公开(公告)号：US07799753B2

公开(公告)日：2010-09-21

申请号：US11565914

申请日：2006-12-01

Applicant: Keykavous Parang ,  Gongqin Sun ,  Anil Kumar ,  Nguyen H. Nam ,  Yue-Hao Wang ,  Guofeng Ye

Inventor： Keykavous Parang ,  Gongqin Sun ,  Anil Kumar ,  Nguyen H. Nam ,  Yue-Hao Wang ,  Guofeng Ye

IPC: A61K38/00

CPC classification number: A61K31/70 ,  A61K47/549 ,  A61K47/62

Abstract: A bisubstrate inhibitor of Src kinases, having a nucleotide or N-heteroaromatic moiety; and a peptide/phosphopeptide, peptidomimetic, or phosphopeptide mimic moiety. The moieties are linked by a rigid or a flexible linker. The nucleotide or N-heteroaromatic moiety is ATP, ATP-mimics, N-heteroaromatics including purine-based derivatives, pyrimidine-based derivatives such as 2,4-diamino-5-substituted pyrimidine derivatives, pyrazole[3,4-d]pyrimidine derivatives, pyrrolo[2,3-d]pyrimidine derivatives, pyrido[2,3-d]pyrimidine derivatives, amino-substituted dihydropyrimido[4,5-d]pyrimidinone derivatives, thieno- and furo-substituted derivatives, quinazoline derivatives, and quinoline derivatives, and several natural products such as aminogenistein. The phosphopeptide mimics comprise phosphonate-based phosphotyrosine mimetics such as phosphonomethylphenylalanine (Pmp) and its analogues, carboxylic acid-based phosphotyrosine mimetics such as malonyltyrosine or phenylalanine analogues and their derivatives such as carboxymethyl phenylalanine, uncharged pTyr mimetics, and conformationally constrained peptides. The phosphopeptide or phosphopeptide mimics inhibits the Src kinases SH2 domain.

Abstract translation: 具有核苷酸或N-杂芳族部分的Src激酶的双底物抑制剂; 和肽/磷酸肽，拟肽或磷酸肽模拟部分。 这些部分通过刚性或柔性接头连接。 核苷酸或N-杂芳族部分是ATP，ATP-模拟物，包括嘌呤类衍生物的N-杂芳族化合物，嘧啶类衍生物如2,4-二氨基-5-取代的嘧啶衍生物，吡唑[3,4-d]嘧啶 衍生物，吡咯并[2,3-d]嘧啶衍生物，吡啶并[2,3-d]嘧啶衍生物，氨基取代的二氢嘧啶并[4,5-d]嘧啶酮衍生物，噻吩并呋喃基取代的衍生物，喹唑啉衍生物和 喹啉衍生物和几种天然产物如氨基前列腺素。 磷酸肽类似物包括基于磷酸酯的磷酸酪氨酸模拟物，例如膦酰基甲基苯丙氨酸（Pmp）及其类似物，羧酸基磷酸酪氨酸模拟物如丙二酰基酪氨酸或苯丙氨酸类似物及其衍生物如羧甲基苯丙氨酸，不带电的pTyr模拟物和构象约束肽。 磷酸肽或磷酸肽模拟物抑制Src激酶SH2结构域。

公开(公告)号：US20110034670A1

公开(公告)日：2011-02-10

申请号：US12775014

申请日：2010-05-06

Applicant: Keykavous Parang ,  Gongqin Sun ,  Anil Kumar ,  Nguyen H. Nam ,  Yue-Hao Wang ,  Guofeng Ye

Inventor： Keykavous Parang ,  Gongqin Sun ,  Anil Kumar ,  Nguyen H. Nam ,  Yue-Hao Wang ,  Guofeng Ye

IPC: C07K2/00 ,  C07K7/06

CPC classification number: A61K31/70

Abstract: A bisubstrate inhibitor of Src kinases, having a nucleotide or N-heteroaromatic moiety; and a peptide/phosphopeptide, peptidomimetic, or phosphopeptide mimic moiety. The moieties are linked by a rigid or a flexible linker. The nucleotide or N-heteroaromatic moiety is ATP, ATP-mimics, N-heteroaromatics including purine-based derivatives, pyrimidine-based derivatives such as 2,4-diamino-5-substituted pyrimidine derivatives, pyrazole[3,4-d]pyrimidine derivatives, pyrrolo[2,3-d]pyrimidine derivatives, pyrido[2,3-d]pyrimidine derivatives, amino-substituted dihydropyrimido[4,5-d]pyrimidinone derivatives, thieno- and furo-substituted derivatives, quinazoline derivatives, and quinoline derivatives, and several natural products such as aminogenistein. The phosphopeptide mimics comprise phosphonate-based phosphotyrosine mimetics such as phosphonomethylphenylalanine (Pmp) and its analogues, carboxylic acid-based phosphotyrosine mimetics such as malonyltyrosine or phenylalanine analogues and their derivatives such as carboxymethyl phenylalanine, uncharged pTyr mimetics, and conformationally constrained peptides. The phosphopeptide or phosphopeptide mimics inhibits the Src kinases SH2 domain.

Abstract translation: 具有核苷酸或N-杂芳族部分的Src激酶的双底物抑制剂; 和肽/磷酸肽，拟肽或磷酸肽模拟部分。 这些部分通过刚性或柔性接头连接。 核苷酸或N-杂芳族部分是ATP，ATP-模拟物，包括嘌呤类衍生物的N-杂芳族化合物，嘧啶类衍生物如2,4-二氨基-5-取代的嘧啶衍生物，吡唑[3,4-d]嘧啶 衍生物，吡咯并[2,3-d]嘧啶衍生物，吡啶并[2,3-d]嘧啶衍生物，氨基取代的二氢嘧啶并[4,5-d]嘧啶酮衍生物，噻吩并呋喃基取代的衍生物，喹唑啉衍生物和 喹啉衍生物和几种天然产物如氨基前列腺素。 磷酸肽类似物包括基于磷酸酯的磷酸酪氨酸模拟物，例如膦酰基甲基苯丙氨酸（Pmp）及其类似物，羧酸基磷酸酪氨酸模拟物如丙二酰基酪氨酸或苯丙氨酸类似物及其衍生物如羧甲基苯丙氨酸，不带电的pTyr模拟物和构象约束肽。 磷酸肽或磷酸肽模拟物抑制Src激酶SH2结构域。