Optimization of diarylazines as anti-HIV agents with dramatically enhanced solubility

• DOI: 10.1016/j.bmcl.2013.06.091
• Publication Date: 2013-07-08T13:03:22Z
• Authors: Mariela Bollini; José A. Cisneros; Krasimir A. Spasov; Karen S. Anderson; William L. Jorgensen
• Keywords: Etravirine; Rilpivirine; Reverse-transcriptase inhibitor

Non-nucleoside inhibitors of HIV-1 reverse transcriptase are reported that have ca. 100-fold greater solubility than the structurally related drugs etravirine and rilpivirine, while retaining high anti-viral activity. The solubility enhancements come from strategic placement of a morpholinylalkoxy substituent in the entrance channel of the NNRTI binding site. Compound 4d shows low-nanomolar activity similar to etravirine towards wild-type HIV-1 and key viral variants.