Chimirri A, Grasso S, Monforte A M, Monforte P, Rao A, Zappalà M, Bruno G, Nicolò F, Pannecouque C, Witvrouw M, De Clercq E
Dipartimento Farmaco-Chimico, Università di Messina, Italy.
Antivir Chem Chemother. 1998 Sep;9(5):431-8. doi: 10.1177/095632029800900507.
A series of novel 1-aryl-3-methyl-1H,3H-thiazolo[3,4-a]benzimidazoles, TBZ analogues, were synthesized and investigated as anti-human immunodeficiency virus (HIV) agents in order to study the effects of structural modifications on antiviral activity and cytotoxicity. They were proved to inhibit significantly HIV-1 replication in vitro without showing inhibitory activity on HIV-2 or simian immunodeficiency virus. Their potency was influenced by the presence of suitable substituents in the phenyl ring at C-1 as well as by their stereochemical characteristics. In fact, the most active compound of the series was the trans-1-(2,6-difluorophenyl)-3-methyl-1H,3H-thiazolo[3,4- a]benzimidazole, in which the butterfly-like conformation is stabilized by two intramolecular hydrogen bonds between the fluorine atoms and H-1 and H-3. This was made possible by the trans arrangement of C-1 and C-3 substituents, as shown by X-ray and NMR analysis.
合成了一系列新型的1-芳基-3-甲基-1H，3H-噻唑并[3,4-a]苯并咪唑类化合物（TBZ类似物），并作为抗人类免疫缺陷病毒（HIV）药物进行了研究，以探讨结构修饰对抗病毒活性和细胞毒性的影响。已证实它们能在体外显著抑制HIV-1复制，但对HIV-2或猴免疫缺陷病毒无抑制活性。其活性受C-1位苯环上合适取代基的存在及其立体化学特征的影响。事实上，该系列中活性最高的化合物是反式-1-(2,6-二氟苯基)-3-甲基-1H，3H-噻唑并[3,4-a]苯并咪唑，其中氟原子与H-1和H-3之间的两个分子内氢键使蝶状构象得以稳定。如X射线和核磁共振分析所示，C-1和C-3取代基的反式排列使得这一点成为可能。
