Astellas Pharma Gmbh

Kei Ohnuki

Masaaki Hirano

Eiji Kawaminami

Shunichiro Matsumoto

Isao Kinoyama

Toshiyuki Kusayama

Kazuyoshi Obitsu

Takashi Shin

Shigeru Yoshida

Takashi Kamikubo

Yuki Sawada

Hirofumi Yamamoto

Takeyuki Nagashima

Takanori Koike

Tomoyuki Saito

Kenji Negoro

Itsuro Shimada

Akio Kamikawa

Hidenori Azami

Yasuhiro Yonetoku

Takatoshi Soga

Hiroyuki Hisamichi

Hisao Hamaguchi

Norio Asai

Yohei Seki

Toru Asano

Kazuyuki Kuramoto

Tatsuhisa Takahashi

Shinji Soga

Toshio Kurosaki

Michinori Akaiwa

Fumiyoshi Iwasaki

Shigetoshi Kikuchi

Kazuhiko Osoda

Takashi Chaen

Yinghua Wang

Javier Ramos Miguelez

Chulwon Kwon

Rika Hoshi

An antibody-drug conjugate of formula (I) or salt thereof of formula I: may have Ab as an anti-CLDN6 antibody or an antigen-binding fragment thereof. The antibody-drug conjugate of formula (I) may be (a) an antibody-drug conjugate comprising Ab bound to 1-{3-[(3S)-4-[(4-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-3-methoxyphenyl)methyl]-3-(fluoromethyl)piperazin-1-yl]-3-oxopropyl}-1H-pyrrole-2,5-dione, (b) an antibody-drug conjugate comprising Ab bound to {(2S)-1-[(4-{[2-amino-7-chloro-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-3-methoxyphenyl)methyl]pyrrolidin-2-yl}methyl[2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl]carbamate, (c) an antibody-drug conjugate comprising Ab bound to N-[(4-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-3-methoxyphenyl)methyl]-N-cyclopropyl-3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propenamide, or (d) an antibody-drug conjugate comprising Ab bound to 1-{3-[(3R)-4-[(4-{[2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]methyl}-3-methoxyphenyl)methyl]-3-(fluoromethyl)piperazin-1-yl]-3-oxopropyl}-1H-pyrrole-2,5-dione.

Antibody-drug complex containing toll-like receptor 7/8 dual agonist compound

Compounds of formula (I) and salts thereof: wherein the variables are defined herein, are useful for the treatment of breast cancer.

Bicyclic nitrogen-containing aromatic heterocyclic amide compound

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

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

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

Growing community of inventors

Tokyo, Japan

Kei Ohnuki