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Current Drug Discovery Technologies


ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

Review Article

Chemistry and Pharmacological Activities of Biginelli Product- A Brief Overview

Author(s): Namy George, Asha Asokan Manakkadan, Ajish Ariyath, Surya Maniyamma, Vishnu Vijayakumar, Rajasree G. Pai and Subin Mary Zachariah*

Volume 16 , Issue 2 , 2019

Page: [127 - 134] Pages: 8

DOI: 10.2174/1570163815666180807141922

Price: $65


Dihydropyrimidinones are extremely advantageous small sized molecules owning adaptable pharmaceutical properties. With a molecular formula C4H6N2O, they hold a wide range of biological activities. It is a heterocyclic moiety having two N-atoms at positions 1 and 3. They are derivatives of pyrimidine containing an additional ketone group. They have inspired development of a wide range of synthetic methods for preparation and chemical transformations. Taking into consideration their structural similarity and involvement with DNA and RNA, they have become very imperative in the world of synthetic organic chemistry. Aryl substituted moieties and their derivatives are significant class of substances in medicinal and organic chemistry. Many alkaloids from natural marine sources comprising dihydropyrimidinones core have been isolated which possess fascinating biological properties. Intensive explorations have been carried out on these compounds because they possess close similitude to clinically used nifedipine, nicardipine etc. which are also Biginelli product analogues. Due to the interesting pharmacological properties associated with the privileged DHPM structures, the Biginelli reaction and related procedures have received increasing attention in recent years.

Keywords: 3, 4-dihydropyrimidine-2-ones, bigenelli compounds, anti-tumor activity, catalyst, DNA, RNA, MCRs.

