Design, Synthesis, and Biological Activity of Novel Octahydro-1Hpyrrolo[3,2-c]pyridine Derivatives as C-C Chemokine Receptor Type 5 (CCR5) Antagonists

A series of novel octahydro-1H-pyrrolo[3,2-c] pyridine derivatives were designed and synthesized as C-C chemokine receptor type 5 (CCR5) antagonists, and their biological activity of anti-human immunodeficiency virus type 1 (HIV-1) is evaluated. A majority of these compounds showed anti-HIV-1 activities. Octahydro-1H-pyrrolo[3,2-c] pyridine derivative 19c exhibited potency against HIV-1 replication less than 1 mu mol circle L-1. Function assay was employed and the result showed that there were other drug targets for HIV-1 inhibition besides CCR5. In addition, the preliminary structure-activity relationship (SAR) of these compounds was rationalized by docking studies.