“Computer based design, synthesis and biological evaluation of pyrazole derivatives as anticancer agents targeting protein kinases”

Abstract

The CDK2 pyrazole inhibitor (AT7519 (19)) (IC50=44nmol/L), was used as reference compound for the design of the new pyrazole series IIa-g and IIIa-c. While the design of the new pyrazolo[1,5-a]pyrimidine targeted compounds VIIa-d and Xa-e depended upon two reference compounds; Roscovitine (17) which worked as the first reference compound that inhibit CDK2 with IC50=450 nmol/L and 4k (BS-194) (21) that acted as the second reference compound due to its selectivity to inhibit CDK2 with IC50=3 nmol/L. The design of the new target compounds was derived from the structure optimization of the reference compounds on the basis of their reported SAR. Synthetic schemes (1, 2, and 3) of the starting materials, intermediates and targeted compounds are also involved in this part.