title: Discovery of second generation quinazolinone non-nucleoside reverse transcriptase inhibitors of HIV-1.
abstract: An intensive research effort to identify potent, viable drugs for the management of acquired immunodeficiency syndrome (AIDS) resulted in the development of SUSTIVA (efavirenz), the first non-nucleoside reverse transcriptase inhibitor (NNRTI) approved by the FDA as a preferred first-line therapy. The search for NNRTIs that possess a broader activity spectrum against mutant viral forms of human immunodeficiency syndrome type-I reverse transcriptase culminated in the discovery that trifluoromethyl-containing quinazolin-2(1H)-ones possess potent activity as non-nucleoside reverse transcriptase inhibitors (NNRTIs). This chapter reviews the discovery and structure activity relationships that resulted in the identification and subsequent preclinical and clinical development of four quinazolinone NNRTIs at the DuPont Pharmaceuticals Company.
authors.affiliation: DuPont Pharmaceuticals Company, Experimental Station, P. O. Box 80500, Wilmington, DE 19880-0500, USA.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Corbett
authors.forename: James D
authors.initials: JD
authors.lastname: Rodgers
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D011799:Quinazolines / Q000737:chemistry / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D011799:Quinazolines; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase