2004
DOI: 10.1021/jm020455u
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Synthesis and Biological Evaluation of 1-Aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one Inhibitors of Cyclin-Dependent Kinases

Abstract: Using a high-throughput screening strategy, a series of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-ones was identified that inhibit the cyclin-dependent kinase (CDK) 4/cyclin D1 complex-mediated phosphorylation of a protein substrate with IC(50)s in the low micromolar range. On the basis of preliminary structure-activity relationships (SAR), a model was proposed in which these inhibitors occupy the ATP-binding site of the enzyme, forming critical hydrogen bonds to the same residue (Val96) to which the am… Show more

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Cited by 97 publications
(65 citation statements)
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“…However, CDK7, CDK8, and CDK9 have been invovled in the regulation of RNA elongation [84]. It is a common feature for uncontrolled CDK activity with increasing evidence interrelated to proliferative diseases such as psoriasis, cancer and restenosis, and many CDK inhibitors have been investigated over the past decade [85][86][87][88][89][90][91].…”
Section: 3 5-triazine Derivatives Targeting Cdkmentioning
confidence: 99%
“…However, CDK7, CDK8, and CDK9 have been invovled in the regulation of RNA elongation [84]. It is a common feature for uncontrolled CDK activity with increasing evidence interrelated to proliferative diseases such as psoriasis, cancer and restenosis, and many CDK inhibitors have been investigated over the past decade [85][86][87][88][89][90][91].…”
Section: 3 5-triazine Derivatives Targeting Cdkmentioning
confidence: 99%
“…Many pyrazolo [3,4-d]pyrimidine derivatives were reported as antitumor agents [6][7][8]. The cytotoxic activity of such compound may attributed to inhibition of several enzymes such as tyrosine kinase [9], Src kinase [10], cyclin dependent kinase (CDK) [11], mammalian target of rapamycin (mTOR) [12] and glycogen synthase kinase (GSK) [13,14]. In addition, the presence of methylsulphanyl group at the 3 position of pyrazolo [3,4-d]pyrimidine nucleus was reported to potentiate the antitumor activity of such nucleus [11,15].…”
Section: Introductionmentioning
confidence: 99%
“…The cytotoxic activity of such compound may attributed to inhibition of several enzymes such as tyrosine kinase [9], Src kinase [10], cyclin dependent kinase (CDK) [11], mammalian target of rapamycin (mTOR) [12] and glycogen synthase kinase (GSK) [13,14]. In addition, the presence of methylsulphanyl group at the 3 position of pyrazolo [3,4-d]pyrimidine nucleus was reported to potentiate the antitumor activity of such nucleus [11,15]. For example, compound 1 and 2 ( Figure 1) were exhibited excellent antitumor activity against breast adenocarcinoma cell line MCF 7 with an IC 50 values of 12.0 and 7.50 µM respectively [16].…”
Section: Introductionmentioning
confidence: 99%
“…[3,4-d] pyrimidines derivatives have gained considerable attention due to their reported anticancer and antileukemic activities [9][10][11][12][13]14]. The biological effect is attributed to their cyclin-dependent kinase inhibitor [15][16][17] and tyrosine kinase inhibitory activity [18][19]. The scaffold has also shown potent xanthine oxidase inhibitors and adenosine receptor antagonistic activity [20].…”
Section: Introductionmentioning
confidence: 99%