| 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]py ridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778) - Devasthale_2013_J.Med.Chem_56_7343 |
| Author(s) : Devasthale P , Wang Y , Wang W , Fevig J , Feng J , Wang A , Harrity T , Egan D , Morgan N , Cap M , Fura A , Klei HE , Kish K , Weigelt C , Sun L , Levesque P , Moulin F , Li YX , Zahler R , Kirby MS , Hamann LG |
| Ref : Journal of Medicinal Chemistry , 56 :7343 , 2013 |
|
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. |
| PubMedSearch : Devasthale_2013_J.Med.Chem_56_7343 |
| PubMedID: 23964740 |
| Gene_locus related to this paper: human-DPP4 |
| Inhibitor | BMS-744891 CHEMBL2441952 |
| Gene_locus | human-DPP4 |
| Structure | 4LKO 4JH0 |
Devasthale P, Wang Y, Wang W, Fevig J, Feng J, Wang A, Harrity T, Egan D, Morgan N, Cap M, Fura A, Klei HE, Kish K, Weigelt C, Sun L, Levesque P, Moulin F, Li YX, Zahler R, Kirby MS, Hamann LG (2013)
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]py ridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778)
Journal of Medicinal Chemistry
56 :7343
Devasthale P, Wang Y, Wang W, Fevig J, Feng J, Wang A, Harrity T, Egan D, Morgan N, Cap M, Fura A, Klei HE, Kish K, Weigelt C, Sun L, Levesque P, Moulin F, Li YX, Zahler R, Kirby MS, Hamann LG (2013)
Journal of Medicinal Chemistry
56 :7343