title: Combinatorial chemistry as a tool for targeting different stages of the replicative HIV-1 cycle.
abstract: In the present era, acquired immunodeficiency syndrome (AIDS) is the most fatal disorder for which no completely successful chemotherapy has been developed so far. The pandemic spread of this disease has prompted an unprecedented scientific and clinical effort to understand and combat it. A number of targets has been identified to stop the replication of the virus at different stages of its life cycle: Reverse Transcriptase (RT), protease (PR) and CCR5 are the most promising targets. Although highly active antiretroviral therapy (HAART) has been effective in reducing the mortality and morbidity in recent years, adverse side effects of the chemotherapy, patient non-compliance and the development of viral resistance remain major problems. With the aim to find better drug candidates with minor adverse side effects in recent years, several groups have investigated combinatorial approaches for the generation of libraries of HIV PR inhibitors while only few contributions to the preparation of libraries of HIV Reverse Transcriptase (RT) and CCR5 inhibitors are available. This review summarizes the recent developments of combinatorial chemistry in this area.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico Università degli Studi di Siena, Via A. Moro 53100 Siena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mugnaini
authors.forename: Elena
authors.initials: E
authors.lastname: Petricci
authors.forename: Federico
authors.initials: F
authors.lastname: Corelli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015195:Drug Design; D015696:Gene Products, tat / Q000037:antagonists & inhibitors / Q000187:drug effects*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D019380:Anti-HIV Agents; D015696:Gene Products, tat; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054322:tat Gene Products, Human Immunodeficiency Virus