Otsuka Pharmaceutical Company, Limited

Otsuka Chemical Co., Ltd.

D. Western Therapeutics Institute, Inc.

Yasuo Koga

Takao Nishi

Kuninori Tai

Kunio Oshima

Yasuhiro Menjo

Shinichi Taira

Tetsuyuki Uno

Katsumi Tamura

Hokuto Yamabe

Makoto Komatsu

Masataka Ueda

Shuuji Matsumura

Yoshio Shu

Takashi Oshiyama

Toshiyuki Onogawa

Kenji Tsujimae

Sunao Nakayama

Gil-Namg Chu

Yusuke Kato

Takashi Hayashi

Minoru Okada

Satoshi Shimizu

Hiroyoshi Hidaka

Takahiro Tomoyasu

Noriaki Takemura

Takao Taki

Kazuaki Kakehi

Hiroaki Asai

Fumitaka Goto

Yoshihiro Inoue

Yoshito Kihara

Norio Fukuda

Yoko Sakamoto

Junji Takaba

Yukio Kimura

Minoru Kashimoto

Naohiro Hayashi

Kazunari Izumi

Masaru Nishida

Wakako Hirano

Atsushi Azuma

Satoru Nakazato

A low-molecular-weight polysulfated hyaluronic acid derivative useful for treatment of an allergic disease. An agent for treatment of an allergic disease selected from pollinosis, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, and asthma, represented by the following general formula (IA) or (IB); wherein n represents a number of 0 to 15; R's each independently represent a hydrogen atom or an SOH group etc.

Low-molecular polysulfated hyaluronic acid derivative and medicine containing same

The present invention provides a novel benzodiazepine compound that blocks the Icurrent or the Kv1.5 channel potently and more selectively than other Kchannels. The benzodiazepine compound of the invention is represented by General Formula (1) wherein R, R, R, and Rare each independently hydrogen or lower alkyl; Rand Rmay be linked to form lower alkylene; wherein Rand Rare each independently hydrogen or organic group;

Benzodiazepine compound and pharmaceutical composition

The present invention provides a novel benzodiazepine compound that blocks the Icurrent or the Kv1.5 channel potently and more selectively than other Kchannels. The benzodiazepine compound of the invention is represented by General Formula (1)  

Carbostyril derivatives

Carbostyril derivatives and salts thereof represented by the general formula (1a), including some known compounds, possess activities for inhibiting adhesion of thrombocytes. ##STR1## Z, A, X, R, R.sup.1 and R.sup.2 are defined in the specification. Some carbostyril derivatives having chemical structural formulas similar to those of carbostyril derivatives and salts thereof represented by the general formula (1a) have been known in prior art references, however the above-mentioned pharmacological activities have not been known to the present date.

Carbostyril derivatives and salts thereof and pharmaceutical

The novel carbostyril derivative represented by the general formula (1) ##STR1## [in the formula, A, R.sup.1, R.sup.2 and the carbon-carbon bond between 3- and 4-positions in the carbostyril skeleton have the same definitions as above] has an excellent platelet aggregation inhibitory activity, a phosphodiesterase inhibitory activity, a venticular contraction activity (a positive contraction activity), an anti-ulcer activity, an anti-inflammatory activity, a cerebral blood flow increasing activity, a thrombus dissociation activity, a thromboxane A.sub.2 antagonism activity, etc. The carbostyril derivative of the present invention is characterized in that it exhibits the above activities for a long time, is low in toxicity (particularly low in toxicity to hearts of cardiovascular hyperplasia, myocardipathy, etc.), and is low in circulation activities such as heart rate increasing activity, blood pressure decreasing activity and the like. Also, the carbostyril derivative of the present invention has advantages in that it is easily absorbed by the intestinal tract and easily migrates into blood. Therefore, the carbostyril derivative of the present invention can be used most suitably as a preventive and remedy for thrombi such as apoplexia, cerebral infarction, myocardial infarction and the like, a cerebral circulation improving agent, an anti-inflammatory agent, an anti-asthmatic agent, a cardiotonic agent and a phosphodiesterase inhibitory agent.

Carbostyril derivative

Carbostyril compounds or salts thereof of the formula ##STR1## wherein A is a C.sub.1 -C.sub.6 alkylene group; R.sup.1 is a C.sub.3 -C.sub.8 cycloalkyl-C.sub.1 -C.sub.6 alkyl group which may have, as a substituent, a group selected from the group consisting of C.sub.1 -C.sub.6 alkoxycarbonyl groups, a carboxy group, C.sub.2 -C.sub.6 alkanoyloxy-C.sub.1 -C.sub.6 alkyl groups, amino-C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 alkylamino-C.sub.1 -C.sub.6 alkyl groups and hydroxy-C.sub.1 -C.sub.6 alkyl groups, a C.sub.3 -C.sub.8 cycloalkyl group, a tetrahydropyranyl-C.sub.1 -C.sub.6 alkyl group, a C.sub.1 -C.sub.3 alkylenedioxy group-substituted C.sub.1 -C.sub.6 alkyl group, a phenyl-C.sub.1 -C.sub.6 alkyl group having, as a substituent on the phenyl ring, 1 to 3 groups selected from the group consisting of C.sub.1 -C.sub.6 alkyl groups and a hydroxyl group, or a piperidinyl-C.sub.1 -C.sub.6 alkyl group having a C.sub.1 -C.sub.6 alkyl group as a substituent; R.sup.2 is a 5-membered or 6-membered saturated or unsaturated heterocyclic-C.sub.1 -C.sub.6 alkyl group, said heterocyclic being selected from the group consisting of pyrrolidinyl, morpholino, piperidinyl, thiomorpholino, imidazolyl, 1,2,4-triazolyl, furyl, piperazinyl, pyridyl, tetrahydropyranyl and 1,3-oxathiolranyl groups which may have, as a substituent thereon 1 to 3 groups selected from the group consisting of hydroxy-C.sub. 1 -C.sub.6 alkyl groups, C.sub.2 -C.sub.6 alkanoyloxy-C.sub.1 -C.sub.6 alkyl groups, a hydroxyl group, C.sub.1 -C.sub.6 alkyl groups, amino-C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 alkylamino-C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 alkoxy groups, C.sub.1 -C.sub.6 alkoxy-C.sub.1 -C.sub.6 alkoxy groups, C.sub.1 -C.sub.6 alkoxy-C.sub.1 -C.sub.6 alkyl groups, a thio group and C.sub.1 -C.sub.6 alkylamido groups; the carbon-carbon bond between the 3- and 4-positions in the carbostyril skeleton being a single bond or a double bond and pharmaceutical compositions containing the compound as the active ingredient.

A carbostyril derivative or pharmaceutically acceptable salt thereof represented by the following general formula: ##STR1## wherein Z, A, XN, R, R.sup.1, and R.sup.2 are as defined in the specification. These carbostyril derivatives are useful in pharmaceutical compositions for inhibiting adhesion of thrombocytes.

Carbostyril derivatives and salts thereof and pharmaceutical composition

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Osaka, Japan

Yasuo Koga