Synthesis And Anagesic activities of Quinazolin-4(3H)-One, 2-Methyl-4(3H)-Quinazolinone and 2–Phenyl-4(3H)-quinazolin-4(3H)–one
Abstract
Background: Objective: The current study is aimed at the synthesis of these quinazolinone derivatives quinazolin-4(3H)-One, 2-Methyl-4(3H)-quinazolinone and 2–Phenyl-4(3H)-quinazolin-4(3H)–one and evaluate them for their analgesic activity. Method: The condensation of 2-amino-methyl-4-methoxybenzoate with acetic anhydride yielded the cyclic compound 2-methyl-4, 5-disubstituted-1, 3-benzo-oxazine-4-one which further produce a novel 2,3-disubstituted quinazolin-4 ones via the reaction with hydrazine hydrate The quinazolinone derivatives quinazolin-4(3H)-One, 2-Methyl-4(3H)-quinazolinone and 2–Phenyl-4(3H)-quinazolin-4(3H)–one were evaluated pharmacologically for their in vivo analgesic activities by acetic acid induced writhing in mice. The compounds synthesized were unequivocally confirmed by means of Infrared, Nuclear Magnetic Resonance (1H and 13C), Gas Chromatography Mass Spectrophotometer and Elemental analysis.The synthesized compounds were screened for their analgesic activity.Compounds 1,2 and 3 showed significant analgesic activity. Discussion: Compound 1 was characterized by the absence of methyl group and the presence of methyl group for compound 2. The test investigated compounds exhibited significant analgesic activity when compared with the control test sample. The compounds synthesized exhibited promising analgesic activities against . Conclusion: The compounds have high analgesic activity. Compound 3 has a higher activity compared to Compound 2 and compound 2 has a higher analgesic activity compared to compound 1. Compound 3 has a higher analgesic activity compared to the standard drugs Aspirin and Indomethacin.
Keywords: quinazolin-4(3H)-One, 2-Methyl-4(3H)-quinazolinone and 2–Phenyl-4(3H)-quinazolin-4(3H)–one quinazolin-4(3H)-one, analgesic activity.
Keywords:
quinazolin-4(3H)-One, 2-Methyl-4(3H)-quinazolinone and 2–Phenyl-4(3H)-quinazolin-4(3H)–one quinazolin-4(3H)-one, analgesic activity
Downloads
Download data is not yet available.
References
1. Crook J, Rideout E, Browne G. The prevalence of pain complaints in a general population. Pain 1984; 18(3):299–314.
2. Levin DN, Cleeland CS, Dar R. Public attitudes toward cancer pain. Cancer 1985; 56:2337–2339.
3. Eggen AE. The Tromsø Study: frequency and predicting factors of analgesic drug use in a freeliving population (12–56 years). J Clin Epidemiol 1993; 46(11):1297–1304.
4. Bostrom M. Summary of the Mayday Fund survey. J Pain Symptom Manage 1997; 13:166–168.
5- Tambaro S, Reali R, Volonterio A, Zanda M, Olimpieri F, Pinna GA, Lazzari P, NESS002 ie: A new fluorinated thiolendopeptidase inhibitor with antinociceptive activity in an animal model of persistent pain, Pharmacology, Biochemistry and Behavior, 2013; 1-7.
6. Harper D [2001]. Online Etymology Dictionary: Analgesia. Retrieved December 3:2012.
7. Deng JS, Chi CS, Huang SS, Shie PH, Lin TH, Huang GJ. Antioxidant, analgesic, and anti-inflammatory activities of the ethanolic extracts of Taxillus liquid ambaricola, Journal of Ethnopharmacology 2011; 137:1161– 1171.
8. Büyüktimkin S. Synthesis, pharmacology and structure-activity relationships of 2-methyl-3-(4-oxo-3-phenyl-thiazolidin-2-ylidenamino)- 4(H)-quinazolinone derivatives. Arch Pharm. 1985; 318:496–501.
9. Büyüktimkin S, Büyüktimkin N, Özdemir O, Rollas S. Synthesis of 3-[2-(2,3-dihydro-5-phenyl-4-substituted-3H-1,2,4-triazole-3-thione2-yl)-acetylamino]-2-methyl-4(3H)-quinazolinones and their pharmacological activities. Arch Pharm. 1989; 322:49–52.
10. Mukherji DD, Nintiyal SR, Prasad CR, Dhawan BN. Pharmacological studies on quinazolinones. Ind J Med Res. 1980; 93:1426–1432.
11. Peet NP, Baugh LE, Sunder S, et al. 3-(1H-tetrazol-5-yl)-4(3H)- quinazolinone sodium salt (MDL 427): a new anti-allergic agent. J Med Chem. 1986; 29:2403–2409.
