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Quinazolinone and Quinazoline Derivatives: Synthesis and Biological Application

Written By

Satyendra Mishra

Submitted: May 6th, 2019 Reviewed: August 16th, 2019 Published: December 13th, 2019

DOI: 10.5772/intechopen.89203

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Drug discovery and optimization comprise one of the most significant targets in medicinal chemistry. Quinazoline and quinazolinone derivatives and nitrogen-containing heterocycles have received significant attention due to their widely and distinct biopharmaceutical activities. Quinazolines and quinazolinones are considered as noteworthy chemical for the synthesis of diverse physiological significance and pharmacological utilized molecules. Quinazolines are building blocks for about 150 naturally occurring alkaloids with a broad range of biological activity. The various substituted quinazolines and quinazolinones displayed important, for example, sedative hypnotics, antibacterial, anti-inflammatory, analgesic, antipsychotic, antifungal, antimalarial, anticonvulsant, anti-Parkinsonism, cancer, and other activities. This chapter aims to highlight the latest evidence of quinazolinone and quinazoline derivatives as a privileged scaffold in medicinal chemistry.


  • quinazoline
  • quinazolinones
  • antioxidant and anticancer
  • antibacterial
  • structure-activity relationship

1. Introduction

Emergence of drug resistance has created a critical and unmet medical requirement for the innovation and development of novel classes of antibacterial agents [1, 2, 3, 4]. Due to the appearance of drug resistance bacterial strains, there is an escalating need for the development of novel antibiotics to treat the resistant bacteria stain. Diverse set of biological activities of quinazolinones (fused heterocyclic system) such as anti-inflammatory, anticonvulsant, anticancer, antibacterial, antifungal, anti-HIV and anti-analgesic [5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16], have encouraged to abundant of medicinal chemists to investigate this fused heterocycles as a novel drug molecules. Several research groups have successfully investigated and reported the promising antimicrobial properties and structure-activity relationships (SAR) of various quinazolinone derivatives.

Quinazolines and quinazolinones emerged as a privileged class of nitrogen containing heterocyclic scaffolds; exhibits a broad spectrum of pharmacological activities, viz. anti-inflammatory, antitubercular, and antiviral activities [17]. Number of quinazoline derived compound have been approved as a drug; for example prazosin and doxazosine are used to treat benign prostatic hyperplasia and post-traumatic stress disorder [18], and erlotinib and gefitinib both are used for the curing of lung and pancreatic cancers ( Figure 1 ) [19].

Figure 1.

Quinazoline and quinazolinone-based drugs.

Several quinazolinone-based drugs including idelalisib and fenquizone have been shown to exhibit a broad spectrum of antimicrobial, antitumor, antifungal, and cytotoxic activities [20]. Lapatinib has been displayed to be effective in combination therapy for breast cancer [21]. In the recent years, various synthetic strategies for the synthesis of quinazolines and quinazolinones derivatives have been developed to accomplish the budding requirements of medicinal chemist [22]. Many research groups have successfully utilized copper catalyzed Ullmann-type coupling procedures of aryl bromides and benzamidines for the synthesis of quinazoline derivatives [23].


2. Synthesis of quinazoline and quinazolinone derivatives

  1. Synthesis of 4(3H)-quinazolinone using anthranilic acid or formyl anthranilamide [24].

  2. Via condensation reaction of 4-chloroanthranilic acid amide with triethyl orthoformate, the 7-chloro-substituted derivative has been prepared [25].

  3. Quinazolin-4(3H)-one was synthesized by the reaction of anthranilic acid with excess formamide at 120°C in an open air. This is also known as Niementowski reaction [26].

  4. 2-styryl-4(3H)-quinazolinone derivatives were prepared using starting substrate 2-aminobenzonitrile with 3-phenyl cinnamoyl chloride. Under alkaline conditions, intramolecular cyclization of cinnamamide derivative was carried out to afford 2-styryl-4(3H)-quinazolinone. This procedure was tolerated to a wide range of different substituted benzene rings [27].

