Synthesis of novel water soluble benzylazolium prodrugs of lipophilic azole antifungals.
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.
Ohwada
Jun
J
Department of Chemistry, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa, Japan.
Murasaki
Chikako
C
Yamazaki
Toshikazu
T
Ichihara
Shigeyasu
S
Umeda
Isao
I
Shimma
Nobuo
N
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*
D000935:Antifungal Agents; D001393:Azoles; D011355:Prodrugs; D013844:Thiazoles; D014230:Triazoles; D017964:Itraconazole; C104066:ER 30346; D007654:Ketoconazole