Sumitomo Chemical Company, Limited

Kao Soap Company, Ltd.

Sumitomo Pharmaceuticals Company Limited

Yoshiaki Takebayashi

Hisao Yamamoto

Toshio Atsumi

Shigeho Inaba

Kenji Kobayashi

Tsuyoshi Kobayashi

Junki Katsube

Kikuo Sasajima

Katsumi Tamoto

Yuzo Tarumi

Keiichi Ono

Akihiko Sano

Takao Kiyohara

Hideki Okajima

Noboru Yoshida

Tetsutaro Sanjiki

Yoshiyuki Kai

Masaru Fukui

Michio Kimura

Kazushi Suwa

Takeshi Nakajima

Shinichi Kaneko, Deceased

A process for the manufacture of a polypeptide (I) having the formula: ##STR1## which comprises steps of: (a) coupling, successively and in the order of the sequence of the polypeptide (I), the four protected fragments A, B, C and D or five protected fragments A, B, C, E and F,

Synthesis of a derivative of GRF and intermediate peptides

There are provided compounds of the formula: ##STR1## wherein either R.sub.1 or R.sub.2 is a hydrogen atom, a hydroxy group, an acyloxy group, a phthalimido group or an acetamido group and the other is a hydrogen atom; either R.sub.3 or R.sub.4 is a hydroxy group or an acyloxy group and the other is a hydrogen atom; either R.sub.5 or R.sub.6 is a hydroxy group or an acyloxy group and the other is a hydrogen atom; either R.sub.7 or R.sub.8 is a hydrogen atom, a methyl group, a hydroxymethyl group, an acyloxymethyl group, an alkoxycarbonyl group, a group of the formula: ##STR2## (wherein X.sub.1 and X.sub.2 are a hydrogen atom or a lower alkyl group), or a carboxyl group and the other is a hydrogen atom; either R.sub.11 or R.sub.12 is a hydrogen atom, a hydroxy group or an acyloxy group and the other is a hydrogen atom; either R.sub.13 or R.sub.14 is a hydroxy group or an acyloxy group and the other is a hydrogen atom; either R.sub.15 or R.sub.16 is a methyl group, a hydroxymethyl group or an acyloxymethyl group and the other is a hydrogen atom; and a process for producing them. These compounds are useful as antitumor agents.

4-Carbamoylimidazolium-5-olate derivatives

There are provided compounds of the formula: ##STR1## wherein R is an adamantoyl group substituted with a lower alkyl group, a lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, an aroyloxy group, a halogen atom, an acetamido group, a nitro group, an azide group, a trifluoromethyl group or a phenyl group which may be substituted with a nitro group, a halogen atom, a lower alkyl group or a lower alkoxy group and a process producing them. These compounds are useful as antitumor agents and immunosuppressants.

Antitumor and immunosuppresive 4-carbamoyl imidazolium-5-olate

A new class of 4-homoisotwistane derivatives of the formula, ##STR1## wherein R.sub.1 is a hydrogen atom or a C.sub.1 -C.sub.3 alkyl group, and R.sub.2 is an alkyl group, a phenyl group which may be either unsubstituted or substituted with a C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy, nitro group or a halogen atom (hereinafter referred to as 'an optionally substituted phenyl group'), a group of the formula, --A--OH in which A is a C.sub.1 -C.sub.3 alkylene group; a group of the formula, --A--B in which A is as defined as above and B is a halogen atom, or a group of the formula, ##STR2## in which A is as defined above and R.sub.3 and R.sub.4 are independently a hydrogen atom or a C.sub.1 -C.sub.3 alkyl group or R.sub.3 and R.sub.4 may, when taken together with the adjacent nitrogen atom to which R.sub.3 and R.sub.4 are linked, form pyrrolidine, piperidine, morpholine, phthalimide or piperazine, which have been found to possess potent antiviral activity, are prepared, for example by reacting a compound of the formula, ##STR3## wherein R.sub.1 is as defined above and X is halogen, with a compound of the formula,

4-Homoisotwistane derivatives

Novel 3-amino-4-homoisotwistane derivatives of the formula, ##STR1## wherein R.sub.1 is a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group or a C.sub.3 -C.sub.5 alkenyl group, and R.sub.2 is a C.sub.1 -C.sub.4 alkyl group or a C.sub.3 -C.sub.5 alkenyl group, or non-toxic pharmaceutically acceptable salts thereof, which are very valuable as medicines for the treatment of virus-caused diseases and as antiviral agents for animals and useful for the treatment of parkinsonean disease.

3-Amino-4-homoisotwistane derivatives

There are provided compounds of the formula: ##STR1## wherein R is an adamantyl group, or a phenyl group unsubstituted or substituted with a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a halogen atom, a nitro group, a cyano group, a methylenedioxy group or an acetamido group, useful as anti-transplanted-tumor agents and immunosuppressants.

5-Carbamoyl imidazoles

Novel benzisoxazole compounds of the formula: ##STR1## wherein R.sub.1 and R.sub.2 are each hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, ar(C.sub.1 -C.sub.3)alkoxy or halogen or, when taken together, they form C.sub.1 -C.sub.2 alkylenedioxy, Alk is C.sub.1 -C.sub.4 alkylene and A is a group of the formula: ##STR2## (wherein R.sub.3 and R.sub.4 are each C.sub.1 -C.sub.4 alkyl or, when taken together with the adjacent nitrogen atom, they represent a 5-6 membered nitrogen-containing heterocyclic ring which may contain any additional hetero atom and R.sub.5 is C.sub.1 -C.sub.4 alkyl or aryl), and non-toxic salts thereof, which possess various pharmaceutical activities.

Benzisoxazole derivatives

Novel benzisoxazole compounds of the formula: ##STR1## wherein R.sub.1 and R.sub.2 are each hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, ar(C.sub.1 14 C.sub.3) alkoxy or halogen or, when taken together, they form C.sub.1 -C.sub.2 alkylenedioxy, Alk is C.sub.1 -C.sub.4 alkylene and A is a group of the formula: ##STR2## (wherein R.sub.3 and R.sub.4 are each C.sub.1 -C.sub.4 alkyl or, when taken together with the adjacent nitrogen atom, they represent a 5-6 membered nitrogen-containing heterocyclic ring which may contain any additional hetero atom and R.sub.5 is C.sub.1 -C.sub.4 alkyl or aryl), and non-toxic salts thereof, which possess various pharmaceutical activities.

3-(Piperazinoalkyl)-benz-2,1-isoxazoles

Ortho-acylated anilide derivatives represented by the formula: ##STR1## wherein R.sub.1, R.sub.2 and R.sub.3 are each C.sub.1 - .sub.3 alkyl, and n is 1 or 2, and salts thereof.

Ortho-acylated anilide derivatives and salts thereof

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 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].

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Toyonaka, Japan

Yoshiaki Takebayashi