Synthesis and activity of HIV protease inhibitors

被引:18
作者
Garrouste, P
Pawlowski, M
Tonnaire, T
Sicsic, S
Dumy, P
de Rosny, E
Reboud-Ravaux, M
Fulcrand, P
Martinez, J
机构
[1] Univ Montpellier 1, Fac Pharm, UMR 5810, F-34060 Montpellier 2, France
[2] Univ Montpellier 2, Fac Pharm, UMR 5810, F-34060 Montpellier, France
[3] Akad Med, Katedra Chemmii Farmaceut, PL-31065 Krakow, Poland
[4] Fac Pharm Chatenay Malabry, Biocis CNRS, URA 1843, F-92296 Chatenay Malabry, France
[5] Univ Lausanne, BCH Dorigny, Inst Organ Chem, CH-1015 Lausanne, Switzerland
[6] Univ Paris 07, Inst Jacques Monod, F-75251 Paris, France
关键词
HIV; protease; inhibitor; pseudopeptide; cyclic peptide;
D O I
10.1016/S0223-5234(98)80043-3
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
We report here the synthesis and activity of HIV protease inhibitors. Ln the first stage hydrophobic compounds incorporating a 'carba' bond surrogate or a beta-homologated residue were synthesized. Secondly, we synthesized cyclic compounds in which we incorporated 2-quinoline carboxylic acid in the P3 position and the amino-hydroxyindane moiety in the P'3. The last part of this work was dedicated to a structure/activity study of a peptide substrate. These modifications allowed us to work up the synthesis of new pseudopeptide bonds: amino-amide and hydroxy-amide, Compounds with activity in the micromolar range were actually a starting point for the synthesis of new protease inhibitors. (C) Elsevier, Paris.
引用
收藏
页码:423 / 436
页数:14
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