Graphical Abstract
Kappe CO. 4-Aryldihydropyrimidines via the Biginelli condensation: Aza-analogs of nifedipine-type calcium channel modulators. Molecules 1998; 3(1): 1-9.
Pankaj A, Rohit B, Jitender GC, et al. Triethylammonium acetate ionic liquid assisted one-pot synthesis of dihydropyrimidinones and evaluation of their antioxidant and antibacterial activitie. Arab J Chem 2017; 10(2): 206-14.
Gupta M, Paul S, Gupta R. General aspects of 12 basic principles of green chemistry with applications. Curr Sci 2010; 99(10): 1341-60.
Zachariah SM, Ramkumar M, George N, Ashif MS. Azetidinones: An overview. Int J Pharm Sci Rev Res 2015; 30(1): 211-8.
Zhu J, Bienayme H. Multicomponent reactionsChemical Int ed 2005; 39: 3168 .
The academic pursuit of screening. Nat Chem Biol 2007; 3: 433.
Kappe CO. The biginelli reaction: Development and application. Tetrahedron 1993; 49: 6937-63.
Dondoni A, Massi A. High efficient solvent free synthesis of Dihydropyrimidinones catalysed by Zinc oxide. Tetrahedron Lett 2001; 42: 7975-8.
Nicolaou KC, Hanko R, Hartwig W. Handbook of Combinatorial Chemistry: Drugs, Catalysts, Materials. Wiley-VCH: Weinheim 2002.
Phucho IT, Nongpiur A, Tumtin S, Nongrum R, Nongkhlaw RL. Recent progress in the chemistry of dihydropyrimidinones. J Chem 2009; 3: 662-76.
Kataki D, Chakraborty P, Sarmah P, Phukan P. Scalable synthesis of 3, 4-dihydropyrimidin-2(1H)-ones under solvent free condition. Ind J Chem Tech 2006; pp. 519-21.
Russowsky D, Canto RF, Sanches SA, et al. Synthesis and differential antiproliferative activity of Biginelli compounds against cancer cell lines: Monastrol,oxo-monastrol and oxygenated analogues. Bioorg Chem 2006; 34: 173-82.
Bhatewara A, Jetti SR, Kadre T, Paliwal P, Jain S. Microwave-assisted synthesis and biological evaluation of dihydropyramidinone derivatives as anti-inflammatory, Antibacterial and antifungal agents. Int J Med Chem 2013; 1-5.
Suman LJ, Singhal S, Sain B. PEG-assisted solvent and catalyst free synthesis of 3, 4 -dihydropyrimidinones under mild teaction. Green Chem 2007; 9: 9740-1.
Akhaja TN, Raval JP. Bioactive dihydropyrimidines: An overview. Eur J Med Chem 2011; 46: 5573-9.
Kaan HYK, Ulaganathan V, Rath O, et al. Green synthetic approaches for biologically relaventdihydropyrimidinone. J Med Chem 2008; 16: 3291.
Chittethu AB, Asha J, Balasubramanian R, Saranya TS, Manakadan AA. Utility of isatinsemicarbazones in mammary carcinoma Cells-A proof of concept study. J Young Pharm 2017; 9: 218.
Thomas N, Zachariah SM, Ramani P. 4‐Aryl‐4H‐chromene‐3‐carbonitrile derivates: Synthesis and preliminary anti‐breast cancer studies. J Heterocycl Chem 2016; 53: 1778.
Wright CM, Chovatiya RJ, Jameson NE, et al. Pyrimidinone-peptoid hybrid molecules with distinct effects on molecular chaperone function and cell proliferation. Bioorg Med Chem 2008; 16: 3291.
Ibrahim DA, El-Metwally AM. N-(Cycloalkylamino)acyl-2-aminothiazole Inhibitors of Cyclin-Dependent Kinase 2. N-[5-[[[5-(1,1-Dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4- piperidinecarboxamide (BMS-387032), a highly efficacious and selective antitumor agent. Eur J Med Chem 2010; 45: 1158.
Patil AD, Kumar NV, Kokke WC, et al. Zinc perchlorate catalyzed one-pot synthesis of 3,4-dihydropyrimidinones under solvent-free condition. J Org Chem 1995; 60: 1182.
Kim J, Park C, Ok T, et al. A novel 3,4-dihydropyrimidin-2(1H)-one: HIV-1 replication inhibitors with improved metabolic stability. Bioorg Med Chem Lett 2012; 22: 2522.
Ji L, Chen FE, De Clercq E. Synthesis and anti-HIV-1 activity evaluation of 5-Alkyl-2-alkylthio-6-(arylcarbonyl or α-cyanoarylmethyl)-3, 4-dihydropyrimidin-4 (3 H)-ones as novel non-nucleoside HIV-1 reverse transcriptase inhibitors. J Med Chem 2007; 50: 1778.
Lloyd J, Finlay HJ, Atwal K, et al. A review on biological activities of dihydropyrimidinones / thiones. Bioorg Med Chem Lett 2009; 19: 5469.
Zorkun IS, Sarac S, Celebib S, Erolb K. Synthesis of 4-aryl-3, 4-dihydropyrimidin-2 (1H)-thione derivatives as potential calcium channel blockers. Bioorg Med Chem 2006; 14: 8582.
Ozair A, Khan SA, Siddiqui N, Ahsan W, Verma SP, Gilani SJ. Antihypertensive activity of newer 1,4-dihydro-5-pyrimidine carboxamides: Synthesis and pharmacological evaluation. Eur J Med Chem 2010; 45: 5113.
Clark AS, Wang GZ, Viet AQ, et al. Potent, selective and orally bioavailable dihydropyrimidine inhibitors of Rho kinase (ROCK1) as potential therapeutic agents for cardiovascular diseases. J Med Chem 2008; 51: 6631.
Singh BK, Mishra M, Saxena N, et al. Synthesis of 2-sulfanyl-6-methyl-1, 4-dihydropyrimidines as a new class of antifilarial agents. Eur J Med Chem 2008; 43: 2717-23.
Atwal KS, Swanson BN, Unger SE, et al. Reilly OX. Dihydropyrimidine calcium channel blockers. 3. 3-Carbamoyl-4-aryl-1,2,3,4-tetrahydro-6-methyl-5-pyrimidinecarboxylic acid esters as orally effective antihypertensive agents. J Med Chem 1991; 34: 806-11.
Rovnyak GC, Kimball SD, Beyer B, et al. Moreland. The generation of dihydropyrimidine libraries utilizing biginelli multicomponent chemistry. J Med Chem 1995; 38: 119-29.
Mayer TU, Kapoor TM, Haggarty SJ, King RW, Schreiber SL, Mitchison TJ. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science 1999; 286(5441): 971-4.
Maliga T, Kapoor TJ. Mitchison. Evidence that monastrol is an allosteric inhibitor of the mitotic kinesin Eg5. Chem Biol 2002; 9: 989-96.

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