12. Chaurasia MR, Sharma SK. Synthesis of some new 4(3H)-quinazolinones as a potent CNS depressant. Arch Pharm. 1982; 315:377–381.
13. Li H, Wang JP, Yang F, et al. Design, synthesis and biological activity evaluation of 2-mercapto-4(3H) quinazolinone derivatives as a novel inhibitor of protein tyrosine phosphatase 1B. Heterocycles. 2012; 85:1897–1911.
14. Chiou WF, Liao JF, Chen CF. Comparative study on the vasodilatory effects of three quinazoline alkaloids isolated from Evodia rutaecarpa. J Nat Prod. 1996; 59:374–378.
15. Nagase T, Mizutani T, Ishikawa S, et al. Synthesis, structure-activity relationships, and biological profiles of a quinazolinone class of histamine H3 receptor inverse agonists. J Med Chem. 2008; 51:4780–4789.
16. Nanthakumar R, Muthumani P, Girija K. Anti-inflammatory and antibacterial activity study of some novel quinazolinones. Arabian J Chem. 2014; 7:1049–1054.
17. Khodarahmi GA, Khajouel MR, Hakimelahi GH, Abedi D, Jafari E, Hassanzadeh F. Antibacterial, antifungal and cytotoxic evaluation of some new 2,3-disubstituted 4(3H)-quinazolinone derivatives. Res Pharm Sci. 2012; 7:151–158.
18. Hemalatha K, Girija K. Synthesis, characterization, preliminary QSAR studies and in vitro antioxidant activity of some novel 2,3-disubstituted quinazolinone derivatives. Int J Pharm Sci. 2012; 4:99–103.
19. Panwar H, Chaudhary N, Singh S, Singh SH. Anti-inflammatory and antimicrobial activity of some new quinazolinones. Rasayan J Chem. 2011; 4:498–505.
20. Cao SL, Feng YP, Jiang YY. Synthesis and in vitro antitumor activity of 4(3H)-quinazolinone derivatives with dithiocarbamate side chains. Bio Org Med Chem 2005; 15:1915-1917.
21. Giri RS, Thaker HM, Giordano T, Williams J. Design, synthesis and characterization of novel 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3Hquinazoline-4-one derivatives as inhibitors of NF-kappaB and AP-1 mediated transcription activation and as potential anti-inflammatory agents. European J Med Chem 2009; 44:2184–2189.
22. Helby, Abdel MH. Design and synthesis of some new derivatives of 3Hquinazolin-4-one with promising anticonvulsant activity. Acta Pharma 2003; 53:127–138.
23. Kadi AA, Azab AS, Alafeefy AM, Abdel SG. Synthesis and biological screening of some new substituted 2-mercapto-4(3H)quinazolinone analogues as anticonvulsant agents. J. Pharma. Sci. 2006; 34:147-158.
24. Jatav V, Mishra P, Kashaw S. CNS depressant and anticonvulsant activities of some novel 3-[5-substituted 1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones. European J Med Chem 2008; 43:1945-1951.
25. Xia Y, Yang ZY, Hour MJ, Kuo SC. Antitumour agents.Part 204: Synthesis and biological evaluation of substituted 2-aryl quinazolinones. Bioorg Med Chem Lett 2001; 11:1193–1196.
26. Jessy EM, Sambanthan AT, Alex J, Sridevi CH, Srinivasan KK. Synthesis and biological evaluation of some novel quinazolones. Indian J Pharm Sci 2007; 69:476-478.
27. Alagarsamy V, Thangathiruppathy A, Mandal SC, Rajasekaran S. Pharmacological evaluation of 2-substituted (1,3,4) thiadiazolo quinazolines. Indian J Pharm Sci 2006; 68:108-111
28. Chen K, Wang K, Kirichian AM et al. In silico design, synthesis, and biological evaluation of radioiodinated quinazolinone derivatives for alkaline phosphatasemediated cancer diagnosis and therapy. Mol Cancer Ther 2006; 5:3001–13.
29. Gene, R.M; Segura, L.; Adzet, T.; Marin, E.; inglesias, J. Heterotheca inuloides: Journal of ethnopharmacology. 1998; 60:157-162.
30. Collier H.O.J; Dinneen L.G.; Johnson C.A.; and Schneider C. The abdominal constriction response and its suppression by analgesic drugs in the mouse. Brit J. Pharmacol. 1968; 32:295-310.
31. Bentley G.A; Newlon S.H.; and Starr J. Evidence for action of morphine and Enkephalins on sensory nerve ending in the mouse peritoneum Br. J. Pharmacol 1981; 73:325-332.
