Synthesis and structure–activity relationships of 2-phenyl-1-[(pyridinyl- and piperidinylmethyl)amino]-3-(1 H-1,2,4-triazol-1-yl)propan-2-ols as antifungal agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 2; pp. 301 - 304
• Main Authors: Giraud, Francis, Guillon, Rémi, Logé, Cédric, Pagniez, Fabrice, Picot, Carine, Borgne, Marc Le, Pape, Patrice Le
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.01.2009; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Biological and medical sciences; Candida albicans; Candida albicans - drug effects; Chemical Sciences; CYP51 inhibitors; Docking; H-bond acceptor; Homology model; Life Sciences; Medical sciences; Medicinal Chemistry; Microbial Sensitivity Tests; Microbiology and Parasitology; Models, Molecular; Mycology; Pharmaceutical sciences; Pharmacology. Drug treatments; Propanols - chemical synthesis; Propanols - chemistry; Propanols - pharmacology; Structure-Activity Relationship; Triazole; H-bond acceptor; Candida albicans; CYP51 inhibitors; Triazole; Antifungal agents; Homology model; Docking; Nitrogen heterocycle; Isozyme; Active site; Homology; Modeling; Pyridine derivatives; Fungi; Antifungal agent; Structure activity relation; Chlorine Organic compounds; Molecular model; Fungi Imperfecti; Chemical synthesis; Unspecific monooxygenase; Aminoalcohol; Enzyme; Cytochrome P450; Benzene derivatives; Enzyme inhibitor; Inhibitor enzyme complex; In vitro; Drug-metabolizing enzyme; Oxidoreductases
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2008.11.101

Synthesis and SAR studies of modified 1-benzylamino-2-phenyl-3-(1 H-1,2,4-triazol-1yl)propan-2-ols as antifungal agents, allowed identification of new derivatives with MIC 80 values ranging from 1410.0 to 23.0 ng mL −1 on the Candida albicans strain. Continuous efforts on the synthesis and structure–activity relationships (SARs) studies of modified 1-benzylamino-2-phenyl-3-(1 H-1,2,4-triazol-1-yl)propan-2-ols as antifungal agents, allowed identification of new 1-[(pyridinyl- and piperidinylmethyl)amino] derivatives with MIC 80 values ranging from 1410.0 to 23.0 ng mL −1 on Candida albicans. These results confirmed both the importance of π–π stacking and hydrogen bonding interactions in the active site of CYP51- C. albicans.