title: A historical sketch of the discovery and development of HIV-1 integrase inhibitors.
abstract: The long process of HIV-1 integrase inhibitor discovery and development can be attributed to both the complexity of HIV-1 integration and poor 'integration' of these researches into mainstream investigations on antiretroviral therapy in the mid-1990s. Of note, some fungal extracts investigated during this period contain the beta-hydroxyketo group, later recognised to be a key structural requirement for keto-enol acids (also referred to as diketo acids) and other integrase inhibitors. This review reconstructs (in the general context of the history of AIDS research) the principal steps that led to the integrase inhibitors currently in clinical trials, and discusses possible future directions.
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità Viale Regina Elena, 299. 00161- Rome, Italy. asavarino@medscape.com
authors.forename: Andrea
authors.initials: A
authors.lastname: Savarino
mesh_terms: D019380:Anti-HIV Agents / Q000266:history* / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000266:history; D015658:HIV Infections / Q000188:drug therapy / Q000266:history; D019427:HIV Integrase / Q000187:drug effects; D019428:HIV Integrase Inhibitors / Q000266:history* / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase