发现 N-取代的 7-氮杂吲哚作为泛 PIM 激酶抑制剂 - 先导优化 - 第三部分。
Discovery of N-substituted 7-azaindoles as Pan-PIM kinases inhibitors - Lead optimization - Part III.
机构信息
IDD Medicinal Chemistry, Sanofi, 153 Second Avenue, Waltham MA 02451, United States.
IDD Medicinal Chemistry, Sanofi, 153 Second Avenue, Waltham MA 02451, United States.
出版信息
Bioorg Med Chem Lett. 2019 Feb 1;29(3):491-495. doi: 10.1016/j.bmcl.2018.12.015. Epub 2018 Dec 10.
PMID:30553737
Abstract
N-substituted azaindoles were discovered as promising pan-PIM inhibitors. Lead optimization is described en route toward the identification of a clinical candidate. Modulation of physico-chemical properties allowed to solve inherent hERG and permeability liabilities. Compound 17 showed tumor growth inhibition in a KG1 tumor-bearing mouse model.
摘要
N-取代的氮杂吲哚被发现是一种很有前途的泛 PIM 抑制剂。本文描述了对先导化合物的优化过程，以确定一个临床候选药物。对理化性质的调节有助于解决内在的 hERG 和通透性问题。化合物 17 在 KG1 荷瘤小鼠模型中显示出肿瘤生长抑制作用。
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