Structure–activity relationships in platelet-activating factor. Part 13: Synthesis and biological evaluation of piperazine derivatives with dual anti-PAF and anti-HIV-1 or pure antiretroviral activity

• Published in: Bioorganic & medicinal chemistry 2006-12, Vol.14 (23), p.8109-8125
• Main Authors: Serradji, Nawal, Bensaid, Okkacha, Martin, Marc, Sallem, Wafa, Dereuddre-Bosquet, Nathalie, Benmehdi, Houcine, Redeuilh, Catherine, Lamouri, Aazdine, Dive, Georges, Clayette, Pascal, Heymans, Françoise
• Format: Article
• Language: English
• Subjects: Acquired Immunodeficiency Syndrome - complications; AIDS dementia complex; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - pharmacology; Anti-HIV-1; Anti-PAF; Anti-Retroviral Agents - chemical synthesis; Anti-Retroviral Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Brain; Dementia - etiology; Dementia - prevention & control; Dose-Response Relationship, Drug; HIV-1; Humans; Medical sciences; Pharmacology. Drug treatments; Piperazines - chemical synthesis; Piperazines - pharmacology; Platelet Activating Factor - antagonists & inhibitors; Structure-Activity Relationship
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2006.07.031

HIV-1 infection of the brain and PAF neurotoxicity are implicated in AIDS dementia complex. We previously reported that a trisubstituted piperazine derivative is able to diminish both HIV-1 replication in monocyte-derived macrophages and PAF-induced platelet aggregation. We report in this work new compounds obtained by modifying its piperazine substituents. The structure–activity relationship study shows that a better dual activity or even pure antiretroviral compounds can be obtained in this series.