title: Design, synthesis and antifungal activity of a novel water soluble prodrug of antifungal triazole.
abstract: A highly potent water soluble triazole antifungal prodrug, RO0098557 (1), has been identified from its parent, the novel antifungal agent RO0094815 (2). The prodrug includes a triazolium salt linked to an aminocarboxyl moiety, which undergoes enzymatic activation followed by spontaneous chemical degradation to release 2. Prodrug 1 showed high chemical stability and water solubility and exhibited strong antifungal activity against systemic candidiasis and aspergillosis as well as pulmonary aspergillosis in rats.
authors.affiliation: Department of Chemistry, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ohwada
authors.forename: Masao
authors.initials: M
authors.lastname: Tsukazaki
authors.forename: Tadakatsu
authors.initials: T
authors.lastname: Hayase
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Oikawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Isshiki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuda
authors.forename: Eisaku
authors.initials: E
authors.lastname: Mizuguchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakaitani
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Shiratori
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Shigeyasu
authors.initials: S
authors.lastname: Ichihara
authors.forename: Isao
authors.initials: I
authors.lastname: Umeda
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shimma
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy / Q000382:microbiology; D001711:Biotransformation; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D015195:Drug Design; D006207:Half-Life; D000882:Haplorhini; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008958:Models, Molecular; D008968:Molecular Conformation; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D012995:Solubility; D012997:Solvents; D014230:Triazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014867:Water
chemical_list: D000935:Antifungal Agents; D011355:Prodrugs; D012997:Solvents; D014230:Triazoles; D014867:Water