Suntory Limited

Hidetsura Cho

Akira Mizuno

Takafumi Ishihara

Toshio Tatsuoka

Mikiko Hamaguchi

Ikuo Morita

Masaru Ueda

Seiitsu Murota

Mie Tamaoka

Kazuo Aisaka

Kunihiro Sumoto

Seiji Miyano

Fumio Satoh

Fumio Sato

Keiyu Shima

Mikiko Miya

Mariko Emon

Disclosed herein are pyrroloazepine derivatives having anti-.alpha..sub.1 activity and anti-serotonin activity represented by the following formula (I): ##STR1## wherein R means a hydrogen atom, a linear or branched C.sub.1-6 alkyl group or a C.sub.7-10 aralkyl group, A denotes a linear or branched C.sub.2-10 alkylene, alkenylene or alkynylene group, Z stands for O, NOR.sub.1 or NOCOR.sub.5 in which R.sub.1 and R.sub.5 is a hydrogen atom or an alkyl, aryl or aralkyl group, and Y means a particular piperidinyl or pyrrolidinyl group; and salts thereof. Their preparation processes are also disclosed.

Pyrroloazepine derivatives

Pyrroloazepine derivative

Disclosed herein are pyrroloazepine derivatives, which are useful as therapeutics for circulatory diseases, represented by the following formula (I): ##STR1## wherein R means a hydrogen atom, a linear or branched C.sub.1-6 alkyl group or a C.sub.7-10 aralkyl group, A denotes a linear or branched C.sub.2-10 alkylene, alkenylene or alkynylene group, Z stands for O, NOR.sub.1 or NOCOR.sub.5 in which R.sub.1 and R.sub.5 is a hydrogen atom or an alkyl, aryl or aralkyl group, and Y means a particular piperidinyl or pyrrolidinyl group; and salts thereof. Their preparation processes are also disclosed.

Described are caffeic acid derivatives represented by the following formula: ##STR1## wherein either one of R.sup.1 and R.sup.2 is a hydrogen atom, a C.sub.1 -C.sub.6 alkyl group, a group --CO.sub.2 R.sup.4, or a group --CONR.sup.5 R.sup.6, R.sup.4, R.sup.5 and R.sup.6 being either a hydrogen atom or a particular group, and the other is the group --CO.sub.2 R.sup.4 or the group --CONR.sup.5 R.sup.6, or R.sup.1 and R.sup.2 are coupled together to represent a 5-membered ring so formed, Y represents a particular group or atom, X represents a substituted or unsubstituted C.sub.6 -C.sub.10 aryl, C.sub.7 -C.sub.12 aralkyl, heterocyclic or heterocyclic ring-alkyl group, m and n stand for particular integers, and R.sup.3 represents a hydrogen atom, a hydroxyl group, a group --OCO.sub.2 R.sup.7, R.sup.7 being a hydrogen atom or a particular group, or a group --OCONR.sup.8 R.sup.9, R.sup.8 representing a C.sub.1 -C.sub.6 alkyl group and R.sup.9 representing a hydrogen atom or a C.sub.1 -C.sub.6 alkyl group, and pharmaceutically acceptable salts thereof. Therapeutic agents containing the derivatives or salts are effective for diseases of the circulatory system.

Caffeic acid derivatives and pharmaceutical compositions containing the

Described are caffeic acid derivatives represented by the following formula: ##STR1## wherein either one of R.sup.1 and R.sup.2 is a hydrogen atom, a C.sub.1 -C.sub.6 alkyl group, a group --CO.sub.2 R.sup.4, or a group --CONR.sup.5 R.sup.6, R.sup.4, R.sup.5 and R.sup.6 being either a hydrogen atom or a particular group, and the other is the group --CO.sub.2 R.sub.4 or the group --CONF.sup.5 R.sup.6, or R.sup.1 and R.sup.2 are coupled together to represent a 5-membered ring so formed, Y represents a particular group or atom, X represents a substituted or unsubstituted C.sub.6 -C.sub.10 aryl, C.sub.7 -C.sub.12 aralkyl, heterocyclic or heterocyclic ring-alkyl group, m and n stand for particular integers, and R.sub.3 represents a hydrogen atom, a hydroxyl group, a group --OCO.sub.2 R.sup.7, R.sup.7 being a hydrogen atom or a particular group, or a group --OCONR.sup.8 R.sup.9, R.sup.8 representing a C.sub.1 -C.sub.6 alkyl group and R.sup.9 representing a hydrogen atom or a C.sub.1 -C.sub.6 alkyl group, and pharmaceutically acceptable salts thereof. Therapeutic agents containing the derivatives or salts are effective for diseases of the circulatory system.

