公开(公告)号：US20110039798A1

公开(公告)日：2011-02-17

申请号：US12668262

申请日：2008-07-09

Applicant: Gustavo F. Doncel ,  Keykavous Parang ,  Hitesh Kumar Agarwal

Inventor： Gustavo F. Doncel ,  Keykavous Parang ,  Hitesh Kumar Agarwal

IPC: A61K31/7076 ,  C07H19/06 ,  C07H19/16 ,  C07D473/34 ,  C07D411/04 ,  A61K31/7072 ,  A61K31/7068 ,  A61K31/522 ,  A61K31/513 ,  A61P31/18 ,  A61P31/22 ,  A61P31/04 ,  A61P31/20 ,  A61P31/00 ,  A61P15/18

CPC classification number: C07H19/06 ,  C07D411/04 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20

Abstract: The present invention relates to fatty acid and fatty alcohol substituted nucleoside derivatives and nucleoside and nucleoside derivatives substituted on multivalent scaffolds (e.g., polymers, peptides, polycarboxylic acid substituted compounds, compounds containing polycycloSaligenyl groups) that display potent anti-HIV activity. Furthermore, they show enhanced activity against multi-drug resistant, R5, and cell-associated virus. Some of them also display activity against other sexually transmitted pathogens and sperm. The present invention provides their methods of synthesis, composition of matter, and methods of use. Emphasis is placed on their application as topical microbicides to treat or prevent sexual transmission of disease, especially HIV/AIDS.

Abstract translation: 本发明涉及脂肪酸和脂肪醇取代的核苷衍生物以及在多价支架（例如，聚合物，肽，多羧酸取代的化合物，含有多环维生素基团的化合物）上取代的核苷和核苷衍生物，其显示有效的抗HIV活性。 此外，它们显示增强的抗多药耐药性，R5和细胞相关病毒的活性。 其中一些还显示针对其他性传播病原体和精子的活动。 本发明提供了它们的合成方法，物质组成和使用方法。 强调其作为局部杀微生物剂的应用，以治疗或预防疾病，特别是艾滋病毒/艾滋病的性传播。

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。