Sankyo Company, Limited

Koichi Fujimoto

Hiroaki Yanagisawa

Takashi Fujita

Takao Yoshioka

Hiroyoshi Horikoshi

Toshihiko Fujiwara

Kunio Wada

Minoru Oguchi

Hiroyuki Koike

Hideo Nakao

Fumitoshi Asai

Naoki Tanaka

Sadao Ishihara

Shinichi Sugawara

Isamu Igarashi

Yasuo Shimoji

Takuro Kanazaki

Yoshio Tsujita

Hiroshi Nishino

Teiichiro Koga

Toshio Sada

Eiji Nakayama

Junya Ide

Yoshiya Amemiya

Taketoshi Ogawa

Ikuko Shimada

Tomiyoshi Ito

Tatsuo Tanimoto

Hayao Matsuhashi

A compound of a formula (1) and pharmacologically acceptable salts thereof:wherein Rrepresents hydrogen, halogen, alkyl or hydroxyl; Rrepresents hydrogen or halogen; Rrepresents hydrogen, alkyl, hydroxyl, carboxyalkyl, alkoxycarbonylalkyl, alkylsulfonyl, alkoxycarbonylalkylsulfonyl, craboxyalkylsulfonyl or carboxyalkylcarbonyl; each of Rand Rrepresents hydrogen, halogen, alkyl, carbamoyl, alkoxy, carboxyl, alkoxycarbonyl, monoalkylcarbamoyl or dialkylcarbamoyl; Rrepresents a heterocycle, hydrogen, alkyl, cycloalkyl, aralkyl, carboxyalkyl, alkoxycarbonyalkyl, aliphatic or aromatic acyl, carbamoyl, alkylsulfonyl, aryl, formimidoyl, 1-iminoalkyl, N-alkylforminidoyl or iminoarylmethyl; each of Rand Rrepresents hydrogen or alkyl; n represents 0, 1 or 2. The compound exhibits excellent activated blood coagulation factor X inhibitory activity and prevents or treats blood coagulation-related diseases.

Benzamidine derivatives

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

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: R.sup.1 represents a saturated heterocyclic group attached to the bond or group represented by A through a ring carbon atom; R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3a, R.sup.3b, R.sup.3c and R.sup.3d are hydrogen or various other groups or atoms; and A represents a single bond or an alkylene group having from 1 to 6 carbon atoms are serotonin 2 receptor antagonists and have the ability to inhibit the activity of squalene synthase. They can not only prevent and inhibit the development and progression of arteriosclerosis but can also inhibit thrombosis in arteriosclerotic lesions and can improve hemodynamics.

Diphenylethane compounds containing a saturated heterocyclic group,

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

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: 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.

Compounds of the following formula (I) or the formula (I).sub.p : ##STR1## wherein R.sup.1 is alkyl or alkenyl; R.sup.2 and R.sup.3 are hydrogen, alkyl, alkenyl, cycloalkyl, aralkyl, aryl, or aryl fused to cycloalkyl; R.sup.4 is hydrogen, alkyl, alkanoyl, alkenoyl, arylcarbonyl, alkoxycarbonyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothienyl, tetrahydrofuryl, a group of formula --SiR.sup.a R.sup.b R.sup.c, in which R.sup.a, R.sup.b and R.sup.c are alkyl or aryl, alkoxymethyl, (alkoxyalkoxy)methyl, haloalkoxymethyl, aralkyl, aryl or alkanoyloxymethoxycarbonyl; R.sup.5 is carboxy or --CONR.sup.8 R.sup.9, wherein R.sup.8 and R.sup.9 hydrogens or alkyl, or R.sup.8 and R.sup.9 together form alkylene; R.sup.6 is hydrogen, alkyl, alkoxy or halogen; R.sup.7 is carboxy or tetrazol-5-yl; R.sub.p.sup.1 is hydrogen, alkyl, cycloalkyl or alkanoyl; R.sub.p.sup.2 is a single bond, alkylene or alkylidene; R.sub.p.sup.3 and R.sub.p.sup.4 are each hydrogen or alkyl; R.sub.p.sup.6 is carboxy or tetrazol-5-yl; and X.sub.p is oxygen or sulfur; and pharmaceutically acceptable salts and esters thereof. The compounds are AII receptor antagonists and thus have hypotensive activity and can be used for the treatment and prophylaxis of hypertension. The compounds may be prepared by reacting a biphenylmethyl compound with an imidazole compound.

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Tokyo, Japan

Koichi Fujimoto