32. Bentley K.W. The Isoquinolin Alkaliods, pergamon, press London, Comprehensive Medicinal Chemistry Pergamon press; Oxford. 1983. 2016. - V. 18, l. 16. - P. 4475-4525.
33. Derardt R, Jongney S, Delvalcee F. and Falhout, M. Release of protagladdins E and F in an analgesic reaction and its inhibition. Eur. J. Pharmacol. 1980; 51:17-24.
34. Levini J.D., Lau W., Kwait G. and Goetal E.J. Leukotriene B4 produces hyperanalgesia that is dependent on the polymorphonuclear leucocytes. Science. 1984; 225:743-745.
35. Dhara A.K, Suba V, Sen T, Pal S. and Chaudhuiri A.K. Preliminary studies on the anti-inflammatory and analgesic activity of methanolic fraction of the root of Tragia involucrate. J. Ethnopharmacol. 2000; 72:265-268.
2. Levin DN, Cleeland CS, Dar R. Public attitudes toward cancer pain. Cancer 1985; 56:2337–2339.
3. Eggen AE. The Tromsø Study: frequency and predicting factors of analgesic drug use in a freeliving population (12–56 years). J Clin Epidemiol 1993; 46(11):1297–1304.
4. Bostrom M. Summary of the Mayday Fund survey. J Pain Symptom Manage 1997; 13:166–168.
5- Tambaro S, Reali R, Volonterio A, Zanda M, Olimpieri F, Pinna GA, Lazzari P, NESS002 ie: A new fluorinated thiolendopeptidase inhibitor with antinociceptive activity in an animal model of persistent pain, Pharmacology, Biochemistry and Behavior, 2013; 1-7.
6. Harper D [2001]. Online Etymology Dictionary: Analgesia. Retrieved December 3:2012.
7. Deng JS, Chi CS, Huang SS, Shie PH, Lin TH, Huang GJ. Antioxidant, analgesic, and anti-inflammatory activities of the ethanolic extracts of Taxillus liquid ambaricola, Journal of Ethnopharmacology 2011; 137:1161– 1171.
8. Büyüktimkin S. Synthesis, pharmacology and structure-activity relationships of 2-methyl-3-(4-oxo-3-phenyl-thiazolidin-2-ylidenamino)- 4(H)-quinazolinone derivatives. Arch Pharm. 1985; 318:496–501.
9. Büyüktimkin S, Büyüktimkin N, Özdemir O, Rollas S. Synthesis of 3-[2-(2,3-dihydro-5-phenyl-4-substituted-3H-1,2,4-triazole-3-thione2-yl)-acetylamino]-2-methyl-4(3H)-quinazolinones and their pharmacological activities. Arch Pharm. 1989; 322:49–52.
10. Mukherji DD, Nintiyal SR, Prasad CR, Dhawan BN. Pharmacological studies on quinazolinones. Ind J Med Res. 1980; 93:1426–1432.
11. Peet NP, Baugh LE, Sunder S, et al. 3-(1H-tetrazol-5-yl)-4(3H)- quinazolinone sodium salt (MDL 427): a new anti-allergic agent. J Med Chem. 1986; 29:2403–2409.
12. Chaurasia MR, Sharma SK. Synthesis of some new 4(3H)-quinazolinones as a potent CNS depressant. Arch Pharm. 1982; 315:377–381.
13. Li H, Wang JP, Yang F, et al. Design, synthesis and biological activity evaluation of 2-mercapto-4(3H) quinazolinone derivatives as a novel inhibitor of protein tyrosine phosphatase 1B. Heterocycles. 2012; 85:1897–1911.
14. Chiou WF, Liao JF, Chen CF. Comparative study on the vasodilatory effects of three quinazoline alkaloids isolated from Evodia rutaecarpa. J Nat Prod. 1996; 59:374–378.
15. Nagase T, Mizutani T, Ishikawa S, et al. Synthesis, structure-activity relationships, and biological profiles of a quinazolinone class of histamine H3 receptor inverse agonists. J Med Chem. 2008; 51:4780–4789.
16. Nanthakumar R, Muthumani P, Girija K. Anti-inflammatory and antibacterial activity study of some novel quinazolinones. Arabian J Chem. 2014; 7:1049–1054.
17. Khodarahmi GA, Khajouel MR, Hakimelahi GH, Abedi D, Jafari E, Hassanzadeh F. Antibacterial, antifungal and cytotoxic evaluation of some new 2,3-disubstituted 4(3H)-quinazolinone derivatives. Res Pharm Sci. 2012; 7:151–158.
