Skip to main content

Synthesis and Biological Evaluation of Some Quinazoline Heterocyclic Derivatives

  • Chapter
  • First Online:
Green Chemistry: Synthesis of Bioactive Heterocycles

Abstract

Owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. This chapter summarizes the recent advances in the investigations of synthesis and biological activities of quinazoline derivatives. According to the main method the authors adopted in their research design, those synthetic methods include microwave-assisted reaction, ultrasound-promoted reaction, metal-mediated reaction, water reaction, and phase-transfer catalysis reaction. The biological activities of the synthesized quinazoline derivatives are also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Chandregowda V, Kush AK, Chandrasekara RG (2009) Synthesis and in vitro antitumor activities of novel 4-anilinoquinazoline derivatives. Eur J Med Chem 44:3046–3055

    Article  CAS  Google Scholar 

  2. Al-Rashood ST, Aboldahab IA, Nagi MN, Abouzeid LA, Abdel-Aziz AA, Abdel-Hamide SG, Al-Obaid AM, El-Subbagh HI (2006) Synthesis, dihydrofolate reductase inhibition, antitumor testing, and molecular modeling study of some new 4(3H)-quinazolinone analogs. Bioorg Med Chem 14:8608–8621

    Article  CAS  Google Scholar 

  3. Vasdev N, Dorff PN, Gibbs AR, Nandanan E, Reid LM, Neil JPO’, VanBrocklin HF (2005) Synthesis of 6-acrylamido-4-(2-[18F] fluoroanilino) quinazoline. A prospective irreversible EGFR binding probe. J Lablelled Compd Rad 48:109–115

    Article  CAS  Google Scholar 

  4. Wakeling AE, Guy SP, Woodburn JR, Ashton SE, Curry BJ, Barker AJ, Gibson KH (2002) An orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res 62:5749–5754

    CAS  Google Scholar 

  5. Alagarsamy V, Solomon VR, Dhanabal K (2007) Synthesis and pharmacological evaluation of some 3-phenyl-2-substituted-3H -quinazolin-4-one as analgesic, anti-inflammatory agents. Bioorg Med Chem 15:235–241

    Article  CAS  Google Scholar 

  6. Baba A, Kawamura N, Makino H, Ohta Y, Taketomi S, Sohda T (1996) Studies on disease-modifying antirheumatic drugs: synthesis of novel quinoline and quinazoline derivatives and their anti-inflammatory effect. J Med Chem 39:5176–5182

    Article  CAS  Google Scholar 

  7. Rohini R, Muralidhar Reddy P, Shanker K, Hu A, Ravinder V (2010) Antimicrobial study of newly synthesized 6-substituted indolo[1,2-c]quinazolines. Eur J Med Chem 45:1200–1205

    Article  CAS  Google Scholar 

  8. Antipenko L, Karpenko A, Kovalenko S, Katsev A, Komarovska-Porokhnyavets E, Novikov V, Chekotilo A (2009) Synthesis of new 2-thio-[1,2,4]triazolo[1,5-c] quinazoline derivatives and its antimicrobial activity. Chem Pharm Bull 57:580–585

    Article  CAS  Google Scholar 

  9. Jatav V, Kashaw S, Mishra P, Gupta V (2008) Synthesis and antimicrobial activity of some new 3–[5-(4-substituted)phenyl-1,3,4-oxadiazole-2yl]-2-styrylquinazoline-4(3H)-ones. Med Chem Res 17:205–211

    Article  Google Scholar 

  10. Aly AA (2003) Synthesis of novel quinazoline derivatives as antimicrobial agents. Chin J Chem 21:339–346

    Article  CAS  Google Scholar 

  11. Li H, Huang R, Qiu D, Yang Z, Liu X, Ma J, Ma Z (1998) Synthesis and bioactivity of 4-quinazoline oxime ethers. Prog Nat Sci 8:359–365

    CAS  Google Scholar 

  12. Chandrika PM, Yakaiah T, Narsaiah B, Sridhar V, Venugopal G, Rao JV, Kumar KP, Murthy USN, Rao ARR (2009) Synthesis leading to novel 2,4,6-trisubstituted quinazoline derivatives, their antibacterial and cytotoxic activity against THP-1, HL-60 and A375 cell lines. Indian J Chem 48B:840–847

    CAS  Google Scholar 

  13. Paneersalvam P, Raj T, Ishar PSM, Singh B, Sharma V, Rather BA (2010) Anticonvulsant activity of Schiff bases of 3-amino-6,8-dibromo-2-phenyl-quinazolin-4(3H)-ones. Indian J Pharm Sci 72:375–378

    Article  CAS  Google Scholar 

  14. Nandy P, Vishalakshi MT, Bhat AR (2006) Synthesis and antitubercular activity of Mannich bases of 2-methyl-3H-quinazolin-4-ones. Indian J Heterocycl Chem 15:293–294

    CAS  Google Scholar 

  15. Saravanan G, Alagarsamy V, Prakash CR (2010) Synthesis and evaluation of antioxidant activities of novel quinazoline derivatives. Int J Pharm Pharm Sci 2:83–86

    CAS  Google Scholar 

  16. Lakhan R, Singh OP, Singh-J RL (1987) Studies on 4 (3H)-quinazolinone derivatives as anti-malarials. J Indian Chem Soc 64:316–318

    CAS  Google Scholar 

  17. Hess HJ, Cronin TH, Scriabine A (1968) Antihypertensive 2-amino-4(3H)-quinazolinones. J Med Chem 11:130–136

    Article  CAS  Google Scholar 

  18. Sasmal S, Balaji G, Kanna Reddy HR, Balasubrahmanyam D, Srinivas G, Kyasa S, Sasmal PK, Khanna I, Talwar R, Suresh J, Jadhav VP, Muzeeb S, Shashikumar D, Harinder Reddy K, Sebastian VJ, Frimurer TM, Rist Ø, Elster L, Högberg T (2012) Design and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists. Bioorg Med Chem Lett 22:3157–3162

    Article  CAS  Google Scholar 

  19. Alvarado M, Barceló M, Carro L, Masaguer CF, Raviña E (2006) Synthesis and biological evaluation of new quinazoline and cinnoline derivatives as potential atypical antipsychotics. Chem Biodivers 3:106–117

    Article  CAS  Google Scholar 

  20. Malamas MS, Millen J (1991) Quinazolineacetic acids and related analogs as aldose reductase inhibitors. J Med Chem 34:1492–1503

    Article  CAS  Google Scholar 

  21. Wagner H, Wolff P (1977) New natural products and plant drugs with pharmacological, biological or therapeutical activity, vol 3. Springer, Berlin, p 642

    Book  Google Scholar 

  22. Malon MH (1977) New natural products and plant drugs with pharmacological, biological or therapeutical activity, vol 3. Springer, Berlin, pp 23–25

    Book  Google Scholar 

  23. Inderjit K, Chauhan PK (2012) Antioxidant and antimicrobial activity of leaf extract of adhatoda vasica against the bacteria isolated from the sputum samples of asthmatic patients. Int J Drug Res Tech 2:273–278

    Google Scholar 

  24. Rachana, Basu S, Kumar M (2011) Review & future perspectives of using vasicine, and related compounds. Indo-Global J Pharm Sci 1:85–98

    Google Scholar 

  25. Baker BR, Schaub RE, McEvoy FJ, Williams JH (1952) An antimalarial alkaloid from hydrangea. xii. synthesis of 3-[β-keto-γ-(3-hydroxy-2-piperidyl) propyl]-4-quinazolone, the alkaloid. J Org Chem 17:132–140

    Article  CAS  Google Scholar 

  26. Yasuo T, Miyo O (2005) Concise Synthesis of dl-Febrifugine. Chem Pharm Bull 53:868–869

    Article  Google Scholar 

  27. Koepfli JB, Mead JF et al (1947) An alkaloid with high antimalarial activity from Dichroa febrifuga. J Am Chem Soc 69:1837

    Article  CAS  Google Scholar 

  28. Gujral ML, Saxena PN, Tiwari RS (1955) Comparative evaluation of quinazolones: a new class of hypnotics. Indian J Med Res 43:637–641

    CAS  Google Scholar 

  29. Snider BB, Zeng H (2003) First total synthesis of fumiquinazolines. J Org Chem 68:545

    Article  CAS  Google Scholar 

  30. Mavandadi F, Lidstrom P (2004) Microwave- assisted chemistry in drug discovery. Curr Top Med Chem 4:773–792

    Article  CAS  Google Scholar 

  31. Gedye R, Smith F, Westaway K, Ali H, Baldisera L et al (1986) The use of microwave ovens for rapid organic synthesis. Tetrahedron Lett 27:279–282

    Article  CAS  Google Scholar 

  32. Liu YP, Yin DC, Chen HT, Sun BG (2010) Rapid synthesis of flavor compound 4-ethyloctanoic acid under microwave irradiation. Int J Mol Sci 11:4165–4174

