Optimization of Activity, Selectivity, and Liability Profiles in 5-0xopyrrolopyridine DPP4 Inhibitors Leading to Clinical Candidate (Sa)-2-(3-(Aminomethyl)-4-(2,4-dichloropheny1)-2-methyl5-oxo-5H-pyrrolo(3,4-b)pyridin-6(7H)-y1)-N,N-dimethylacetamide (BMS-767778)
Optimization of Activity, Selectivity, and Liability Profiles in 5-0xopyrrolopyridine DPP4 Inhibitors Leading to Clinical Candidate (Sa)-2-(3-(Aminomethyl)-4-(2,4-dichloropheny1)-2-methyl5-oxo-5H-pyrrolo(3,4-b)pyridin-6(7H)-y1)-N,N-dimethylacetamide (BMS-767778)
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DOI：
10.1021/jm4008906
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发表时间：
2013-09-26
影响因子：
7.3
通讯作者：
Hamann, Lawrence G.
中科院分区：
文献类型：
--
作者：
Devasthale, Pratik;Wang, Ying;Hamann, Lawrence G.
基于我们先前对许多相关双环系列的工作开发的结构活性关系（SAR），对5-氧代吡咯并吡啶系列进行优化，得到化合物2（BMS-767778），其总体活性、选择性、有效性、PK和可开发性特征适合于进展至临床。SAR的系列和表征的2s进行了说明。
Optimization of a 5-oxopyrrolopyridine series based upon structure activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the clinic. SAR in the series and characterization of 2s are described.