Monge A, Alvarez E, San Martín C, Nadal E, Ruiz I, Font M, Martínez-Irujo J J, Santiago E, Prieto I, Lasarte J J, Sarobe P, Borrás F
Medicinal Chemistry, Universidad de Navarra, Pamplona, Spain.
Drug Des Discov. 1997 Apr;14(4):291-303.
The synthesis and preliminary evaluation of new benzo[f]quinoline and pyridine derivatives, obtained by application of the Reissert method and its modifications, as HIV-1 RT inhibitors and anti-infectives are presented. The most active products against HIV-1 RT wild type are the ethyl 2-cyano-1,2-dihydrobenzo[f]quinoline-1-carboxylate 2b, propyl 2-cyano-1,2-dihydrobenzo[f]quinoline-1-carboxylate 2c, and 2-cyano-1-(2'-furoyl)-1,2-dihydrobenzo[f]quinoline 2n, which maintain their activity against the mutant type P236L, resulting inactive against the Y181C type. Using the data previously obtained by our research team for analogous series derived from quinoline as reference, the compounds which have now been obtained present an increase in the cytotoxic character attributable to the introduction of a benzene ring fused with the quinoline base nucleus, as well as a decrease of the activity as HIV-1 RT inhibitors when the quinoline benzenic ring is eliminated.
本文介绍了通过应用赖瑟特方法及其改进方法获得的新型苯并[f]喹啉和吡啶衍生物作为HIV-1逆转录酶抑制剂和抗感染药物的合成及初步评价。对HIV-1 RT野生型最具活性的产物是2-氰基-1,2-二氢苯并[f]喹啉-1-羧酸乙酯2b、2-氰基-1,2-二氢苯并[f]喹啉-1-羧酸丙酯2c和2-氰基-1-(2'-呋喃甲酰基)-1,2-二氢苯并[f]喹啉2n，它们对突变型P236L保持活性，但对Y181C型无活性。以我们研究团队先前获得的喹啉类似系列数据为参考，现已获得的化合物因与喹啉碱核稠合的苯环的引入而使细胞毒性特征增加，并且当喹啉苯环消除时作为HIV-1 RT抑制剂的活性降低。
