Novel pyrazolopyrimidines as highly potent B-Raf inhibitors

Grandi, Martin J. Di; Berger, Dan M.; Hopper, Darrin W.; Zhang, Chunchun; Dutia, Minu; Dunnick, Alejandro L.; Torres, Nancy; Levin, Jeremy I.; Diamantidis, George; Zapf, Christoph W.; Bloom, Jonathan D.; Hu, Yongbo; Powell, Dennis; Wojciechowicz, Donald; Collins, Karen; Frommer, Eileen

doi:10.1016/j.bmcl.2009.10.058

Cited by 25 publications

(13 citation statements)

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“…All additional information pertaining to characterization of the compounds using synthesis of pyrazolo [1,5a]pyrimidine derivatives (Schemes S1-6), 1H-NMR spectra ( Figures S1, 3, 4, 7, 9, 11, 13, 15, 17, 19, 20, 22, 24, 26), Mass spectrum ( Figure S6), 13C-NMR spectra (Figures S2,5,8,10,12,14,16,18,21,23,25,27) are given in Supplementary Information. The recovery and recycling of deep eutectic solvent (Table S1), Optimization of solvent and catalysts for the synthesis of dioxo pyrrolidones and dioxoisoindol (Table S2), antibacterial activity of compounds (Table S3) and antifungal activity of compounds (Table S4) are also given in the Supporting Information, available at www.ias.ac.in/ chemsci.…”

Section: Supplementary Information (Si)mentioning

confidence: 99%

An efficient synthesis of pyrazolo[1,5-a]pyrimidines and evaluation of their antimicrobial activity

et al. 2016

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A series of new pyrazolo[1,5-a]pyrimidine derivatives has been synthesized by using 7-hydrazinyl-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile 1 and 7-amino-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile 2 as precursors. The pyrazolo[3,4-d] pyrimidines 3a-b have been synthesized by a three-step reaction starting with 1. Compound 1 was utilized for the synthesis of dioxopyrrolidindolinylamio-pyrazolo-pyrimidines 4a-b, and dioxoisoindolin-pyrazolo-pyrimidines 4c-d. Also, compounds 4a-d were synthesized using deep eutectic solvents (DES). This method using DES provides several advantages such as benign environment, high yield, scalable and simple work-up procedure. Similarly, the cyclocondensation of 2 with α-acetylγ-butyrolactone afforded pyrazolo-pyrido-pyrimidine 5 and dihydrofuro-pyrido-pyrazolo-pyrimidine 6. All synthesized compounds were screened for antimicrobial activity.

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Section: Supplementary Information (Si)mentioning

confidence: 99%

An efficient synthesis of pyrazolo[1,5-a]pyrimidines and evaluation of their antimicrobial activity

et al. 2016

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“…Although these compounds bind to the dopamine in vitro , their behavioral effects are generally different from those of the typical dopamine uptake inhibitors, of which cocaine is a prototype . Recently, interest has been directed towards the construction of a tropane scaffold attached to heterocyclic residue as a substituent or in a fused ring system, for example, pyrazolo[1,5‐ a ]pyrimidines which are shown to be potent B‐Raf inhibitors .…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Synthesis, Structural and Spectroscopic Study of 4,5,11‐Triazatricyclo[6.2.1.02,6]Undec‐5‐ene

Mabied

Girgis

Shalaby

et al. 2015

Journal of Heterocyclic Chem

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in Wiley Online Library (wileyonlinelibrary.com).3-(2,4-Dichlorophenyl)-7-[(2,4-dichlorophenyl)methylidene]-11-methyl-4-phenyl-4,5,11-triazatricyclo [6.2.1.0*2,6*]undec-5-ene (3) was synthesized in a stereoselective manner. Single crystal X-ray study of 3 revealed that the structure belongs to the triclinic system with space group P1 . The structure is further stabilized by an intermolecular C-H … π interaction. Molecular mechanics force field (MM + ), followed by either semi-empirical AM1 or PM3, was used to calculate the optimized geometrical parameters of 3. The determined theoretical geometry parameters were found to be in good agreement with the parameters obtained by a single-crystal study. Vibrational frequencies and gauge-independent atomic orbital, 1 H-NMR and 13 C-NMR chemical shifts were computed at B3LYP/6-31G(d) level of theory. Moreover, the molecular electrostatic potential of 3 has been calculated exhibiting that the most electrophilic site of 3 is the N-3 atom; however, the nucleophilic site is distributed on the H atoms of dichlorophenyl groups. The frontier molecular orbitals of 3 have been determined by the same technique.

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“…In addition, several pyrazolopyrimidines have proved to elicit inhibitory activity on the growth of several human tumor cell lines besides being active against cyclin dependent kinases (CDKs) 21–23, Moreover, purine derivatives such as olomoucine and roscovitine; structurally related to pyrazolopyrimidines, were found to exhibit moderate activity but good selectivity toward several CDKs 24. Furthermore, some pyrazolopyrimidines proved to possess potent inhibitory activity against other enzymes that contribute to the cell cycle such as glycogen synthase kinase‐3 25, 26 and B‐Raf kinase 27, 28.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Some Novel Fused Pyrazolopyrimidines as Potential Anticancer and Antimicrobial Agents

Razik

Wahab

2010

Archiv der Pharmazie

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Synthesis and evaluation of anticancer and antimicrobial activity of some novel pyrazolopyrimidines and fused pyrazolopyrimidines are reported. Twelve analogs were selected to be evaluated for their in vitro anticancer potential against a panel of three human tumor cell lines: hepatocellular carcinoma HepG2, cervical carcinoma HelaS3 and colon carcinoma CaCo. The obtained data revealed that eight compounds namely; 6b, 6d, 7c, 8c, 10b, 12b, 13a and 13b were able to exhibit variable degrees of anticancer activities against the three used cell lines, of which compound 6d proved to be the most active. On the other hand, all the newly synthesized compounds were subjected to in vitro antibacterial and antifungal screening. Almost all the tested compounds were found to possess variable degrees of antimicrobial activities. Collectively, compounds 7c, 8c, 12b, 13a and 13b could be considered as possible agents with dual anticancer and antimicrobial activities.

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Novel pyrazolopyrimidines as highly potent B-Raf inhibitors

Cited by 25 publications

References 10 publications

An efficient synthesis of pyrazolo[1,5-a]pyrimidines and evaluation of their antimicrobial activity

An efficient synthesis of pyrazolo[1,5-a]pyrimidines and evaluation of their antimicrobial activity

Stereoselective Synthesis, Structural and Spectroscopic Study of 4,5,11‐Triazatricyclo[6.2.1.02,6]Undec‐5‐ene

Synthesis and Biological Evaluation of Some Novel Fused Pyrazolopyrimidines as Potential Anticancer and Antimicrobial Agents

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Novel pyrazolopyrimidines as highly potent B-Raf inhibitors

Cited by 25 publications

References 10 publications

An efficient synthesis of pyrazolo[1,5-a]pyrimidines and evaluation of their antimicrobial activity

An efficient synthesis of pyrazolo[1,5-a]pyrimidines and evaluation of their antimicrobial activity

Stereoselective Synthesis, Structural and Spectroscopic Study of 4,5,11‐Triazatricyclo[6.2.1.0*2,6*]Undec‐5‐ene

Synthesis and Biological Evaluation of Some Novel Fused Pyrazolopyrimidines as Potential Anticancer and Antimicrobial Agents

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Stereoselective Synthesis, Structural and Spectroscopic Study of 4,5,11‐Triazatricyclo[6.2.1.02,6]Undec‐5‐ene