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).
J Med Chem
; 56(18): 7343-57, 2013 Sep 26.
Article
de En
| MEDLINE
| ID: mdl-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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Pyrroles
/
Conception de médicament
/
Dipeptidyl peptidase 4
/
Composés hétérocycliques bicycliques
/
Inhibiteurs de la dipeptidyl-peptidase IV
/
Acétamides
Limites:
Animals
/
Humans
/
Male
Langue:
En
Journal:
J Med Chem
Sujet du journal:
QUIMICA
Année:
2013
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique