Conformationally Constrained Analogues of Diacylglycerol Having a Perhydrofuro[3,4-c]furan-1,4-dione Bis-${\gamma}$-butyrolactone Skeleton

  • Lee, Jee-Woo (College of Pharmacy, Seoul National University) ;
  • Nancy-E. Lewin (Laboratories of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Isntitute of Health) ;
  • Peter-M. Blumberg (Laboratories of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Isntitute of Health) ;
  • Victor-E. Marquez (Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, National Institutes of Health)
  • 발행 : 1998.04.01

초록

Bis-${\gamma}$-lactones (1,2) having a perhydrofuro[3,4-c]furan-1,4-dione skeleton were designed as conformationally constrained diacylglycerol analogues. They were synthesized from D-apiose in 11 steps, and evaluated as $PKC-{\alpha}$ ligands by measuring their ability to displace bound $^3H$]PDBU from the enzyme. The compounds showed moderate binding affinities with $K_i$ values of 13.89 (${\pm}5.67$) ${\mu}M$ and 11.47 (${\pm}0.89$) ${\mu}M$, respectively. Their similar binding affinities indicate that these two bicyclic compounds were not effectively discriminated by $PKC-{\alpha}$ in terms of the direction of the side chain as other ligands built on similar bis-${\gamma}$-lactones.

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