Design and synthesis of 3,7-diarylimidazopyridines as inhibitors of the VEGF-receptor KDR

Wu, Zhicai; Fraley, Mark E.; Bilodeau, Mark T.; Kaufman, Mildred L.; Tasber, Edward S.; Balitza, Adrienne E.; Hartman, George D.; Coll, Kathleen E.; Rickert, Keith; Shipman, Jennifer M.; Shu, Bin; Sepp‐Lorenzino, Laura; Thomas, Kenneth A.

doi:10.1016/j.bmcl.2003.12.007

Cited by 43 publications

(24 citation statements)

References 16 publications

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“…The structure of all products were confirmed by their 1 H-NMR, 13 C-NMR and FT-IR spectral data and by elemental analysis.…”

Section: Resultsmentioning

confidence: 90%

“…1 H-NMR, 13 C-NMR and FT-IR spectral data for compounds 4a-m are available as supplementary information.…”

Section: Supplementary Informationmentioning

confidence: 99%

“…9 The pyrazolo [1,5-a]pyrimidines as bicyclic heterocycles have an important synthetic value in the preparation of drugs with anticancer activities. [10][11][12][13][14][15] The most common methods for synthesis of pyrazolo [1,5-a]pyrimidine derivatives are cyclocondensations of 5-aminopyrazoles with bifunctional reagents. 16 The synthesis of 2-anilinopyrazolo [1,5-a]pyrimidine derivatives as c-Src kinase inhibitors has been reported.…”

Section: Introductionmentioning

confidence: 99%

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The synthesis of new pyrazolo[1,5-a]pyrimidine derivatives

Marjani¹,

Khalafy²,

Salami³

et al. 2015

Arkivoc

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“…The structure of all products were confirmed by their 1 H-NMR, 13 C-NMR and FT-IR spectral data and by elemental analysis.…”

Section: Resultsmentioning

confidence: 90%

“…1 H-NMR, 13 C-NMR and FT-IR spectral data for compounds 4a-m are available as supplementary information.…”

Section: Supplementary Informationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The synthesis of new pyrazolo[1,5-a]pyrimidine derivatives

Marjani¹,

Khalafy²,

Salami³

et al. 2015

Arkivoc

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show abstract

“…Derivative (85), bearing a basic piperidine terminal group, possesses IC 50 values of 28 and 51 nM towards VEGFR-2 in enzymatic and cell assays, respectively, and demonstrates increased water solubility in comparison to other members of this class. It shows modest selectivity towards VEGFR-1, -3 and PDGFR-, while is selective against FGFR-1, -2 and Src [182].…”

Section: Pyridine Derivativesmentioning

confidence: 95%

Antiangiogenic Agents: an Update on Small Molecule VEGFR Inhibitors

Schenone¹,

Bondavalli²,

Botta

2007

CMC

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Angiogenesis is a tightly regulated process that leads to the formation of new blood vessels sprouting from pre-existing microvasculature and occurs in limited physiological conditions or under pathological situations such as retinopathies, arthritis, endometriosis and cancer. Blockade of angiogenesis is an attractive approach for the treatment of such diseases. Particularly in malignancies, antiangiogenic therapy should be less toxic in comparison with conventional treatments such as chemotherapy, as angiogenesis is a process relatively restricted to the growing tumor. Vascular endothelial growth factor (VEGF) is one of the most important inducers of angiogenesis and exerts its cellular effects mainly by interacting with two high-affinity transmembrane tyrosine kinase receptors: VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). It has been proven that inhibition of VEGF receptor activity reduces angiogenesis. For these reasons, the inhibition of VEGF or its receptor signalling system is an attractive target for therapeutic intervention. The most studied and developed inhibitors are monoclonal antibodies that neutralize VEGF, ribozymes, and small molecule VEGFR kinase inhibitors. Many important reviews dealing with VEGF-induced angiogenesis and its inhibition through the block of VEGF receptors have been reported, especially from a biological point of view. Here, we will review small synthetic VEGFR inhibitors that have appeared in literature in the last few years, focusing our attention on their medicinal chemistry in terms of chemical structure, mechanisms of action and structure-activity relationships. In fact, there have been an increased number of tyrosine kinase inhibitors in the most recent literature reports; their biological profile is extremely interesting and could be of great importance to medicinal chemists working in this area in improving their efficacy.

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“…Activation of the VEGF pathway is a fundamental regulation of angiogenesis, the formation of new capillaries from established blood vessels. In molecular mechanisms, the mitogenic signal of VEGF is mediated through the receptor tyrosine kinase KDR (VEGFR-2) [10]. Substituted 2-(N-trifluoroacetylamino)imidazopyridines are known to arrest cell cycle at G2/M phase and induce apoptosis in SK-LU-1 human cancer cell line [11].…”

Section: Introductionmentioning

confidence: 99%