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    • 86. 发明授权
    • Indolinone combinatorial libraries and related products and methods for the treatment of disease
    • 吲哚酮组合文库及相关产品及治疗方法
    • US07202265B2
    • 2007-04-10
    • US10784917
    • 2004-02-24
    • Peng Cho TangConnie Li SunGerald McMahonKlaus Peter HirthLaura Kay Shawver
    • Peng Cho TangConnie Li SunGerald McMahonKlaus Peter HirthLaura Kay Shawver
    • A61K31/404C07D403/06
    • C07D209/34
    • The present invention relates to organic molecules capable of modulating, regulating and/or inhibiting protein kinase signal transduction. Such compounds are useful for the treatment of diseases related to unregulated protein kinase signal transduction, including cell proliferative diseases such as cancer, atherosclerosis, arthritis and restenosis and metabolic diseases such as diabetes. The present invention features indolinone compounds that potently inhibit protein kinases and related products and methods. Inhibitors specific to the FLK protein kinase can be obtained by adding chemical substituents to the 3-[(indole-3-yl)methylene]-2-indolinone, in particular at the 1′ position of the indole ring. Indolinone compounds that specifically inhibit the FLK and platelet derived growth factor protein kinases can harbor a tetrahydroindole or cyclopentano-b-pyrrol moiety. Indolinone compounds that are modified with substituents, particularly at the 5 position of the oxindole ring, can effectively activate protein kinases. This invention also features novel hydrosoluble indolinone compounds that are tyrosine kinase inhibitors and related products and methods.
    • 本发明涉及能够调节,调节和/或抑制蛋白激酶信号转导的有机分子。 这些化合物可用于治疗与未调节的蛋白激酶信号转导相关的疾病,包括细胞增殖性疾病如癌症,动脉粥样硬化,关节炎和再狭窄以及诸如糖尿病的代谢疾病。 本发明具有抑制蛋白激酶及相关产物和方法的吲哚啉酮化合物。 可以通过向3 - [(吲哚-3-基)亚甲基] -2-二氢吲哚酮,特别是在吲哚环的1'位置添加化学取代基来获得对FLK蛋白激酶特异性的抑制剂。 特异性抑制FLK和血小板衍生生长因子蛋白激酶的吲哚酮化合物可以含有四氢吲哚或环戊基-b-吡咯部分。 被取代基修饰的吲哚啉酮化合物,特别是在羟吲哚环的5位,可以有效地激活蛋白激酶。 本发明还具有酪氨酸激酶抑制剂和相关产物和方法的新型水溶性吲哚啉酮化合物。