PDBsum entry 4jh0

Hydrolase

PDB id: 4jh0

Contents

Protein chain

728 a.a.

Ligands

1MD ×2

Waters ×74

References listed in PDB file

Key reference

• Title: Optimization of activity, Selectivity, And liability profiles in 5-Oxopyrrolopyridine dpp4 inhibitors leading to clinical candidate (sa)-2-(3-(Aminomethyl)-4-(2,4-Dichlorophenyl)-2-Methyl-5-Oxo-5h-Pyrrolo[3,4-B]pyridin-6(7h)-Yl)-N,N-Dimethylacetamide (bms-767778).
• Authors: P.Devasthale, Y.Wang, W.Wang, J.Fevig, J.Feng, A.Wang, T.Harrity, D.Egan, N.Morgan, M.Cap, A.Fura, H.E.Klei, K.Kish, C.Weigelt, L.Sun, P.Levesque, F.Moulin, Y.X.Li, R.Zahler, M.S.Kirby, L.G.Hamann.
• Ref.: J Med Chem, 2013, 56, 7343-7357. [DOI no: 10.1021/jm4008906]
• PubMed id: 23964740

Abstract

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.