    Article  CAS  Google Scholar 

  33. Cleophax J, Liagre M, Loupy A, Petit A (2000) Application of focused microwaves to the scale-up of solvent-free organic reactions. Org Process Res Dev 4:498–504

    Article  CAS  Google Scholar 

  34. Luo H, Hu D, Wu J, He M, Jin L, Yang S, Song B (2012) Rapid synthesis and antiviral activity of (quinazolin-4-ylamino)methyl-phosphonates through microwave irradiation. Int J Mol Sci 13:6730–6746

    Article  CAS  Google Scholar 

  35. Tu S, Li C, Li G, Cao L, Shao Q, Zhou D, Jiang B, Zhou J, Xia M (2007) Microwave-assisted combinatorial synthesis of polysubstituent imidazo[1,2-a] quinoline, pyrimido[1,2-a]quinoline and quinolino[1,2-a]quinazoline derivatives. J Comb Chem 9:1144–1148

    Article  CAS  Google Scholar 

  36. Kidwai M, Saxena S, Khan MKR, Thukral SS (2005) Synthesis of 4-aryl-7, 7-dimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2-one/thione-5-one derivatives and evaluation as antibacterials. Eur J Med Chem 40:816–819

    Article  CAS  Google Scholar 

  37. Besson T, Alexandre F-R, Berecibar A (2003) Synthesis of Niementowski Quinazolinone. Tetrahedron 59:141

    Article  Google Scholar 

  38. Besson T, Alexandre F-R, Berecibar A (2005) microwave irradiation and/or Appel’s salt, new efficient routes to various substituted and fused quinazolines. Tetrahedron 59:141

    Google Scholar 

  39. Dandia A, Singh R, Sarawgi P (2005) Green chemical multi-component one-pot synthesis of fluorinated 2,3-disubstituted quinazolin-4(3H)-ones under solvent-free conditions and their anti-fungal activity. J Fluor Chem 126:307

    Article  CAS  Google Scholar 

  40. Liu J-F, Lee J, Dalton AM, Bi G, Baldino CM, McElory E, Brown M (2005) Facile one-pot synthesis of 2,4(1H,3H)-quinazolinediones has been developed recently as a green chemical procedure. Tetrahedron Lett 46:1241

    Article  CAS  Google Scholar 

  41. Zhang L, Gao Z, Peng C, Bin ZY, Zhao D, Wu J, Xu Q, Li JX (2012) Ultrasound-promoted synthesis and immunosuppressive activity of novel quinazoline derivatives. Mol Divers 16:579–590

    Article  CAS  Google Scholar 

  42. Khalil AK (2005) Phase-transfer catalyzed alkylation and cycloalkylation of 2-mercaptoquinazolin-4(3H)-one. Phosphorus Sulfur Silicon Relat elem 180:2533–2541

    Article  CAS  Google Scholar 

  43. Ardakan MN, Smalley RK, Smith RH (1983) Acylation of N-methylamides with 2-azidobenzoyl chloride. J Chem Soc Perkin Trans 1:2501

    Article  Google Scholar 

  44. Takeuchi H, Eguchi S (1989) Aza–Wittig reaction yield exclusively 3-methylquinazolin-4(3H)-ones. Tetrahedron Lett 30:3313

    Article  CAS  Google Scholar 

  45. Safari J, Gandomi-Ravandi S (2013) Microwave-accelerated three components cyclocondensation in the synthesis of 2,3-dihydroquinazolin-4(1H)-ones promoted by Cu-CNTs. J Mol Catal A Chem 371:135–140

    Article  CAS  Google Scholar 

  46. Bharathi A, Roopan SM, Kajbafvala A, Padmaja RD, Darsana MS, Kumari GN (2013) Catalytic activity of TiO2 nanoparticles in the synthesis of some 2,3-disubstituted dihydroquinazolin-4(1H)-ones. Chin Chem Lett 25:324–326. http://dx.doi.org/10.1016/j.cclet.2013.11.040

    Article  Google Scholar 

  47. Muthukrishnan J, Seifert K, Hoffmann KH, Lorenz MW (1999) Inhibition of juvenile hormone biosynthesis in Gryllus bimaculatus by Glycosmis pentaphylla leaf compounds. Phytochemistry 50:249–254

    Article  CAS  Google Scholar 

  48. Ager I R, Harrison D R, Kennewell P D, Taylor J B (1977) Synthesis of 2-methyl-3-(o-tolyl)-4(3H)-quinazolone. J Med Chem 20:380

