鉴定 5H-色烯并[3,4-c]吡啶和 6H-异色烯并[3,4-c]吡啶衍生物为强效和选择性双重 ROCK 抑制剂。
Identification of 5H-chromeno[3,4-c]pyridine and 6H-isochromeno[3,4-c]pyridine derivatives as potent and selective dual ROCK inhibitors.
机构信息
Research & Early Development, Bristol Myers Squibb, P.O. Box 5400, Princeton, NJ 08543-5400, USA.
Research & Early Development, Bristol Myers Squibb, P.O. Box 5400, Princeton, NJ 08543-5400, USA.
出版信息
Bioorg Med Chem Lett. 2020 Nov 1;30(21):127474. doi: 10.1016/j.bmcl.2020.127474. Epub 2020 Aug 15.
A novel series of 5H-chromeno[3,4-c]pyridine, 6H-isochromeno[3,4-c]pyridine and 6H-isochromeno[4,3-d]pyrimidine derivatives as dual ROCK1 and ROCK2 inhibitors is described. Optimization led to compounds with sub-nanomolar inhibitory affinity for both kinases and excellent kinome selectivity. Compound 19 exhibited ROCK1 and ROCK2 IC of 0.67 nM and 0.18 nM respectively.
本文描述了一系列新型的 5H-色烯并[3,4-c]吡啶、6H-异色烯并[3,4-c]吡啶和 6H-异色烯并[4,3-d]嘧啶衍生物，它们是双重 ROCK1 和 ROCK2 抑制剂。通过优化，得到了对两种激酶均具有亚纳摩尔抑制亲和力和极佳激酶选择性的化合物。化合物 19 对 ROCK1 和 ROCK2 的 IC50 分别为 0.67 nM 和 0.18 nM。
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