Sugeac Elena, Fossey Christine, Ladurée Daniel, Schmidt Sylvie, Laumond Geraldine, Aubertin Anne-Marie
Centre d'Etudes et de Recherche sur le Médicament de Normandie, U.F.R. des Sciences, Pharmaceutiques, 5, Rue Vaubénard, F-14032, Caen Cedex, France.
J Enzyme Inhib Med Chem. 2003 Apr;18(2):175-86. doi: 10.1080/1475636032000069846.
Expected for their ability to inhibit HIV replication, four heterodimers with a Nucleoside Reverse Transcriptase Inhibitor (NRTI) and a Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) bound by a linker arm were designed and synthesized. For the NRTIs, d4U, d2U, d4T and 5'-O-acetyl-5-(3-hydroxypropynyl)d2U were chosen. For the NNRTI, a Trovirdine Analogue (belonging to the phenethylthiazolylthiourea class) was chosen. The conjugation of the two different inhibitors (NRTI and NNRTI) was performed using the succinyl-glycine moiety as a spontaneously cleavable linker.
鉴于它们抑制HIV复制的能力，设计并合成了四种异二聚体，其中核苷类逆转录酶抑制剂（NRTI）和非核苷类逆转录酶抑制剂（NNRTI）通过连接臂结合。对于NRTI，选择了d4U、d2U、d4T和5'-O-乙酰基-5-(3-羟丙炔基)d2U。对于NNRTI，选择了一种曲氟尿苷类似物（属于苯乙基噻唑基硫脲类）。使用琥珀酰甘氨酸部分作为可自发裂解的连接体进行两种不同抑制剂（NRTI和NNRTI）的偶联。