  5. Reaction of anthranilic acid with ammonium acetate, followed by formamide under microwave at 200 W yields the desired 2-substituted-4(3H)-quinazolinones products [28].

  6. Reaction of anthranilamide with substituted aldehydes or ketones in 2,2,2-trifluoroethanol under reflux condition led to the formation of 2-substituted-2,3-dihydro-4(1H)-quinazolinones in excellent yields [27].

  7. The amino-quinazolin-4(3H)-one was synthesized by means of the reaction of the corresponding methyl anthranilate with an excess amount of guanidine in ethyl alcohol containing sodium ethoxide in moderate yield [29].

  8. 4-Arylaminoquinazolines has vast biological potential as anticancer agents, thus there has been great interest in their syntheses. Through the reaction of 2-aminobenzonitrile with different substituted anilines and anhydrous aluminum chloride, amidines were readily produced. Highest yield of the amidine intermediates was obtained, when excess amounts of suitable aniline and aluminum chloride were used [30].

  9. 2,3-disubstituted-4(3H)-quinazolinone derivatives were prepared through the treatment of N-acylanthranilic acid with the appropriate aryl amines in the presence of phosphorous oxychloride [31].

  10. Benzoxazinone derivatives are the most widespread intermediates in the formation of 2,3-disubstituted quinazolinone derivatives. 2-methyl-4H-benzo[d][1,3]oxazin-4-one was prepared by refluxing mixture of anthranilic acid with acetic anhydride in acetic acid [32].

  11. The reaction of 2-aminobenzonitrile with Grignard reagents yields the intermediates. The produced intermediate derivatives were very significant for getting many types of quinazoline derivatives. Upon their cyclization with acid chlorides, anhydrides, and formates, they formed the corresponding quinazoline derivatives in moderate to good yields. This general method for the preparation of various 2,4-disubstituted quinazoline derivatives is highly flexible and useful [33].

  12. As shown in the scheme 2-chloromethyl-4-methyl-quinazoline derivatives were synthesized by the reaction 1-(2-amino-phenyl)-ethanone with HCl gas in anhydrous condition in presence of chloro acetonitrile to get 2-chloromethyl-4-methyl-quinazoline. Subsequently treatment of 2-chloromethyl-4-methyl-quinazoline with different amine derivative in presence of base furnished 2-chloromethyl-4-methyl-quinazoline derivatives [34].


3. Biological activities of quinazolinone and quinazoline derivatives

Subsequently the innovation of quinazoline ring numeral of structural modifications have been made in order to raise the biological activities such as antitubercular, antihistaminic, analgesic, anticonvulsant, antibacterial, antifungal, and anti-inflammatory activity which attracted the interest of medicinal chemists.

Cancerous augmentation is the main reasons of global human mortality. Numerous antineoplastic drugs are in the market and the majority of the compounds are under clinical trials. Studies make known that these antineoplastic drugs have exhibited the diverse kinds of side effects, as a result researchers around the world are engaged in the designing of more proficient and novel antineoplastic drugs. Recently, quinazoline and its derivatives have been considered as a novel class of neoplastic chemotherapeutic agents to facilitate activity against diverse tumors. Quinazoline is one of the most attractive novel bioactive compounds between all the heterocyclic compounds.

Quinazolinone derivatives, the privileged structures in the field of medicinal chemistry not only act as good anticancer agents but also act as good DNA intercalates [1, 2]. A systematic report is depicted herein for quinazoline ring. A number of quinazolinone and quinazoline derivatives (compounds 124) have been reported for their various anticancer activities ( Figure 2 ) [35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56].

Figure 2.

Anticancer activities of quinazolinone and quinazoline derivatives.

A series of quinazolinone derived Schiff base derivatives were synthesized and evaluated for their in vitro H+/K+-ATPase inhibition. Many quinazolinone derived Schiff base exhibited outstanding potency, compared to the reference drug omeprazole. Especially, hydroxy and methoxy derivatives were the most potent compounds, contributing positively to gastric H+/K+-ATPase inhibition. Preliminary structure-activity relationship revealed that the compounds 2530with electron donating moiety (OH, OCH3) were found to be excellent activity and compounds 3134with electron withdrawing moiety (Cl and NO2) were found to be least antiulcer agents [57].

Quinazolinone derived Schiff base derivatives were also used as novel antioxidants and anti-inflammatory agents. The in vitro antioxidant activities of these compounds were evaluated and compared with commercial antioxidants viz. ascorbic acid (AA), gallic acid (GA), butylated hydroxytoluene (BHT), (DPPH) assay, etc. Data illustrates that quinazolinone derived Schiff base with electron donating moiety (OH, OCH3) were found to be excellent antioxidants and compounds with electron withdrawing moiety (Cl, NO2) were found to be excellent anti-inflammatory agents [58].

Plausible pathways induced by inhibitors were assessed by evaluating the cytotoxic effect of inhibitors such as 3-(5-chloro-2-hydroxybenzylideneamino)-2-(5-chloro-2-hydroxyphenyl)-2,3-dihydroquinazolin-41(H)-one (35) and 3-(5-nitro-2-hydroxybenzylideneamino)-2-(5-nitro-2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (36) on MCF-7, MDA-MB-231, MCF-10A and WRL-68 cells. MTT assay results of both the compounds showed significant inhibition of MCF-7 cell viability [59].

Azaisatins derivative containing 4(3H) quinazolinones has been designed and synthesized and were screened for their potential antimicrobial activities, which exhibited some authentic results towards testing organism in vitroand in vivostudies. Azaisatins derivatives with –C6H13 (40) display good antimicrobial activity compare to other synthesized Azaisatins [60].

Quinazolinone derivatives containing 3-acrylamino motifs were screened for antifungal activities against four phytopathogenic fungi by minimum inhibitory concentration (MIC) method. Compounds 4143, exhibited broad antifungal activities and substituent’s play important role in activities [61].

A series of novel quinazolinone derivatives containing an amino substituted amino moiety were reported for their cytotoxic and antibacterial activities. Among the synthesized compounds 4749showed broad-spectrum cytotoxic activities giants at least four cancer cell lines at low concentrations. Compounds 4446exhibited good to moderate antibacterial activities against gram positive and gram negative bacterial strains [62].

Quinazolinone derivatives manipulate mutant p53 proteins and their corresponding cellular response in p53 mutant cancer cells. Compounds 50and 51exhibited promising broad-spectrum anti-cancer effects, while 50demonstrated selective and exclusive inhibition activity in p53 mutant cancer cell lines. Quinazolinone derivatives 50dictate mutant p53 function for apoptotic cell death [63].

2-(4-bromophenyl)-quinazolin-4(3H)-one (52A) and 2-(4-chlorophenyl)-quinazolin-4(3H)-one (52B) exhibited α-glucosidase inhibitory activity with IC50 values of 12.5 ± 0.1 lM and 15.6 ± 0.2 lM, respectively. Spectroscopy methods were performed to analyze the inhibitory mechanisms of both compounds on α-glucosidase. The outcome of inhibitory mechanism disclosed, that the compounds, inhibited α-glucosidase in reversible and non-competitive manner. Briefly, the quinazolinone derivatives could be potentially promising candidates in the field of anti-diabetic agents development [64].

RAD51 is an essential component of the homologous recombination DNA repair pathway and is over expressed in drug-resistant cancers, including aggressive triple negative breast cancer (TNBC). Structure activity relationships study of quinazolinone derivatives showed that inhibitor (53) as a novel RAD51 inhibitor exhibited up to 15-fold enhanced inhibition of cell growth. Furthermore, inhibitors 17 notably hamper TNBC cell sensitivity to DNA damage. This would be potentially targeted therapy for cancer treatment [65].

