Combinatorial synthesis of CCR5 antagonists

Herein we report the preparation of a combinatorial library of compounds with potent CCR5 binding affinity. The library design was aided by SAR generated in a traditional medicinal chemistry effort. Compounds with novel combinations of subunits were discovered that have high binding affinity for the CCR5 receptor. A potent CCR5 antagonist from the library, compound 11 was found to have moderate anti-HIV-1 activity. The synthesis of the combinatorial library of CCR5 antagonists is reported. Compound 2 was discovered, which has a 1 nM IC 50 in a CCR5 binding assay and inhibits HIV-1 replication with an IC 95 of 580 nM.