    Google Scholar 

  49. Povarov LS (1967) α, β-Unsaturated ethers and their analogues in reactions of diene synthesis. Rus Chem Rev 36:656–669

    Article  Google Scholar 

  50. Reymond S, Cossy J (2008) Copper-catalyzed Diels-alder reactions. Chem Rev 108:5359–5406

    Article  CAS  Google Scholar 

  51. Chen X, Wei H, Yin L, Li X (2010) A convenient synthesis of quinazoline derivatives via cascade imimo-Diels-Alder and oxidation reaction. Chin Chem Lett 21:782–786

    Article  CAS  Google Scholar 

  52. Molina P, Vilaplana MJ (1994) Iminophosphoranes useful building blocks for the preparation of nitrogen-containing heterocycles. Synthesis 19:1197–1218

    Article  Google Scholar 

  53. He P, Nie YB, Wu J, Ding MW (2011) Unexpected synthesis of indolo[1,2-c] quinazolines by a sequential ugi 4CC-Staudinger-aza-Wittig-nucleophilic addition reaction. Org Biomol Chem 9:1429–1436

    Article  CAS  Google Scholar 

  54. Ding MW, Yang SJ, Chen YF (2004) Synthesis and fungicidal activities of 2-alkoxy-3H-quinazolin-4-ones. Chin J Org Chem 24:923–926

    CAS  Google Scholar 

  55. Sang P, Xie YJ, Zou JW, Zhang YH (2012) Copper-catalyzed sequential Ullmann N-arylation and aerobic oxidative C-H amination: a convenient route to indolo[1,2-c]quinazoline derivatives. Org Lett 14:3894–3897

    Article  CAS  Google Scholar 

  56. Jiang M, Li J, Wang F, Zhao YC, Zhao F, Dong XC, Zhao WL (2012) A facile copper-catalyzed one-pot domino synthesis of 5,12-dihydroindolo[2,1-b] quinazolines. Org Lett 14:1420–1423

    Article  CAS  Google Scholar 

  57. Dabiri M, Salehi P, Mohammadi AA, Baghbanzadeh M (2005) One-pot procedure for the synthesis of mono-and disubstituted (3H)-quinazolin-4-ones. Synth Commun 35:279

    Article  CAS  Google Scholar 

  58. Battistuzzi G, Cacchi S, Fabrizi G, Marinelli F, Parisi LM (2002) Regioselective synthesis of 4(3H)-quinazolinone derivatives and indoloquinazolines. Org Lett 4:1355

    Article  CAS  Google Scholar 

  59. Kundu NG, Chaudhuri G (2001) Region- and stereoselective route to 2-(2-arylvinyl)-1,2,3,4- tetrahydroquinazolin-4-ones. Tetrahedron 57:6833

    Article  CAS  Google Scholar 

  60. Saxena S, Verma M, Saxena AK, Shanker K (1991) Antiinflammatory quinazolinones. Indian J Pharm Sci 53:48–52

    CAS  Google Scholar 

  61. Srivastava B, Shukla JS, Prabhakar YS, Saxena AK (1991) Synthesis and QSAR of 2,3,6,8- substituted 1,3-quinazolin-4(3H)-ones as potential anthelmintics. Indian J Chem 30B:332–339

    CAS  Google Scholar 

  62. Fisnerova L, Brunova B, Maturova E, Grimova J, Tikalova J, Kocfeldova Z (1991) Preparation of keto derivatives of 4(3H)-quinazolinone as analgesics. Chem Pharm Bull 115:293

    Google Scholar 

  63. Abdel-Rahman MM, Mangoura SA, El-Bitar HI (1990) Possible CNS depressant effects of some newly synthesized quinazolinone derivatives. Bull Pharm Sci Assiut Univ 13:137–144

    CAS  Google Scholar 

  64. Hori M, Iemura R, Hara H, Ozaki A, Sukamoto T, Ohtaka H (1990) Novel 4-phenoxy-2-(1-piperazinyl)quinazolines as potent anticonvulsive and antihypoxic agents. Chem Pharm Bull 38:681–687

    Article  CAS  Google Scholar 

  65. Brown DJ (1984) In Comprehensive Heterocyclic Chemistry 2:148

    Google Scholar 

  66. Jackman AL, Kimbell R, Aherne GW, Brunton L, Jansen G, Stephens TC, Smith MN, Wardleworth JM, Boyle FT (1997) Cellular pharmacology and in vivo activity of a new anticancer agent, ZD9331: a water-soluble, nonpolyglutamatable, quinazoline-based inhibitor of thymidylate synthase. Clin Cancer Res 3:911–921

