Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides

Naoyuki Masuda, Osamu Yamamoto, Masahiro Fujii, Tetsuro Ohgami, Jiro Fujiyasu, Toru Kontani, Ayako Moritomo, Masaya Orita, Hiroyuki Kurihara, Hironobu Koga, Hideaki Nakahara, Shunji Kageyama, Mitsuaki Ohta, Hiroshi Inoue, Toshifumi Hatta, Hiroshi Suzuki, Kenji Sudo, Yasuaki Shimizu, Eiichi Kodama, Masao MatsuokaMasatoshi Fujiwara, Tomoyuki Yokota, Shiro Shigeta, Masanori Baba

研究成果: Article査読

22 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)6171-6182
ページ数12
ジャーナルBioorganic and Medicinal Chemistry
12
23
DOI
出版ステータスPublished - 2004 12 1
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

フィンガープリント

「Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル