Shionogi Company Limited

Shionogi Seiyaku Kabushiki Kaisha

Teikoku Hormone Mfg. Co., Ltd.

Teruyuki Ishiba

Kentaro Hirai

Toshio Fujishita

Shigeru Matsutani

Hirohiko Sugimoto

Itsuo Makino

Kazuyuki Sasakura

Koichi Otani

Masami Doteuchi

Haruo Koike

Masamichi Watanabe

Kentato Hirai

Hiroshiko Sugimoto

Masami Doeteuchi

The compounds of the present invention inhibit the HMG-CoA reductase, and subsequently suppress the biosynthesis of cholesterol. And they are useful in the treatment of hypercholesterolemia, hyperlipoproteinemia, and atherosclerosis.

Pyrimidine derivatives

The compounds of the present invention inhibit HMG-CoA reductase, and subsequently suppress the synthesis of cholesterol. And they are useful in the treatment of hypercholesterolemia, hyperlipoproteinemia, and atherosclerosis. The compounds have the formula ##STR1## wherein R.sup.1, R.sup.2, and R.sup.3 each is independently hydrogen, optionally substituted lower alkyl, or optionally substituted aryl; R.sup.4 is lower alkyl, aralkyl, aryl, or heteroaryl, each of which is optionally substituted; X is vinylene or ethylene; Y is ##STR2## where R.sup.5 is hydrogen, lower alkyl, aryl, aralkyl, or a cation capable of forming a non-toxic pharmaceutically acceptable salt.

Pyrrole derivatives

An aminoalkylbenzene derivative of the formula: ##STR1## [wherein A is oxygen or sulfur;

Aminoalkylbenzene derivatives

Substituted aminoalkylbenzene type lower acylamides

4,1-Benzoxazepines of the following formula are novel central nervous system: ##STR1## wherein R is hydrogen or C.sub.1 to C.sub.5 alkyl;

Triazolo-4,1-benzoxazepines having CNS activity

4,1-Benzoxazepines of the following formula are central nervous system drugs: ##STR1## wherein R is hydrogen or C.sub.1 to C.sub.5 alkyl; X is hydrogen, halogen, or nitro; Y is phenyl, 2-halophenyl, 4-halophenyl, 2-trifluoromethylphenyl, or pyridyl; and ##STR2## is a group of the formula: ##STR3## (wherein Q is oxygen, sulfur, or hydrazono, with a proviso that, when Y is phenyl or 2-halophenyl and R is hydrogen, Q is neither oxygen nor sulfur;

4,1-Benzoxazepines and compositions

4,1-Benzoxazepines and thia analogs thereof of the formula: ##STR1## (wherein --A--B-- is the following group: ##STR2## (wherein R.sup.1 is hydrogen, C.sub.1 to C.sub.3 alkyl, or C.sub.7 to C.sub.9 aralkyl;

4,1-Benzoxazepines and thia analogs thereof

A compound of the formula: ##STR1## [wherein R is dimethylamino or 1-pyrrolidinyl;

Thioethylamide derivatives

Pyridinecarbonamido-oxy or thio

4,1-Benzoxazepines

A compound of the formula: ##STR1## wherein R is hydrogen, 2-5C alkoxycarbonyl, 1-7C acyl, 1-4C alkylthio, 7-10C phenylalkylthio, phenylthio, halo-phenylthio, disubstituted aminothio, ##STR2## R.sup.1 is hydrogen or halogen; R.sup.2 is halogen or nitro; and its pharmaceutically acceptable acid addition salts. The compounds and salts thereof are useful as psychotropic agents and as anxiolytics, anticonvulsants and hypnotics.

