Evers M, Poujade C, Soler F, Ribeill Y, James C, Lelièvre Y, Gueguen J C, Reisdorf D, Morize I, Pauwels R, De Clercq E, Hénin Y, Bousseau A, Mayaux J F, Le Pecq J B, Dereu N
Rhône-Poulenc Rorer S.A., Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France.
J Med Chem. 1996 Mar 1;39(5):1056-68. doi: 10.1021/jm950670t.
A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and evaluated for activity in CEM 4 and MT-4 cell cultures against human immunodeficiency virus type 1 (HIV-1) strain IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a, and 17b, were all derivatives of betulinic acid (3beta-hydroxylup-20(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activity with poly(C).oligo(dG) as template/primer, nor did it inhibit HIV-1 protease. Additional mechanistic studies revealed that this class of compounds interfere with HIV-1 entry in the cells at a postbinding step.
合成了一系列羽扇-20(29)-烯-28-酸衍生物的ω-十一碳酰胺，并在CEM 4和MT-4细胞培养物中评估了它们对1型人类免疫缺陷病毒（HIV-1）IIIB/LAI株的活性。筛选出的强效HIV抑制剂化合物5a、16a和17b均为桦木酸（3β-羟基羽扇-20(29)-烯-28-酸）的衍生物。未发现对HIV-2 ROD株有活性。化合物5a以聚（C）·寡聚（dG）为模板/引物时，未显示出对HIV-1逆转录酶活性的抑制作用，也未抑制HIV-1蛋白酶。进一步的机制研究表明，这类化合物在结合后的步骤中干扰HIV-1进入细胞。
