Suppr超能文献

发现新型氨基喹唑啉-7-基 6,7-二氢-吲哚-4-酮类化合物，作为热休克蛋白 90 的有效、选择性抑制剂。

Discovery of novel aminoquinazolin-7-yl 6,7-dihydro-indol-4-ones as potent, selective inhibitors of heat shock protein 90.

机构信息

Serenex Inc., 323 Foster Street, Durham, NC 27701, USA.

出版信息

Bioorg Med Chem Lett. 2012 Apr 1;22(7):2550-4. doi: 10.1016/j.bmcl.2012.01.137. Epub 2012 Feb 15.

DOI:10.1016/j.bmcl.2012.01.137
PMID:22386527
Abstract

A novel class of Hsp90 inhibitors, structurally distinct from previously reported scaffolds, was developed from rational design and optimization of a compound library screen hit. These aminoquinazoline derivatives, represented by compound 15 (SNX-6833) or 1-(2-amino-4-methylquinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one, selectively bind to Hsp90 and inhibit its cellular activities at concentrations as low as single digit nanomolar.

摘要

开发了一类新型的 Hsp90 抑制剂，其结构与以前报道的支架明显不同，是从化合物库筛选命中的合理设计和优化而来。这些氨基喹唑啉衍生物以化合物 15（SNX-6833）或 1-（2-氨基-4-甲基喹唑啉-7-基）-3,6,6-三甲基-6,7-二氢-1H-吲哚-4（5H）-酮为代表，以低至个位数纳摩尔的浓度选择性结合 Hsp90 并抑制其细胞活性。

相似文献

1
Discovery of novel aminoquinazolin-7-yl 6,7-dihydro-indol-4-ones as potent, selective inhibitors of heat shock protein 90.
Bioorg Med Chem Lett. 2012 Apr 1;22(7):2550-4. doi: 10.1016/j.bmcl.2012.01.137. Epub 2012 Feb 15.
2
Discovery of benzamide tetrahydro-4H-carbazol-4-ones as novel small molecule inhibitors of Hsp90.
Bioorg Med Chem Lett. 2008 Jun 15;18(12):3517-21. doi: 10.1016/j.bmcl.2008.05.023. Epub 2008 May 9.
3
Tricyclic series of heat shock protein 90 (Hsp90) inhibitors part I: discovery of tricyclic imidazo[4,5-c]pyridines as potent inhibitors of the Hsp90 molecular chaperone.
J Med Chem. 2011 Oct 27;54(20):7206-19. doi: 10.1021/jm200784m. Epub 2011 Oct 5.
4
Discovery of benzisoxazoles as potent inhibitors of chaperone heat shock protein 90.
J Med Chem. 2008 Feb 14;51(3):373-5. doi: 10.1021/jm701385c. Epub 2008 Jan 16.
5
A novel class of Hsp90 inhibitors isolated by structure-based virtual screening.
Bioorg Med Chem Lett. 2007 Nov 15;17(22):6345-9. doi: 10.1016/j.bmcl.2007.08.069. Epub 2007 Sep 1.
6
Fragment-based hit discovery and structure-based optimization of aminotriazoloquinazolines as novel Hsp90 inhibitors.
Bioorg Med Chem. 2014 Aug 1;22(15):4135-50. doi: 10.1016/j.bmc.2014.05.056. Epub 2014 Jun 14.
7
Novel inhibitors of epidermal growth factor receptor: (4-(Arylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)(1H-indol-2-yl)methanones and (1H-indol-2-yl)(4-(phenylamino)thieno[2,3-d]pyrimidin-6-yl)methanones.
Bioorg Med Chem. 2012 Jan 1;20(1):125-36. doi: 10.1016/j.bmc.2011.11.023. Epub 2011 Nov 20.
8
Discovery of 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones as potent and selective Hsp90 inhibitors.
Bioorg Med Chem Lett. 2009 May 15;19(10):2860-4. doi: 10.1016/j.bmcl.2009.03.074. Epub 2009 Mar 24.
9
Optimization of potent, selective, and orally bioavailable pyrrolodinopyrimidine-containing inhibitors of heat shock protein 90. Identification of development candidate 2-amino-4-{4-chloro-2-[2-(4-fluoro-1H-pyrazol-1-yl)ethoxy]-6-methylphenyl}-N-(2,2-difluoropropyl)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxamide.
J Med Chem. 2011 May 12;54(9):3368-85. doi: 10.1021/jm200128m. Epub 2011 Apr 20.
10
Novel 3,4-isoxazolediamides as potent inhibitors of chaperone heat shock protein 90.
J Med Chem. 2011 Dec 22;54(24):8592-604. doi: 10.1021/jm201155e. Epub 2011 Nov 23.

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型，支持多种主流文档格式。

立即体验