Design of new antifungal agents: synthesis and evaluation of 1-[(1H-indol-5-ylmethyl)amino]-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols.
We previously reported on the design and synthesis of 1-[((hetero)aryl- or piperidinylmethyl)amino]-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols showing various degrees of antifungal activity against Candida albicans and Aspergillus fumigatus strains. Now we have identified a series of 1-[(1H-indol-5-ylmethyl)amino] derivatives which exhibited potent MICs (<65 ng mL(-1)) against C. albicans strain. The synthesis and SAR behind the indole scaffold will be discussed.
Guillon
Rémi
R
Université de Nantes, Nantes Atlantique Universités, Département de Pharmacochimie, Cibles et Médicaments des Infections, de l'Immunité et du Cancer, IICIMED-EA 1155, UFR Sciences Pharmaceutiques, 1 rue Gaston Veil, Nantes F-44035 Cedex 1, France.
Giraud
Francis
F
Logé
Cédric
C
Le Borgne
Marc
M
Picot
Carine
C
Pagniez
Fabrice
F
Le Pape
Patrice
P
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002176:Candida albicans / Q000187:drug effects; D003198:Computer Simulation; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015195:Drug Design; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D020005:Propanols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D005656:Fungal Proteins; D020005:Propanols; D014230:Triazoles; C465525:cytochrome P-450 CYP51, Candida albicans; D003577:Cytochrome P-450 Enzyme System