title: Efavirenz a nonnucleoside reverse transcriptase inhibitor of first-generation: Approaches based on its medicinal chemistry.
abstract: Acquired immunodeficiency syndrome (AIDS) is a disease caused by human immunodeficiency virus (HIV) that affects individuals on all continents. In 1987, the antiretroviral therapy began increasing survival rates and improving the quality of life for patients. Efavirenz (EFV) is a drug widely used in the treatment of HIV-AIDS since 1998. Belonging to a class of nonnucleoside reverse transcriptase inhibitors (NNRTI), it directly blocks the action of the enzyme and consequently the multiplication of the virus. Although EFV has provided excellent results in reducing viral load, cases of resistance associated with adverse effects have led to the search to find new analogs of this drug. Although many researchers are involved in this quest, curiously there is still no clinical substitute for EFV. To develop a second-generation version of EFV, it is essential understand the structure-activity relationships of the derivative compounds. Thus, the aims of the present review are to compare EFV and its derivatives using medicinal chemistry and to describe the main synthetic routes.
authors.affiliation: Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos, Farmanguinhos - Fiocruz, Departamento de Síntese de Fármacos, Manguinhos, 21041-250, Rio de Janeiro, RJ, Brazil.
authors.forename: Mônica M
authors.initials: MM
authors.lastname: Bastos
authors.affiliation: Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos, Farmanguinhos - Fiocruz, Departamento de Síntese de Fármacos, Manguinhos, 21041-250, Rio de Janeiro, RJ, Brazil; Universidade Federal Fluminense, Departamento de Química Orgânica, Instituto de Química, Campus do Valonguinho, CEP 24020-150, Niterói, RJ, Brazil.
authors.forename: Carolina C P
authors.initials: CCP
authors.lastname: Costa
authors.affiliation: Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos, Farmanguinhos - Fiocruz, Departamento de Síntese de Fármacos, Manguinhos, 21041-250, Rio de Janeiro, RJ, Brazil; PROBIN - Abeu - Centro Universitário UNIABEU, Rua Itaiara 301, CEP 26113-400, Belford Roxo, RJ, Brazil.
authors.forename: Talitha C
authors.initials: TC
authors.lastname: Bezerra
authors.affiliation: Universidade Federal Fluminense, Departamento de Química Orgânica, Instituto de Química, Campus do Valonguinho, CEP 24020-150, Niterói, RJ, Brazil.
authors.forename: Fernando de C
authors.initials: FC
authors.lastname: da Silva
authors.affiliation: Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos, Farmanguinhos - Fiocruz, Departamento de Síntese de Fármacos, Manguinhos, 21041-250, Rio de Janeiro, RJ, Brazil. Electronic address: boechat@far.fiocruz.br.
authors.forename: Núbia
authors.initials: N
authors.lastname: Boechat
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D048588:Benzoxazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D003521:Cyclopropanes; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008968:Molecular Conformation; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; C098320:efavirenz
keywords: AIDS; Efavirenz; HIV; NNRTIs; Reverse transcriptase; Structure–activity relationship; Synthesis