title: Design, synthesis, and biological evaluation of thiazoles targeting flavivirus envelope proteins.
abstract: A series of third-generation analogues of methyl 4-(dibromomethyl)-2-(4-chlorophenyl)thiazole-5-carboxylate (1), which had the most potent antiviral activity among the first- and second-generation compounds, have been synthesized and tested against yellow fever virus using a cell-based assay. The compounds were designed with the objectives of improving metabolic stability, therapeutic index, and antiviral potency. The biological effects of C4 and C5 substitution were examined. The methylthio ester and the dihydroxypropylamide analogues had the best antiviral potencies and improved therapeutic indices and metabolic stabilities relative to the parent compound 1.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy and Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, United States.
authors.forename: Abdelrahman S
authors.initials: AS
authors.lastname: Mayhoub
authors.forename: Mansoora
authors.initials: M
authors.lastname: Khaliq
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kuhn
authors.forename: Mark
authors.initials: M
authors.lastname: Cushman
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D006224:Cricetinae; D003716:Dengue Virus / Q000378:metabolism; D015195:Drug Design; D004355:Drug Stability; D004952:Esters; D005416:Flavivirus / Q000187:drug effects* / Q000378:metabolism; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008647:Mesocricetus; D008958:Models, Molecular; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*; D015005:Yellow fever virus / Q000187:drug effects
chemical_list: D000577:Amides; D000998:Antiviral Agents; D004952:Esters; D007659:Ketones; D013844:Thiazoles; D014759:Viral Envelope Proteins