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Current Bioactive Compounds

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ISSN (Online): 1875-6646

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Review Article

Quinazolin-4-One: A Varsatile Molecule

Author(s): Rakesh D. Amrutkar*, Sunil V. Amrutkar and Mahendrasing S. Ranawat

Volume 16, Issue 4, 2020

Page: [370 - 382] Pages: 13

DOI: 10.2174/1573407215666181120115313

Price: $65

Abstract

Background: Quinazolines and quinazolinones constitute a major class of biologically active molecules both from natural and synthetic sources. We will limit this review to compounds possessing the 4(3H)-quinazolinone skeleton, which is found in compounds displaying significant biological and pharmacological properties. The molecular design of potential lead compound is still a key line of approach for the discovery and development of new chemical entities. A combination of two or more chemical moieties into one is a common approach of operation and this can most likely result in the improvement of pharmacological activity and removal of unwanted side effects.

Methods: We undertake search for peer-reviewed and research literature on quinazolinone moiety using different tools of literature survey. The quality of superior papers was assess using standard tools. The distinctiveness of screened papers was shorted and high-quality content was reorganiz and written in own language.

Results: The review will be expressed in two main sections, the first section will be related to synthetic procedures and the second section includes the biological importance of Quinazoline derivatives. Total hundred (100) to one hundred and ten (110) research papers ware searched. Out of these, seventy-eight papers were included in the review, the majority of research papers were from international journals. Fifty fours papers defined the different synthetic schemes considering the general strategies using orthosubstituted anilines such as 2-aminobenzoic acid (anthranilic acid) and its analogues, or isatoic anhydride as starting materials, which are condensed with acid chlorides, imidates or aldehydes. Microwave irradiation was also proven to be very useful to improve the yields, and in particular, it has been successfully applied to the Niementowski procedure involving the fusion of anthranilic acid with formamide. The remaining part of the review focuses on biological importance of the 4(3H)-quinazolinone scaffold as therapeutic agents and a broad range of activities like antibacterial, antifungal, antiviral, anticonvulsant, antitumor, antihypertensive, analgesic and anti-inflammatory agents has been highlighted.

Conclusion: The present review focuses on simplified, efficient and widespread literature of the methods of synthesis and diverse pharmacological activities of quinazoline and its derivatives have been highlighted.

Keywords: Quinazoline-4-one, pharmacophore, discovery, organic chemistry, antitumor, hypotensive.