1-Substituted thiomethyltriazolobenzodiazepines and production thereof

Dipeptide derivatives represented by the formula: ##STR1## wherein R represents hydrogen, C.sub.1 -C.sub.6 alkyl group, C.sub.2 -C.sub.7 alkenyl group, C.sub.2 -C.sub.7 cyanoalkyl group, C.sub.2 -C.sub.7 carbamoylalkyl group, C.sub.3 -C.sub.10 dialkylaminoalkyl group or cyclopropylmethyl group, R.sup.1 represents hydrogen, C.sub.1 -C.sub.6 alkyl group, C.sub.7 -C.sub.14 aralkyl group, C.sub.7 -C.sub.14 hydroxyaralkyl group, C.sub.6 -C.sub.12 aryl group, C.sub.2 -C.sub.7 carbamoylalkyl group, C.sub.2 -C.sub.7 carboxyalkyl group, C.sub.1 -C.sub.6 aminoalkyl group, C.sub.4 -C.sub.10 guanidylalkyl group, C.sub.1 -C.sub.6 mercaptoalkyl group, C.sub.2 -C.sub.7 alkylthioalkyl group, C.sub.9 -C.sub.15 indolylalkyl group or C.sub.4 -C.sub.9 imidazolylalkyl group, R.sup.2 represents hydrogen, C.sub.1 -C.sub.6 alkyl group, C.sub.7 -C.sub.14 aralkyl group, C.sub.6 -C.sub.12 aryl group, glycyl group or glycyl-glycyl group, R.sup.3 represents hydrogen, C.sub.1 -C.sub.6 alkyl group or amino-protecting group, R.sup.1 and R.sup.2 optionally combine to from C.sub.2 -C.sub.4 alkylene group, group ##STR2## optionally represents phthalimido group, piperidino group, 4-hydroxy-4-(p-halogenophenyl)piperidino, morpholino, or piperazino group substituted by C.sub.1 -C.sub.6 alkyl group or phenyl group, A ring represents benzene ring or pyridine ring optionally substituted by halogen and B ring represents benzene ring or thiophene ring optionally substituted by halogen, trifluoromethyl group, methylsulfonyl group, nitro group or C.sub.1 -C.sub.6 alkyl group and their acid addition salts, being useful as anxiolytics, sedatives, anticonvulsants, hypnotics, muscle relaxants, or their synthetic intermediates, are prepared.

Dipeptide derivatives and their production

1-Substituted thiomethyltriazolobenzodiazepines

Dipeptide derivatives represented by the formula: ##STR1## wherein R represents hydrogen, C.sub.1 -C.sub.6 alkyl group, C.sub.2 -C.sub.7 alkenyl group, C.sub.2 -C.sub.7 cyanoalkyl group, C.sub.2 -C.sub.7 carbamoylalkyl group, C.sub.3 -C.sub.10 dialkylaminoalkyl group or cyclopropylmethyl group, R.sup.1 represents hydrogen, C.sub.1 -C.sub.6 alkyl group, C.sub.7 -C.sub.14 aralkyl group, C.sub.7 -C.sub.14 hydroxyaralkyl group, C.sub.6 -C.sub.12 aryl group, C.sub.2 -C.sub.7 carbamoylalkyl group, C.sub.2 -C.sub.7 carboxyalkyl group, C.sub.1 -C.sub.6 aminoalkyl group, C.sub.4 -C.sub.10 guanidylalkyl group, C.sub.1 -C.sub.6 mercaptoalkyl group, C.sub.2 -C.sub.7 alkylthioalkyl group, C.sub.9 -C.sub.15 indolylalkyl group or C.sub.4 -C.sub.9 imidazolylalkyl group, R.sup.2 represents hydrogen, C.sub.1 -C.sub.6 alkyl group, C.sub.7 -C.sub.14 aralkyl group, C.sub.6 -C.sub.12 aryl group, glycyl group or glycyl-glycyl group, R.sup.3 represents hydrogen, C.sub.1 -C.sub.6 alkyl group or amino-protecting group, R.sup.1 and R.sup.2 optionally combine to form C.sub.2 -C.sub. 4 alkylene group, group ##STR2## optionally represents phthalimido group, piperidino group, 4-hydroxy-4-(p-halogenophenyl)piperidino, morpholino, or piperazino group each substituted by C.sub.1 -C.sub.6 alkyl group or phenyl group, A ring represents benzene ring or pyridine ring optionally substituted by halogen and B ring represents benzene ring or thiophene ring optionally substituted by halogen, trifluoromethyl group, methylsulfonyl group, nitro group or C.sub.1 -C.sub.6 alkyl group and their acid addition salts, being useful as anxiolytics, sedatives, anticonvulsants, hypnotics, muscle relaxants, or their synthetic intermediates, are prepared.

Growing community of inventors

Takatsuki, Japan

Teruyuki Ishiba