Extension into the entrance channel of HIV-1 reverse transcriptase--crystallography and enhanced solubility

  • Bioorg Med Chem Lett. 2013 Sep 15;23(18):5209-12. doi: 10.1016/j.bmcl.2013.06.093.
Mariela Bollini  1 ,  Kathleen M Frey ,  José A Cisneros ,  Krasimir A Spasov ,  Kalyan Das ,  Joseph D Bauman ,  Eddy Arnold ,  Karen S Anderson ,  William L Jorgensen
Affiliations
  • 1. Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA.
PMID: 23899617 DOI: 10.1016/j.bmcl.2013.06.093
Abstract

Non-nucleoside inhibitors of HIV-1 Reverse Transcriptase (HIV-RT) are reported that feature extension into the entrance channel near Glu138. Complexes of the parent anilinylpyrimidine 1 and the morpholinoethoxy analog 2j with HIV-RT have received crystallographic characterization confirming the designs. Measurement of aqueous solubilities of 2j, 2k, the parent triazene 2a, and Other NNRTIs demonstrate profound benefits for addition of the morpholinyl substituent.

Keywords
Anti-HIV agent; Crystal structures; Drug solubility; NNRTI.