Synthesis of New Thienyl Ring Containing HIV-1 Protease Inhibitors: Promising Preliminary Pharmacological Evaluation against Recombinant HIV-1 Proteases
| Autor: | Federico Berti, Carlo Bonini, Francesco Tramutola, Paolo Lupattelli, Rocco Pandolfo, Margherita De Bonis, Maria Funicello, Lucia Chiummiento, Nadia Di Blasio |
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| Přispěvatelé: | Carlo, Bonini, Lucia, Chiummiento, Margherita De, Boni, Nadia Di, Blasio, Maria, Funicello, Paolo, Lupattelli, Rocco, Pandolfo, Francesco, Tramutola, Berti, Federico |
| Rok vydání: | 2010 |
| Předmět: |
Proteases
Stereochemistry medicine.medical_treatment stereoselectivity Structure-Activity Relationship HIV Protease HIV-1 protease HIV protease Drug Discovery medicine HIV Protease Inhibitor Protease inhibitor (pharmacology) Saquinavir Nelfinavir Protease biology Chemistry peptidomimetics Stereoisomerism Biological activity HIV Protease Inhibitors biochemical phenomena metabolism and nutrition peptidomimetic Recombinant Proteins Mutation Quinolines biology.protein Molecular Medicine Asparagine medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 53:1451-1457 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | A series of new thienyl ring containing analogues of nelfinavir and saquinavir with different substitution patterns were synthesized from suitable enantiopure diols. Their inhibitory activity against wild type recombinant HIV-1 protease was evaluated. In general thienyl groups spaced from the core by a methylene group gave products showing IC(50) in the nanomolar range, irrespective of the type and the substitution pattern of the heterocycle. The range of activity of the two most active compounds is substantially maintained or even increased against two commonly selected mutants, under drug pressure, such as V32I and V82A. |
| Databáze: | OpenAIRE |
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