Sankyo Company, Limited

Ciba-Geigy Corporation

Takao Yoshioka

Tomoyuki Kurumada

Syoji Morimura

Takashi Fujita

Hiroyoshi Horikoshi

Toshihiko Fujiwara

Keisuke Murayama

Kunio Wada

Hiroaki Yanagisawa

Koichi Fujimoto

Minoru Oguchi

Nobuo Soma

Eiko Mori

Toshimasa Toda

Hideo Horiuchi

Susumu Higashida

Katsuaki Matsui

Noriyuki Ohta

Shinji Yoshioka

Hisayou Ohsawa

Hiroyuki Koike

Mitsuo Yamazaki

Tsutomu Kanai

Hisayou Osawa

Yuichi Aizawa

Sadao Ishihara

Kazuo Hasegawa

Hiroshi Mizuno

Eiichi Kitazawa

Fujio Saito

Shigeki Miyake

Horoyoshi Horikoshi

Yoshio Iizuka

Noriyuki Ohata

Takahide Nishi

Takeshi Kinoshita

Hiroshi Nishino

Toyonori Takebayashi

Kanichi Nakamura

Keisuku Murayama

Kunihiro Sasahara

Syoji Moriyama

Syoji Moromura

Yomoyuki Kurumada

Eiici Kitazawa

Kazou Hasegawa

Takayuki Onodera

Compound of formula (I): ##STR1## [wherein: X represents an unsubstituted or substituted indolyl, indolinyl, azaindolyl, azaindolinyl, imidazopyridyl or imidazopyrimidinyl group; Y represents an oxygen or sulphur atom; Z represents a 2,4-dioxothiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxooxazolidin-5-ylmethyl, 3,5-dioxooxadiazolidin-2-ylmethyl or N-hydroxyureidomethyl group; R represents a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, a hydroxy group, a nitro group, an aralkyl group or a unsubstituted or substituted amino group; and m is an integer of from 1 to 5] have hypoglycemic and anti-diabetic activities.

Heterocyclic compounds having anti-diabetic activity and their use

A compound of the formula ##STR1## wherein R.sup.7 is a hydrogen atom or an acetyl group, and process for preparing said compounds.

5-(4-hydroxy-OR 4-acetoxy-benzyl)-3-

Compounds of formula (I): ##STR1## [wherein: X represents an unsubstituted or substituted indolyl, indolinyl, azaindolyl, azaindolinyl, imidazopyridyl or imidazopyrinidinyl group; Y represents an oxygen or sulfur atom; Z represents a 2,4-dioxo-thiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxooxazolidin-5-ylmethyl, 3,5-dioxo-oxadiazolidin-2-ylmethyl or N-hydroxyureidom ethyl group; R represents a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, a hydroxy group, a nitro group, an aralkyl group or a unsubstituted or substituted amino group; and m is an inzeger of from 1 to 5] have hypoglycemic and anti-diabetic activities.

Heterocyclic compound having anti-diabetic activity

Compounds of formula (I): ##STR1## wherein: R.sup.1 is hydrogen or alkyl; R.sup.2 is alkylene; R.sup.3 is hydrogen, alkyl, alkoxy, alkylthio, halogen, nitro group, amino group, monoalkylamino, dialkylamino, aryl, or aralkyl; X is aryl, or aromatic heterocyclic; Y is oxygen, sulfur or a group of formula &gt;N--R.sup.4, in which R.sup.4 is hydrogen, alkyl or acyl; and Z is a group of formula (Za), (Zb), (Zc) or (Zd): ##STR2## and salts thereof can be used to treat or prevent are included those arising from hyperlipidemia, hyperglycemia, obesity, impaired glucose tolerance (IGT), insulin resistant non-IGT (NGT), non-diagnostic glucose tolerance, insulin resistance, diabetic complications, fatty liver, polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM); in addition the compounds of the present invention have aldose reductase inhibitory activity.

Oxime derivatives, their preparation and their therapeutic use

Compounds of formula (I): ##STR1## �wherein: X represents an unsubstituted or substituted indolyl, indolinyl, azaindolyl, azaindolinyl, imidazopyridyl or imidazopyrimidinyl group; Y represents an oxygen or sulfur atom; Z represents a 2,4-dioxo-thiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxooxazolidin-5-ylmethyl, 3,5-dioxo-oxadiazolidin-2-ylmethyl or N-hydroxyureidomethyl group; R represents a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, a hydroxy group, a nitro group, an aralkyl group or a unsubstituted or substituted amino group; and m is an integer of from 1 to 5! have hypoglycemic and anti-diabetic activities.

Compounds of formula (I): ##STR1## �wherein: X represents an optionally substituted benzimidazole group; Y represents an oxygen or sulfur atom; Z represents a 2,4-dioxothiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxooxazolidin-5-ylmethyl, 3,5-dioxooxadiazolidin-2-ylmethyl or N-hydroxyureidomethlyl group; R represents hydrogen, alkyl, alkoxy, halogen, hydroxy, nitro, amino or aralkyl; and m is an integer from 1 to 5!; have valuable activity for the treatment and/or prophylaxis of a variety of disorders, including one or more of: hyperlipemia, hyperglycemia, obesity, impaired glucose tolerance (IGT), insulin resistance and diabetic complications.

