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

  • Bioorg Med Chem Lett. 2013 Sep 15;23(18):5213-6. doi: 10.1016/j.bmcl.2013.06.091.
Mariela Bollini  1 ,  José A Cisneros ,  Krasimir A Spasov ,  Karen S Anderson ,  William L Jorgensen
Affiliations
  • 1. Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA.
PMID: 23937980 DOI: 10.1016/j.bmcl.2013.06.091
Abstract

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.

Keywords
Anti-HIV agent; Drug solubility; NNRTI.