Astellas Pharma Gmbh

Yamanouchi Pharmaceutical Company Ltd.

Toshiyuki Kusayama

Masaaki Hirano

Eiji Kawaminami

Shunichiro Matsumoto

Isao Kinoyama

Kei Ohnuki

Minoru Okada

Hiroyuki Moritomo

Norio Seki

Akira Toyoshima

Ryutaro Wakayama

Kazuyoshi Obitsu

Hirofumi Yamamoto

Takanori Koike

Itsuro Shimada

Hiroyuki Hisamichi

Tatsuhisa Takahashi

Takashi Shin

Kazuhiko Osoda

Compounds useful as GnRH receptor antagonists are provided. The present inventors have further examined propane-1,3-dione derivatives and confirmed as a result that a propane-1,3-dione having 2-(1,3-dihydro-2H-benzimidazol-2-ylidene), or a compound which has benzene or thiophene ring substituted with a group derived from 1-hydroxymethyl, shows excellent availability, in addition to its excellent GnRH receptor antagonism, thereby accomplishing the invention. Since the compound of the invention shows excellent availability, in addition to its strong GnRH receptor antagonism, it can be expected that it exerts superior drug effect in the living body, and it is useful for the treatment of sex hormone dependent diseases such as prostate cancer, breast cancer, endometriosis, uterine leiomyoma, benign prostatic hypertrophy and the like. In addition, since the compound of the invention is excellent in metabolic stability in human and also is less in drug interaction, it has more desirable properties as a medicament to be used for the aforementioned diseases.

Benzimidazolylidene propane-1,3-dione derivative or salt thereof

It is intended to provide a compound useful as a GnRH receptor antagonist. The inventors further investigated propane-1,3-dione derivatives. As a result, they confirmed that a compound having a benzene ring or a thiophene ring substituted with a group represented by &#x2014;SO&#x2014;Rin a propane-1,3-dione derivative having 2-(1,3-dihydro-2H-benzimidazol-2-ylidene) has an excellent GnRH receptor antagonistic effect and accomplished the present invention. Because the compound of the present invention has a potent GnRH receptor antagonistic effect, it is useful for the treatment of sex hormone-dependent diseases, particularly GnRH-related diseases. Further, because the compound of the present invention has an excellent metabolic stability in human and few drug interactions, therefore it has preferable characteristics as a pharmaceutical used for the above-mentioned diseases.

Propane-1,3-dione derivative or salt thereof

Benzimidazolylidene propane-1,3 dione derivative or salt thereof

Provided is a pharmaceutical composition containing a propane-1,3-dione derivative as the active ingredient, particularly a GnRH receptor antagonist. Also, provided is a propane-1,3-dione derivative having a GnRH antagonistic effect.

Propane-1, 3-dione derivative

Propane-1,3-dione derivative

Growing community of inventors

Chuo-ku, Japan

Toshiyuki Kusayama