Synthesis and antiviral activity of new 3-methyl-1,5-diphenyl-1H-pyrazole derivatives

被引:0
作者
Atif S. Tantawy
Magda N. A. Nasr
Magda A. A. El-Sayed
Samar S. Tawfik
机构
[1] Mansoura University,Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy
来源
Medicinal Chemistry Research | 2012年 / 21卷
关键词
Antiviral activity; Isoxazoline; Plaque reduction; Pyrazoles; Pyrazolines; Pyridine; Pyrimidine;
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中图分类号
学科分类号
摘要
A new series of 4-substituted 3-methyl-1,5-diphenyl-1H-pyrazoles 4–11 has been synthesized and evaluated for its in vitro antiviral activity and cytotoxicity against herpes simplex virus type-1 grown on Vero African green monkey kidney cells through plaque-reduction assay method using acyclovir as a positive control. The synthesis was achieved through Claisen-Schmidt condensation reaction of 3-methyl-1,5-diphenyl-1H-pyrazole-4-carbaldehyde (3) with acetophenone derivatives to give various enones 4a–f which are considered an important synthon for the construction of different heterocyclic rings as isoxazoline, pyrazoline, pyrimidine, pyridine, and fused pyridine via several synthetic routes. Biological evaluation of the prepared compounds showed that 3-(4-methylphenyl)-5-(3-methyl-1,5-diphenyl-1H-pyrazol-4-yl)-4,5-dihydroisoxazole (5f), 6-(4-methylphenyl)-N-[(3-(methylsulfanyl)phenyl)]-4-(3-methyl-1,5-diphenyl-1H-pyrazol-4-yl)pyrimidin-2-amine (7), 6-(4-bromophenyl)-4-(3-methyl-1,5-diphenyl-1H-pyrazol-4-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (8), and 2-amino-6-(4-bromophenyl)-4-(3-methyl-1,5-diphenyl-1H-pyrazol-4-yl) pyridine-3-carbonitrile (9) exhibited strong antiviral activity with IC50 (0.02, 0.04, 0.03, 0.03), respectively, compared to the used reference drug. The synthesized compounds were characterized by physical constants and the structures of the title compounds were confirmed by IR, 1H NMR, mass spectra, and elemental analyses.
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页码:4139 / 4149
页数:10
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[1]  
Abadi AH(2009)Design, synthesis and biological evaluation of novel pyridine derivatives as anticancer agents and phosphodiesterase 3 inhibitors Bioorg Med Chem 17 5974-5982
[2]  
Ibrahim TM(2010)Novel substituted and fused pyrrolizine derivatives: synthesis, anti-inflammatory and ulcerogenecity studies Eur J Med Chem 45 482-491
[3]  
Abouzid KM(1995)Differential activities of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives against different human immunodeficiency virus type 1 mutant strains Antimicrob Agents Chemother 39 998-1002
[4]  
Lehmann J(2011)Pyrazole: a versatile moiety Int J ChemTech Res 3 11-17
[5]  
Tinsley HN(2010)Synthesis, anti HSV-1 and cytotoxic activities of some new pyrazole- and isoxazole-based heterocycles Med Chem Res 20 912-919
[6]  
Gary BD(2000)Synthesis, DNA-binding, and antiviral activity of certain pyrazolo[3,4-d]pyrimidine derivatives Arch. Pharm. (Weinheim) 333 99-103
[7]  
Piazza GA(2000)Synthesis and biological evaluation of certain α,β-unsaturated ketones and their corresponding fused pyrimidines as antiviral and antitumer agents J Med Chem 43 2915-2921
[8]  
Abbas SE(2009)Synthesis and antiviral activity of new pyrazole and thiazole derivatives Eur J Med Chem 44 3746-3753
[9]  
Awadallah FM(2000)Novel 1,5-diphenylpyrazole non-nucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: lead identification and SAR of 3- and 4-substituted derivatives J Med Chem 43 1034-1040
[10]  
Ibrahim NA(2010)Cytotoxicity and utility of 1-indanone in the synthesis of some new heterocycles Chem Pharm Bull 58 479-483