Medicinal Chemistry Research

, Volume 22, Issue 2, pp 768–774 | Cite as

Synthesis and antimicrobial activity of coumarin pyrazole pyrimidine 2,4,6(1H,3H,5H)triones and thioxopyrimidine4,6(1H,5H)diones

Original Research


A series of 5-((3-(2-oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-trione (4af) and dihydro-5-((3-(2-oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxopyrimidine-4,6(1H,5H)-dione (5af) derivatives were synthesized by the condensation of 3-(2-oxo2H-chromen-3-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde (3af) with barbituric acid and thiobarbituric acid in acetic acid under microwave irradiation method. The newly synthesized compounds were evaluated for their antibacterial activity against Bcillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeoginosa, and Klebsiella pneumoniae. All the compounds were found to be moderately active against used microorganisms, whereas compounds (4d) and (4e) exhibited good antifungal activity against Aspergillus niger.


Antimicrobial activity Barbituric acid Coumarin Microwave irradiation Pyrazole Thiobarbituric acid 


  1. Brouwer WG, Felauerand EE (1991) Bell Chem Abstr 114:185539Google Scholar
  2. Brouwer WG, Felauerand EE, Bell AR (1990) U.S. Patent, vol 779, p 982Google Scholar
  3. Caddick S (1995) Microwave assisted organic reactions. Tetrahedron 51:10403–10432CrossRefGoogle Scholar
  4. Chodankar NK, Sequeira S, Seshadri S (1986) Synthesis of 3-hetarylcoumarins from 3-acetylcoumarines. Dyes Pigment 7:231–236CrossRefGoogle Scholar
  5. Chopra I, Schofield C, Everett M, O’Neill A, Miller K, Wilcox M, Frere JM, Dawson M, Czapiewski L, Urleb (2008) Lancet infectious diseases treatment of healthcare associated infections caused by gram negative bacteria a consensus statement. Lancet Infect Dis 8:133–139PubMedCrossRefGoogle Scholar
  6. Diana P, Carbone A, Barraja P, Martorana A, Gia O, DallaVia L, Cirrincione G (2007) 3,5-Bis(3′-indolyl)pyrazoles, analogues of marine alkaloid nortopsentin: synthesis and antitumor properties. Bioorg Med Chem Lett 17:6134–6137PubMedCrossRefGoogle Scholar
  7. Emmanuel-Giota AA, Fylaktakidou KC, Hadjipavlou-Litina DJ, Litinas KE, Nicolaides DN (2001) Synthesis and biological evalution of several 3-(coumarin-4-yl) tetrahydroisoxazole and 3-(coumarin-4-yl)dihydropyrazole derivatives. J Heterocycl Chem 38:717–722CrossRefGoogle Scholar
  8. Esanu A (1985) BE Patent, vol 902, p 232Google Scholar
  9. Esanu A (1986) Chem Abstr 104:130223Google Scholar
  10. Francesca SL (2011) Anti-microbial properties of Scutellaria baicalensis and Coptis chinensis , two traditional Chinese medicines. Biosc Horiz 1:119–127Google Scholar
  11. Gadakh AV, Pandit C, Rindhe SS, Karale BK (2010) Synthesis and antimicrobial activity of novel fluorine containing 4-(substituted-2-hydroxybenzoyl)-1H-pyrazoles and pyrazolyl benzo[d]oxazoles. Bioorg Med Chem Lett 20:5572–5576PubMedCrossRefGoogle Scholar
  12. Gnerre C, Catto M, Leonetti F, Weber P, Carrupt P-A, Altomare C, Carotti A, Testa B (2000) Inhibition of monoamine oxidases by functionalized coumarin derivatives:  biological activities, QSARs, and 3D-QSARs. J Med Chem 43:4747–4758PubMedCrossRefGoogle Scholar
  13. Jih Ru, Hwu S-YL, Tsay S-C, De Clercq E, Leyssen P, Neyts J (2011) Coumarin–purine ribofuranoside conjugates as new agents against hepatitis C virus. J Med Chem 54:2114–2126CrossRefGoogle Scholar
  14. Kawase M, Varu B, Shah A, Motohashi N, Tani S, Saito S, Debnath S, Mahapatra S, Dastidar SG, Chakrabarty AN (2001) Antimicrobial activity of new coumarin derivatives. Arzneimittelforschung 51:67–71PubMedGoogle Scholar
  15. Khan KM, Saify ZS, Khan MZ, Zia-Ullah, Choudhary IM, Atta-ur-Rahman, Perveen S, Chohan ZH, Supuran CT (2004) Synthesis of coumarin derivatives with cytotoxic, antibacterial and antifungal activity. J Enz Inhib Med Chem 19:373–379CrossRefGoogle Scholar
  16. Linday ME (1962) Practical introduction to microbiology. E and F.N. Spon Ltd., New York, p 17Google Scholar
  17. Manolov I, Danchev ND (1995) Synthesis,toxicological and pharmacological assessment of some 4-hydroxycoumarin. Eur J Med Chem 30:531–536CrossRefGoogle Scholar
