Yamanouchi Pharmaceutical Company Ltd.

Noriki Ito

Yasuo Isomura

Kazuo Kubo

Isao Souzu

Hiroshige Homma

Yuichi Iizumi

Masuo Murakami

Tomoyuki Yasunaga

Tomio Araki

Takashi Fujikura

Toichi Takenaka

Yuzo Matsumoto

Masaharu Asano

Akihiro Tanaka

Koyo Matsuda

Yoshinobu Nagano

Shunichi Watanabe

Koichiro Takahashi

Yoso Numasaki

Kiyoshi Iwaoka

Hiroshi Ogawara

Isao Yanagisawa

Yasufumi Hirata

Masaaki Takeda

Yoshio Ishii

Shinichi Tsukamoto

Pharmaceutical composition of certain dihydropyridine compounds and salts thereof are provided which exhibit both Ca.sup.2+ -antagonistic and adrenergic beta-receptor blocking activities and therefore are useful for the treatment of ischemic heart diseases and hypertension. The pharmaceutical compositions contains either 4-(2-hydroxy-3-phenoxy-propylamino)-butyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate or 6-(2-hydroxy-3-phenoxypropylamino) hexyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate or their pharmaceutically acceptable salts.

Dihydropyridine composition

Urea derivatives of the general formula (I) ##STR1## and salts thereof, pharmaceutical compositions containing the same, and methods for producing the same are-disclosed. The urea derivatives of the general formula (I) and salts thereof are novel compounds having the acyl-CoA cholesterol acyltransferase (ACAT) inhibiting activity.

Urea derivatives and salts thereof

Diurea derivatives are provided which can be represented by the following general formula and salts thereof: ##STR1## wherein, R.sup.1 and R.sup.2 are the same or different, and each represents C.sup.1 -10 alkyl group, a C.sup.3 -18 cycloalkyl group, or a lower alkyl group substituted by cycloalkyl radical(s);

Diurea derivatives useful as medicaments and processes for the

Urea derivatives of the general formula (I) ##STR1## and salts thereof, pharmaceutical compositions containing the same, and methods for producing the same are disclosed. The urea derivatives of the general formula (I) and salts thereof are novel compounds having the acyl-CoA cholesterol acyltransferase (ACAT) inhibiting activity.

Urea derivatives and salts thereof in method for inhibiting the ACAT

Diurea derivatives are provided which can be represented by the following general formula and salts thereof: ##STR1## Illustrative derivatives include 1,3-bis[[1-cycloheptyl-3-(3-pyridyl)ureido]-methyl]benzene, 1,3-bis[[1-cycloheptyl-3-(2-pyridyl)ureido]-methyl]benzene, and 1,3-bis[[1-cycloheptyl-3-(4-pyridyl)ureido]-methyl]benzene. The above compounds inhibit acyl-coenzyme A cholesterol acyltransferase (ACAT enzyme), and thereby control the accumulation of cholesterol ester to the smooth muscle of arterial wall in the blood vessel.

Diurea Derivatives represented by the following general formula and salts thereof: ##STR1## The above compounds inhibit acyl-coenzyme A chloresterol acyl-transferase (ACAT enzyme), and thereby control the accumulation of cholesterol ester to the smooth muscle of arterial wall in the blood vessel.

Dihydropyridine compounds and salts thereof are provided which exhibit both Ca.sup.2+ -antagonistic and adrenergic beta-receptor blocking activities and therefore are useful for the treatment of ischemic heart diseases and hypertension. The compounds have the formula ##STR1## wherein A represents a straight or branched carbon chain alkylene group having 1 to 10 carbon atoms which may be interrupted by an oxygen atom(s); R.sup.1 and R.sup.4, which may be the same or different, each represents a lower alkyl group; R.sup.2 represents an amino group, ##STR2## R.sup.3 represents a straight or branched carbon chain alkyl group having 1 to 10 carbon atoms which may be interrupted by an oxygen atom(s), or ##STR3## R.sup.5 and R.sup.6, which may be the same or different, each represents a hydrogen atom, a nitro group, a halogen atom, a trifluoromethyl group, a cyano group, a lower alkyl group, a lower alkoxy group or a lower alkenyloxy group; R.sup.7 represents a hydrogen atom, a cyano group, a halogen atom, a lower alkoxy group or a lower alkanoyl group; R.sup.8 and R.sup.9, which may be the same or different, each represents a lower alkyl group or an aralkyl group; and n represents an integer of 1 to 2: these symbols, hereafter, have the same significances.

Dihydropyridine compounds which process both calcium (2+)-antagonistic

Diurea derivatives are provided which are represented by the following general formula and salts thereof: ##STR1## The above compounds inhibit acyl-coenzyme A cholesterol acyl-transferase (ACAT enzyme), and thereby control the accumulation of cholesterol ester on the smooth muscle of arterial wall in the blood vessels.

Novel phenoxy derivatives are provided such as 6-[p-5-(1-imidazolyl)pentyloxy]phenoxy]-2,2-dimethyl-hexanoic acid, pharmaceutical compositions containing the derivative and their use in treating tumors.

