Heterocyclic HIV-1 Protease Inhibitors

Abstract

[formula: see text] A series of simple heterocyclic HIV-1 protease inhibitors were developed on the basis of size, shape, and electronic complementarity to the active site of the enzyme. The C2-symmetric heterocycles do not contain a transition-state isostere nor are they active site directed irreversible inhibitors; thus, they represent the success of a new design strategy. The first generation heterocycles inhibit the protease in the micromolar range, whereas control compounds show no bioactivity at the same concentrations.

Parallel Synthesis of a Library of Symmetrically- and Dissymmetrically-disubstituted Imidazole-4,5-dicarboxamides Bearing Amino Acid Esters

“…We have been using the imidazole-4,5-dicarboxylic acid (I45DA) scaffold to design compounds that inhibit specific biological targets [11-13], as well as for the synthesis of chemical libraries to be used in the MLSCN screening effort. Nevertheless, no dissymmerically-disubstituted I45DCs bearing only α-amino acid esters and only two symmetrically-disubstituted I45DCs bearing α-amino acids esters have been previously reported in the literature.…”

Poly[[μ2-aqua-μ3-(4-carboxy-2-propyl-1H-imidazole-5-carboxylato-κ4N3,O4:O4:O5)-sodium] hemihydrate]

“…For the properties and biological activity of imidazole-4,5dicarboxylic acid and its derivatives, see: Baures (1999); Bogdanova et al (1992); Borodkin et al (1984); Reichardt et al (1992); Su et al (2001).…”

“…E67, m408 (Su et al, 2001). Imidazole-4,5-dicarboxylic acid and derivatives have been studied in terms of their physical properties as well as for their diverse biological activities (Bogdanova et al, 1992;Borodkin et al, 1984;Reichardt et al, 1992), including the use of imidazole-4,5-dicarboxylic acid amides in the development of human immunodeficiency virus (HIV-1) protease inhibitors (Baures, 1999). Here we present the synthesis and structure of the title complex derived from 2-propyl-1H-imidazole-4,5-dicarboxylic acid.…”

Nano copper and cobalt ferrites as heterogeneous catalysts for the one-pot synthesis of 2,4,5-tri substituted imidazoles

“…Tri aryl imidazole is the main structural unit in some widely used drugs such as ketoconazole, 3 proton pump inhibitors omeprazole, 4 cimetidine, 5 clotrimazole 6 and metronidazole, 7 potential inhibitor of P 38 mapkinase, 8 therapeutic agents 9 and anti HIV-I protease. 10 Numerous methods have been developed for the synthesis of substituted imidazoles. 2,4,5-trisubstituted imidazoles can be prepared by a three-component cyclo condensation in the presence of acetic acid, 11 silica supported sulphuric acid, 12 InCl 3 .3H 2 O, 13 ceric ammonium nitrate, 14 iodine, 15 trichloroisocyanuric acid (TCCA), 16 NiCl 2 .6H 2 O/Al 2 O 3 , 17 ionic liquids, 18 zeoliteHY/silica gel 19 and ZrCl 4 20 under reflux conditions.…”