Masuda Naoyuki, Yamamoto Osamu, Fujii Masahiro, Ohgami Tetsuro, Fujiyasu Jiro, Kontani Toru, Moritomo Ayako, Orita Masaya, Kurihara Hiroyuki, Koga Hironobu, Nakahara Hideaki, Kageyama Shunji, Ohta Mitsuaki, Inoue Hiroshi, Hatta Toshifumi, Suzuki Hiroshi, Sudo Kenji, Shimizu Yasuaki, Kodama Eiichi, Matsuoka Masao, Fujiwara Masatoshi, Yokota Tomoyuki, Shigeta Shiro, Baba Masanori
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Bioorg Med Chem. 2004 Dec 1;12(23):6171-82. doi: 10.1016/j.bmc.2004.08.050.
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.
已经开展了一项随机高通量筛选（HTS）计划，以发现新型非核苷类逆转录酶抑制剂（NNRTIs），该计划使用MT-4细胞对抗对奈韦拉平耐药的病毒HIV-1（IIIB-R）。初步筛选出的一种噻唑烷苯磺酰胺衍生物具有良好的活性。一项系统修饰计划研究了噻唑环上3位、4位和5位的各种取代基，得到了具有增强抗HIV-1和逆转录酶（RT）抑制活性的化合物。这些结果证实了这些位置上的取代基以及噻唑烷苯磺酰胺基序作为下一代NNRTIs有价值的先导系列的重要作用。
