Literature

Abstract

Thirteen novel seco-DCK analogs (4-16) with several new skeletons were designed, synthesized and screened for in vitro anti-HIV-1 activity. Among them, three compounds (5, 13, and 16) showed moderate activity, and compound 9 exhibited the best activity with an EC(50) value of 0.058 microM and a therapeutic index (TI) of 1000. The activity of 9 was better than that of 4-methyl DCK (2, EC(50): 0.126 microM, TI: 301.2) in the same assay. Additionally, 9 also showed antiviral activity against a multi-RT inhibitor-resistant strain (RTMDR), which is insensitive to most DCK analogs. Compared with 2, compound 9 has a less complex structure, fewer hydrogen-bond acceptors, and a reduced log P value. Therefore, it is likely to exhibit better ADME, and appears to be a promising new lead for further development as an anti-HIV candidate.

DOI： 10.1016/j.bmc.2010.04.089

Anti-AIDS agents 82: Synthesis of seco-(3′R,4′R)-3′,4′-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives as novel anti-HIV agents

Bioorganic & Medicinal Chemistry 2010.0

Anti-AIDS agents. Part 58: Synthesis and anti-HIV activity of 1-thia-di-O-(−)-camphanoyl-(+)-cis-khellactone (1-thia-DCK) analogues

Bioorganic & Medicinal Chemistry Letters 2004.0

Anti-AIDS Agents. 42. Synthesis and Anti-HIV Activity of Disubstituted (3‘R,4‘R)-3‘,4‘-Di-O-(S)-camphanoyl-(+)-cis-khellactone Analogues

Journal of Medicinal Chemistry 2001.0

Anti-AIDS agents. Part 47: synthesis and anti-HIV activity of 3-substituted 3′,4′-Di-O-(S)-camphanoyl-(3′R,4′R)-(+)-cis-khellactone derivatives

Bioorganic & Medicinal Chemistry Letters 2001.0

Anti-AIDS agents 84. Synthesis and anti-human immunodeficiency virus (HIV) activity of 2′-monomethyl-4-methyl- and 1′-thia-4-methyl-(3′R,4′R)-3′,4′-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs☆

Bioorganic & Medicinal Chemistry 2010.0

Anti-AIDS agents-XXVIII.1 Synthesis and Anti-HIV activity of methoxy substituted 3′,4′-Di-O-(−)-camphanoyl-(+)-cis-khellactone (DCK) analogues