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Cell adhesion promoting agent and method of promoting cell adhesion

外国特許コード F120006121
整理番号 S2008-0654
掲載日 2012年1月6日
出願国 アメリカ合衆国
出願番号 99980509
公報番号 20110117651
公報番号 8685976
出願日 平成21年6月16日(2009.6.16)
公報発行日 平成23年5月19日(2011.5.19)
公報発行日 平成26年4月1日(2014.4.1)
国際出願番号 JP2009060950
国際公開番号 WO2009154201
国際出願日 平成21年6月16日(2009.6.16)
国際公開日 平成21年12月23日(2009.12.23)
優先権データ
  • 特願2008-159369 (2008.6.18) JP
  • 2009JP060950 (2009.6.16) WO
発明の名称 (英語) Cell adhesion promoting agent and method of promoting cell adhesion
発明の概要(英語) The subject invention discloses an agent for promoting cell adhesion to a support, comprising a dispirotripiperazine derivative represented by Formula I below or a salt thereof; a method for promoting cell adhesion to a support comprising adding the dispirotripiperazine derivative represented by Formula I below or a salt thereof to a culture medium, or applying the same to a support; and an agonist of a heparin sulfate that comprises the dispirotripiperazine derivative represented by Formula I below or a salt thereof, and that promotes cell adhesion and/or cell growth.
特許請求の範囲(英語) [claim1]
1. A dispirotripiperazine derivative represented by Formula I below or a salt thereof,
wherein R1 and R2 are the same or different, and each represent hydrogen, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkylalkyl group, an aryl group, a heteroaryl group, an aryl-substituted alkyl group, a heteroaryl-substituted alkyl group (excluding the case where both R1 and R2 are hydrogen; at least one of R1 and R2 being bonded with a substance having integrin-binding activity, wherein the substance comprises Arg-Gly-Asp amino acid sequence; the alkyl group, the alkenyl group, the alkynyl group, and each alkyl moiety are optionally substituted with at least one atom or one group selected from halogen, hydroxyl (the hydroxy being optionally acylated, carbamated or etherified), cyano, nitro, amino, mono- or di-substituted amino, carbamoyl and sulfamoyl; the alkyl group, the alkenyl group, the alkynyl group, the cycloalkyl group, each alkyl moiety and each cycloalkyl moiety are optionally interrupted by -- O -- , -- S -- , -- SO -- , -- SO2 -- , -- OSO2 -- , -- NH -- , -- CO -- , -- CH.dbd.CH -- , -- C≡C -- , -- CONH -- , -- NHCO -- , -- NHCOO -- , -- OCH2CONH -- , or -- OCH2CO -- ; and the aryl group, each aryl moiety, the heteroaryl group, each heteroaryl moiety, the cycloalkyl group and each cycloalkyl moiety are optionally substituted with at least one atom or one group selected from halogen, hydroxyl, formyl, alkyl, hydroxyalkyl, alkoxy, alkylthio, cyano, nitro, amino, mono- or di-substituted amino, carbamoyl, sulfamoyl, alkyl sulfonyl, alkyl sulfonylamino, alkyl carbonylamino, methylenedioxy, and aryl) or a group represented by Formula II below (excluding the case where both of R1 and R2 are a group represented by Formula II),
wherein R1a represents an alkylene group, an alkenylene group, an alkynylene group, a cycloalkylene group, a cycloalkylalkylene group, an arylene group, a heteroarylene group, an aryl-substituted alkylene group, or a heteroaryl-substituted alkylene group (the alkylene group, the alkenylene group, the alkynylene group, and each alkylene moiety being optionally substituted with at least one atom or one group selected from halogen, hydroxyl (the hydroxy being optionally acylated, carbamated or etherified), cyano, nitro, amino, mono- or di-substituted amino, carbamoyl and sulfamoyl; the alkylene group, the alkenylene group, the alkynylene group, the cycloalkylene group, each alkylene moiety and each cycloalkyl moiety are optionally interrupted by -- O -- , -- S -- , -- SO -- , -- SO2 -- , -- OSO2 -- , -- NH -- , -- CO -- , -- CH.dbd.CH -- , -- C≡C -- , -- CONH -- , -- NHCO -- , -- NHCOO -- , -- OCH2CONH -- , or -- OCH2CO -- ; and the arylene group, each aryl moiety, the heteroarylene group, each heteroaryl moiety, the cycloalkylene group and each cycloalkyl moiety are optionally substituted with at least one atom or one group selected from halogen, hydroxyl, formyl, alkyl, hydroxyalkyl, alkoxy, alkylthio, cyano, nitro, amino, mono- or di-substituted amino, carbamoyl, sulfamoyl, alkyl sulfonyl, alkyl sulfonylamino, alkyl carbonylamino, methylenedioxy, and aryl); and R2a has the same definition as those of R1 and R2.
[claim2]
2. A dispirotripiperazine derivative represented by Formula Ia below or a salt thereof,
wherein R3 represents a monocyclic aryl group or a monocyclic heteroaryl group (R3 being optionally derivatized with dansylhydrazine or bonded with a substance having integrin-binding activity or a Arg-Gly-Asp peptide; and the aryl group and the heteroaryl group are optionally substituted with at least one atom or one group selected from halogen, hydroxyl formyl, alkyl, hydroxyalkyl, alkoxy, alkylthio, cyano, nitro, amino, mono- or di-substituted amino, carbamoyl, sulfamoyl, alkyl sulfonyl, alkyl sulfonylamino, alkyl carbonylamino, methylenedioxy, and aryl); and R4 represents a group represented by Formula IIa below,
wherein R3a represents a monocyclic arylene group or monocyclic heteroarylene group, (the arylene group and heteroarylene group being optionally substituted with at least one atom or one group selected from the group consisting of halogen, hydroxyl, formyl, alkyl, hydroxyalkyl, alkoxy, alkylthio, cyano, nitro, amino, mono- or di-substituted amino, carbamoyl, sulfamoyl, alkyl sulfonyl, alkyl sulfonylamino, alkyl carbonylamino, methylenedioxy, and aryl), and R4a has the same definition as that of R3.
[claim3]
3. A dispirotripiperazine derivative or a salt thereof selected from the groups below:
[claim4]
4. A method for promoting cell adhesion to a support, comprising either adding the dispirotripiperazine derivative or a salt thereof according to claim 1 to a culture medium, or applying the dispirotripiperazine derivative or a salt thereof according to claim 1 to a support.
[claim5]
5. The method according to claim 4, wherein the support is a cell culture vessel.
[claim6]
6. The method according to claim 4, wherein the cell is a nonadherent cell.
[claim7]
7. A method for promoting cell adhesion to a support, comprising either adding the dispirotripiperazine derivative or a salt thereof according to claim 2 to a culture medium, or applying the dispirotripiperazine derivative or a salt thereof according to claim 2 to a support.
[claim8]
8. The method according to claim 7, wherein the support is a cell culture vessel.
[claim9]
9. The method according to claim 7, wherein the cell is a nonadherent cell.
[claim10]
10. A method for promoting cell adhesion to a support, comprising either adding the dispirotripiperazine derivative or a salt thereof according to claim 3 to a culture medium, or applying the dispirotripiperazine derivative or a salt thereof according to claim 3 to a support.
[claim11]
11. The method according to claim 10, wherein the support is a cell culture vessel.
[claim12]
12. The method according to claim 10, wherein the cell is a nonadherent cell.
  • 発明者/出願人(英語)
  • UESUGI MOTONARI
  • YAMAZOE SAYUMI
  • KYOTO UNIVERSITY
国際特許分類(IPC)
米国特許分類/主・副
  • 514/245
  • 514/252.13
  • 544/212
  • 544/296
  • 544/359
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