Eisai Company, Limited

Eisai R&d Management Co., Ltd.

Hiroshi Obaishi

Shinya Abe

Isao Yamatsu

Hiroyuki Yoshimura

Shigeru Souda

Yoshimasa Machida

Shuhei Miyazawa

Kouji Yamada

Tetsuya Kawahara

Kenzo Muramoto

Mitsuaki Miyamoto

Koukichi Harada

Osamu Asano

Kazuo Okano

Kouichi Katayama

Satoshi Katayama

Hajime Tsunoda

Yoshimori Sakuma

Naoyuki Shimomura

Richard S Clark

Tomohiro Matsushima

Tatsuo Watanabe

Yasuhiro Funahashi

Keiko Takahashi

Junji Matsui

Masayuki Matsukura

Akihiko Tsuruoka

Yuji Yamamoto

Toru Haneda

Junichi Kamata

Kazuki Miyazaki

Yoshio Fukuda

Setsuo Funasaka

Takayuki Nakagawa

Atsumi Yamaguchi

Katsuji Nakamura

Fusayo Mimura

Sachi Suzuki

Ken-ichi Nomoto

Yasuyuki Suzuki

Shuji Shirotori

Masaki Goto

Yoshikazu Kuboi

Yoshihito Eguchi

Itaru Arimoto

Ken-ichi Chiba

Takako Yoshiba

Kenji Matsui

Richar S Clark

Naoyuki Kimomura

Ken-Ichi Nomoto

The present invention relates to a therapeutic agent represented by the General formula (I), or a pharmacologically acceptable salt thereof, or a solvate of the compound or the salt thereof:  The therapeutic agent comprises a substance having the activity of inhibiting kinase activity of fibroblast growth factor receptor 2 ('FGFR2'). The therapeutic agent can be used for treating undifferentiated gastric cancer, and can also be used to treat organisms comprising a cell overexpressing FGFR2 or a cell expressing mutant FGFR2, or both. The present invention further relates to a pharmaceutical composition comprising an FGFR2 inhibitory and methods of treatment therewith. The present invention also relates to a method for predicting the effect of an FGFR2 inhibitory substance on a patient.

Antitumor agent for undifferentiated gastric 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.), salts thereof or hydrates of the foregoing.

Nitrogen-containing aromatic derivatives

A compound represented by the following formula, or a salt thereof or a hydrate of the foregoing, has excellent hepatocyte growth factor receptor (HGFR) inhibitory activity, and exhibits anti-tumor activity, angiogenesis inhibitory activity, and cancer metastasis inhibitory activity. Rrepresents a 3- to 10-membered non-aromatic heterocyclic group or the like; Rand Rrepresent hydrogen; R, R, R, and Rmay be the same or different and each represents hydrogen, halogen, Calkyl or the like; Rrepresents hydrogen or the like; Rrepresents a 3- to 10-membered non-aromatic heterocyclic group or the like; n represents an integer of 1 or 2; X represents &#x2014;CH&#x2550;, nitrogen or the like.

Pyridine derivatives and pyrimidine derivatives (3)

A method of treating esophageal cancer, containing the step of administering to a patient suffering from esophageal cancer, a compound or a salt thereof, wherein the compound is: N-(2-fluoro-4-{[2-({[4-(4-methylpiperazin-1-yl)piperidin-1-yl]carbonyl}amino)pyridin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, N-[4-({2-[(azetidin-1-ylcarbonyl)amino]pyridin-4-yl}oxy)-2-fluorophenyl]-N&#x2032;-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, N-{2,5-difluoro-4-[(2-{[(3-hydroxyazetidin-1-yl)carbonyl]amino}pyridin-4-yl)oxy]phenyl}-N&#x2032;-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, N-(2,5-difluoro-4-{[2-({[4-(4-methylpiperazin-1-yl)piperidin-1-yl]carbonyl}amino)pyridin-4-yl]oxy}phenyl)-N&#x2032;-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, N-(2,5-difluoro-4-{[2-({[methyl(1-methyl-piperidin-4-yl)amino]carbonyl}amino)pyridin-4-yl]oxy}phenyl)-N&#x2032;-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide, or N-(2,5-difluoro-4-{[2-({[3-(hydroxymethyl)azetidin-1-yl]carbonyl}amino)pyridin-4-yl]oxy}phenyl)-N&#x2032;-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide.

Pharmaceutical composition for treating esophageal 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.)],salts thereof or hydrates of the foregoing.

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.

A compound represented by the following formula, a salt thereof or a hydrate of the foregoing has an excellent hepatocyte growth factor receptor (HGFR) inhibitory activity, and exhibits anti-tumor activity, angiogenesis inhibitory activity and cancer metastasis inhibitory activity. [Rrepresents Calkyl or the like; Rand Rrepresent hydrogen; R, R, R, and Rmay be the same or different and each represents hydrogen, halogen, Calkyl or the like; Rrepresents hydrogen or the like; Rrepresents Calkyl or the like; Vrepresents oxygen or the like; Vrepresents oxygen or sulfur; W represents &#x2014;NH&#x2014; or the like; X represents &#x2014;CH&#x2550;, nitrogen or the like; and Y represents oxygen or the like.]

