Discovery of 3-acetyl-4-hydroxy-2-pyranone derivatives and their difluoridoborate complexes as a novel class of HIV-1 integrase inhibitors

HIV-1 integrase (IN) has emerged as an important therapeutic target for anti-HIV drug development. Its uniqueness to the virus and its critical role in the viral life cycle makes IN suitable for selective inhibition. The recent approval of Raltegravir (MK-0518) has created a surge in interest and great optimism in the field. In our ongoing IN drug design research, we herein report the discovery of substituted analogs of 3-acetyl-4-hydroxy-2-pyranones and their difluoridoborate complexes as novel IN inhibitors. In many of these compounds, complexation with boron difluoride increased the potency and selectivity of IN inhibition. Compound 9 was most active with an IC(50) value of 9 microM and 3 microM for 3'-processing and strand transfer inhibition, respectively.     

Coat Polymorphism in Eurasian Lynx: Adaptation to Environment or Phylogeographic Legacy?

Journal of Mammalian Evolution - We studied the relationship between the variability and contemporary distribution of pelage phenotypes in one of most widely distributed felid species and an array...     

Acylhydrazones of 20-keto steroids and their transformations: I. Synthesis and properties of 1′-acyl-substituted 3′-methylandrosteno[16,17-<Emphasis Type="Italic">d</Emphasis>]pyrazolines

Acetates of 3β-hydroxy-3′-methyl-1′(N)-acylandrost-5-eno[16,17-d]pyrazolines bearing monothiooxamide acyl groups were synthesized during the study of approaches to the synthesis of 3′-methylandrosteno[16,17-d]azoles, promising biologically active analogues of 20-keto pregnenanes, and their properties were investigated. The cyclization of Δ¹⁶-20-thiooxamidohydrazones to the corresponding heterocycles was shown to proceed under rigorous conditions and to depend partially on the nature of the oxamide grouping.     

Synthesis and antiviral activity of 3-(beta-D-ribofuranosyl)-1,2,4-oxadiazole-5-carboxamide

3-(beta-D-Ribofuranosyl)-1,2,4-oxadiazole-5-carboxamide (5) was prepared by condensation reaction of amidoxime 6 with monoethyl oxaloyl chloride followed by reaction with ammonia. The compound 5, however, did not exhibit any significant activity against herpes simplex virus type-I (HSV-I) and semliki forest virus (SFV).