4-Aryl-5-cyano-2-aminopyrimidines as VEGF-R2 inhibitors: Synthesis and biological evaluation

Hughes, Terry V.; Emanuel, Stuart L.; Beck, Amanda K.; Wetter, Steven K.; Connolly, Peter J.; Karnachi, Prabha; Reuman, Michael; Seraj, Jabed; Fuentes‐Pesquera, Angel R.; Gruninger, Robert H.; Middleton, Steven A.; Lin, Ronghui; Davis, Jeremy; Moffat, David

doi:10.1016/j.bmcl.2007.04.021

Cited by 43 publications

(26 citation statements)

References 6 publications

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“…Thirty-two inhibitors were taken from the literature (Hughes et al, 2007) with their biological activities in terms of IC 50 values. The IC 50 values, i.e., the concentration (lM) of inhibitor that produces 50% inhibition to VEGFR-2, were converted to molar concentrations and then into pIC 50 values as reported in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Pharmacophore based 3D-QSAR study of VEGFR-2 inhibitors

et al. 2008

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The growth and metastasis of solid tumors are dependent on angiogenesis. The vascular endothelial growth factor (VEGF) is of particular interest since it is essential for angiogenesis. The development of novel inhibitors of VEGF receptor type 2 (VEGFR-2) is important. Quantitative structure-activity relationship (QSAR) studies were performed to understand the structural factors affecting inhibitory potency of 4-aryl-5-cyano-2-aminopyrimidines. Pharmacophore models indicate that the importance of steric and hydrogen bond acceptor groups. The bestfitted pharmacophore-based alignment was used for comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Both CoMFA (q 2 = 0.62, r 2 = 0.87, and r 2 predictive = 0.7) and CoMSIA (q 2 = 0.54, r 2 = 0.86, and r 2 predictive = 0.61) gave reasonable results. Factors such as steric bulkiness, electrostatic effect, and hydrogen bond acceptor were found to be important for the inhibitory activity. It is suggested that negatively charged, bulky H-bond accepting groups around the piperazine nitrogen would enhance inhibition against VEGFR-2.

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Section: Methodsmentioning

confidence: 99%

Pharmacophore based 3D-QSAR study of VEGFR-2 inhibitors

et al. 2008

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“…Some notable biological activities of pyrimidine derivatives include as adenosine receptor antagonists 1 , as kinase inhibitors 2 , analgesic 3 , anti-inflammatory 3 , as inhibitors of cyclin-dependent kinases 1 and 2 4 , as calcium channel antagonists 5 , antihistaminic 6 , and antitubercular 7 activities. Substituted aminopyrimidine nuclei are common in marketed drugs such as anti-atherosclerotic aronixil, anti-histaminic thonzylamine, anti-anxiolytic buspirone, anti-psoriatic enazadrem, and other medicinally relevant compounds.…”

Section: Introductionmentioning

confidence: 99%

4-(4-Morpholinophenyl)-6-arylpyrimidin-2-amines: synthesis, spectral analysis, and in vitro microbiological evaluation

Thanusu

Kanagarajan

Gopalakrishnan

2009

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…In recent years, pyrimidine nucleus has attracted increase attention owing to their diverse biological activities [1][2][3][4][5]. Substituted pyrimidines, particularly with an amino group at 2 or 4 positions, are known pharmacophores in several structure-based drug-design approaches in medicinal chemistry [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%