Optically active antifungal azoles. II. Synthesis and antifungal activity of polysulfide derivatives of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H- 1,2,4-triazol-1-yl)-2-butanol.
In an effort to find potent antifungal agents, a variety of optically active triazole derivatives with a polysulfide structure, 3, 4 and 5, were prepared and evaluated for antifungal activity against Candida albicans in vitro and in vivo. The symmetrical polysulfides 3 (m = 2-4) were obtained by an oxidative coupling reaction of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl )-2-butanol (1) or by the treatment of its thiocarbonate derivative 8 with potassium tert-butoxide. The unsymmetrical disulfides 5 were synthesized by the reaction of the thiol 1 with Bunte salts 11 or the thiosulfinate 12 or by the reaction of the thiocarbonate 8 with various thiols 13. All of these polysulfides showed potent antifungal activity against candidosis in mice.
Tasaka
A
A
Pharmaceutical Research Laboratories III, Takeda Chemical Industries, Ltd., Osaka, Japan.
Tamura
N
N
Matsushita
Y
Y
Hayashi
R
R
Okonogi
K
K
Itoh
K
K
D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001393:Azoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D002177:Candidiasis / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010084:Oxidation-Reduction; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use
D000935:Antifungal Agents; D001393:Azoles; D013438:Sulfhydryl Compounds; D014230:Triazoles; C083107:2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol