title: Synthesis, antifungal activity and CoMFA analysis of novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives.
abstract: In order to search novel agrochemicals with higher antifungal activity, a series of new 1,2,4-triazolo[1,5-a]pyrimidine derivatives bearing 1,3,4-oxadiazole moieties were designed and synthesized. Their antifungal activities against Rhizoctonia solani were evaluated in vitro. By determining the EC(50) values of all the newly synthesized compounds and 10 formerly synthesized compounds, compound 8r, 2-((5-(sec-butylthio)-1,3,4-oxadiazol-2-yl)-methylthio)-5-dimethyl-1,2,4-triazolo-[1,5-a]pyrimidine, was found to display the highest antifungal activity (EC(50)=6.57 microg mL(-1)). Based on the quantitative structure-activity relationships analyses, 2-(1-(5-(sec-butylthio)-1,3,4-oxadiazol-2-yl)ethylthio)-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (9j) was designed and synthesized, which was found to display much higher activity (EC(50)=3.34 microg mL(-1)) than compound 8r and the control. To further explore the comprehensive structure-activity relationships, a 3D-QSAR analysis using the method of comparative molecular field analysis (CoMFA) was performed and a statistically reliable model with good predictive power (r(2)=0.929, q(2)=0.588) was achieved on the basis of the common substructure-based alignment. According to the CoMFA model, the structure-antifungal activity relationship was explained reasonably.
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Chen
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Zhu
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Jiang
authors.forename: Zu-Ming
authors.initials: ZM
authors.lastname: Liu
authors.forename: Guang-Fu
authors.initials: GF
authors.lastname: Yang
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D020128:Inhibitory Concentration 50; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012232:Rhizoctonia / Q000187:drug effects; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles