Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides.
Bioorganic & medicinal chemistry 2004 Dec 1; 12(23):6171-82
Masuda N N, Yamamoto O O, Fujii M M, Ohgami T T, Fujiyasu J J, Kontani T T, Moritomo A A, Orita M M, Kurihara H H, Koga H H, Nakahara H H, Kageyama S S, Ohta M M, Inoue H H, Hatta T T, Suzuki H H, Sudo K K, Shimizu Y Y, Kodama E E, Matsuoka M M, Fujiwara M M, Yokota T T, Shigeta S S, Baba M 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.