A series of novel carbazolyloxy phenylquinazoline derivatives have been developed as angiotensin converting enzyme (ACE) inhibitors. Amongst them compounds (5456) showed maximum inhibitory potency in enzyme based assays. The most potent (5456) compounds have common active site with the Lisinopril binding site [66].

Compounds, 3-(5-chloro-2-hydroxybenzylideneamino)-2-(5-chloro-2-hydroxyphenyl)-2,3-dihydroquinazolin-41(H)-one (57) and 3-(5-nitro-2-hydroxybenzylideneamino)-2-(5-nitro-2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (58) were screened for their cytotoxic effect on MCF-7, MDA-MB-231, MCF-10A and WRL-68 cells. The mechanism involved in apoptosis, induced by compound 57and 58was also evaluated. Additionally, caspase-8 illustrates significant potency, followed by inhibition of NF-κB activation in 57- and 58-treated MCF-7 cells. The results indicated that A and B could induce apoptosis via a mechanism that involves either extrinsic or intrinsic pathways [59].

Substituted quinazolinones derivatives were tested for their antimicrobial activity against Gram-negative bacteria and Gram-positive bacteria. Among the prepared products, 3-benzyl-2-(4-chlorophenyl) quinazolin-4(3H)-one (3a) was found to exhibits the most potent in vitroanti-microbial activity against Staphylococcus aureus.


4. Conclusions

Over the past few decades, more effort has been established into searching of better drugs with minimal side effects. Herein number versatile synthetic procedures are discussed for the synthesis of quinazolinone and quinazoline derivatives. In general, quinazolinone and quinazoline derivatives are known to possess wide range of activities. A specific activity depends on the substituent present at an appropriate position of quinazoline. The study of natural and synthetic quinazolinone and quinazoline derivatives identified as potentially promising candidates for developing as novel therapeutic agents. There is possibility for further development as new research into study of medicinal chemistry related field.



Department of Science and Technology, India (DST-SERB/ECR/2015/000363) to SM.


Conflict of interest

The author declares no conflict of interest.


