Santen Pharmaceutical Co., Ltd.

Masakazu Ban

Hiroshi Suhara

Masato Horiuchi

Shiro Mita

Noriyoshi Yamamoto

Takahiro Honda

Hiroyuki Inoue

Hiroshi Enomoto

Minoru Yamamoto

Kenji Kawashima

Hisashi Tajima

Ken-ichi Fujimura

Kazuyoshi Okamoto

Yoshimasa Sasabuchi

Kazuo Nishimura

Kazuhiro Kudou

Masanori Hori

Atsushi Ohno

Eiko Matsumoto

Hiroyuki Aono

Koushi Fujisawa

A method of manufacturing a compound or a salt thereof expressed with a formula (III) below, characterized by causing a compound or a salt thereof expressed with a formula (I) below and a compound or a salt thereof expressed with a formula (II) below to react in the presence of carbonate and copper salt or in the presence of hydroxide salt, carbonate, and copper salt. 

3-hydroxy-6H-benzo [C] chromene-6-one derivative and manufacturing method thereof

3-hydroxy-6H-benzo [c] chromene-6-one derivative and manufacturing method thereof

A compound having the following formula [I] or a pharmaceutically acceptable salt thereof: wherein A is an aromatic five-membered heterocycle which optionally is fused with a cycloalkane ring; B is an alkylene; Rand Rare hydrogen, hydroxyl, alkoxy, aryloxy, alkyl, cycloalkyl, aryl, heterocycle, amino, alkylamino, arylamino or acyl, or Rand Rjoin together to form a heterocycle; X and Y are hydrogen, halogen, hydroxyl, alkoxy, aryloxy, alkyl, cycloalkyl, aryl, mercapto, alkylthio, arylthio, carboxyl, an ester of carboxyl, an amide of carboxyl, cyano or nitro; p is 0, 1 or 2; and q is 0 or 1. The compound is useful for treating diseases in which angiogenesis or augmentation of vascular permeability is involved.

Compounds having 4-pyridylalkylthio group as a substituent

A compound having the following formula [I] or a pharmaceutically acceptable salt thereof: wherein A is benzene or an aromatic five-membered heterocycle which optionally is fused with a cycloalkane ring; B is an alkylene; Rand Rare hydrogen, hydroxy, alkoxy, aryloxy, alkyl, cycloalkyl, aryl, heterocycle, amino, alkylamino, arylamino or acyl, or Rand Rjoin together to form a heterocycle; X and Y are hydrogen, halogen, hydroxy, alkoxy, aryloxy, alkyl, cycloalkyl, aryl, mercapto, alkylthio, arylthio, carboxyl, an ester of carboxyl, an amide of carboxyl, cyano or nitro; p is 0, 1 or 2; and q is 0 or 1. The compound is useful for treating diseases in which angiogenesis or augmentation of vascular permeability is involved.

Compounds having a 4-pyridylalkylthio group as a substituent

The present invention relates to Compounds represented by the formula (I) or salts thereof. In the formula (I), the ring A represents a benzene ring, a thiophene ring, or a pyridine ring; Rrepresents a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group; the ring B represents a pyridine ring, a pyrimidine ring, or a quinoline ring; the ring C represents a benzene ring; a pyridine ring, a quinoline ring, or an isoquinoline ring; X and Y, the same or different, represent an oxygen atom or a sulfur atom, with the proviso that the case X is a sulfur atom and Y is an oxygen atom be excluded; Rrepresents a hydrogen atom, a halogen atom, an amino group, a cycloalkylamino group, an alkylcarbonylamino group, an alkyloxycarbonylamino group, an alkylaminocarbonyl group, or a non-aromatic heterocyclic group; and Rand R', the same or different, represent a hydrogen atom, a halogen atom, an alkyl group, a halogeno-alkyl group, or a halogeno-alkoxy group. 

Oxadiazole derivatives and thiadiazole derivatives having neovascularization inhibitory activity

A compound having the following formula wherein A is &#x2014;O&#x2014;; B is alkylene or alkenylene optionally containing &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;(NR)&#x2014;, &#x2014;CO&#x2014; or &#x2014;N&#x2550;; Rand Rare alkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl is unsubstituted or substituted by halogen, cycloalkyl, aryl, adamantyl or amino; Ris a substituted or unsubstituted pyridine ring; Rand Rare hydrogen or alkyl; Ris hydrogen or alkyl; X is O or S; and each hydrogen of the said amino is unsubstituted or substituted by alkyl, alkoxycarbonyl, cycloalkyloxycarbonyl, arylalkoxycarbonyl or halogenoalkyloxycarbonyl. The compound is a TNF-&#x3b1; production inhibitor that is useful for treating autoimmune diseases such as rheumatoid arthritis.

