Astellas Pharma Gmbh

Kotobuki Pharmaceutical Co Ltd

Yamanouchi Pharmaceutical Company Ltd.

Kotobuki Pharmaceuticals Co., Ltd.

Ryota Shiraki

Masakazu Imamura

Takeshi Murakami

Yoshinori Kobayashi

Atsushi Noda

Norio Seki

Hiroyuki Koshio

Hiroshi Tomiyama

Fukushi Hirayama

Yuzo Matsumoto

Yuji Koga

Keizo Sugasawa

Tsukasa Ishihara

Souichirou Kawazoe

Takashi Sugane

Kazuhiro Ikegai

Shunichiro Hachiya

Takeshi Shigenaga

Fumiyoshi Iwasaki

Eiji Kurosaki

Kayoko Kitta

Hiroyuki Moritomo

Keita Nakanishi

Takahiko Tobe

Shimpei Kawakami

Makoto Ohmiya

Makoto Takeuchi

Seiji Yoshimura

Noriyuki Kawano

Kenichi Onda

Takehiko Ohkawa

Tomofumi Takuwa

Masahiro Iwata

Daisuke Sasuga

Hiroki Fukudome

Tomoaki Kawano

Makoto Kasai

Miki Kobayashi

Yutaka Inoki

Mitsuru Hosaka

Hirofumi Ishii

Masamichi Yuda

Atsushi Nakamura

Kousuke Komenoi

A compound which is useful as a dopamine D1 receptor positive allosteric modulator (D1 PAM) is provided. The present inventors have studied a compound which has a dopamine D1 receptor positive allosteric modulating activity and is useful as an active ingredient of a pharmaceutical composition for preventing and/or treating cognitive impairment, negative symptoms of schizophrenia, Parkinson's disease, Alzheimer's disease, Huntington's disease, drug addictions, or the like, and they have thus found that a heterocyclic acetamide compound has a dopamine D1 receptor positive allosteric modulating activity, thereby completing the present invention. The heterocyclic acetamide compound of the present invention has a dopamine D1 receptor positive allosteric modulating activity and can be used as an agent for preventing and/or treating cognitive impairment, negative symptoms of schizophrenia, Parkinson's disease, Alzheimer's disease, Huntington's disease, drug addictions, or the like.

Heterocyclic acetamide compound

[Problem] A compound which is useful as a dopamine D1 receptor positive allosteric modulator (D1 PAM) is provided. [Means for Solution] The present inventors have studied a compound which has a dopamine D1 receptor positive allosteric modulating activity and is useful as an active ingredient of a pharmaceutical composition for preventing and/or treating cognitive impairment, negative symptoms of schizophrenia, Parkinson's disease, Alzheimer's disease, Huntington's disease, drug addictions, or the like, and they have thus found that a heterocyclic acetamide compound has a dopamine D1 receptor positive allosteric modulating activity, thereby completing the present invention. The heterocyclic acetamide compound of the present invention has a dopamine D1 receptor positive allosteric modulating activity and can be used as an agent for preventing and/or treating cognitive impairment, negative symptoms of schizophrenia, Parkinson's disease, Alzheimer's disease, Huntington's disease, drug addictions, or the like.

To provide a compound which has an anticoagulation action based upon inhibition of activated blood coagulation factor X and is useful as an anticoagulant or an agent for prevention and treatment of diseases caused by thrombus or embolus. A diazepan derivative such as 4-[(3-carbamimidoylphenylamino)methyl]-3-[4-(4-methyl-1,4-diazepan-1-yl)benzoylamino]benzoic acid and 3-hydroxy-4'-methoxy-2-{[4-(4-methyl-1,4-diazepan-1-yl)benzoyl]amino}benzanilide or a salt thereof is an effective ingredient.

Diazepan derivatives or salts thereof

The present invention provides a method for producing a C-glycoside derivative, which can produce the C-glycoside derivative at a high yield and at a low cost, which conforms to environmental protection, and which is applicable industrially. The C-glycoside derivative is useful for treating and preventing diabetes such as insulin-dependent diabetes (type 1 diabetes), non-insulin-dependent diabetes (type 2 diabetes) and the like and various diabetes-related diseases including insulin-resistant diseases and obesity.

Method for producing C-glycoside derivative and intermediate for synthesis thereof

A cocrystal of (1S)-1,5-anhydro-1-[3-(1-benzothien-2-ylmethyl)-4-fluorophenyl]-D-glucitol and L-proline. It is a cocrystal of known compound A, which has a constant quality, is superior in storage stability, has no moisture absorptivity, and is suitable as a crystal of a drug substance used for preparing pharmaceuticals.

Cocrystal of C-glycoside derivative and L-proline

The present invention provides C-glycoside derivatives and salts thereof, wherein B ring is bonded to A ring via &#x2014;X&#x2014; and A ring is directly bonded to the glucose residue, and it is usable as a Na-glucose cotransporter inhibitor, especially for a therapeutic and/or preventive agent for diabetes such as insulin-dependent diabetes (type 1 diabetes) and insulin-independent diabetes (type 2 diabetes), as well as diabetes related diseases such as an insulin-resistant diseases and obesity.

C-glycoside derivatives and salts thereof

There is provided a compound which can be used for therapy of diseases in which 11&#x3b2;-hydroxysteroid dehydrogenase type 1 (11&#x3b2;-HSD1) participates, in particular diabetes, insulin resistance. It has been found that a triazole derivative wherein the triazole ring is substituted with a trisubstituted methyl group in the 2-position or a pharmaceutically acceptable salt thereof has a strong 11&#x3b2;-HSD1 inhibitory activity. Moreover, the triazole derivative of the invention exhibits an excellent blood-glucose level-lowering action and hence can be used for therapy of diabetes, insulin resistance.

Triazole derivative or salt thereof

2-Oxo-1,2-dihydro-1,8-naphthyridine derivatives characterized by bearing a specific substituent, &mdash;X&mdash;R , at the 3-position and a cyclic substituent, R , at the 4-position; or salts thereof. The derivatives and the salts are useful as drugs, particularly preventive or therapeutic agents for respiratory diseases related to PDE IV.

Naphthyridine derivatives

To provide a compound which has an anticoagulation action based upon inhibition of activated blood coagulation factor X and is useful as an anticoagulant or an agent for prevention and treatment of diseases caused by thrombus or embolus. A diazepan derivative such as 4-&lsqb;(3-carbamimidoylphenylamino)methyl&rsqb;-3-&lsqb;4-(4-METHYL-1,4-diazepan-1-yl)benzoylamino&rsqb;benzoic acid and 3-hydroxy-4&prime;-methoxy-2-&lcub;&lsqb;4-(4-methyl-1,4-diazepan-1-yl)benzoyl&rsqb;amino&rcub;benzanilide or a salt thereof is an effective ingredient.

Growing community of inventors

Tokyo, Japan

Ryota Shiraki