2. Academic Validation
  3. Physicochemical property-driven optimization of diarylaniline compounds as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

Physicochemical property-driven optimization of diarylaniline compounds as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

  • Bioorg Med Chem Lett. 2014 Aug 15;24(16):3719-23. doi: 10.1016/j.bmcl.2014.07.011.
Na Liu 1,  Bingjie Qin 1,  Lian-Qi Sun 1,  Fei Yu 2,  Lu Lu 3,  Shibo Jiang 2,  Kuo-Hsiung Lee 4,  Lan Xie 5
Affiliations

Affiliations

  • 1 Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, China.
  • 2 Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China; Lindsley F. Kimball Research Institute, New York Blood Center, NY 10065, USA.
  • 3 Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China.
  • 4 Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA; Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan. Electronic address: khlee@unc.edu.
  • 5 Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, China. Electronic address: lanxie4@gmail.com.
PMID: 25042339 DOI: 10.1016/j.bmcl.2014.07.011
Abstract

Using physicochemical property-driven optimization, twelve new diarylaniline compounds (DAANs) (7a-h, 11a-b and 12a-b) were designed and synthesized. Among them, compounds 12a-b not only showed high potency (EC50 0.96-4.92 nM) against both wild-type and drug-resistant viral strains with the lowest fold change (FC 0.91 and 5.13), but also displayed acceptable drug-like properties based on aqueous solubility and lipophilicity (LE>0.3, LLE>5, LELP<10). The correlations between potency and physicochemical properties of these DAAN analogues are also described. Compounds 12a-b merit further development as potent clinical trial candidates against AIDS.

Keywords

Anti-HIV agents; Diarylaniline; NNRTIs; Physicochemical property.

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