TNF-&#x3b1; production inhibitors

A subject of the present invention is to provide a novel aromatic five- or six-memberd heterocyclic derivative having 4-pyridylalkylthio as a substituent or a salt thereof which is useful as a pharmaceutical. Compound represented by the following general formula [I] or salts thereof are useful as therapeutic agents for diseases in which angiogenesis or augmentation of vascular permeability is involved. In the formula, ring 'A' is a benzene ring or an aromatic five- or six-memberd heterocycle which can be fused with a cycloalkane ring, 'B' is alkylene, Rand R, the same or different, are H, OH, substituted or unsubstituted alkoxy and the like, X and Y, the same or different, are group(s) selected from H, halogen, OH, substituted or unsubstituted alkoxy and the like respectively, p is 0, 1 or 2, and q is 0 or 1.

Compounds having 4-pyridylalkylthio group as substituent

A purpose of the present invention is to provide TNF-&#x3b1; production inhibitors being useful as therapeutic agents for autoimmune diseases such as rheumatoid arthritis. Novel compounds having the structure represented by the general formula [1] or salts thereof according to the present invention have excellent TNF-&#x3b1; production inhibitory activities, wherein 'A' is &#x2014;(NR)&#x2014;, &#x2014;(CRR)&#x2014; or &#x2014;O&#x2014;, 'B' is alkylene or alkenylene, R, R, R, Rand Rare hydrogen, alkyl, alkenyl, adamantyl or the like, Ris aryl or an unsaturated heterocycle, and &#x201c;X&#x201d; is oxygen or sulfer respectively.

A purpose of the present invention is to provide TNF-&#x3b1; production inhibitors being useful as therapeutic agents for autoimmune diseases such as rheumatoid arthritis. Novel compounds having the structure represented by the general formula [1] or salts thereof according to the present invention have excellent TNF-&#x3b1; production inhibitory activities, wherein A is &#x2014;(NR)&#x2014;, &#x2014;(CRR)&#x2014; or &#x2014;O&#x2014;, B is alkylene or alkenylene, R, R, R, Rand Rare hydrogen, alkyl, alkenyl, adamantyl or the like, Ris aryl or an unsaturated heterocycle, and X is oxygen or sulfer respectively.

A compound having 3-oxo-3, 4-dihydro-2H-1, 4-thiazine 4-tetrahydropyrazine as a main skeleton. The compound is a chymase inhibitor and is represented by the following formula [I] and salts thereof:In the formula [I], X is S; Rand Rare H, alkyl, cycloalkyl or aryl; Rand Rare H, alkyl, cycloalkyl, aryl or an aromatic heterocycle; Ris H, alkyl, cycloalkyl, aryl or -A-A-R; Ris H, alkyl, cycloalkyl, hydroxy, alkoxy, aryl, aryloxy or an aromatic heterocycle; Ris H, alkyl, hydroxy, alkoxy, aryl, aryloxy, amino, alkylamino, arylamino, an aromatic heterocycle or a nonaromatic heterocycle; Ais alkylene; Ais carbonyl or sulfonyl; Ais alkylene; Ais carbonyl or oxalyl; and n is 0 or 1.

Thiazine derivatives

Urea derivatives useful as synthetic intermediates

A compound which is a chymase inhibitor and which is represented by a formula &lsqb;I&rsqb; and salts thereof. In the formula &lsqb;I&rsqb;, X is R &mdash;(A ) &mdash;N, R and R are H, alkyl, cycloalkyl or aryl, R and R are H, alkyl, cycloalkyl, aryl or aromatic heterocycle, R is H, alkyl, cycloalkyl, aryl or &mdash;A &mdash;A &mdash;R , R is H, alkyl, cycloalkyl, OH, alkoxy, aryl, aryloxy or an aromatic heterocycle, R is H, alkyl, OH, alkoxy, aryl, aryloxy, amino, alkylamino, arylamino, an aromatic heterocycle or a nonaromatic heterocycle, A is alkylene, A is carbonyl or sulfonyl, A is alkylene, A is carbonyl or oxalyl and n is o or 1. The formula &lsqb;I&rsqb; is

Thiazine or pyrazine derivatives

N-Substituted-N&prime;-substituted urea derivatives represented by the following formula, analogs thereof or pharmaceutically acceptable salts thereof are herein provided. These compounds show a TNF-&agr; production inhibitory activity.

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Osaka, Japan

Masakazu Ban