Sankyo Company, Limited

Hiroyoshi Horikoshi

Takao Yoshioka

Toshihiko Fujiwara

Takashi Fujita

Kunio Wada

Hiroaki Yanagisawa

Koichi Fujimoto

Minoru Oguchi

Koichi Kojima

Hitoshi Kurata

Takakazu Hamada

Tsutomu Kanai

Koki Ishibashi

Yuichi Aizawa

Yoshio Tsujita

Shinji Yoshioka

Takashi Ito

Hiroyuki Koike

Kazuo Hasegawa

Takahide Nishi

Takeshi Kinoshita

Hiroshi Nishino

Masaaki Miyamoto

Shinichi Kurakata

Masaharu Fukami

Yoshihiko Baba

Tsunemichi Hosokawa

Kanichi Nakamura

Masashi Shiomi

Junichiro Fukushige

Koichi Iwasaki

Kunihiro Sasahara

Insulin sensitivity enhancers, such as troglitazone, have the ability to treat and/or prevent hyperuricemia and may thus be used for the therapy or prophylaxis of such diseases as gout, urinary calculus, hyperuricemic nephropathy and Lesch-Nyhan syndrome.

Method for the treatment and prevention of hyperuricemia

A combination of one or more HMG-CoA reductase inhibitors (for example pravastatin, lovastatin, simvastatin, fluvastatin, rivastatin or atorvastatin) with one or more insulin sensitizers (for example troglitazone, pioglitazone, englitazone, BRL-49653, 5-(4-{2-[1-(4-2'-pyridylphenyl)ethylideneaminooxy]ethoxy}benzyl)thiazolidi ne-2,4-dione, 5-{4-(5-methoxy-3-methylimidazo[5,4-b]pyridin-2-ylmethoxy)benzyl}thiazolid ine-2,4-dione or its hydrochloride, 5-[4-(6-methoxy-1-methylbenzimidazol-2-ylmethoxy)benzyl]thiazolidine-2,4-d ione, 5-[4-(1-methylbenzimidazol-2-ylmethoxy)benzyl]thiazolidine-2,4-dione and 5-[4-(5-hydroxy-1,4,6,7-tetramethylbenzimidazol-2-ylmethoxy)benzyl]thiazol idine-2,4-dione) exhibits a synergistic effect and is significantly better at preventing and/or treating arteriosclerosis and/or xanthoma than is either of the components of the combination alone.

Treatment of arteriosclerosis and xanthoma

A method for preventing or treating autoimmune diseases (excluding type I diabetes) by administering an insulin resistance improving substance as an active ingredient.

Method for preventing and for treating autoimmune disease

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: 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## where R.sup.1, R.sup.2, R.sup.4 and R.sup.5 are hydrogen or alkyl and R.sup.3 is hydrogen, alkyl or various organic groups are effective against osteoporosis at doses at which they also effectively control diabetes.

Treatment and prophylaxis of osteoporosis

A combination of one or more HMG-CoA reductase inhibitors (for example pravastatin, lovastatin, simvastatin, fluvastatin, rivastatin or atorvastatin) with one or more insulin sensitizers (for example troglitazone, pioglitazone, englitazone, BRL-49653, 5-(4-{2-�1-(4-2'-pyridylphenyl)ethylideneaminooxy!-ethoxy}benzyl)thiazolid ine-2,4-dione, 5-{4-(5-methoxy-3-methylimidazo�5,4-b!pyridin-2-yl-methoxy)benzyl}thiazoli dine-2,4-dione or its hydrochloride, 5-�4-(6-methoxy-l-methylbenzimidazol-2-ylmethoxy)benzyl!thiazolidine-2,4-d ione, 5-�4-(l-methylbenzimidazol-2-ylmethoxy)benzyl!-thiazolidine-2,4-dione and 5-�4-(5-hydroxy-1,4,6,7-tetramethylbenzimidazol-2-ylmethoxy) benzyllthiazolidine-2,4-dione) exhibits a synergistic effect and is significantly better at preventing and/or treating arteriosclerosis and/or xanthoma than is either of the components of the combination alone.

Compounds of formula (I): ##STR1## �wherein: R.sup.1 is hydrogen, alkyl, aryl-substituted alkyl or aromatic heterocyclic-substituted alkyl; R.sup.2 is: aryl-substituted alkyl, aromatic heterocyclic-substituted alkyl or diarylamino; and R.sup.3 is carboxy or a group of formula --CONHSO.sub.2 R.sup.4 wherein R.sup.4 is alkyl!; and pharmaceutically acceptable salts and esters thereof have valuable 5.alpha.-reductase inhibitory activity and can thus be used for the treatment and prophylaxis of, inter alia, prostatic hypertrophy as well as other disorders arising from excess levels of 5.alpha.-dihydrotestosterone.

Steroid derivatives for the treatment of prostatic hypertrophy, their

Insulin sensitizers, especially thiazolidinedione compounds, such as troglitazone, are useful for the treatment and prevention of pancreatitis.

Treatment and prophylaxis of pancreatitis

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.

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Tokyo, Japan

Hiroyoshi Horikoshi