Bioisostere of valtrate, anti-HIV principle by inhibition for nuclear export of Rev.
Rational design by the MO calculation disclosed 5,6-dihydrovaltrate (2) as the bioisostere of valtrate (1), the Rev-export inhibitor with anti-HIV activity. The synthesis of 2 was accomplished by ingenious use of asymmetric Diels-Alder reaction and stereoselective epoxidation associated with the adjacent hydroxyl group. Because of similar biological potency to 1, the analog 2 should be recognized as a promising scaffold for new anti-HIV agents with an unprecedented mechanism of action, inhibition for nuclear export of Rev protein, in the conventional remedy.
Tamura
Satoru
S
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Shimizu
Nobuhiro
N
Fujiwara
Katsuaki
K
Kaneko
Masafumi
M
Kimura
Tominori
T
Murakami
Nobutoshi
N
D021581:Active Transport, Cell Nucleus / Q000187:drug effects*; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D015694:Gene Products, rev / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy; D006367:HeLa Cells; D006801:Humans; D039823:Iridoids / Q000737:chemistry* / Q000494:pharmacology*; D008968:Molecular Conformation
D019380:Anti-HIV Agents; D015694:Gene Products, rev; D039823:Iridoids; C030127:valtrate