  1. 1. Sugden R, Kelly R, Davies S. Combating antimicrobial resistance globally. Nature Microbiology. 2016;1:16187-16187
  2. 2. Ventola CL. The antibiotic resistance crisis: Part 2: Management strategies and new agents. Pharmacology & Therapeutics. 2015;40:344-352
  3. 3. Toner E, Adalja A, Gronvall GK, Cicero A, Inglesby TV. Antimicrobial resistance is aglobal health emergency. Health Security. 2015;13:153-155
  4. 4. Bassetti M, Merelli M, Temperoni C, Astilean A. New antibiotics for bad bugs: Where arewe? Annals of Clinical Microbiology and Antimicrobials. 2013;12:22
  5. 5. Khan I, Zaib S, Batool S, Abbas N, Ashraf Z, Iqbal J, et al. Quinazolines and quinazolinones as ubiquitous structural fragments in medicinal chemistry: An update on the development of synthetic methods and pharmacological diversification. Bioorganic & Medicinal Chemistry. 2016;24:2361-2381
  6. 6. Abbas SY, El-Bayouki KA, Basyouni WM, Mostafa EA. New series of 4 (3H)-quinazolinone derivatives: Syntheses and evaluation of antitumor and antiviral activities. Medicinal Chemistry Research. 2018;27:571-582
  7. 7. EI-Hashash MAEAM, Salem MS, Al-Mabrook SAM. Synthesis and anticancer activity ofnovel quinazolinone and benzamide derivatives. Research on Chemical Intermediates. 2018;44:2545-2559
  8. 8. Noolvi MN, Patel HM, Bhardwaj V, Chauhan A. Synthesis andin vitroantitumor activity of substituted quinazoline and quinoxaline derivatives: Search for anticancer agent. European Journal of Medicinal Chemistry. 2011;46:2327-2346
  9. 9. Dohle W, Jourdan FL, Menchon G, Prota AE, Foster PA, Mannion P, et al. Quinazolinone based anticancer agents: Synthesis, antiproliferative SAR, antitubulin activity, and tubulin co-crystal structure. Journal of Medicinal Chemistry. 2018;61:1031-1044
  10. 10. Ighachane H, Sedra MH, Lazrek H. Synthesis and evaluation of antifungal activities of (3H)-quinazolin-4-one derivatives against tree plant fungi. Journal of Materials and Environmental Science. 2017;8:134-143
  11. 11. Alaa AM, Abou-Zeid LA, ElTahir KEH, Ayyad RR, Magda AA, El-Azab AS. Synthesis, anti-inflammatory, analgesic, COX-1/2 inhibitory activities and molecular docking studies of substituted 2-mercapto-4 (3H)-quinazolinones. European Journal of Medicinal Chemistry. 2016;121:410-421
  12. 12. Abuelizz HA, El-Dib RA, Marzouk M, Al-Salahi R.In vitroevaluation of new 2-phenoxy-benzo [g][1, 2, 4] triazolo [1, 5-a] quinazoline derivatives as antimicrobial agents. Microbial Pathogenesis. 2018;117:60-67
  13. 13. Yang L, Ge S, Huang J, Bao X. Synthesis of novel (E)-2-(4-(1H-1,2,4-triazol-1-yl) styryl)-4-(alkyl/arylmethyleneoxy) quinazoline derivatives as antimicrobial agents. Molecular Diversity. 2018;22:71-82
  14. 14. Zhang L, Chen Q , Li XQ , Wu SQ , Wan JL, Ouyang GP. Synthesis and antibacterial activity of 2-substitued-(3-pyridyl)-quinazolinone derivatives. Journal of Heterocyclic Chemistry. 2018;55:743-749
  15. 15. Al-Salahi R, Abuelizz HA, Ghabbour HA, El-Dib R, Marzouk M. Molecular docking study and antiviral evaluation of 2-thioxo-benzo[g]quinazolin-4(3H)-one derivatives. Chemistry Central Journal. 2016;19:10-21
  16. 16. Alagarsamy V, Chitra K, Saravanan G, Raja Solomon V, Sulthana MT, Narendhar B. An overview of quinazolines: Pharmacological significance and recent developments. European Journal of Medicinal Chemistry. 2018;151:628-685
  17. 17. Gupta T, Rohilla A, Pathak A, Akhtar MJ, Haider MR, Yar MS. Current perspectives on quinazolines with potent biological activities: A review. Synthetic Communications. 2018;48:1099-1127
  18. 18. Akduman B, Crawford ED. Terazosin, doxazosin, and prazosin: Current clinical experience. Urology. 2001;58:49-54
  19. 19. McConnell JD et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. The New England Journal of Medicine. 2003;349:2387-2398
  20. 20. Pao W, Miller VA. Epidermal growth factor receptor mutations, small-molecule kinase inhibitors, and non-small-cell lung cancer: Current knowledge and future directions. Journal of Clinical Oncology. 2005;23:2556-2568
