Lian-Qi Sun

Publications (2)7.45 Total impact

• Article: Design, synthesis, and preclinical evaluations of novel 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) drug candidates.

  Lian-Qi Sun, Lei Zhu, Keduo Qian, Bingjie Qin, Li Huang, Chin Ho Chen, Kuo-Hsiung Lee, Lan Xie
  [show abstract] [hide abstract]
  ABSTRACT: Twenty-one new 4-substituted diarylaniline compounds (DAANs) (series 13, 14, and 15) were designed, synthesized, and evaluated against wild-type and drug resistant HIV-1 viral strains. As a result, approximately a dozen new DAANs showed high potency with low nano- to subnanomolar EC(50) values ranging from 0.2 to 10 nM. The three most promising compounds 14e, 14h, and 15h exhibited high potency against wild-type and drug-resistant viral strains with EC(50) values at the subnanomolar level (0.29-0.87 nM) and were comparable to or more potent than the new NNRTI drug riplivirine (2) in the same assays. Druglike physicochemical property assessments revealed that the most active DAANs (EC(50) < 10 nM) have better aqueous solubility (>1-90 μg/mL at pH 7.4 and pH 2) and metabolic stability in vitro than 2, as well as desirable log P values (<5) and polar surface areas (PSA) (<140 Å(2)). These promising results warrant further development of this novel compound class as potential potent anti-AIDS clinical trial candidates.
  Journal of Medicinal Chemistry 08/2012; 55(16):7219-29. · 4.80 Impact Factor
• Article: Optimization of 2,4-diarylanilines as non-nucleoside HIV-1 reverse transcriptase inhibitors.

  Lian-Qi Sun, Bingjie Qin, Li Huang, Keduo Qian, Chin-Ho Chen, Kuo-Hsiung Lee, Lan Xie
  [show abstract] [hide abstract]
  ABSTRACT: The current optimization of 2,4-diarylaniline analogs (DAANs) on the central phenyl ring provided a series of new active DAAN derivatives 9a-9e, indicating an accessible modification approach that could improve anti-HIV potency against wild-type and resistant strains, aqueous solubility, and metabolic stability. A new compound 9e not only exhibited extremely high potency against wild-type virus (EC(50) 0.53 nM) and several resistant viral strains (EC(50) 0.36-3.9 nM), but also showed desirable aqueous solubility and metabolic stability, which were comparable or better than those of the anti-HIV-1 drug TMC278 (2). Thus, new compound 9e might be a potential drug candidate for further development of novel next-generation NNRTIs.
  Bioorganic & medicinal chemistry letters 02/2012; 22(7):2376-9. · 2.65 Impact Factor