6-[p-[5-(1-imidazolyl)pentyloxy]phenoxy]-2,2-dimethyl-hexanoic acid

Novel isoflavone derivatives are provided which have the formula ##STR1## and which exhibit cancerocidal and immunosuppressive activity. The invention also provides pharmaceutical compositions containing the derivatives, methods of use and processes for their preparation.

Isoflavone derivatives, salts thereof, and oncostatic and

Novel phenoxy derivatives are provided which can be represented by the general formula: ##STR1## wherein the various substituents are as defined, and include compounds such as benzyl 6-[p-[5-(1-imidazolyl)pentyloxy]phenoxy]-2,2-dimethylhexanoate. The invention also encompasses pharmaceutical compositions containing the derivatives and their use in treating tumors.

Phenoxy imidazole compound

Isoflavone derivatives, and salts thereof, and cancerocidal and

A dihydropyridine compound of the following general formula (I) or a salt thereof: ##STR1## wherein R.sup.1 and R.sup.2, which are the same or different, each represents a C.sub.1 to C.sub.10 alkyl group, a lower alkyl group which is interrupted by oxygen atom(s), or a lower alkyl group substituted by C.sub.3 to C.sub.6 alicyclic group(s); R.sup.3 and R.sup.4, which are the same or different, each represents a lower alkyl group; R.sup.5 and R.sup.6, which are the same or different, each represents a hydrogen atom, a nitro group, a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkylsulfonyl group, or a lower alkylsulfinyl group; R.sup.7 and R.sup.8, which are the same or different, each represents a hydrogen atom, a halogen atom, a cyano group, a lower alkoxy group, or a lower alkanoylamino group, or R.sup.7 may combine with R.sup.8 to form a naphthyl group together with the adjacent phenyl group; A represents a single bond, a vinylene group (--CH.dbd.CH--), or a ethynylene group (--C.dbd.C--); B represents a single bond or --CH.sub. 2 O--; and m and n, which are the same or different, each represents 0 or an integer of 1 to 5. The compounds are useful for the treatment of various cardiovascular disorders, since they possess both Ca.sup.2+ -antagonistic and adrenergic beta-receptor blocking activities.

Dihydropyridine compounds and pharmaceutical compositions containing them

Nitrogen containing heterocyclic compounds shown by the formula ##STR1## wherein Y represents an oxygen atom, a sulfur atom, or a group shown by ##STR2## (wherein m is 1 or 2); n represents 0 or 1; R.sub.1 and R.sub.4, which may be the same or different, each represents a hydrogen atom, a lower alkyl group, or a lower alkenyl group; R.sub.2 and R.sub.3, which may be the same or different, each represents a hydrogen atom, a hydroxyl groups, a lower alkanoyloxy group, a lower alkyl group or a lower alkenyl group; said R.sub.2 and R.sub.3 may further form together a double bond; R.sub.5 and R.sub.6, which may be the same or different, each represents by hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, an amino group, a lower alkoxy group, a mono or di lower alkylamino group, or a lower alkyl group; said R.sub.5 and R.sub.6 may further form together a lower alkylenedioxy group; and R.sub.7 represents a hydrogen atom, a halogen atom, a lower alkanoyl group, a phenyl group, a phenyl lower alkyl group, a lower alkyl group, a hydroxy lower alkyl group, a di lower alkylamino lower alkyl group, a pyrrolidino lower alkyl group, a piperidino lower alkyl group, a morpholino lower alkyl group, or a 4-lower alkylpiperazino lower alkyl group;

Thiazolo[3,2-6]isoquinolines, compositions and use thereof

Novel nitrogen-containing heterocyclic compounds shown by the formula ##STR1## wherein Y represents an oxygen atom, a sulfur atom, or a group shown by ##STR2## (wherein m is 1 or 2); n represents 0 or 1; R.sub.1 and R.sub.4, which may be the same or different, each represents a hydrogen atom, a lower alkyl group, or a lower alkenyl group; R.sub.2 and R.sub.3, which may be the same or different, each represents a hydrogen atom, a hydroxyl group, a lower alkanoyloxy group, a lower alkyl group or a lower alkenyl group; said R.sub.2 and R.sub.3 may further form together a double bond; R.sub.5 and R.sub.6, which may be the same or different, each represents a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, an amino group, a lower alkoxy group, a mono or di lower alkylamino group, or a lower alkyl group; said R.sub.5 and R.sub.6 may further form together a lower alkylenedioxy group; and R.sub.7 represents a hydrogen atom, a halogen atom, a lower alkanoyl group, a phenyl group, a phenyl lower alkyl group, a lower alkyl group, a hydroxy lower alkyl group, a di lower alkylamino lower alkyl group, a pyrrolidino lower alkyl group, a piperidino lower alkyl group, a morpholino lower alkyl group, or a 4-lower alkylpiperazino lower alkyl group;

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Saitama, Japan

Noriki Ito