构象受限的环状砜作为强效和选择性的 mTOR 激酶抑制剂。
Conformationally-restricted cyclic sulfones as potent and selective mTOR kinase inhibitors.
机构信息
Pfizer Global Research and Development, Chemistry Department, La Jolla, CA 92120, USA.
出版信息
Bioorg Med Chem Lett. 2012 Aug 1;22(15):5114-7. doi: 10.1016/j.bmcl.2012.05.104. Epub 2012 Jun 6.
PMID:22765900
Abstract
Novel conformationally-restricted mTOR kinase inhibitors with cyclic sulfone scaffold were designed. Synthesis and structure-activity relationship (SAR) studies are described with emphasis on optimization of the mTOR potency and selectivity against class I PI3Kα kinase. PF-05139962 was identified with excellent mTOR biochemical inhibition, cellular potency, kinase selectivity and in vitro ADME properties.
摘要
设计了具有环状砜骨架的新型构象受限的 mTOR 激酶抑制剂。描述了合成和结构-活性关系 (SAR) 研究，重点是优化 mTOR 对 I 类 PI3Kα 激酶的效力和选择性。PF-05139962 具有优异的 mTOR 生化抑制、细胞效力、激酶选择性和体外 ADME 性质。
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