Eisai Company, Limited

Eisai R&d Management Co., Ltd.

Mercian Corporation

Merican Corporation

Yoshio Fukuda

Tomohiro Matsushima

Mitsuo Nagai

Yoshihiko Kotake

Jun Niijima

Takashi Nakashima

Akihiko Tsuruoka

Masayuki Matsukura

Keiko Takahashi

Kazuki Miyazaki

Toshio Tsuchida

Junichi Kamata

Regina Mikie Kanada

Masahi Yoshida

Shinya Abe

Shigeru Souda

Katsuya Tagami

Hironori Ikuta

Tatsuo Watanabe

Kenji Hayashi

Kazutoshi Miyake

Makoto Okita

Hitoshi Oinuma

Yasuhiro Funahashi

Hideyuki Adachi

Naoki Yoneda

Yuji Yamamoto

Hiroshi Obaishi

Junji Matsui

Toru Haneda

Makoto Kotake

Masanori Mizuno

Mamoru Saito

Toshiyuki Matsuoka

Naoki Kobayashi

Shinji Suda

Issei Ohtsuka

Makoto Kaino

Yoshihito Eguchi

Hironobu Hiyoshi

Atsumi Yamaguchi

Takeshi Sudo

Masayuki Namiki

Katsuji Nakamura

Makoto Nakagawa

Ichirou Yoshida

Ken-ichi Nomoto

Fusayo Mimura

Sachi Suzuki

Yasuyuki Suzuki

Masashi Yoshida

Tomohiro Sameshima

Susumu Takeda

Itaru Arimoto

Takako Yoshiba

Kenji Matsui

Ken-Ichi Nomoto

Mikie Regina Kanada

The present invention relates to a compound represented by the formula (I): (wherein, R, R, Rand Rare the same as or different from one another and each represents a hydroxyl group etc.), a pharmacologically acceptable salt thereof or a hydrate of them. The compound (I) of the present invention suppresses angiogenesis, in particular, suppresses VEGF production in a hypoxic condition and is useful as a therapeutic agent for treating solid cancer.

Physiologically active substances

Compounds represented by the following general formula: [wherein Ais an optionally substituted 5- to 14-membered heterocyclic group, etc.; Xis &#x2014;O&#x2014;, &#x2014;S&#x2014;, etc.; Yis an optionally substituted Caryl group, an optionally substituted 5- to 14-membered heterocyclic group, etc.; and Tis a group represented by the following general formula: (wherein Eis a single bond or &#x2014;N(R)&#x2014;, Rand Reach independently represent a hydrogen atom, an optionally substituted Calkyl group, etc. and Zrepresents a Calkyl group, a Calicyclic hydrocarbon group, a Caryl group, etc.)], salts thereof or hydrates of the foregoing.

Nitrogen-containing aromatic derivatives

A compound represented by the general formula: wherein Xrepresents a nitrogen atom or a group represented by the formula &#x2014;CR&#x2550;; Xrepresents a nitrogen atom or a group represented by the formula &#x2014;CR&#x2550;; Y represents an oxygen atom or the like; Rrepresents a Calkoxy group, an optionally substituted Caryloxy group, a group represented by the formula &#x2014;NRRor the like; Rrepresents a hydrogen atom, an optionally substituted Calkyl group, or the like; R, R, R, R, R, R, Rand Reach independently represent a hydrogen atom, a halogen atom, an optionally substituted Calkyl group, or the like; Rrepresents a group represented by the formula &#x2014;NRRor the like; and R, R, Rand Reach independently represent a hydrogen atom, an optionally substituted Calkyl group, or the like,a salt thereof, or a hydrate of the foregoing.

Compounds represented by the following general formula (I), pharmacologically acceptable salts thereof or hydrates of the same: (I) wherein W represents and R, R, R, R, R, Rand Rare the same or different and each represents hydrogen, etc. Because of inhibiting angiogenesis and inhibiting the production of VEGF particularly in hypoxia, the compounds (I) are useful as remedies for solid cancer.

Compounds represented by the following general formula: [wherein Ais an optionally substituted 5- to 14-membered heterocyclic group, etc.; Xis &#x2014;O&#x2014;, &#x2014;S&#x2014;, etc.; Yis an optionally substituted Caryl group, an optionally substituted 5- to 14-membered heterocyclic group, etc.; and Tis a group represented by the following general formula: (wherein Eis a single bond or &#x2014;N(R)&#x2014;, Rand Reach independently represent a hydrogen atom, an optionally substituted Calkyl group, etc. and Zrepresents a Calkyl group, a Calicyclic hydrocarbon group, a Caryl group, etc.)],

A compound represented by the general formula: wherein Xrepresents a nitrogen atom or a group represented by the formula &#x2014;CR&#x2550;; Xrepresents a nitrogen atom or a group represented by the formula &#x2014;CR&#x2550;; Y represents an oxygen atom or the like; Rrepresents a Calkoxy group, an optionally substituted Caryloxy group, a group represented by the formula &#x2014;NRRor the like; Rrepresents a hydrogen atom, an optionally substituted Calkyl group, or the like; R, R, R, R, R, R, Rand Reach independently represent a hydrogen atom, a halogen atom, an optionally substituted Calkyl group, or the like; Rrepresents a group represented by the formula &#x2014;NRRor the like; and Rand Reach independently represent a hydrogen atom, an optionally substituted Calkyl group, or the like, a salt thereof, or a hydrate of the foregoing.

The present invention relates to a substituted thiazolo[3,2-a] azepine derivative having inhibitory activity against angiotensin I converting enzyme and neutral endpeptidase and is represented by the following general formula (I): ##STR1##

Substituted thiazolo[3,2-a]azepine derivatives

Substituted thiazolo �3,2-a!azepine derivatives

Phosphonic acid derivatives

Phosphorus-containing isoprenoid derivatives

Growing community of inventors

Tsukuba, Japan

Yoshio Fukuda