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)

被引：40

作者：

Devasthale, Pratik ^{[1
]}

Wang, Ying ^{[1
]}

Wang, Wei ^{[1
]}

Fevig, John ^{[1
]}

Feng, JianXin ^{[1
]}

Wang, Aiying ^{[2
]}

Harrity, Tom ^{[2
]}

Egan, Don ^{[2
]}

Morgan, Nathan ^{[2
]}

Cap, Michael ^{[2
]}

Fura, Aberra ^{[3
]}

Klei, Herbert E. ^{[4
]}

Kish, Kevin ^{[4
]}

Weigelt, Carolyn ^{[5
]}

Sun, Lucy ^{[3
]}

Levesque, Paul ^{[3
]}

Moulin, Frederic ^{[3
]}

Li, Yi-Xin ^{[3
]}

Zahler, Robert ^{[1
]}

Kirby, Mark S. ^{[2
]}

Hamann, Lawrence G. ^{[1
]}

机构：

[1] Bristol Myers Squibb Res & Dev, Metab Dis Chem, Princeton, NJ 08543 USA

[2] Bristol Myers Squibb Res & Dev, Metab Dis Biol, Princeton, NJ 08543 USA

[3] Bristol Myers Squibb Res & Dev, Pharmaceut Candidate Optimizat, Princeton, NJ 08543 USA

[4] Bristol Myers Squibb Res & Dev, Prot Sci & Struct, Princeton, NJ 08543 USA

[5] Bristol Myers Squibb Res & Dev, Comp Assisted Drug Design, Princeton, NJ 08543 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 56卷 / 18期

关键词：

PEPTIDASE-IV INHIBITOR; ACID-CHLORIDES; POTENT; DISCOVERY; REDUCTION; SAR;

D O I：

10.1021/jm4008906

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：7343 / 7357

页数：15

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