Novel derivatives of caffeic acid of the general formula (I): ##STR1## wherein X is hydrogen atom or hydroxy; R.sup.1 is hydrogen atom, a straight or branched alkyl or alkenyl having 1 to 20 carbon atoms or a group of the formula:

Derivative of caffeic acid and pharmaceutical composition containing the

N-substituted 3,4-dihydropyrimidine compounds of the formula: ##STR1## wherein R is straight, branched, cyclic or cyclo-straight alkyl having from one to four carbon atoms; and X.sup.1, X.sup.2 and X.sup.3 are the same or different and are hydrogen, halogen, lower alkyl having from one to four carbon atoms, lower alkoxy having from one to four carbon atoms, nitro, trifluoromethyl, hydroxy, or t-butyldimethylsilyloxy with the proviso that the case wherein X.sup.1, X.sup.2 and X.sup.3 are all hydrogen is not applicable have substantially strong and lasting vasodilative effects. Therefore, the compounds are useful as agents for treating disorders of the cardiovascular system, for example, antihypertensive agents, circulation improver and antianginal agents.

N-substituted 3,4-dihydropyrimidine compounds as agents for treating

1,4-Dihydropyridine derivatives of the formula (1): ##STR1## wherein X is a halogen; R.sup.1 is a straight, branched or cyclic alkyl group having 1 to 10 carbon atoms, the group --(CH.sub.2).sub.n -Y [where n is an integer of 0 to 8, provided that n is an integer of 2 to 8 when Y is not bonded to COO-- through carbon; Y is a cyclic alkyl group having 3-6 carbon atoms, an aryl group having 6-10 carbon atoms, a pyrrolidinyl group, an imidazolidinyl group, a thienyl group, a furyl group, an imidazolyl group, a pyridyl group, a pyrimidinyl group, a morpholinyl group, a thiomorpholinyl group or a pyrrolizidinyl group, the group ##STR2## (where D is an aryl or aralkyl group having 6-15 carbon atoms which may be substituted by a halogenated alkyl group), or a 3-piperidinyl group substituted by a phenylalkyl group of 7-10 carbon atoms which may be substituted by one or two halogens], the group --(CH.sub.2).sub.m --O--Z (where m is an integer of 1 to 8; and Z is an alkyl or aryl group), or the group ##STR3## (where l is an integer of 1-7; A is a hydrogen atom, an alkyl group or an aryl group; and R.sup.3 and R.sup.4 which may be the same or different represent an alkyl, aryl or aralkyl group); and R.sup.2 is a lower alkyl group, and pharmaceutically acceptable acid addition salts thereof are effective for treating disorders of the circulatory system and are useful as hypotensives, cerebral circulation improvers and antianginal agents. Processes for producing the above copounds economically and effectively are also disclosed.

Novel 1,4-dihydropyridine derivatives, process for preparing the same,

A N-substituted 3,4-dihydropyrimidine derivative of the formula (1): ##STR1## Wherein R.sup.1 is --(CH.sub.2).sub.n --X; X is substituted aminoethyl, substituted sulfideethyl, substituted or nonsubstituted heterocyclo-ethyl wherein the ethylene group is directly bonded to a hetero atom in the heterocyclic ring, or substituted or nonsubstituted heterocyclo-methyl wherein the methylene group is directly bonded to a carbon atom in the heterocyclic ring; n is an integer from 0 to 8; R.sup.2 is straight, branched cyclic or cyclo-straight alkyl having from one to thirteen carbon atoms, or aralkyl having from seven to thirteen carbon atoms and pharmacologically acceptable acid additional salts thereof have substantially strong and long lasting effects. Therefore the compounds are useful as agents for treating disorders of the cardiovascular system, and are useful, for example, as antihypertensive agents, circulation improvers and antianginal agents. A process for producing the above compounds economically and effectively is also disclosed.

N-substituted 3,4-dihydropyrimidine derivatives as agents for treating

N-substituted 3,4-dihydropyrimidine derivatives of the formula: ##STR1## wherein X.sup.1, X.sup.2 and X.sup.3 are the same or different and are hydrogen, nitro, halogen, cyano, trifluoromethyl, methylthio or lower alkoxy;

2,6-Dimethyl-3N,5-disubstituted-4-(substituted

A 3N-substituted 3,4-dihydropyrimidine derivative of the formula: ##STR1## wherein R.sup.1 is methyl or ethyl, R.sup.2 is methyl or ethyl, R is phenyl or substituted phenyl, X is chloro or methyl and pharmaceutically acceptable acid addition salts thereof have substantially the same strong vasodilative and Ca.sup.++ antagonistic effects as nicardipine and therefore are useful as agents for treating disorders of the cardiovascular system, for example, hypotensive agents, agents for amelioration of brain circulation and anti-angina pectoris agents. Processes for producing the above compounds economically and effectively are also disclosed.

3N-substituted 3,4-dihydropyrimidines as agents for treating disorders

A novel 1-substituted pyrrolizidine derivative having the formula: ##STR1## (wherein R.sup.1 is hydrogen or a lower alkyl group; R.sup.2 is hydrogen, a lower alkyl or lower alkoxy group, or a halogen; R.sup.3 is hydrogen, a lower alkyl, lower alkoxy or amino group, or a halogen), which can be produced by reacting 1-chlorocarbonyl (or alkoxycarbonyl)pyrrolizidine with a corresponding substituted aniline (or an alkali metal salt thereof). The pyrrolizidine derivative has antiarrhythmic activity.

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Ibaraki, Japan

Hidetsura Cho