title: Allosteric inhibitors against HIV-1 reverse transcriptase: design and synthesis of MKC-442 analogues having an omega-functionalized acyclic structure.
abstract: Based on X-ray crystallographic analysis of MKC-442/human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) complex, analogues in which the N1-substituent is replaced with omega-functionalized alkyl groups were designed to improve the affinity for the enzyme. Synthesis of these compounds was carried out starting from MKC-442 by a sequence of reactions (N3-protection, removal of N1-ethoxymethyl group, alkylation, and N3-deprotection). The compounds were evaluated for anti-HIV activity. Structure-activity relationships are discussed in terms of the possible interaction with the enzyme.
authors.affiliation: School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: R T
authors.initials: RT
authors.lastname: Walker
authors.forename: A L
authors.initials: AL
authors.lastname: Hopkins
authors.forename: J
authors.initials: J
authors.lastname: Ren
authors.forename: E Y
authors.initials: EY
authors.lastname: Jones
authors.forename: K
authors.initials: K
authors.lastname: Fujimoto
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Miyasaka
authors.forename: M
authors.initials: M
authors.lastname: Baba
authors.forename: D K
authors.initials: DK
authors.lastname: Stammers
authors.forename: D I
authors.initials: DI
authors.lastname: Stuart
mesh_terms: D000495:Allosteric Site / Q000187:drug effects*; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D054303:HIV Reverse Transcriptase / Q000737:chemistry; D015497:HIV-1 / Q000201:enzymology*; D006860:Hydrogen Bonding; D013058:Mass Spectrometry; D008958:Models, Molecular; D015394:Molecular Structure; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D014498:Uracil / Q000031:analogs & derivatives* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D014498:Uracil; D054303:HIV Reverse Transcriptase; C083858:emivirine