Pyridine derivative and pyrimidine derivative

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.)],

The present invention provides a compound which has cytokine production inhibitory activity and is useful for the treatment of diseases which is associated with cytokine. The compound is represented by the following general formula (I) [wherein A represents a cyclic group which may be substituted; the partial structure -DE- represents a group represented by &#x2014;CHCH&#x2014; or &#x2014;CH&#x2550;CH&#x2014;; W represents a group represented by &#x2014;CH&#x2014;, &#x2014;CHCH&#x2014;, &#x2014;CH&#x2550;CH&#x2014; or &#x2014;CH&#x2550;; the partial structure &#x3e;XY&#x2014; represents a group represented by &#x3e;CH&#x2014;(CH)&#x2014;, &#x3e;C&#x2550;CH&#x2014;, &#x3e;CH&#x2014;CH&#x2014;CH(OH)&#x2014;, &#x3e;CH&#x2014;CH&#x2014;C(&#x2550;O)&#x2014;, &#x3e;CH&#x2014;O&#x2014; or &#x3e;CH&#x2014;O&#x2014;CO&#x2014;, provided that when W is &#x2014;CH&#x2550;, then XY&#x2014; represents C&#x2014;(CH)&#x2014;; Z represents a divalent aliphatic hydrocarbon group; Rand R, which may be the same or different, each represents a hydrogen atom, or a hydroxyl, alkoxy or alkoxyalkoxy group; m is an integer of 0 or 1].

Cyclooctanone derivatives and cyclodecanone derivative, and use thereof

A triazolo-1,4-di-azepine compound of the below given formula and a pharmacologically acceptable salt thereof are useful in the pharmaceutical field, especially in treating allergic diseases. ##STR1## in which R.sup.1 and R.sup.2 are hydrogen or an alkyl, R.sup.3 is hydrogen or a halogen, R.sup.4 is hydrogen or an alkyl, X is --OCO--, and Y is a cycloalkyl, a cycloalkylalkyl, an alkynyl or others.

1,4-diazepine derivative and its pharmaceutical use

A triazolo-1,4-di-azepine compound of the below given formula and a pharmacologically acceptable salt thereof are disclosed and useful in the pharmaceutical field, especially to allergic diseases. ##STR1## in which R.sup.1 and R.sup.2 are hydrogen or an alkyl, R.sup.3 is hydrogen or a halogen, R.sup.4 is hydrogen or an alkyl, X is --OCO--, --NHCO--, --CO-- or others and Y is a cycloalkyl, a cycloalkylalkyl, an alkynyl or others.

A triazolo-1,4-di-azepine compound of the below given formula and a pharmacologically acceptable salt thereof are disclosed and useful in the pharmaceutical field, especially to allergic diseases. ##STR1## in which R1 and R2 are hydrogen or an alkyl, R3 is hydrogen or a halogen, R4 is hydrogen or an alkyl, X is --OOO--, --NHCO--, --CO-- or others and Y is a cycloalkyl, a cycloalkylalkyl, an alkynyl or others.

A triazolo-1,4-di-azepine compound of the below given formula and a pharmacologically acceptable salt thereof are disclosed and useful in the pharmaceutical field, especially to treat allergic diseases: ##STR1## in which R1 and R2 are hydrogen or an alkyl, R3 is hydrogen or a halogen, R4 is hydrogen or an alkyl, X is --OCO--, --NHCO--, --CO-- or others and Y is a cycloalkyl, a cycloalkylalkyl, an alkynyl or others.

A triazolo-1,4-azepine compound of the below given formulas and a pharmacologically acceptable salt thereof are disclosed and useful in the pharmaceutical field, especially to allergic diseases. ##STR1## in which R1 and R2 are hydrogen or an alkyl, R3 is hydrogen or a halogen, R4 is hydrogen or an alkyl, X is --OCO--, --NHCO--, --CO-- or others and Y is a cycloalkyl, a cycloalkylalkyl, an alkynyl or others.

Triazolo-1,4-diazepine derivatives and their use in pharmaceuticals

A triazolo-1,4-di-azepine compound of the below given formula and a pharmacologically acceptable salt thereof are disclosed and useful in the pharmaceutical field, especially to allergic diseases, ##STR1## in which R.sup.1 and R.sup.2 are hydrogen or an alkyl, R.sup.3 is hydrogen or a halogen, R.sup.4 is hydrogen or an alkyl, X is --OCO--, --NHCO--, --CO-- or others and Y is a cycloalkyl, a cycloalkylalkyl, an alkynyl or others.

Growing community of inventors

Tsukuba, Japan

Hiroshi Obaishi