Title of article :
Modeling assisted rational design of novel, potent, and selective pyrrolopyrimidine DPP-4 inhibitors
Author/Authors :
Yingduo Gao، نويسنده , , Dennis Feng، نويسنده , , Robert P. Sheridan، نويسنده , , Giovanna Scapin، نويسنده , , Sangita B. Patel، نويسنده , , Joseph K. Wu، نويسنده , , Xiaoping Zhang، نويسنده , , Ranabir Sinha-Roy، نويسنده , , Nancy A. Thornberry، نويسنده , , Ann E. Weber، نويسنده , , Tesfaye Biftu، نويسنده ,
Abstract :
Molecular modeling was used to improve potency of the cyclohexylamine series. In addition, a 3-D QSAR method was used to gain insight for reducing off-target DPP-8/9 activities. Compounds 3, 4, and 5 were synthesized and found to be potent DPP-4 inhibitors, in particular 4 and 5 are designed to be highly selective against off-target DASH enzymes while maintaining potency on DPP-4.
Keywords :
DPP-4 , Molecular modeling , Potency , Selectivity against DPP-8/9
