887138-63-8

Upstream product

• 261959-40-4 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difuorophenyl)-3-(N-methylamino)-2-propanol 
• 16004-15-2 1-bromomethyl-4-iodobenzene 
• 86386-77-8 1-[2-(2,4-difluorophenyl)-2,3-epoxypropyl]-1H-1,2,4-triazole methanesulfonate 

Relevant academic research and scientific papers

Design, Synthesis, and Biological Evaluation of 1-[(Biarylmethyl)methylamino]-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as Potent Antifungal Agents: New Insights into Structure-Activity Relationships

We recently reported the design and synthesis of azole antifungal agents with a focus on modifications to the side chain appended to the propanol group. Herein we have identified a series of new 1-[(biarylmethyl)methylamino] derivatives with broad-spectrum antifungal activities against the most prevalent human pathogenic fungi (Candida spp. and Aspergillus fumigatus). Compounds containing a flexible benzylamine moiety were clearly shown to yield the best antifungal activities, without the need for a hydrogen-bond acceptor substituent directly attached to the para position. We were also able to determine that selected compounds are able to overcome gene overexpression and point mutations that lead to reduced susceptibility or resistance against current treatments, such as fluconazole. As the minor differences observed with small structural modifications cannot be explain with only a three-dimensional model of CYP51, adequate physicochemical parameters must be evaluated in terms of antifungal potency, bioavailability, and toxicity. Therefore, structure-activity relationship studies such as these reveal new insights for the development of future antifungal therapies. Attacking the fungus among us: 1-[(Biarylmethyl)methylamino] derivatives with broad-spectrum antifungal activities against the most prevalent human pathogenic fungi (Candida spp. and Aspergillus fumigatus) are described, revealing further information about their structure-activity relationships.

Structure-based optimization of azole antifungal agents by CoMFA, CoMSIA, and molecular docking

In a continuing effort to develop highly potent azole antifungal agents, the three-dimensional quantitative structure-activity relationship methods, CoMFA and CoMSIA, were applied using a set of novel azole antifungal compounds. The binding mode of the compounds at the active site of lanosterol 14α-demethylase was further explored using the flexible docking method. Various hydrophobic, van der Waals, π-π stacking, and hydrogen bonding interactions were observed between the azoles and the enzyme. Based on results from the molecular modeling, a receptor-based pharmacophore model was established to guide the rational optimization of the azole antifungal agents. Thus, a total of 57 novel azoles were designed and synthesized by a three-step optimization process. In vitro antifungal assay revealed that the antifungal activities of these novel azoles were greatly improved, which confirmed the reliability of the model from molecular modeling.