Benzimidazole derivatives, their preparation and their therapeutic use

Compounds of formula (I): ##STR1## wherein: X represents an unsubstituted or substituted indolyl, indolinyl, azaindolyl, azaindolinyl, imidazopyridyl or imidazopyrimidinyl group; Y represents an oxygen or sulfur atom; Z represents a 2,4-dioxo-thiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxooxazolidin-5-ylmethyl, 3,5-dioxo-oxadiazolidin-2-ylmethyl or N-hydroxyureidom ethyl group; R represents a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, a hydroxy group, a nitro group, an aralkyl group or a unsubstituted or substituted amino group; and m is an integer of from 1 to 5 have hypoglycemic and anti-diabetic activities.

Compounds of formula (I): ##STR1## �wherein: X represents an unsubstituted or substituted indolyl, indolinyl, azaindolyl, azaindolinyl, imidazopyridyl or imidazopyrimidinyl group; Y represents an oxygen or sulfur atom; Z represents a 2,4-dioxo-thiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxooxazolidin-5-ylmethyl, 3,5-dioxooxadiazolidin-2-ylmethyl or N-hydroxyureidomethyl group; R represents a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, a hydroxy group, a nitro group, an aralkyl group or a unsubstituted or substituted amino group; and m is an integer of from 1 to 5! have hypoglycemic and anti-diabetic activities. Disclosed also are intermediate compounds for the preparation of compounds of formula I.

Intermediate compounds in the preparation of heterocyclic compounds

An amino acid compound of the formula: R.sup.1 NH--CH(R.sup.2)--COHN--A--ONO.sub.2, wherein R.sup.1 represents a hydrogen atom, a C.sub.1 -C.sub.7 alkanoyl group, a C.sub.1 -C.sub.6 alkoxycarbonyl group, a C.sub.6 -C.sub.10 arylcarbonyl group, a C.sub.7 -C.sub.13 aralkylcarbonyl group, a C.sub.7 -C.sub.13 aralkyloxycarbonyl group or a 5- or 6-membered aromatic heterocyclic carbonyl group; R.sup.2 represents a substituted C.sub.1 -C.sub.6 alkyl group; and A represents a C.sub.2 -C.sub.5 alkylene group; and pharmacologically acceptable salts thereof. The amino acid compound has an excellent vasodilator action for collateral vessels and is useful for treating angina pectoris.

Amino acid derivatives

Compounds of formula (I): ##STR1## wherein: R.sup.1 is hydrogen or alkyl; R.sup.2 is alkylene; R.sup.3 is hydrogen, alkyl, alkoxy, alkylthio, halogen, nitro group, amino group, monoalkylamino, dialkylamino, aryl, or aralkyl; X is aryl, or aromatic heterocyclic; Y is oxygen, sulfur or a group of formula &gt;N-R.sup.4, in which R.sup.4 is hydrogen, alkyl or acyl; and Z is a group of formula (Za), (Zb), (Zc) or (Zd): ##STR2## and salts thereof can be used to treat or prevent are included those arising from hyperlipidemia, hyperglycemia, obesity, impaired glucose tolerance (IGT), insulin resistant non-IGT (NGT), non-diagnostic glucose tolerance, insulin resistance, diabetic complications, fatty liver, polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM); in addition the compounds of the present invention have aldose reductase inhibitory activity.

Compounds of formula (I): ##STR1## Z is a group of formula (iii), (iv),: ##STR2## and salts, esters and solvates thereof and pro-drugs therefor are useful for the treatment and/or prophylaxis of a variety of disorders, including one or more of: hyperlipemia, hyperglycemia, obesity, glucose tolerance insufficiency, insulin resistance and diabetic complications.

Thiazolidine and oxazolidine derivatives their preparation and their

Compounds of formula (I): ##STR1## (wherein: R.sup.0 is hydrogen, methyl or hydroxymethyl; R.sup.1 is substituted alkyl; R.sup.2 and R.sup.3 are each hydrogen, halogen, hydroxy, alkoxy, carboxy, alkoxycarbonyl, alkyl, nitro, haloalkyl, or substituted alkyl; X is oxygen or sulfur; and Ar optionally substituted phenyl or naphthyl); and pharmaceutically acceptable salts thereof have a variety of valuable pharmaceutical activities, including anti-diabetic and anti-obesity activities; in addition, they are capable of treating or preventing hyperlipemia and hyperglycemia and, by inhibiting the action of aldose reductase, they can also be effective in the treatment and prevention of complications of diabetes.

Aromatic amino-alcohol derivatives having anti-diabetic and anti-obesity

Compounds of formula (I): ##STR1## [wherein: X represents an unsubstituted or substituted indolyl, indolinyl, azaindolyl, azaindolinyl, imidazopyridyl or imidazopyrimidinyl group; Y represents an oxygen or sulfur atom; Z represents a 2,4-dioxothiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxooxazolidin-5-ylmethyl, 3,5-dioxooxadiazolidin-2-ylmethyl or N-hydroxyureidomethyl group; R represents a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, a hydroxy group, a nitro group, an aralkyl group or a unsubstituted or substituted amino group; and m is an integer of from 1 to 5] have hypoglycemic and anti-diabetic activities.

Thiazolidine derivatives of formula (I): ##STR1## (in which: R.sup.1, R.sup.2, R.sup.4, R.sup.5 are each hydrogen or alkyl; and R.sup.3 is hydrogen, aliphatic acyl, alkoxy-carbonyl, or arylcarbonyl and pharmaceutically acceptable salts thereof are anti-hypertensive agents and are useful in the treatment of obesity-related hypertension.

Thiazolidine derivatives having anti-hypertensive activity and their

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Tokyo, Japan

Takao Yoshioka