Author/Authors :
Shou-Fu Lu، نويسنده , , Binglong Chen، نويسنده , , Dave Davey، نويسنده , , Laura Dunning، نويسنده , , Stefan Jaroch، نويسنده , , Karen May-Newman، نويسنده , , James Onuffer، نويسنده , , Gary Phillips، نويسنده , , Babu Subramanyam، نويسنده , , Jih-Lie Tseng، نويسنده , , Robert G. Wei، نويسنده , , Ming Wei، نويسنده , , Bin Ye، نويسنده ,
Abstract :
The guanylhydrazone of 2-(4-chlorobenzyloxy)-5-bromobenzaldehyde, 1, with an IC50 of 840 nM against the CCR5 receptor was identified using high-throughput screening. Optimization efforts led to the discovery of a novel piperidine series of CCR5 antagonists. In particular, the 4-hydroxypiperidine derivative, 6k, had improved potency against CCR5, and was a starting point for further optimization. SAR elaboration using parallel synthesis led to the identification of 10h, a potent CCR5 antagonist with an IC50 of 11 nM.
