Scaffold Oriented Synthesis. Part 1. Design, Preparation, and Biological Evaluation of Thienopyrazoles as Kinase Inhibitors.

Akritopoulou‐Zanze, Irini; Darczak, Daria; Sarris, Kathy; Phelan, Kathleen; Huth, Jeffrey R.; Song, Danying; Johnson, Eric F.; Jia, Yong; Djurić, Stevan W.

doi:10.1002/chin.200613132

Cited by 8 publications

(11 citation statements)

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“…Pyrazole heterocyclic compounds also have antifungal activity, herbicidal activity, and nematocidal activity . However, compounds containing thieno[2,3‐ c ]pyrazole moiety are a group of bioactive systems that have created a concern in medicinal chemistry due to their high efficiency as antitumor, antiviral, and antiinflammatory agents…”

Section: Introductionmentioning

confidence: 99%

Synthesis, reactions, and spectral characterization of some new biologically active compounds derived from thieno[2,3‐c]pyrazole‐5‐carboxamide

Saber

Zaki

El‐Dean

et al. 2019

Journal of Heterocyclic Chem

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The starting compound 4-amino-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole-5-carboxamide (1), that has been previously synthesized according to the literature procedure, underwent a reaction with the anhydride of phthalic acid either in AcOH or DMF to give isoindolinylpyrazole-5-carboxamide 3 and pyrazolothienopyrimidoisoindoledione 4, respectively. Also, it was subjected to react with diethylmalonate followed by hydrazinolysis by hydrazine hydrate to yield the pyrazolothienopyrimidinyl acetohydrazide 5. The carbohydrazide derivative 5 was used as a key intermediate for the preparation of other new heterocyclic systems containing pyrazolylacetyl pyrazolothienopyrimidines and pyrazolothieno-pyrimidotriazepine compounds 6-11. The structures of these new heterocycles have been characterized by using analytical and spectroscopic analyses (IR, 1 H-NMR, 13 C-NMR and MS). Some derivatives of the synthesized compounds exhibited remarkable antibacterial and antifungal activities against many bacterial and fungal strains.

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Section: Introductionmentioning

confidence: 99%

Synthesis, reactions, and spectral characterization of some new biologically active compounds derived from thieno[2,3‐c]pyrazole‐5‐carboxamide

Saber

Zaki

El‐Dean

et al. 2019

Journal of Heterocyclic Chem

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“…As an example, (90) shows an IC 50 value of 350 nM and no activity towards a panel of other kinases, thus becoming an interesting lead to develop more active compounds [192].…”

Section: Miscellaneous Compoundsmentioning

confidence: 99%

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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“…The pyrazole ring is a predominant pharmacophore in many drugs such as celecoxib, pyrazofurin and, notably, rimonabant, having a pyrazole core with N-acylhydrazone. The bioactive system containing thieno [2,3-c]pyrazole derivatives are a class of fused heterocyclic compounds which have attracted interest in medicinal chemistry owing to their antitumor [18][19][20][21][22], antiviral [23], anti-inflammatory [24] activities. Several other compounds containing the thieno[2,3-c]pyrazole scaffold were described as inhibitory for phosphodiesterase 7A (PDE7A) [25] and as potassium channel inhibitors [26].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, biological evaluation and molecular docking studies of N-acylheteroaryl hydrazone derivatives as antioxidant and anti-inflammatory agents

et al. 2015

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In search of new therapeutics with greater potency, three new series of 3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole-5-carbohydrazide derivatives have been synthesized and evaluated for their in vitro antioxidant and anti-inflammatory activities. The hydrazones bearing a core pyrazole, chromone and tetrazolo[1,5-a]quinoline scaffold showed promising activities. Interestingly, compounds 3a (EC 50 = 06.00 ± 2.36) and 5c (EC 50 = 07.21 ± 0.67) showed the most potent antioxidant activity, while compounds 3a (EC 50 = 10.25 ± 1.08), 7b (EC 50 = 10.50 ± 0.99) and 7c (EC 50 = 11.18 ± 0.15) showed significant anti-inflammatory activity. Furthermore, molecular docking studies also revealed a significant correlation between the binding score and biological activity for these compounds to describe the molecular basis for the structure activity relationship (SAR) results. As these compounds are good cyclooxygenase inhibitors, isoenzyme inhibitory potency studies are warranted.

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Scaffold Oriented Synthesis. Part 1. Design, Preparation, and Biological Evaluation of Thienopyrazoles as Kinase Inhibitors.

Cited by 8 publications

References 1 publication

Synthesis, reactions, and spectral characterization of some new biologically active compounds derived from thieno[2,3‐c]pyrazole‐5‐carboxamide

Synthesis, reactions, and spectral characterization of some new biologically active compounds derived from thieno[2,3‐c]pyrazole‐5‐carboxamide

Antiangiogenic Agents: an Update on Small Molecule VEGFR Inhibitors

Synthesis, biological evaluation and molecular docking studies of N-acylheteroaryl hydrazone derivatives as antioxidant and anti-inflammatory agents

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