Soler F, Poujade C, Evers M, Carry J C, Hénin Y, Bousseau A, Huet T, Pauwels R, De Clercq E, Mayaux J F, Le Pecq J B, Dereu N
Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France.
J Med Chem. 1996 Mar 1;39(5):1069-83. doi: 10.1021/jm950669u.
A novel series of omega-aminoalkanoic acid derivatives of betulinic acid were synthesized and evaluated for their activity against human immunodeficiency virus (HIV). The anti-HIV-1 activity of several members of this new series was found to be in the nanomolar range in CEM 4 and MT-4 cell cultures. The optimization of the omega-aminoalkanoic acid side chain is described. The presence of an amide function within the side chain was found important for optimal activity. RPR 103611 (14g), a statine derivative, was found to be inactive against HIV-1 protease, reverse transcriptase, and integrase as well as on gp120/CD4 binding. "Time of addition" experiments suggested interaction with an early step of HIV-1 replication. As syncytium formation, but not virus-cell binding, seems to be affected, betulinic acid derivatives are assumed to interact with the postbinding virus-cell fusion process.
合成了一系列新型的桦木酸ω-氨基链烷酸衍生物，并对其抗人免疫缺陷病毒（HIV）的活性进行了评估。在CEM 4和MT-4细胞培养中，发现该新系列的几个成员的抗HIV-1活性处于纳摩尔范围。描述了ω-氨基链烷酸侧链的优化。发现侧链内酰胺功能的存在对最佳活性很重要。发现一种他汀类衍生物RPR 103611（14g）对HIV-1蛋白酶、逆转录酶和整合酶以及gp120/CD4结合均无活性。“添加时间”实验表明其与HIV-1复制的早期步骤相互作用。由于似乎受影响的是合胞体形成而非病毒-细胞结合，因此推测桦木酸衍生物与结合后病毒-细胞融合过程相互作用。
