Synthesis of a new series of pyrazolo[1,5-a]pyrimidines as CDK2 inhibitors and anti-leukemia

Synthesis, biological evaluation, and in silico studies of new CDK2 inhibitors based on pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine scaffold with apoptotic activity

“…In addition to the hydrogen binding via the para fluoro group with Lys89 in compounds 8 , 9 , 11 , and 13 . As in reported compound VII where it was published that substitution of the phenyl ring with halogen atom is preferable to the un-substituted ring for its cytotoxic effect, with either bromo, fluoro, or chloro group 25 . While a halogen hydrogen bond formation by compound 11 with Glu8 and compounds 14 and 15 with Asp145 was observed too.…”

“…Pyrazolopyrimidine is considered an appealing scaffold for the development of new antitumor agents 19–24 . This scaffold is considered an adenine bioisostere that retains the essential interactions of ATP at the kinase domain 25–28 . The pyrazolo[3,4- d ]pyrimidine bicycle showed great potential in CDK inhibition in drug discovery.…”

“…They also possess significant and specific pharmacological activity in CDK2/Cyclin A inhibition 11 . Among the known drugs of potent CDK2 inhibition are Dinaciclib, Ibrutinib, and Roscovitine 1 , 9 , 12 , 25 , 34 , 35 ( Figure 1 ).…”

Discovery of pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives as novel CDK2 inhibitors: synthesis, biological and molecular modeling investigations

“…9,10 The pyrazolopyrimidine moiety represents a common heterocycle nucleus used in the design of many pharmaceutical compounds, 11,12 that have a variety of medicinal applications including antimicrobial, antitumor, 13 antidiabetic, anti-Alzheimer's disease, anti-inammatory 14,15 and antioxidant applications. [16][17][18] Recently, pyrazolopyrimidine is considered an appealing scaffold for pharmacologically active agents development with [3,4-d]pyrimidines derivatives (IV), (V) & (VI) as CDK2 inhibitors [9,12,25,34].…”

Design, Synthesis of Amide Derivatives of Scutellarin And Their Anti-Leukemia And Neuroprotective Activities

“…According to the latest statistics, leukaemia is the leading cause of death among all cancers in the adolescents and young adults of China [5]. Traditional chemotherapeutic agents are found to be successful in destroying leukemic cells, however, it is restricted by the chemo-resistant and side-effect of anticancer drugs [6,7]. Therefore, the development of new anti-leukemia drugs is urgent.…”