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

Mariela Bollini; José A. Cisneros; Krasimir A. Spasov; Karen S. Anderson; William L. Jorgensen

doi:10.1016/j.bmcl.2013.06.091

Abstract

1 min read

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.

Related publications

Article2023

Discovery of diarylpyrimidine derivatives bearing piperazine sulfonyl as potent HIV-1 nonnucleoside reverse transcriptase inhibitors

Xiangyi Jiang, Boshi Huang, Shawn Rumrill, David Pople, Waleed A. Zalloum, Dongwei Kang, Fabao Zhao, Xiangkai Ji, Zhen Gao, Lide Hu, Zhao Wang, Minghui Xie, De Clercq Erik, Francesc X. Ruiz, Eddy Arnold, Christophe Pannecouque, Xinyong Liu, Peng Zhan

Article2015

Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase

Won-Gil Lee, Kathleen M. Frey, Ricardo Gallardo‐Macias, Krasimir A. Spasov, Albert H. Chan, Karen S. Anderson, William L. Jorgensen

Bioorganic & Medicinal Chemistry Letters

Article2016

Computer-aided discovery of anti-HIV agents

William L. Jorgensen

Bioorganic & Medicinal Chemistry

Article2013

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

Mariela Bollini, Kathleen M. Frey, José A. Cisneros, Krasimir A. Spasov, Kalyan Das, Joseph D. Bauman, Eddy Arnold, Karen S. Anderson, William L. Jorgensen

Bioorganic & Medicinal Chemistry Letters

Article2012

Discovery of dimeric inhibitors by extension into the entrance channel of HIV-1 reverse transcriptase

Anil R. Ekkati, Mariela Bollini, Robert A. Domaoal, Krasimir A. Spasov, Karen S. Anderson, William L. Jorgensen

Bioorganic & Medicinal Chemistry Letters

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

Abstract

Discussion(0)

Related publications

Discovery of diarylpyrimidine derivatives bearing piperazine sulfonyl as potent HIV-1 nonnucleoside reverse transcriptase inhibitors

Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase

Computer-aided discovery of anti-HIV agents

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

Discovery of dimeric inhibitors by extension into the entrance channel of HIV-1 reverse transcriptase