Santen Pharmaceutical Co., Ltd.

Hisashi Tajima

Minoru Yamamoto

Takahiro Honda

Kenji Kawashima

Kazuyoshi Okamoto

Yusuke Yamazaki

Shinji Yoneda

Hiroyuki Mogi

Noriko Mishina

Katsuhiko Watanabe

Junko Fujikawa

Masakazu Ban

Yoshimasa Sasabuchi

Takaaki Inaba

Yuriko Takeno

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 method of treating a disease associated with angiogenesis by administering a therapeutically effective amount of a compound represented by the formula (1) or a salt thereof wherein the ring X represents Rand Rindependently represent a hydrogen atom, an alkyl, an aryl or an aromatic heterocyclic; Rrepresents a hydrogen atom, a halogen atom, a hydroxy, an alkoxy, an aryloxy, an alkyl, an aryl, an amino, an alkylamino, a cycloalkylamino, an arylamino, an alkylcarbonylamino, an arylcarbonylamino, a mercapto, an alkylthio, an arylthio, an alkylsulfinyl or a nonaromatic heterocyclic; Arepresents a sulfur atom, a sulfinyl or a sulfonyl; and Arepresents an alkylene.

Cyclic compound having pyrimidinylalkylthio group

A compound of formula (1): wherein Rand Rrepresent hydrogen, lower alkyl, lower alkenyl, lower alkynyl or Rrepresents hydroxyl, lower alkoxy, lower cycloalkyloxy, aryloxy, carboxy, lower alkoxycarbonyl, or NRRof the formula Rand Rrepresent halogen, lower alkyl, hydroxyl, or lower alkoxy; Rrepresents halogen, lower alkyl, aryl, heterocyclic, hydroxy, lower alkoxy, mercapto, lower alkylthio, lower alkylcarbonyl, amino, nitro or cyano; Rrepresents lower alkyl, hydroxyl or lower alkoxy; Rand Rrepresent hydrogen or lower alkyl; ring A represents a cyclic hydrocarbon or a heterocyclic ring; ring B represents a heterocyclic ring; X represents lower alkylene; Z represents a single bond or lower alkylene; Y represents lower alkylene and W&#x2014;Wrepresents CH&#x2014;CH, or Y represents a single bond and W&#x2014;Wrepresents N&#x2014;CH, CH&#x2014;N or CH&#x2014;CH; and 1, m, n and o represent 0, 1, 2, or 3.

Thiophenediamine derivative having urea structure

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

A compound having the following formula (1) or a salt thereof: wherein Rand Rrepresent hydrogen, a lower alkyl, a lower alkenyl, a lower alkynyl or a group having the following formula (2):(R)&#x2014;{circle around (A)}&#x2014;Z&#x2014;&#x2003;&#x2003;(2),Rrepresents hydroxy, a lower alkoxy, a lower cycloalkyloxy, an aryloxy, carboxy, a lower alkoxycarbonyl, or &#x2014;NRRhaving the following formula (3):(R)&#x2014;{circle around (B)}&#x2014;&#x2003;&#x2003;(3),Rand Rrepresent halogen, a lower alkyl, hydroxy, or a lower alkoxy; Rrepresents halogen, a lower alkyl, an aryl group, a heterocyclic, a hydroxy, a lower alkoxy, mercapto, a lower alkylthio, a lower alkylcarbonyl, amino, nitro or cyano; Rrepresents a lower alkyl, hydroxy or a lower alkoxy; Rand Rrepresent hydrogen or a lower alkyl; the ring A represents a cyclic hydrocarbon or a heterocyclic ring; the ring B represents a heterocyclic ring having one or more heteroatoms selected from the group consisting of nitrogen and oxygen; X represents a lower alkylene; Y represents a lower alkylene; Z represents a single bond or a lower alkylene; W-Wrepresents N&#x2014;CH or C&#x2014;N and l, m, n and o represent 0, 1, 2, or 3.

