Suppr超能文献

基于吡咯并吡啶和氨基吡啶的口服活性Met激酶抑制剂的发现。

Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors.

作者信息

Cai Zhen-Wei, Wei Donna, Schroeder Gretchen M, Cornelius Lyndon A M, Kim Kyoung, Chen Xiao-Tao, Schmidt Robert J, Williams David K, Tokarski John S, An Yongmi, Sack John S, Manne Veeraswamy, Kamath Amrita, Zhang Yueping, Marathe Punit, Hunt John T, Lombardo Louis J, Fargnoli Joseph, Borzilleri Robert M

机构信息

Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.

出版信息

Bioorg Med Chem Lett. 2008 Jun 1;18(11):3224-9. doi: 10.1016/j.bmcl.2008.04.047. Epub 2008 Apr 25.

DOI:10.1016/j.bmcl.2008.04.047
PMID:18479916
Abstract

A series of acylurea analogs derived from pyrrolopyridine and aminopyridine scaffolds were identified as potent inhibitors of Met kinase activity. The SAR at various positions of the two kinase scaffolds was investigated. These studies led to the discovery of compounds 3b and 20b, which demonstrated favorable pharmacokinetic properties in mice and significant antitumor activity in a human gastric carcinoma xenograft model.

摘要

一系列源自吡咯并吡啶和氨基吡啶骨架的酰脲类似物被鉴定为Met激酶活性的有效抑制剂。研究了这两种激酶骨架不同位置的构效关系。这些研究导致发现了化合物3b和20b，它们在小鼠中表现出良好的药代动力学性质，并在人胃癌异种移植模型中具有显著的抗肿瘤活性。

相似文献

1
Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors.
Bioorg Med Chem Lett. 2008 Jun 1;18(11):3224-9. doi: 10.1016/j.bmcl.2008.04.047. Epub 2008 Apr 25.
2
Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors.
Bioorg Med Chem Lett. 2010 May 1;20(9):2998-3002. doi: 10.1016/j.bmcl.2010.01.042. Epub 2010 Jan 20.
3
Identification of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors.
Bioorg Med Chem Lett. 2008 Jan 1;18(1):386-90. doi: 10.1016/j.bmcl.2007.10.018. Epub 2007 Oct 17.
4
Discovery of novel 2-aminopyridine-3-carboxamides as c-Met kinase inhibitors.
Bioorg Med Chem. 2012 Sep 1;20(17):5169-80. doi: 10.1016/j.bmc.2012.07.007. Epub 2012 Jul 16.
5
Discovery of a potent, selective, and orally bioavailable c-Met inhibitor: 1-(2-hydroxy-2-methylpropyl)-N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (AMG 458).
J Med Chem. 2008 Jul 10;51(13):3688-91. doi: 10.1021/jm800401t. Epub 2008 Jun 14.
6
Discovery of a novel and potent series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases.
Bioorg Med Chem Lett. 2008 May 1;18(9):2793-8. doi: 10.1016/j.bmcl.2008.04.009. Epub 2008 Apr 9.
7
Discovery of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines as potent inhibitors of the insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase.
Bioorg Med Chem Lett. 2009 Jun 1;19(11):3136-40. doi: 10.1016/j.bmcl.2008.12.110. Epub 2009 Jan 6.
8
Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily.
J Med Chem. 2009 Mar 12;52(5):1251-4. doi: 10.1021/jm801586s.
9
Synthesis, SAR, and Evaluation of 4-[2,4-Difluoro-5-(cyclopropylcarbamoyl)phenylamino]pyrrolo[2,1-f][1,2,4]triazine-based VEGFR-2 kinase inhibitors.
Bioorg Med Chem Lett. 2008 Feb 15;18(4):1354-8. doi: 10.1016/j.bmcl.2008.01.012. Epub 2008 Jan 9.
10
Discovery of pyrrolopyrimidine inhibitors of Akt.
Bioorg Med Chem Lett. 2010 Oct 1;20(19):5607-12. doi: 10.1016/j.bmcl.2010.08.053. Epub 2010 Aug 13.

引用本文的文献

1
Novel 3-phenylquinazolin-2,4(1H,3H)-diones as dual VEGFR-2/c-Met-TK inhibitors: design, synthesis, and biological evaluation.
Sci Rep. 2023 Oct 30;13(1):18567. doi: 10.1038/s41598-023-45687-y.
2
Type II c-Met inhibitors: molecular insight into crucial interactions for effective inhibition.
Mol Divers. 2022 Jun;26(3):1411-1423. doi: 10.1007/s11030-021-10267-7. Epub 2021 Jul 11.
3
Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors.
Bioorg Med Chem Lett. 2016 Aug 15;26(16):4101-5. doi: 10.1016/j.bmcl.2016.06.065. Epub 2016 Jun 25.
4
The azaindole framework in the design of kinase inhibitors.
Molecules. 2014 Nov 28;19(12):19935-79. doi: 10.3390/molecules191219935.
5
Discovery and Biological Evaluation of Novel Dual EGFR/c-Met Inhibitors.
ACS Med Chem Lett. 2014 Jan 30;5(4):298-303. doi: 10.1021/ml4003309. eCollection 2014 Apr 10.
6
Exploration of type II binding mode: A privileged approach for kinase inhibitor focused drug discovery?
ACS Chem Biol. 2014 Jun 20;9(6):1230-41. doi: 10.1021/cb500129t. Epub 2014 Apr 29.
7
Docking and quantitative structure-activity relationship studies for 3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)aniline, 3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)aniline, and 4-(4-amino-2-fluorophenoxy)-2-pyridinylamine derivatives as c-Met kinase inhibitors.
J Comput Aided Mol Des. 2011 Apr;25(4):349-69. doi: 10.1007/s10822-011-9425-1. Epub 2011 Apr 13.
8
Type-II kinase inhibitor docking, screening, and profiling using modified structures of active kinase states.
J Med Chem. 2008 Dec 25;51(24):7921-32. doi: 10.1021/jm8010299.

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