1 structure: 3SX4: Crystal structure of human DPP-IV in complex with SA-(+)-3-(aminomethyl)-4-(2,4-dichlorophenyl)-6-(2-methoxyphenyl)-2-methyl-5H-pyrrolo[3,4-B]pyridin-7(6H)-one
Design, synthesis, and SAR of 7-oxopyrrolopyridine-derived DPP4 inhibitors are described. The preferred stereochemistry of these atropisomeric biaryl analogs has been identified as Sa. Compound (+)-3t, with a K(i) against DPP4, DPP8, and DPP9 of 0.37 nM, 2.2, and 5.7 muM, respectively, showed a significant improvement in insulin response after single doses of 3 and 10 mumol/kg in ob/ob mice.