Graphical Abstract

[1]
Reddy, P.S.; Reddy, P.P.; Vasantha, T. Synthesis of ethyl 2-(2-methyl-4-oxoquinazolin-3 (4H)-yl) acetate as important analog and intermediate of 2, 3 disubstituted quinazolinones. Heterocycles, 2003, 60, 183-191.
[2]
El-Hiti, G.A. Synthesis of Substituted Quinazolin-4(3H)-ones and quinazolines via directed lithiation. Heterocycles, 2000, 53, 1839-1868.
[http://dx.doi.org/10.3987/REV-00-535]
[3]
El-Hiti, G.A. Abdel-Megeed. Synthesis of glycosides containing quinazolin-4(3H)-one ring system. Heterocycles, 2005, 65, 3007-3019.
[http://dx.doi.org/10.3987/REV-05-602]
[4]
Ghorab, M.M.; Abdel-Gawad, S.M.; El-Gaby, M.S. Synthesis and evaluation of some new fluorinated hydroquinazoline derivatives as antifungal agents. Farmaco, 2000, 55(4), 249-255.
[http://dx.doi.org/10.1016/S0014-827X(00)00029-X] [PMID: 10966155]
[5]
Dandia, A.; Singh, R.; Sarawagi, P. 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., 2005, 126, 307.
[http://dx.doi.org/10.1016/j.jfluchem.2004.10.015]
[6]
Nakagami, K.; Yokoi, S.; Honda, T. 4-Aminoquinazoline compounds useful as agricultural fungicides. US Patent 4323680. 1982.
[7]
Haley, G.J. Substituted quinazoline fungicidal agents. US Patent 5373011A. 1994.
[8]
Martin, J. Deetz; Jeremiah P. Malerich; Alicia M. Beatty; Bradley D. Smith. One-step synthesis of 4(3H)-quinazolinones. Tetrahedron Lett., 2001, 42, 1851-1854.
[9]
Kumar, A.; Tyagi, M.; Shrivastav, V.K. Newer potential quinazolinones as hypotensive agents. Indian J. Chem., 2003, 42(B), 2142.
[http://dx.doi.org/10.1002/chin.200352170]
[10]
EI-Brollosy, N.R.; Abdel-Megeed, M.F.; Genady, A.R. Alexandria. J. Pharm. Sci., 2003, 17(1), 17.
[11]
Hans, J. Hess.; Timothy H. Cronin; Alexander Scriabine. Antihypertensive 2-amino-4(3H)-quinazolinones. Med. Chem. (N.Y.), 1968, 11, 130-136.
[http://dx.doi.org/10.1021/jm00307a028]
[12]
Shivram, H.B.; Padmaja, M.T.; Shivanada, M.K. Akabarali. P.M. Indian J. Chem, 1998, 37B, 715-729.
[13]
Khili, M.A.; Soliman, R.; Furghuli, A.M.; Bekhit, A.A. Arch. Pharm (Weighnein, Germany), 1994, 27, 327.
[14]
Mhaske, S.B.; Argade, N.P. The chemistry of recently isolated naturally occurring quinazolinone alkaloids. Tetrahedron, 2006, 62(42), 9787-9826.
[http://dx.doi.org/10.1016/j.tet.2006.07.098]
[15]
Mahato, AK; Srivastava, B; Nithya, S Chemistry, structure activity relationship and biological activi-ty of quinazoline-4(3H)-one derivatives. Inventi Rapid Med Chem., 2011, 2(1)
[16]
Armarego, W.L.F. Quinazolines.Advances in Heterocyclic Chemistry, 1st ed; Wiley & Sons: New York, 1963.
[17]
Rajput, R.; Mishra, A.P. A Review on Biological Activity of Quinazolinones. Int. J. Pharm. Sci., 2012, 4(2), 66-70.
[18]
Pati, B.; Banerjee, S. Quinazolines: An illustrated review. J. Adv. Pharm. Educ. Res., 2013, 3(3), 136-151.
[19]
Vijayakumar, B.; Prasanthi, P.; Teja, K.M. quinazoline derivatives & pharmacological activities: A review. Int. J. Med. Chem., 2013, 3(1), 10-21.
[20]
Daidon, G.; Raffa, D.; Plescia, S.; Mantione, L. Microwave assisted synthesis of quinazolinone using different bases. Eur. J. Med. Chem., 2001, 36, 737.
[21]
El-Meligic, S.; El-Ansary, AK.; Said, M.M.; Hussein, M.M. Synthesis of ethyl 2-(2- methyl-4-oxoquinazolin-3(4H)-yl) acetate as important analogue and intermediate of 2,3-disubstituted quinazolinones. Indian J. Chem., 2001, 40(B), 62-68.
[22]
Asif, M. Chemical characteristics, synthetic methods, and biological potential of quinazoline and quinazolinone derivatives. Int. J. Med. Chem., 2014, 2014395637
[http://dx.doi.org/10.1155/2014/395637] [PMID: 25692041]
[23]
Archana, ; Srivastava, V.K.; Kumar, A. Synthesis of newer thiadiazolyl and thiazolidinonyl quinazolin-4 3H-ones as potential anticonvulsant agents. Eur. J. Med. Chem., 2002, 37(11), 873-882.
[http://dx.doi.org/10.1016/S0223-5234(02)01389-2] [PMID: 12446046]
[24]
Al-Omar, M.A.; El-Azab, A.S.; El-Obeid, H.A.; Abdel, S.G. In vitro Interaction of 6-Iodo-4-oxoquinazoline derivatives with cytosolic molybdenum hydroxylases. J. Saudi Chem. Soc., 2006, 10, 113.
[25]
Audeval, B; Bouchacourt, P Journal of medical de France, 1988, 95(25), 70-72.
[26]
Mouren, P.; Giraud, F.; Pinsard, N. [Clinical use of a new psycholeptic: Mecloqualone]. Mars. Med., 1963, 100, 599-602.
[PMID: 13936358]
[27]
Williams, D.A.; Lemke, T.L. Foye’s Principles of Medicinal Chemistry, 5th ed; Wollters Kluwer Health New Delhi, 2007.
[28]
Lednicer, D.; Mitscher, L.A. The Organic Chemistry of Drug Synthesis; Wiley-Interscience New York, , Vol. 3, . 1929.
[29]
Griffin, R.J.; Srinivasan, S.; Bowman, K.; Calvert, A.H.; Curtin, N.J.; Newell, D.R.; Pemberton, L.C.; Golding, B.T. Resistance-modifying agents. 5. Synthesis and biological properties of quinazolinone inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP). J. Med. Chem., 1998, 41(26), 5247-5256.
[http://dx.doi.org/10.1021/jm980273t] [PMID: 9857092]
[30]
Ormaza, V.A. Chemical Abstract, Spanish patent 549881. 1986.
[31]
Spinks, A.; Waring, W.S. Medicinal Chemistry; Ellis, G.P; West, G.S., Ed.; Butterworth’s: Washington, 1963, Vol. 3, . In Progress
[32]
www.biam2.org
[33]
Ishikawa, T.; Kamide, R.; Niimura, M. Photoleukomelanodermatitis (Kobori) induced by afloqualone. J. Dermatol., 1994, 21(6), 430-433.
[http://dx.doi.org/10.1111/j.1346-8138.1994.tb01768.x] [PMID: 8064007]
[34]
Burch, H.A. Nitrofuryl heterocycles. IV. 4-amino-2-(5-nitro-2-furyl)quinazoline derivatives. J. Med. Chem., 1966, 9(3), 408-410.
[http://dx.doi.org/10.1021/jm00321a034] [PMID: 5960915]
[35]
Parmar, S.S.; Kishor, K.; Seth, P.K.; Arora, R.C. Role of alkyl substitution in 2,3-disubstituted and 3-substituted 4-quinazolones on the inhibition of pyruvic acid oxidation. J. Med. Chem., 1969, 12(1), 138-141.
[http://dx.doi.org/10.1021/jm00301a035] [PMID: 4303122]
[36]
For synthesis of quinazolin-4(3H)-ones: a) Yoo CL; Fettinger JC; Kurth M.J. J. Org. Chem. 2005, 70, 6941. b) Kamal A; Reddy KS; Prasad BR; Babu AH; Ramana AV., Tetrahedron Lett. 2004,45,6517. c) Alexandre FR; Berecibar A; Wrigglesworth R; Besson T.; Tetrahedron, 2003,59,1413; d) Shimizu M.; Oishi A.; Taguchi Y.; Gama Y.; Shibuya I. Chem. Pharm. Bul, 2002, 50, 426. e) Stevenson TM.; Kazmierczak F.; Leonard NJ. J. Org. Chem., 1986, 51, 616.
[37]
For synthesis of quinazolin-2, 4-diones: a) Connolly TJ.; McGary P.; Sukhtankar S. Green Chem., 2005, 7, 586. b) Schwinn D.;Glatz H.; Bannwarth W. Helv. Chim. Acta, 2003, 86, 188. c) Shao H.; Colucci M.; Tong S.; Zhang H.; Castelhano AL. Tetrahedron Lett, 1998, 39, 7235. d) Gordeev MF.; Hui H.C.; Gordon EM.; Patel DV. Tetrahedron Letter, 1997, 38, 1729. e) Buckman BO.; Mohan R., Tetrahedron Letter, 1996, 37, 4439. f) Gouilleux L.; Martinez J.; Winternitz F.; Fehrentz JA. Tetrahedron Lett., 1996, 37, 7031. g) Larsen SD.; Connell MA.; Cudahy MM.; Evans BR.; May PD.; Meglasson MD.; O’Sullivan TJ.; Schostarez HJ.; Sih JC.; Stevens FC.; Tanis SP.; Tegley CM.; Tucker JA.; Vaillancourt VA.; Vidmar TJ.; Watt W.; Yu JH. J. Med. Chem., 2001, 44, 1217. h) Klemm LH.; Weakley T.J.R.; Gilbertson RD.; Song YH. J. Heterocycl. Chem., 1998, 35, 1269.
[38]
Niementowski, V. Novel syntheis of 3-substituted/2,3-disubstituted 4(3-H) quinazolineones. J. Prakt. Chem., 1895, 551-564.
[39]
Li, F. Yiqing Feng.; Qingqing Meng.; Wenhua Li.; Zhiming Li.; Quanrui Wang.; Fenggang Tao. An efficient construction of quinazolin-4(3-H)-ones under microwave irradiation. ARKIVOC, 2007, 40-50.
[40]
Santagati, N.A.; Bousquet, E.; Spadaro, A.; Ronsisvalle, G. 4-quinazolinones: synthesis and reduction of prostaglandin E2 production. Farmaco, 1999, 54(11-12), 780-784.
[http://dx.doi.org/10.1016/S0014-827X(99)00102-0] [PMID: 10668179]
[41]
Khosropour, A.R. Mohammad poor-Baltork, I.; Ghorbankhani, H., Bi(TFA)3-[nbp]FeCl4: a new, efficient and reusable promoter system for the synthesis of 4(3H)-quinazolinone derivatives. Tetrahedron Lett., 2006, 47(21), 3561-3564.
[http://dx.doi.org/10.1016/j.tetlet.2006.03.079]
[42]
Li, R.; Kenyon, G.L.; Cohen, F.E.; Chen, X.; Gong, B.; Dominguez, J.N.; Davidson, E.; Kurzban, G.; Miller, R.E.; Nuzum, E.O. In vitro antimalarial activity of chalcones and their derivatives. J. Med. Chem., 1995, 38(26), 5031-5037.
[http://dx.doi.org/10.1021/jm00026a010] [PMID: 8544179]
[43]
Koehrle, J.; Auf’mkolk, M.; Rokos, H.; Hesch, R.D.; Cody, V. Rat liver iodothyronine monodeiodinase. Evaluation of the iodothyronine ligand-binding site. J. Biol. Chem., 1986, 261(25), 11613-11622.
[PMID: 3745159]
[44]
Sui, Z.H.; Nguyen, V.N.; Altom, J.; Fernandez, J.; Hilliard, J.J. synthesis of Quinazolin-4-one derivatives by condensation reaction at room temperature by using ionic liquids. Eur. J. Med. Chem., 1999, 34, 381-387.
[http://dx.doi.org/10.1016/S0223-5234(99)80087-7]
[45]
Raid, J. Abdel-Jalil; Wolfgang Voelter; Muhammad Saeed. A novel method for the synthesis of 4(3H)-quinazolinones. Tetrahedron Lett., 2004, 45, 3475-3476.
[http://dx.doi.org/10.1016/j.tetlet.2004.03.003]
[46]
Beney, C.; Hadjeri, M.; Mariotte, A.M. Boumendjel. A convenient method for the synthesis of 3,5,7-trimethoxy-2-phenyl-4-quinolones. Tetrahedron Lett., 2000, 41, 7037-7039.
[http://dx.doi.org/10.1016/S0040-4039(00)01226-0]
[47]
Fougerousse, A.; Gonzalez, E.; Brouillard, R. A convenient method for synthesizing 2-aryl-3-hydroxy-4-oxo-4H-1-benzopyrans or flavonols. J. Org. Chem., 2000, 65(2), 583-586.
[http://dx.doi.org/10.1021/jo990735q] [PMID: 10813976]
[48]
Bavetsias, V. J. Heterocycl. Chem., 1999, 36, 827-835.
[49]
Smith, K.; El-Hiti, G.A.; Abdo, M.A.; Abdel-Megeed, M.F. Regiospecific electrophilic substitution of aminoquinazolinones: directed lithiation of 3-(pivaloylamino) and 3-(acetylamino)-2-methylquinazolin-4(3H)-ones. J. Chem. Soc., 1995, 8, 1029-1033.
[50]
David, J. Connolly; Declan Cusack; Timothy P.; O’Sullivan; Patrick J. Guiry; Synthesis of quinazolinones and quinazolines. Tetrahedron, 2005, 61, 10153-10202.
[51]
Jyotirling, R. Mali; Umesh R. Pratap; Prashant D. Netankar; Ramrao A. An efficient synthetic route for quinazolinyl 4-thiazolidinones. Tetrahedron Lett., 2009, 50, 5025-5027.
[http://dx.doi.org/10.1016/j.tetlet.2009.06.086]
[52]
Priya, M.G.R. Ecofriendly synthesis of 4-(3H)-quinazolinones by microwave assisted tandem reaction. Int. J. Pharma Bio Sci., 2011, 2(1), 295-301.
[53]
Li, F. An efficient construction of quinazolin-4(3H)-ones under microwave irradiation. ARKIVOC, 2007, 1, 40-50.
[54]
Palle, V.; Acharyulu, R. Synthesis of new 4(3H)-quinazolinone derivatives under solvent-free conditions using PEG-400. ARKIVOC, 2008, (xi), 104-111.
[55]
Rajveer, Ch. Synthesis and biological evaluation of some novel oxo-quinazoline derivatives for their anti-bacterial activity. Res. J. Pharm. Biol. Chem. Sci., 2010, 1(2), 366-371.
[56]
Rajveer, Ch. Synthesis of 6-Bromooxo quinazoline derivatives and their pharmacological activities. Int. J. Chemtech Res., 2010, 1(1), 21-24.
[57]
Niraj Kumar Sinha. A novel approach towards development of quinazoline derivatives in pain management. Asian J. Pharm. Clin. Res., 2013, 6(3), 200-204.
[58]
Amrutkar, S.V.; Ranawat, M.S. Synthesis, characterization and biological evaluation of 2-[(2′-ethyl-4′-oxoquinazolin-3′-yl]amino-N-aryl acetamide derivatives. Int. J. Drug Des. Disc., 2012, 3(3), 846-850.
[59]
Al-Khuzaie Majidi. Synthesis, characterization and evaluation antimicrobial activity of some new substituted 2-Mercapto-3-Phenyl-4(3H)-Quinazolinone. Iraqi J. Sci., 2014, 55(2B), 582-593.
[60]
Sánchez, A.I.; Martínez-Barrasa, V.; Burgos, C.; Vaquero, J.J.; Alvarez-Builla, J.; Terricabras, E.; Segarra, V. Synthesis and evaluation of quinazoline derivatives as phosphodiesterase 7 inhibitors. Bioorg. Med. Chem., 2013, 21(8), 2370-2378.
[http://dx.doi.org/10.1016/j.bmc.2013.01.067] [PMID: 23454131]
[61]
Poudapally, S.; Battu, S.; Velatooru, L.R.; Bethu, M.S.; Janapala, V.R.; Sharma, S.; Sen, S.; Pottabathini, N.; Iska, V.B.R.; Katangoor, V. Synthesis and biological evaluation of novel quinazoline-sulfonamides as anti-cancer agents. Bioorg. Med. Chem. Lett., 2017, 27(9), 1923-1928.
[http://dx.doi.org/10.1016/j.bmcl.2017.03.042] [PMID: 28351589]
[62]
Zhang, Y.; Zhang, Y.; Liu, J.; Chen, L.; Zhao, L.; Li, B.; Wang, W. Synthesis and in vitro biological evaluation of novel quinazoline derivatives. Bioorg. Med. Chem. Lett., 2017, 27(7), 1584-1587.
[http://dx.doi.org/10.1016/j.bmcl.2017.02.027] [PMID: 28238614]
[63]
Madhavi, S.; Sreenivasulu, R.; Yazala, J.P.; Raju, R.R. Synthesis of chalcone incorporated quinazoline derivatives as anticancer agents. Saudi Pharm. J., 2017, 25(2), 275-279.
[http://dx.doi.org/10.1016/j.jsps.2016.06.005] [PMID: 28344479]
[64]
Abuelizz, H.A.; Marzouk, M.; Ghabbour, H.; Al-Salahi, R. Synthesis and anticancer activity of new quinazoline derivatives. Saudi Pharm. J., 2017, 25(7), 1047-1054.
