrogen atom or a methyl group; R.sub.7 and R.sub.8 are independently a hydrogen atom or a C.sup.1 - C.sup.2 alkyl group; and n is an integer of 0 - 2; or an acid addition salt thereof, and a pharmaceutically acceptable carrier or diluent, is disclosed.

Analgesic compositions containing 2-cyanoalkylbenzomorphan derivatives

A novel 2-substituted-6,7-benzomorphan derivative of the formula: ##SPC1## And its acid addition salts, which are useful as non-addicting analgesics and antitussives and can be prepared by reacting a 2-unsubstituted-6,7-benzomorphan derivative of the formula: ##SPC2## With the reactive derivative of an alcohol of the formula:

6,7-Benzomorphan derivatives

A novel process for preparing 2-benzoylalkylbenzomorphan derivatives and salts thereof, represented by the formula ##SPC1## Wherein n, R, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as defined in the specification. The process comprises reacting a pyridinium derivative of the formula, ##SPC2## Wherein X is a halogen atom and Y' is an ethylenedioxy group; with a Grignard reagent of the formula, ##SPC3## Wherein R' is a hydrogen atom or a C.sub.1 -C.sub.3 alkoxy group and Z is a halogen atom, to yield a 1,2-dihydropyridine derivative of the formula; ##SPC4## And then reducing the said 1,2-dihydropyridine derivative to give a 1,2,5,6-tetrahydropyridine derivative of the formula, ##SPC5## Wherein Y is an oxygen atom or an ethylenedioxy group, and further cyclizing the obtained 1,2,5,6-tetrahydropyridine derivative.

Preparation of 2-benzoylalkylbenzomorphan

A 3-benzazocine compound of the formula: ##SPC1## Wherein R.sub.1, R.sub.3, R.sub.4, R.sub.5 and R.sub.8 are each hydrogen or lower alkyl, R.sub.2 is hydrogen, lower alkyl or phenyl and R.sub.6 and R.sub.7 are each lower alkyl, and its pharmaceutically acceptable acid addition salts, which are useful as analgesics and can be produced by reacting a tetrahydropyridine compound of the formula: ##SPC2## Wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are each as defined above or its salt with a Lewis acid.

3-Benzazocine compounds

2-Ketoethyl-6,7-benzomorphan derivatives of the formula: ##SPC1## And their pharmaceutically acceptable non-toxic salts, which are useful as non-addictive analgesics and pain-relieving agents and can be prepared by reacting the corresponding 6,7-benzomorphan derivative of the formula: ##SPC2## With a vinyl carbonyl compound of the formula: ##EQU1## [wherein R' is a hydrogen atom or a group of the formula: --OR' (wherein R' is a hydrogen atom, an alkanoyl group, an alkyl group, an aralkyl group, an alkoxycarbonylmethyl group or a tetrahydropyranyl group), R.sub.1 is a hydrogen atom, an alkyl group or a substituted or unsubstituted aryl group, R.sub.2 is a hydrogen atom or an alkyl group and A is an alkyl group, an alkoxy group, a substituted or unsubstituted aryl group or a substituted or unsubstituted amino group].

Growing community of inventors

Takarazuka, Japan

Kenji Kobayashi