VICRIVIROC MALEATE

Vicriviroc is a chemokine (C-C motif) receptor 5 (CCR5) antagonist (K_i = 2.5 nM). It selectively inhibits CCR5 over M₁ and M₂ muscarinic acetylcholine receptors (K_is = >10,000 nM for both) and human-ether-a-go-go (hERG) potassium channels (IC₅₀ = 5.8 μM). Vicriviroc decreases chemotaxis induced by chemokine (C-C motif) ligand 3 (CCL3) in Ba/F3 cells expressing recombinant human CCR5 with an IC₅₀ value of 0.91 nM. It inhibits the replication of 30 R5-tropic HIV-1 clinical isolates in peripheral blood mononuclear cells (PBMCs; EC₅₀s = 0.04-1.4 nM) and reduces viral entry of seven drug-resistant strains of HIV-1 in U87 cells expressing CD4 and CCR5 (EC₅₀s = 8.7-32.9 nM).

Antiviral, CCR5 antagonist, treatment of autoimmune conditions.

[1] JAYARAM R. TAGAT. Piperazine-Based CCR5 Antagonists as HIV-1 Inhibitors. IV. Discovery of 1-[(4,6-Dimethyl-5-pyrimidinyl)carbonyl]- 4-[4-{2-methoxy-1(R)-4-(trifluoromethyl)phenyl}ethyl-3(S)-methyl-1-piperazinyl]- 4-methylpiperidine (Sch-417690/Sch-D), a Potent, Highly Selective, and Orally Bioavailable CCR5 Antagonist[J]. Journal of Medicinal Chemistry, 2004, 47 10: 2405-2408. DOI: 10.1021/jm0304515
[2] JULIE M STRIZKI. Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against human immunodeficiency virus type 1.[J]. Antimicrobial Agents and Chemotherapy, 2005: 4911-4919. DOI: 10.1128/aac.49.12.4911-4919.2005