Kashiwada Y, Chiyo J, Ikeshiro Y, Nagao T, Okabe H, Cosentino L M, Fowke K, Morris-Natschke S L, Lee K H
Niigata College of Pharmacy, Japan.
Chem Pharm Bull (Tokyo). 2000 Sep;48(9):1387-90. doi: 10.1248/cpb.48.1387.
3-Alkylamido-3-deoxy-betulinic acids were synthesized and evaluated for anti-HIV activity as part of the structure-activity relationship study of the potent anti-HIV agent 3-O-(3',3'-dimethyl)-succinyl-betulinic acid (DSB) (2). 3Alpha-diglycorylamide-3-deoxy-betulinic acid demonstrated relatively potent anti-HIV activity (EC50 0.24 microm, TI 728). However, replacing the ester group at C-3 in 2 and its analogues with an amido group yielded inactive or much less potent compounds against HIV replication, indicating that the ester group at C-3 in 2-4 is essential for potent anti-HIV activity.
作为强效抗HIV药物3 - O -（3'，3' - 二甲基）- 琥珀酰 - 桦木酸（DSB）（2）构效关系研究的一部分，合成了3 - 烷基酰胺基 - 3 - 脱氧 - 桦木酸并对其抗HIV活性进行了评估。3α - 二甘氨酰胺基 - 3 - 脱氧 - 桦木酸表现出相对较强的抗HIV活性（EC50为0.24微摩尔，治疗指数为728）。然而，用酰胺基取代2及其类似物中C - 3位的酯基会产生无活性或抗HIV复制活性低得多的化合物，这表明2 - 4中C - 3位的酯基对于强效抗HIV活性至关重要。
