title: Synthesis of novel water soluble benzylazolium prodrugs of lipophilic azole antifungals.
abstract: Water soluble N-benzyltriazolium or N-benzylimidazolium salt type prodrugs of several highly lipophilic triazole or imidazole antifungals have been synthesized. They were designed to undergo an enzymatic activation followed by a self-cleavage to release a parent drug. The prodrugs such as 16 had enough chemical stability and water solubility for parenteral use and were rapidly and quantitatively converted to the active substance in human plasma.
authors.affiliation: Department of Chemistry, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ohwada
authors.forename: Chikako
authors.initials: C
authors.lastname: Murasaki
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* / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects; D001393:Azoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006207:Half-Life; D006801:Humans; D017964:Itraconazole / Q000031:analogs & derivatives / Q000494:pharmacology; D007654:Ketoconazole / Q000031:analogs & derivatives / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D012995:Solubility; D013844:Thiazoles / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D011355:Prodrugs; D013844:Thiazoles; D014230:Triazoles; D017964:Itraconazole; C104066:ER 30346; D007654:Ketoconazole