Balzarini J, Brouwer W G, Felauer E E, De Clercq E, Karlsson A
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Antiviral Res. 1995 Jun;27(3):219-36. doi: 10.1016/0166-3542(95)00006-8.
A large variety of carboxanilide derivates in which the original oxathiin moiety present in the prototype compound UC84 was replaced by a non-cyclic lipophilic entity has been evaluated for their inhibitory effect against wild-type human immunodeficiency virus type 1 (HIV-1/IIIB) and several mutant viruses derived thereof (i.e. HIV-1/138-Lys, HIV-1/181-Cys, HIV-1/106-Ala and HIV-1/100-IIe). Isopropoxy was the most favorable substituent resulting in molecules that were markedly inhibitory to the wild-type (EC50 0.004-0.04 microgram/ml) as well as the mutant HIV-1 strains (EC50 0.06-0.75 microgram/ml). In this respect, they proved superior to several other HIV-1-specific non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are currently the subject of clinical trials. One of the most potent HIV-1 inhibitors among the thiocarboxanilide derivatives, namely UC38, selected for a mutant virus strain in which Lys at position 101 and Gly at position 190 of the reverse transcriptase was replaced by Glu.
已经评估了多种羧酰苯胺衍生物，其中原型化合物UC84中存在的原始恶二唑部分被非环状亲脂性实体取代，评估了它们对野生型人类免疫缺陷病毒1型（HIV-1/IIIB）及其衍生的几种突变病毒（即HIV-1/138-Lys、HIV-1/181-Cys、HIV-1/106-Ala和HIV-1/100-IIe）的抑制作用。异丙氧基是最有利的取代基，产生的分子对野生型（EC50为0.004-0.04微克/毫升）以及突变型HIV-1菌株（EC50为0.06-0.75微克/毫升）具有明显的抑制作用。在这方面，它们被证明优于目前正在进行临床试验的其他几种HIV-1特异性非核苷逆转录酶抑制剂（NNRTIs）。硫代羧酰苯胺衍生物中最有效的HIV-1抑制剂之一，即UC38，被选用于一种突变病毒株，其中逆转录酶第101位的赖氨酸和第190位的甘氨酸被谷氨酸取代。
