title: Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides.
abstract: 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.
authors.affiliation: Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. masuda.naoyuki@yamanouchi.co.jp
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Masuda
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujii
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ohgami
authors.forename: Jiro
authors.initials: J
authors.lastname: Fujiyasu
authors.forename: Toru
authors.initials: T
authors.lastname: Kontani
authors.forename: Ayako
authors.initials: A
authors.lastname: Moritomo
authors.forename: Masaya
authors.initials: M
authors.lastname: Orita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kurihara
authors.forename: Hironobu
authors.initials: H
authors.lastname: Koga
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakahara
authors.forename: Shunji
authors.initials: S
authors.lastname: Kageyama
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Ohta
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hatta
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Kenji
authors.initials: K
authors.lastname: Sudo
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kodama
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokota
authors.forename: Shiro
authors.initials: S
authors.lastname: Shigeta
authors.forename: Masanori
authors.initials: M
authors.lastname: Baba
mesh_terms: 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
chemical_list: D001557:Benzenesulfonates; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; D013844:Thiazoles; D019829:Nevirapine; D054303:HIV Reverse Transcriptase