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Diarylaniline derivatives as a distinct class of HIV-1 non-nucleoside reverse transcriptase inhibitors.

Publication ,  Journal Article
Qin, B; Jiang, X; Lu, H; Tian, X; Barbault, F; Huang, L; Qian, K; Chen, C-H; Huang, R; Jiang, S; Lee, K-H; Xie, L
Published in: J Med Chem
July 8, 2010

By using structure-based drug design and isosteric replacement, diarylaniline and 1,5-diarylbenzene-1,2-diamine derivatives were synthesized and evaluated against wild type HIV-1 and drug-resistant viral strains, resulting in the discovery of diarylaniline derivatives as a distinct class of next-generation HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) agents. The most promising compound 37 showed significant EC(50) values of 0.003-0.032 microM against HIV-1 wild-type strains and of 0.005-0.604 microM against several drug-resistant strains. Current results also revealed important structure-activity relationship (SAR) conclusions for diarylanilines and strongly support our hypothesis that an NH(2) group on the central benzene ring ortho to the aniline moiety is crucial for interaction with K101 of the NNRTI binding site in HIV-1 RT, likely by forming H-bonds with K101. Furthermore, molecular modeling studies with molecular mechanism/general Born surface area (MM/GBSA) technology demonstrated the rationality of our hypothesis.

Duke Scholars

Published In

J Med Chem

DOI

EISSN

1520-4804

Publication Date

July 8, 2010

Volume

53

Issue

13

Start / End Page

4906 / 4916

Location

United States

Related Subject Headings

  • Structure-Activity Relationship
  • Spectrometry, Mass, Electrospray Ionization
  • Reverse Transcriptase Inhibitors
  • Models, Molecular
  • Medicinal & Biomolecular Chemistry
  • Magnetic Resonance Spectroscopy
  • Hydrogen Bonding
  • Humans
  • HIV-1
  • HIV Reverse Transcriptase
 

Citation

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Qin, B., Jiang, X., Lu, H., Tian, X., Barbault, F., Huang, L., … Xie, L. (2010). Diarylaniline derivatives as a distinct class of HIV-1 non-nucleoside reverse transcriptase inhibitors. J Med Chem, 53(13), 4906–4916. https://doi.org/10.1021/jm1002952
Qin, Bingjie, Xingkai Jiang, Hong Lu, Xingtao Tian, Florent Barbault, Li Huang, Keduo Qian, et al. “Diarylaniline derivatives as a distinct class of HIV-1 non-nucleoside reverse transcriptase inhibitors.J Med Chem 53, no. 13 (July 8, 2010): 4906–16. https://doi.org/10.1021/jm1002952.
Qin B, Jiang X, Lu H, Tian X, Barbault F, Huang L, et al. Diarylaniline derivatives as a distinct class of HIV-1 non-nucleoside reverse transcriptase inhibitors. J Med Chem. 2010 Jul 8;53(13):4906–16.
Qin, Bingjie, et al. “Diarylaniline derivatives as a distinct class of HIV-1 non-nucleoside reverse transcriptase inhibitors.J Med Chem, vol. 53, no. 13, July 2010, pp. 4906–16. Pubmed, doi:10.1021/jm1002952.
Qin B, Jiang X, Lu H, Tian X, Barbault F, Huang L, Qian K, Chen C-H, Huang R, Jiang S, Lee K-H, Xie L. Diarylaniline derivatives as a distinct class of HIV-1 non-nucleoside reverse transcriptase inhibitors. J Med Chem. 2010 Jul 8;53(13):4906–4916.
Journal cover image

Published In

J Med Chem

DOI

EISSN

1520-4804

Publication Date

July 8, 2010

Volume

53

Issue

13

Start / End Page

4906 / 4916

Location

United States

Related Subject Headings

  • Structure-Activity Relationship
  • Spectrometry, Mass, Electrospray Ionization
  • Reverse Transcriptase Inhibitors
  • Models, Molecular
  • Medicinal & Biomolecular Chemistry
  • Magnetic Resonance Spectroscopy
  • Hydrogen Bonding
  • Humans
  • HIV-1
  • HIV Reverse Transcriptase