The present invention relates to a study on the synthesis of a novel N-(2-aminophenyl)benzamide derivative having an urea structure and represented by the general formula (1); and the utilization of a pharmacological effect of the derivative. A compound represented by the general formula (1) or a salt thereof has an effect of cellular morphological change on trabecular meshwork cells and is effective in the prevention and/or treatment of a disease considered to be related to intraocular pressure. In the formula, Rand Rrepresent a hydrogen atom, a lower alkyl group, or the like; Rrepresents a hydroxy group, a lower alkoxy group, a lower cycloalkyloxy group, an aryloxy group, or the like; Rand Rrepresent a halogen atom, a lower alkyl group, a hydroxy group, a lower alkoxy group, or the like; X represents a lower alkylene group or the like; Y represents a single bond, a lower alkylene group, or the like; l and m represent 0, 1, 2, or the like. 

N- (2-aminophenyl) benzamide derivative having urea structure

Objects of the present invention are to study the synthesis of a novel pyridinecarboxylic acid (2-aminophenyl)amide derivative having a novel urea structure and to find a pharmacological effect of the derivative. The invention provides a compound represented by the formula (1) or a salt thereof. In the formula, Rand Rrepresent a hydrogen atom, a lower alkyl group or the like; Rrepresents a hydroxy group, a lower alkoxy group, a lower cycloalkyloxy group, an aryloxy group, a carboxy group, a lower alkoxycarbonyl group, &#x2014;OCONRR, &#x2014;NRRor the like; Rand Rrepresent a halogen atom, a lower alkyl group, a hydroxy group, a lower alkoxy group or the like; Rand Rrepresent a hydrogen atom, a lower alkyl group, a lower cycloalkyl group, an aryl group, a heterocyclic group or the like; Rand Rrepresent a hydrogen atom, a lower alkyl group, a lower cycloalkyl group, an aryl group or the like; X represents a lower alkylene group; Y represents a single bond, a lower alkylene group; W-Wrepresents N&#x2014;C or C&#x2014;N; and l and m represent 0, 1, 2 or 3. 

Pyridinecarboxylic acid (2-aminophenyl) amide derivative having urea structure

The present invention has its object to study synthesis of novel cyclic compounds having a pyrimidinylalkylthio group and to find pharmacological actions of the compounds. According to the present invention, a compound represented by the formula (1) or a salt thereof is provided. In the formula, the ring X represents: Rand Rindependently represent a hydrogen atom, an alkyl group, an aryl group, an aromatic heterocyclic group or the like; Rrepresents a hydrogen atom, a halogen atom, a hydroxy group, an alkoxy group, an aryloxy group, an alkyl group, an aryl group, an amino group, an alkylamino group or the like; Arepresents a sulfur atom or the like; and Arepresents an alkylene group.

The present invention relates to a synthesis study of novel cyclic compounds having a quinolylalkylthio group represented by the formula (1), and pharmacological actions of the compounds. In the formula, the ring X represents: which may have halogen and/or alkyl; Rand Rindependently represent hydrogen, alkyl, cycloalkyl, aryl or a (non) aromatic heterocycle; Rrepresents qinolyl; A represents sulfur, sulfinyl or sulfonyl; and B represents alkylene.

Cyclic compound having quinolylalkylthio group

A novel cyclic compound having a 4-pyridylalkylthio group having an (un)substituted amino group introduced therein or a salt thereof. They are useful as a medicine. The cyclic compound is a compound represented by the following formula (1), which is useful for the treatment of diseases in which angiogenesis participates. In the following formula (1), ring A represents a benzene ring or a 5- or 6-membered aromatic heterocycle optionally fused with a cycloalkane ring; B represents alkylene; Rand Reach represents H, (substituted) aryl, (substituted) heterocyclic group, etc.; Rand Reach represents H, (substituted) alkyl, (substituted) cycloalkyl, -Z-R, etc.; Rrepresents (substituted) alkyl, (substituted) aryl, (substituted) heterocyclic group, etc.; X and Y each represents H, etc.; Z represents &#x2014;CO&#x2014;, &#x2014;COO&#x2014;, &#x2014;CONR&#x2014;, &#x2014;SO&#x2014;, etc.; Rrepresents H, etc.; p is 0, 1, or 2; and q is 0 or 1. 

Cyclic compound having 4-pyridylalkylthio group having substituted or unsubstituted amino group introduced therein

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.

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Ikoma, Japan

Hisashi Tajima