Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides.
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.
Masuda
Naoyuki
N
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. masuda.naoyuki@yamanouchi.co.jp
Yamamoto
Osamu
O
Fujii
Masahiro
M
Ohgami
Tetsuro
T
Fujiyasu
Jiro
J
Kontani
Toru
T
Moritomo
Ayako
A
Orita
Masaya
M
Kurihara
Hiroyuki
H
Koga
Hironobu
H
Nakahara
Hideaki
H
Kageyama
Shunji
S
Ohta
Mitsuaki
M
Inoue
Hiroshi
H
Hatta
Toshifumi
T
Suzuki
Hiroshi
H
Sudo
Kenji
K
Shimizu
Yasuaki
Y
Kodama
Eiichi
E
Matsuoka
Masao
M
Fujiwara
Masatoshi
M
Yokota
Tomoyuki
T
Shigeta
Shiro
S
Baba
Masanori
M
D001557:Benzenesulfonates; D001665:Binding Sites; D024882:Drug Resistance, Viral; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects; D015394:Molecular Structure; D019829:Nevirapine; D011485:Protein Binding; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology; D013844:Thiazoles; D014779:Virus Replication / Q000187:drug effects
D001557:Benzenesulfonates; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; D013844:Thiazoles; D019829:Nevirapine; D054303:HIV Reverse Transcriptase