  18. Mathers DA, Wan X (2007) Barbituric acid activation and modulation of GABA receptors in neocortex. Neuropharmacology 52:1160–1168PubMedCrossRefGoogle Scholar
  19. Mavandadi FM, Lidström P (2004) Microwave-assisted chemistry in drug discovery. Curr Topics Drug Discov 4:773–792Google Scholar
  20. National Committee for Clinical Laboratory Standards (NCCLS) (1982) Standard methods for dilution antimicrobial susceptibility tests for bacteria, which grows aerobically. National Committee for Clinical Laboratory Standards, Villanova, p 242Google Scholar
  21. Padmaja A, Payani T, Dinneswara RG, Padmavathi V (2009) Synthesis, antimicrobial and antioxidant activities of substituted pyrazoles, isoxazoles, pyrimidine and thioxopyrimidine derivatives. Eur J Med Chem 44:4557–4566PubMedCrossRefGoogle Scholar
  22. Padmaja A, Rajasekhar C, Muralikrishna A, Padmavathi V (2011) Synthesis and antioxidant activity of oxazolyl/thiazolylsulfonylmethyl pyrazoles and isoxazoles. Eur J Med Chem 46:5034–5038PubMedCrossRefGoogle Scholar
  23. Sauzem PD, Machado P, Rubin MA, da Sant’Anna GS, Faber HB, de Souza AH, Mello CF, Beck P, Burrow RA, Bonacorso HG, Zanatta N, Martins MAP (2008) Design and microwave-assisted synthesis of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles: novel agents with analgesic and anti-inflammatory properties. Eur J Med Chem 43:1237–1247PubMedCrossRefGoogle Scholar
  24. Selvi S, Perumal PT (2002a) Facile synthesis of [1]benzopyrano[4,3-c] pyrazoles, 1- aryl-3- (2formamidophenyl)pyrazoles and 1-aryl-3-phenyl-4-alkylpyrazoles using vilsmeier reagent. Indian J Chem 41B:1887–1893Google Scholar
  25. Selvi S, Perumal PT (2002b) A short, facile method for the synthesis of 1-aryl-3-phenyl-4-alkylpyrazoles using microwave irradiation. J Heterocycl Chem 39:1129–1131CrossRefGoogle Scholar
  26. Singh P, Kaur M, Verma P (2009) Design, synthesis and anticancer activities of hybrids of indole and barbituric acids identification of highly promising leads. Bioorg Med Chem Lett 19:3054–3058PubMedCrossRefGoogle Scholar
  27. Smyth T, Ramachandran VN, Smyth WF (2009) A study of the antimicrobial activity of selected naturally occurring and synthetic coumarins. Int J Antimicrob Agents 33:421–426PubMedCrossRefGoogle Scholar
  28. Sundriyal S, Viswanad B, Poduri R, Chakraborti AK, Bharatam PV (2008) New PPARγ ligands based on barbituric acid: virtual screening, synthesis and receptor binding studies. Bioorg Med Chem Lett 18:4959–4962PubMedCrossRefGoogle Scholar
  29. Suresh Kuarm B, Thirupathi Reddy Y, Venu Madhav J, Crooks PA, Rajitha B (2011) 3-[Benzimidazo- and 3-[benzothiadiazoleimidazo-(1,2-c)quinazolin-5-yl]-2H-chromene-2-ones as potent antimicrobial agents. Bio Org Med Chem Lett 21:524–527CrossRefGoogle Scholar
  30. Thirupathi Reddy Y, Konjeti R, Sekhar, Nidhish Sasi, Narsimha Reddy P, Michael L, Freeman, Crooks PA (2010) Novel substituted (Z)-5-((N-benzyl-1H-indol-3-yl) methylene)imidazolidine-2,4-diones and 5-((N-benzyl-1H-indol-3-yl)methylene) pyrimidine-2,4,6(1H,3H,5H)-triones as potent radio-sensitizing agents. Bioo. Bioorg Med Chem Lett 20:600–602CrossRefGoogle Scholar
  31. Verma RS (1999) Solvent-free organic syntheses using supported reagents and microwave Irradiation. Green Chem 1:43–55CrossRefGoogle Scholar
  32. Vijaya Laxmi S, Thirupathi Reddy Y, Suresh Kuarm B, Narsimha Reddy P, Crooks PA, Rajitha B (2011) Synthesis and evaluation of chromenyl barbiturates and thiobarbiturates as potential antitubercular agents. Bio Org Med Chem Lett 21:4329–4331CrossRefGoogle Scholar
  33. Villanova Pa (1984) National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial disk susceptibility tests, 3rd National Committee for Clinical Laboratory Standards, Villanova, 120Google Scholar
  34. Yan Q, Cao R, Yi W, Chen Z, Wen H, Ma L, Song H (2009) Inhibitory effects of 5-benzylidene barbiturate derivatives on mushroom tyrosinase and their antibacterial activities. Eur J Med Chem 44:4235–4243PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of ChemistryNational Institute of TechnologyWarangalIndia

Personalised recommendations