1. Academic Validation
  2. Structure-activity modifications of the HIV-1 inhibitors (+)-calanolide A and (-)-calanolide B

Structure-activity modifications of the HIV-1 inhibitors (+)-calanolide A and (-)-calanolide B

  • J Med Chem. 1996 Oct 25;39(22):4507-10. doi: 10.1021/jm9602827.
D L Galinis 1 R W Fuller T C McKee J H Cardellina 2nd R J Gulakowski J B McMahon M R Boyd
Affiliations

Affiliation

  • 1 Laboratory of Drug Discovery Research and Development, National Cancer Institute, Frederick, Maryland 21702-1201, USA.
Abstract

The delta 7,8 olefinic linkages within (+)-calanolide A(1) and (-)-calanolide B(2) were catalytically reduced to determine impact on the anti-HIV activity of the parent compounds. In addition, a series of structure modifications of the C-12 hydroxyl group in (-)-calanolide B was made to investigate the importance of that substituent to the HIV-1 inhibitory activity of these Coumarins. A total of 14 analogs were isolated or prepared and compared to (+)-calanolide A and (-)-calanolide B in the NCI primary anti-HIV assay. While none of the compounds showed activity superior to the two unmodified leads, some structure-activity requirements were apparent from the relative anti-HIV potencies of the various analogs.

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