Insecticidal lead identification by screening benzopyrano[4,3-c] pyrazol-3(2H)-ones library constructed from multiple-parallel synthesis under microwave irradiation.
A rapid library-generation via liquid-phase multiple-parallel synthesis of 2-(substituted)benzyl-1-benzopyrano[4,3-c]pyrazol-3(2H)-ones, bearing two points of diversity, under microwave irradiation was successfully performed using chromenone-3-carboxylic acids as starting materials. Compared to an identical library generated by conventional parallel synthesis, microwave-assisted parallel synthesis dramatically decreased reaction times from an average of 16h to 13min, and the yields of products and intermediates were improved in most cases. A bioassay indicated that the compounds of the library exhibited excellent insecticidal activity against T. cinnabarinus at the dosage of 250mgL(-1), and some compounds still exhibited insecticidal activity when the dosage was reduced to 50mgL(-1). This shows that 2-(substituted) benzyl-1-benzopyrano[4,3-c]pyrazol-3(2H)-ones might be used as lead structures for further optimization. To our knowledge, this is the first report about the application of solution-phase multiple-parallel synthesis under microwave irradiation to construct libraries of benzopyrano-[4,3-c]pyrazol-3(2H)-ones with insecticidal activity. The coupling of microwave technology with liquid-phase parallel synthesis constitutes a novel and particularly attractive avenue for the rapid generation of structurally diverse libraries for lead discovery.
Zhou
Zhong-Zheng
ZZ
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China.
Yang
Guang-Fu
GF
D000818:Animals; D020650:Combinatorial Chemistry Techniques; D007306:Insecticides / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008872:Microwaves; D015394:Molecular Structure; D019151:Peptide Library; D011720:Pyrazoles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D040102:Tetranychidae / Q000187:drug effects*
D007306:Insecticides; D019151:Peptide Library; D011720:Pyrazoles; C031280:pyrazole