1265592-08-2Relevant academic research and scientific papers
PROCESSES AND INTERMEDIATES FOR PREPARING SUBSTITUTED HEXAHYDROFURO [2,3-B] FURANS
-
, (2012/06/16)
The invention described herein pertains to processes and compounds useful in the preparation of bis-tetrahydrofurans. The invention described herein also pertains to compounds useful for treating HIV infections.
Design, synthesis, and X-ray structure of substituted bis-tetrahydrofuran (bis-THF)-derived potent HIV-1 protease inhibitors
Ghosh, Arun K.,Martyr, Cuthbert D.,Steffey, Melinda,Wang, Yuan-Fang,Agniswamy, Johnson,Amano, Masayuki,Weber, Irene T.,Mitsuya, Hiroaki
, p. 298 - 302 (2011/06/21)
We investigated substituted bis-THF-derived HIV-1 protease inhibitors in order to enhance ligand-binding site interactions in the HIV-1 protease active site. In this context, we have carried out convenient syntheses of optically active bis-THF and C4-substituted bis-THF ligands using a [2,3]-sigmatropic rearrangement as the key step. The synthesis provided convenient access to a number of substituted bis-THF derivatives. Incorporation of these ligands led to a series of potent HIV-1 protease inhibitors. Inhibitor 23c turned out to be the most potent (Ki = 2.9 pM; IC50 = 2.4 nM) among the inhibitors. An X-ray structure of 23c-bound HIV-1 protease showed extensive interactions of the inhibitor with the protease active site, including a unique water-mediated hydrogen bond to the Gly-48 amide NH in the S2 site.