    CAS  Google Scholar 

  67. Rafi I, Taylor GA, Calvete JA, Boddy AV, Balmanno K, Bailey N, Lind M, Calvert AH, Webber S, Jackson RC, Johnston A, Clendeninn N, Newell DR (1995) Clinical pharmacokinetic and pharmacodynamic studies with the nonclassical antifolate thymidylate synthase inhibitor 3,4- dihydro-2-amino-6-methyl-4-oxo-5-(4-pyridylthio)-quinazolone dihydrochloride(AG337) given by 24-hour continuous intravenous infusion. Clin Cancer Res 1:1275–1284

    CAS  Google Scholar 

  68. Brown DJ (1996) Quinazolines. In: Taylor EC (ed) The chemistry of heterocyclic compounds supplement I, vol 55. Wiley, New York, p 1123

    Chapter  Google Scholar 

  69. Seijas JA, Va´zquez-Tato, MP, Martı´nez MM (2000) Microwave-enhanced synthesis of 4-aminoquinazolines. Tetrahedron Lett 41:2215–2217

    Article  CAS  Google Scholar 

  70. Alexandre FR, Berecibar A, Besson T (2002) Microwave-assisted Niementowski reaction: back to the roots. Tetrahedron Lett 43:3911–3913

    Article  CAS  Google Scholar 

  71. Dandia A, Singh R, Sarawgi P (2005) Green chemical multi-component one-pot synthesis of fluorinated 2,3-disubstituted quinazolin-4(3H)-ones under solventfree conditions and their anti-fungal activity. J Fluor Chem 126:307

    Article  CAS  Google Scholar 

  72. Perreux L, Loupy A (2001) A tentative rationalization of microwave effects in organic synthesis according to the reaction medium, and mechanistic considerations. Tetrahedron 57:9199–9223

    Article  CAS  Google Scholar 

  73. Lidstrom P, Tierney J, Wathey B, Westman J (2001) Microwave-assisted organic synthesis—a review. Tetrahedron 57:9225–9283

    Article  CAS  Google Scholar 

  74. Qiu G, He Y, Wu J (2012) Preparation of quinazolino[3,2-a]quinazolines via a palladium-catalyzed three-component reaction of carbodiimide isocyanide and amine. Chem Commun 48:3836–3838

    Article  CAS  Google Scholar 

  75. Bergman J, Brynolf A, Elman B, Vuolinen A (1986) Various quinazolines from 2-aminobenzonitrile using organometallic reagents. Tetrahedron 42:3697

    Article  CAS  Google Scholar 

  76. Wiklund P, Bergman J (2003) Synthesis, and application of organometallic reagents. Org Biomol Chem 1:36

    Article  Google Scholar 

  77. Matheson SL, Brahimi F, Jean-Claude BJ (2004) The combi-targeting concept: intracellular fragmentation of the binary epidermal growth factor (EGFR)/DNA targeting “combi-triazene” SMA41. Biochem Pharmacol 67:1131–1138

    Google Scholar 

  78. Wang GW, Miao CB (2006) Environmentally benign one-pot multi-component approaches to the synthesis of novel unsymmetrical 4-arylacridinediones. Green Chem 8:1080–1085

    Article  CAS  Google Scholar 

  79. Bauer L, Suresh KS (1963) Synthesis of anti-malarial compound. J Org Chem 28:1604

    Article  CAS  Google Scholar 

  80. Baek DJ, Park YK, Heo HI, Lee MH, Yang ZY, Chio MH (1998) Synthesis of 5-substituted quinazolinone derivatives and their inhibitory activity in vitro. Bio Org Med Chem Lett 83:287

    Google Scholar 

Download references

Acknowledgments

The authors are thankful to Prof. G. L. Talesara, Retd. Professor, Department of Chemistry, Mohan Lal Sukhadia University Udaipur, and Dr. Sunil Jhakoria, Dean, Faculty of Arts, Science and Technology (FASC), Mody University of Science and Technology, for their constant encouragement during this work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K. L. Ameta .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer India

About this chapter

Cite this chapter

Dangi, R., Chundawat, N., Ameta, K. (2014). Synthesis and Biological Evaluation of Some Quinazoline Heterocyclic Derivatives. In: Ameta, K., Dandia, A. (eds) Green Chemistry: Synthesis of Bioactive Heterocycles. Springer, New Delhi. https://doi.org/10.1007/978-81-322-1850-0_13

Download citation

Publish with us

Policies and ethics