Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides.
Masuda N,
Yamamoto O,
Fujii M,
Ohgami T,
Fujiyasu J,
Kontani T,
Moritomo A,
Orita M,
Kurihara H,
Koga H,
Nakahara H,
Kageyama S,
Ohta M,
Inoue H,
Hatta T,
Suzuki H,
Sudo K,
Shimizu Y,
Kodama E,
Matsuoka M,
Fujiwara M,
Yokota T,
Shigeta S,
Baba M.
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. masuda.naoyuki@yamanouchi.co.jp
A random high-throughput screening (HTS) program to discover novel nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been carried out with MT-4 cells against a nevirapine-resistant virus, HIV-1(IIIB-R). The primary hit, a thiazolidenebenzenesulfonamide derivative, possessed good activity. A systematic modification program examining various substituents at the 3-, 4-, and 5-positions on the thiazole ring afforded compounds with enhanced anti-HIV-1 and reverse transcriptase (RT) inhibitory activities. These results confirm the important role of the substituents at these positions and the thiazolidenebenzenesulfonamide motif as a valuable lead series for the next generation NNRTIs.
PMID: 15519161 [PubMed - indexed for MEDLINE]