title: Extension into the entrance channel of HIV-1 reverse transcriptase--crystallography and enhanced solubility.
abstract: Non-nucleoside inhibitors of HIV-1 reverse transcriptase (HIV-RT) are reported that feature extension into the entrance channel near Glu138. Complexes of the parent anilinylpyrimidine 1 and the morpholinoethoxy analog 2j with HIV-RT have received crystallographic characterization confirming the designs. Measurement of aqueous solubilities of 2j, 2k, the parent triazene 2a, and other NNRTIs demonstrate profound benefits for addition of the morpholinyl substituent.
authors.affiliation: Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA.
authors.forename: Mariela
authors.initials: M
authors.lastname: Bollini
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Frey
authors.forename: José A
authors.initials: JA
authors.lastname: Cisneros
authors.forename: Krasimir A
authors.initials: KA
authors.lastname: Spasov
authors.forename: Kalyan
authors.initials: K
authors.lastname: Das
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Bauman
authors.forename: Eddy
authors.initials: E
authors.lastname: Arnold
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.forename: William L
authors.initials: WL
authors.lastname: Jorgensen
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D011743:Pyrimidines; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
keywords: Anti-HIV agent; Crystal structures; Drug solubility; NNRTI
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