TY - JOUR
T1 - Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1
T2 - Design and synthesis of thiazolidenebenzenesulfonamides
AU - Masuda, Naoyuki
AU - Yamamoto, Osamu
AU - Fujii, Masahiro
AU - Ohgami, Tetsuro
AU - Fujiyasu, Jiro
AU - Kontani, Toru
AU - Moritomo, Ayako
AU - Orita, Masaya
AU - Kurihara, Hiroyuki
AU - Koga, Hironobu
AU - Nakahara, Hideaki
AU - Kageyama, Shunji
AU - Ohta, Mitsuaki
AU - Inoue, Hiroshi
AU - Hatta, Toshifumi
AU - Suzuki, Hiroshi
AU - Sudo, Kenji
AU - Shimizu, Yasuaki
AU - Kodama, Eiichi
AU - Matsuoka, Masao
AU - Fujiwara, Masatoshi
AU - Yokota, Tomoyuki
AU - Shigeta, Shiro
AU - Baba, Masanori
PY - 2004/12/1
Y1 - 2004/12/1
N2 - A series of thiazolidenebenzenesulfonamides have been discovered as nonnucleoside reverse transcriptase inhibitors. Compound 17a exhibited the most potent inhibitory activity against the Y181C mutant reverse transcriptase (RT). The introduction of the 4-chloro-5-isopropyl moiety (17k) markedly increased the activity against the wild type RT. Both 17a and 17k strongly inhibited HIV-1 replication. 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.
AB - A series of thiazolidenebenzenesulfonamides have been discovered as nonnucleoside reverse transcriptase inhibitors. Compound 17a exhibited the most potent inhibitory activity against the Y181C mutant reverse transcriptase (RT). The introduction of the 4-chloro-5-isopropyl moiety (17k) markedly increased the activity against the wild type RT. Both 17a and 17k strongly inhibited HIV-1 replication. 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.
KW - Benzenesulfonamide
KW - Nonnucleoside HIV-1 reverse transcriptase inhibitor
KW - Thiazolidene
UR - http://www.scopus.com/inward/record.url?scp=7444224177&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=7444224177&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2004.08.050
DO - 10.1016/j.bmc.2004.08.050
M3 - Article
C2 - 15519161
AN - SCOPUS:7444224177
VL - 12
SP - 6171
EP - 6182
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 23
ER -
