Astellas Pharma Gmbh

Yamanouchi Pharmaceutical Company Ltd.

Yasuhiro Yonetoku

Makoto Takeuchi

Yoshinori Okamoto

Masahiko Hayakawa

Keizo Sugasawa

Souichirou Kawazoe

Akira Toyoshima

Hirokazu Kubota

Masashi Funatsu

Jun Ishikawa

Shigeru Yoshida

Hiroyuki Moritomo

Kenji Negoro

Yasuo Isomura

Ken Ikeda

Kenichi Onda

Norio Asai

Takahiro Nigawara

Kazuhiko Iikubo

Ryo Naito

Daisuke Sasuga

Takahide Ohishi

Daisuke Yamashita

Takashi Sugane

Takafumi Shimizu

Takatoshi Soga

Kyoichi Maeno

Kei Ohnuki

Takuya Makino

Toshio Kurosaki

Naomi Hosogai

Hisashi Mihara

Daisuke Tanabe

Fumiyoshi Iwasaki

Kazuhiko Osoda

Keizou Sugasawa

To provide a compound which can be used as an MCreceptor agonist. The present inventors have investigated MCreceptor agonists, and have found that a piperazine derivative has an action related to the agonists, thereby completing the present invention. That is, the piperazine derivative of the present invention has an MCreceptor agonistic action, and can be used as an agent for preventing or treating bladder and/or urinary tract diseases, in particular, underactive bladder, hypotonic bladder, acontractile bladder, detrusor underactivity, neurogenic bladder, urethral relaxation failure, detrusor-external urethral sphincter dyssynergia, and voiding dysfunctions in benign prostatic hyperplasia.

Piperazine derivative

A compound which can be used as a pharmaceutical, particularly a insulin secretion promoter or a agent for preventing/treating disease in which GPR40 is concerned such as diabetes or the like, is provided. It was found that an oxadiazolidinedione compound which is characterized by the possession of a benzyl or the like substituent binding to the cyclic group via a linker at the 2-position of the oxadiazolidinedione ring, or a pharmaceutically acceptable salt thereof, has excellent GPR40 agonist action. In addition, since the oxadiazolidinedione compound of the present invention showed excellent insulin secretion promoting action and blood glucose level-lowering action, it is useful as an insulin secretion promoter or an agent for preventing/treating diabetes.

Oxadiazolidinedione compound

The present invention provides a condensed pyrimidine compound represented by formula (I) or pharmaceutically acceptable salt thereof: where A represents a ring where at least one carbon atom within said ring is optionally substituted with one or more groups selected from the group consisting of lower alkyl, &#x2014;O-(lower alkyl), halogen atom, carboxyl, &#x2014;CO-(lower alkyl), and carbamoyl, Rrepresents: (1) phenyl substituted with at least three halogen atoms, which may have at least one additional substituent, or (2) cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, each of which is optionally substituted; and Rrepresents a group represented by formula (II) or an optionally substituted cyclic amino: wherein Rand Rmay be identical or different and each represents &#x2014;H, lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, phenyl, heteroaryl, non-aromatic heterocyclyl, or &#x2014;O-(lower alkyl), each of which is optionally substituted.

Pyrimidine derivative condensed with a non-aromatic ring

There are provided novel pyrimidine derivatives which has been fused with an aromatic heterocycle selected from thiophene, thiazole and pyridine or pharmaceutically acceptable salts thereof; and a pharmaceutical composition comprising said compound as an active ingredient. These compounds exhibit excellent promoting activity on insulin secretion and activity against hyperglycemia. Hence, the pharmaceutical compositions comprising such compounds as active ingredients, based on these actions, are useful for treating and/or preventing insulin-dependent diabetes (type 1 diabetes), non-insulin-dependent diabetes (type 2 diabetes), insulin-resistant diseases, obesity, and the like.

Aromatic-ring-fused pyrimidine derivative

Drugs, in particular, pyrazole derivatives represented by the following general formula (I) which have a calcium release-activated calcium channel inhibitory effect and medicinal compositions, in particular, calcium release-activated calcium channel inhibitors containing the above compounds as the active ingredient, (in the formula, each symbol has the following meaning:D: pyrazolyl which may have 1 to 3 substituents selected from the group consisting of -Alk, -lower alkenyl, -lower alkynyl, -halogeno-lower alkyl, -Alk-cycloalkyl, -Alk-O-Alk, -cycloalkyl, &#x2014;O-Alk, &#x2014;COOH, &#x2014;COO-Alk and -Hal,n: 0 or 1,B: phenylene, a nitrogen-containing, divalent, saturated ring group, or a monocyclic, divalent heteroaromatic ring group which may be substituted with Alk,X: &#x2014;NR&#x2014;CRR&#x2014;, &#x2014;CRR&#x2014;NR&#x2014;, &#x2014;NR&#x2014;SO&#x2014;, &#x2014;SO&#x2014;NR&#x2014; or &#x2014;CR&#x2550;CR&#x2014;, andA: benzene ring which may have one or more substituents; mono-, di- or tricyclic fused heteroaryl which may have one or more substituents; cycloalkyl which may have one or more substituents; a nitrogen-containing, saturated ring group which may have one or more substituents; lower alkenyl which may have one or more substituents; lower alkynyl which may have one or more substituents; or Alk which may have one or more substituents).

Pyrazole derivative

Drugs, in particular, pyrazole derivatives represented by the following general formula (I) which have a calcium release-dependent calcium channel inhibitory effect and medicinal compositions, in particular, calcium release-dependent calcium channel inhibitors containing the above compounds as the active ingredient, (in the formula, each symbol has the following meaning:

The present invention is directed to drugs, in particular, pyrazole derivatives represented by the following general formula (I)which have a calcium release-activated calcium channel inhibitory effect and medicinal compositions, in particular, calcium release-activated calcium channel inhibitors containing the above compounds as the active ingredient, wherein each substituent is defined in the specification. The present invention also relates to a pharmaceutical composition containing an effective amount of the compound of formula (I) and a pharmaceutically effective carrier. The present invention further relates to methods of treatment of diseases associated with calcium release-activated calcium channels, diseases associated with IL-2 production, and methods of treatment of allergic, inflammatory or auto-immune diseases.

Pharmaceutical compound comprising a pyrazole derivative and methods of using the same for the treatment of calcium release-activated calcium channel associated diseases

Quinuclidine derivatives represented by general following general formula (I), salts, N-oxides or quaternary ammonium salts thereof, and medicinal compositions containing the same.

Quinuclidine derivatives and medicinal composition thereof

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Ibaraki, Japan

Yasuhiro Yonetoku