[http://dx.doi.org/10.1016/j.jsps.2017.04.022] [PMID: 29158714]
[65]
Tu, Y.; Wang, C.; Xu, S.; Lan, Z.; Li, W.; Han, J.; Zhou, Y.; Zheng, P.; Zhu, W. Design, synthesis, and docking studies of quinazoline analogues bearing aryl semicarbazone scaffolds as potent EGFR inhibitors. Bioorg. Med. Chem., 2017, 25(12), 3148-3157.
[http://dx.doi.org/10.1016/j.bmc.2017.04.001] [PMID: 28428040]
[66]
P. R. Vijay anand. Synthesis of Quinazoline Derivatives and their Biological Activities. Asian J. Chem., 2009, 21(9), 6656-6660.
[67]
Mohamed, F. Zayed. Synthesis, Modelling, and anticonvulsant studies of new quinazolines showing three highly active compounds with low toxicity and high affinity to the GABA-A receptor. Molecules, 2017, 22, 188.
[http://dx.doi.org/10.3390/molecules22020188]
[68]
Mukherjee, T. Synthesis, Characterization and Anticonvulsant activity of Substituted 4-Chloro-2-(4-Piperazin-1-yl) Quinazolines. Int. J. Pharm. Pharm. Sci., 2016, 6(5), 567-571.
[69]
Mohamed, F. Zayed. New fluorinated quinazolinone derivatives as anticonvulsant agents. Journal of Taibah University Medical Sciences, 2014, 2, 104-109.
[70]
El-Azab, A.S.; Eltahir, K.E. Design and synthesis of novel 7-aminoquinazoline derivatives: antitumor and anticonvulsant activities. Bioorg. Med. Chem. Lett., 2012, 22(5), 1879-1885.
[http://dx.doi.org/10.1016/j.bmcl.2012.01.071] [PMID: 22326394]
[71]
Mohamed-Kamal Ibrahim. Design, synthesis, molecular docking and anticonvulsant evaluation of novel 6-iodo-2-phenyl- 3-substituted-quinazolin-4(3H)-ones. Bull. Fac. Pharm. Cairo Univ., 2015, 53, 101-116.
[http://dx.doi.org/10.1016/j.bfopcu.2015.05.001]
[72]
Al-Obaid, A.M.; Abdel-Hamide, S.G.; El-Kashef, H.A.; Abdel-Aziz, A.A.; El-Azab, A.S.; Al-Khamees, H.A.; El-Subbagh, H.I. Substituted quinazolines, part 3. Synthesis, in vitro antitumor activity and molecular modeling study of certain 2-thieno-4(3H)-quinazolinone analogs. Eur. J. Med. Chem., 2009, 44(6), 2379-2391.
[http://dx.doi.org/10.1016/j.ejmech.2008.09.015] [PMID: 18950904]
[73]
Kathiravan, M.K. Synthesis and antihyperlipidemic activity of somenovel 4-substituted-2-substitutedmethyltriazino[6,1-b]quinazolin-10-ones and 2,4-disubstituted-6,7-dimethoxy quinazoline. Arab. J. Chem., 2016, 9, S395-S403.
[http://dx.doi.org/10.1016/j.arabjc.2011.05.009]
[74]
Omar, A.; Ahmed, M.A. Synthesis of some new 3H-quinazolin-4-one derivatives as potential antitubercular agents. World Appl. Sci. J., 2008, 5(1), 94-99.
[75]
Kunes, J.; Bazant, J.; Pour, M.; Waisser, K.; Slosárek, M.; Janota, J.Í.; Kune, J. Quinazoline derivatives with antitubercular activity. Farmaco, 2000, 55(11-12), 725-729.
[http://dx.doi.org/10.1016/S0014-827X(00)00100-2] [PMID: 11204949]
[76]
Werbel, L.M.; Degnan, M.J. Synthesis and antimalarial and antitumor effects of 2-amino-4-(hydrazino and hydroxyamino)-6-[(aryl)thio]quinazolines. J. Med. Chem., 1987, 30(11), 2151-2154.
[http://dx.doi.org/10.1021/jm00394a038] [PMID: 3669022]
[77]
Yadav, M.K.; Tripathi, L.; Goswami, D. Evaluation of anticonvulsant activity and toxicity screening of semicarbazones derived from quinazolinone scaffold. Curr. Bioact. Compd., 2018, 14, 1.

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