Synthesis and Initial SAR Studies of 3,6-Disubstituted Pyrazolo[1,5-a]pyrimidines: A New Class of KDR Kinase Inhibitors

Fraley, Mark E.; Hoffman, William F.; Rubino, Robert S.; Hungate, Randall W.; Tebben, Andrew J.; Rutledge, Ruth Z.; McFall, Rosemary C.; Huckle, William R.; Kendall, Richard; Coll, Kathleen E.; Thomas, Kenneth A.

doi:10.1016/s0960-894x(02)00525-5

Cited by 115 publications

(50 citation statements)

References 17 publications

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“…New series of isoxazolines has been synthesized and has shown moderate antimicrobial activity 59 [70]. Pyrimidine analogues: N-fused analogues of chalcones particularly pyrimidines have received augmented interest due to their plethora of biological actions such as antifungal [71], antibacterial [72], antitumor [73], analgesics [74], anti-inflammatory [75], anti-trichomonal [76], KDR kinase inhibition [77], CRF-1 receptor antagonists [78,79] estrogen receptor ligands, and COX-2 selective inhibition [80]. Sharma et al synthesized a series of quinolinyl chalcones and quinolinyl pyrimidines and screened them against M. tuberculosis and NF-54 strains of P. falciparum among all compounds with 4-amino linkage showed promising activity against NF-54 strains of P. falciparum.…”

Section: Analogues Of Chalcones Pyrazoline Analogues With Various Phamentioning

confidence: 99%

Chalconoid Derived Heterocycles as Potent Bioactive Molecules: A Review

Sapra¹,

Sharma²

2016

Chem Sci J

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Although chalcones symbolize an important pharmacophore for variety of biological actions, however their analogues are also reported to be equally important for plethora of biological actions. In the present review, a comprehensive study of chalcones derived molecules (like pyrazoles, isoxazoles, pyridine, pyrimidine) their pharmacological actions, mechanism of action, structure activity relationship studies have been described. which includes anti-proliferative, anti-inflammatory, antioxidant, proapoptotic, anti-bacterial and anti-adhesive effects [18]. Analogues of chalcones Pyrazoline analogues with various pharmacological activities:Pyrazole nucleus present in compounds exhibit wide range of biological activity. Introduction of a pyrazole ring in the chalcones between the two aryl rings increase the cytotoxic activity against a series of human cancer cell lines. Dhar et al. [19] synthesized a series of 1-acetyl-3,5-diaryl-4,5-dihydro-(H)-pyrazoles and assayed for in vitro cytotoxicity against PC-3, OVCAR, IMR-32, HEP-2 human cancer cell lines, compound 1 showed broad spectrum cytotoxic activity against all the four cell lines. The activity shown by the compounds conclude that (i) Substitution on phenyl ring showed marked effect on cytotoxic activity, (ii) Presence of electron donating groups on phenyl ring led to enhanced activity whereas electron withdrawing group except NO 2 reduces the cytotoxic activity, (iii) Replacement of phenyl ring with heterocyclic ring also reduces the cytotoxic potential and napthyl ring on both sides are more beneficial for cytotoxic potential Chemical Sciences JournalChem ic a l S cience s J o u rnal

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Section: Analogues Of Chalcones Pyrazoline Analogues With Various Phamentioning

confidence: 99%

Chalconoid Derived Heterocycles as Potent Bioactive Molecules: A Review

Sapra¹,

Sharma²

2016

Chem Sci J

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“…Among these isomeric families of compounds, 1, 2, 4-triazolo [1, 5-a]pyrimidine derivatives are thermodynamically more stable and thus, the most studied ones 1 , a few of them being commercially available. Revisions surveying the synthesis, reactivity, spectroscopic characterization and crystallographic studies of 1,2,4-triazolo [1,5- 5,6 , inhibition of KDR kinase 7 , antifungal effect 8 and macrophage activation 9 . They have proved to be promising anticancer agents with dual mechanisms of tubulin polymerization promotion as well as cycling dependent kinases 2 inhibition 10 .…”

Section: Introductionmentioning

confidence: 99%

Microwave Assisted Synthesis and Biological Evaluation of 1, 2, 4-Triazolo[1, 5-a]pyrimidines

2017

Chem Sci Trans

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Abstract:A microwave assisted synthesis of three new series of of 1, 2, 4-triazolo[1, 5-a]pyrimidines (PK-101 to PK-110) has been synthesized by the mixture of 5-(methylthio)-2H-1,2,4-triazol-3-amine (0.01 mol), 4,4,4-trifluoro-1-(4-methoxyphenyl)butane-1,3-dione (0.01 mol) and an appropriate aromatic aldehyde (0.01 mol) in ethanol (5 mL) was irradiated under microwave conditions at 120 °C for 10-15 min. The structures of all the newly synthesized compounds are elucidated by FT-IR, mass spectra, 1 H NMR and elemental analysis. The newly synthesized compounds are subjected to various biological activities viz., antimicrobial, antimycobacterial, anticancer and antiviral.

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“…Recently, 1,2,4-triazolo [1,5-a]pyrimidines have aroused increasing attention from the chemical and biological view points, due to their diverse pharmacological activities, such as antitumor potency [1,2] inhibition of KDR kinase [3], antifungal effect [4] and macrophage activation [5]. They have proved to be promising anticancer agents with dual mechanisms of tubulin polymerization promotion [1,2] as well as cyclin dependent kinases [2] inhibition [6].…”

Section: Introductionmentioning

confidence: 99%