18. Hemalatha K, Girija K. Synthesis, characterization, preliminary QSAR studies and in vitro antioxidant activity of some novel 2,3-disubstituted quinazolinone derivatives. Int J Pharm Sci. 2012; 4:99–103.
19. Panwar H, Chaudhary N, Singh S, Singh SH. Anti-inflammatory and antimicrobial activity of some new quinazolinones. Rasayan J Chem. 2011; 4:498–505.
20. Cao SL, Feng YP, Jiang YY. Synthesis and in vitro antitumor activity of 4(3H)-quinazolinone derivatives with dithiocarbamate side chains. Bio Org Med Chem 2005; 15:1915-1917.
21. Giri RS, Thaker HM, Giordano T, Williams J. Design, synthesis and characterization of novel 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3Hquinazoline-4-one derivatives as inhibitors of NF-kappaB and AP-1 mediated transcription activation and as potential anti-inflammatory agents. European J Med Chem 2009; 44:2184–2189.
22. Helby, Abdel MH. Design and synthesis of some new derivatives of 3Hquinazolin-4-one with promising anticonvulsant activity. Acta Pharma 2003; 53:127–138.
23. Kadi AA, Azab AS, Alafeefy AM, Abdel SG. Synthesis and biological screening of some new substituted 2-mercapto-4(3H)quinazolinone analogues as anticonvulsant agents. J. Pharma. Sci. 2006; 34:147-158.
24. Jatav V, Mishra P, Kashaw S. CNS depressant and anticonvulsant activities of some novel 3-[5-substituted 1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones. European J Med Chem 2008; 43:1945-1951.
25. Xia Y, Yang ZY, Hour MJ, Kuo SC. Antitumour agents.Part 204: Synthesis and biological evaluation of substituted 2-aryl quinazolinones. Bioorg Med Chem Lett 2001; 11:1193–1196.
26. Jessy EM, Sambanthan AT, Alex J, Sridevi CH, Srinivasan KK. Synthesis and biological evaluation of some novel quinazolones. Indian J Pharm Sci 2007; 69:476-478.
27. Alagarsamy V, Thangathiruppathy A, Mandal SC, Rajasekaran S. Pharmacological evaluation of 2-substituted (1,3,4) thiadiazolo quinazolines. Indian J Pharm Sci 2006; 68:108-111
28. Chen K, Wang K, Kirichian AM et al. In silico design, synthesis, and biological evaluation of radioiodinated quinazolinone derivatives for alkaline phosphatasemediated cancer diagnosis and therapy. Mol Cancer Ther 2006; 5:3001–13.
29. Gene, R.M; Segura, L.; Adzet, T.; Marin, E.; inglesias, J. Heterotheca inuloides: Journal of ethnopharmacology. 1998; 60:157-162.
30. Collier H.O.J; Dinneen L.G.; Johnson C.A.; and Schneider C. The abdominal constriction response and its suppression by analgesic drugs in the mouse. Brit J. Pharmacol. 1968; 32:295-310.
31. Bentley G.A; Newlon S.H.; and Starr J. Evidence for action of morphine and Enkephalins on sensory nerve ending in the mouse peritoneum Br. J. Pharmacol 1981; 73:325-332.
32. Bentley K.W. The Isoquinolin Alkaliods, pergamon, press London, Comprehensive Medicinal Chemistry Pergamon press; Oxford. 1983. 2016. - V. 18, l. 16. - P. 4475-4525.
33. Derardt R, Jongney S, Delvalcee F. and Falhout, M. Release of protagladdins E and F in an analgesic reaction and its inhibition. Eur. J. Pharmacol. 1980; 51:17-24.
34. Levini J.D., Lau W., Kwait G. and Goetal E.J. Leukotriene B4 produces hyperanalgesia that is dependent on the polymorphonuclear leucocytes. Science. 1984; 225:743-745.
35. Dhara A.K, Suba V, Sen T, Pal S. and Chaudhuiri A.K. Preliminary studies on the anti-inflammatory and analgesic activity of methanolic fraction of the root of Tragia involucrate. J. Ethnopharmacol. 2000; 72:265-268.
Crossmark
Statistics
787 Views | 489 Downloads
How to Cite
1.
Osarumwense P, Edema M, Usifoh C. Synthesis And Anagesic activities of Quinazolin-4(3H)-One, 2-Methyl-4(3H)-Quinazolinone and 2–Phenyl-4(3H)-quinazolin-4(3H)–one. JDDT [Internet]. 15Aug.2020 [cited 20May2024];10(4-s):87-1. Available from: https://jddtonline.info/index.php/jddt/article/view/4209
Section
Research
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
.