  21. 21. Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. Journal of Clinical Oncology. 2009;27:5538-5546
  22. 22. Kshirsagar UA. Recent developments in the chemistry of quinazolinone alkaloids. Organic & Biomolecular Chemistry. 2015;13:9336-9352
  23. 23. Khan I, Ibrar A, Abbas N, Saeed A. Recent advances in the structural library of functionalized quinazoline and quinazolinone scaffolds. Synthetic approaches and multifarious applications. European Journal of Medicinal Chemistry. 2014;76:193-244
  24. 24. Omar MA, Conrad J, Beifuss U. Copper-catalyzed domino reaction between 1-(2-halophenyl)methanamines and amidines or imidates for the synthesis of 2-substituted quinazolines. Tetrahedron. 2014;70:3061-3072
  25. 25. MK MK, RL MK, Bost RW. 7-Chloro-4-(1-diethylamino-4-pentylamino)-quinazoline. Journal of the American Chemical Society. 1947;69:184-1184
  26. 26. Alexandre F, Berecibar A, Wrigglesworth R, Besson T. Novel series of 8Hquinazolino[4,3-b]quinazolin-8-ones via two Niementowski condensations. Tetrahedron. 2003;59:1413-1419
  27. 27. Qiao RZ, Xu BL, Wang YH. A facile synthesis of 2-substituted-2,3-dihydro-4(1H)-quinazolinones in 2,2,2-trifluoroethanol. Chinese Chemical Letters. 2007;18:656-658
  28. 28. Nouira I, Kostakis IK, Dubouilh C, Chosson E, Iannelli M, Besson T. Decomposition of formamide assisted by microwaves, a tool for synthesis of nitrogen-containing heterocycles. Tetrahedron Letters. 2008;49:7033-7036
  29. 29. Hess HJ, Cronin TH, Scriabine A. Antihypertensive 2-amino-4(3H)-quinazolinones. Journal of Medicinal Chemistry. 1968;11:130-136
  30. 30. Szczepankiewicz W, Suwinski J, Bujok R. Synthesis of 4-arylaminoquinazolines and 2-aryl-4-arylaminoquinazolines from 2-aminobenzonitrile, anilines and formic acid or benzaldehydes. Tetrahedron. 2000;56:9343-9349
  31. 31. Ager IR, Harrison DR, Kennewell PD, Taylor JB. Synthesis and central nervous system activity of quinazolones related to 2-methyl-3-(o-tolyl)-4(3H)-quinazolone (methaqualone). Journal of Medicinal Chemistry. 1977;20:379-386
  32. 32. Welch WM, Ewing FE, Huang J, Menniti FS, Pagnozzi MJ, Kelly K, et al. Atropisomeric quinazolin-4-one derivatives are potent noncompetitive amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. Bioorganic & Medicinal Chemistry Letters. 2001;11:177-181
  33. 33. Bergman J, Brynolf A, Elman B, Vuorinen E. Synthesis of quinazolines. Tetrahedron. 1986;42:3697-3706
  34. 34. Dempcy J, Searle MS, Maynard AJ, Williams HE. Design of 2-ethenyl and 2-(2′-haloethyl) substituted quinazolinones (3) as anticancer agents. Bioorganic & Molecular Chemistry. 1992;7:60
  35. 35. Arnold D, Hassan SY, Khattab SN, Bekhit AA, Amer A. A series of novel 4,5,6,7-tetra substituted quinazolines and screened for anticancer activity. Bioorganic & Medicinal Chemistry Letters. 1995;16:1753
  36. 36. Raffa D, Elder MC, Daidone G, Maggio B, Merickech M, Plescia S, et al. Synthesis, cytotoxicity and inhibitory effects on tubulin polymerization of a new 3-heterocyclo substituted 2-styryl quinazolinones. European Journal of Medicinal Chemistry. 2004;39:299-304
  37. 37. Tian W, Qin L, Song Q , He L, Ai M, Jin Y, et al. A novel synthetic analog of 5,8-disubstituted quinazolines blocks mitosis and induces apoptosis of tumor cells by inhibiting microtubule polymerization. PLoS ONE. 2010;5(5):10499-10506
  38. 38. Fathima ASE, Awadallah FM, Ibrahin NA, Said EG, Kamel G. Synthesis of novel 4-aryl amino-6,7-disubstituted quinazolin derivatives as antitumor activity. European Journal of Medicinal Chemistry. 1999;53:141
  39. 39. Yan SJ, Zheng H, Huang C, Yan YY, Lin J. Synthesis of highly functionalized 2,4-diaminoquinazolines as anticancer and anti HIV agents. Bioorganic & Medicinal Chemistry Letters. 2010;20(15):4432-4435
  40. 40. Al-Rashood ST, Aboldahb IA, Nagi MN, Abdel-Aziz AAM, Abdel-Hamide SG, Yousef KM, et al. Synthesis, dihydrofolate reductase inhibition, antitumor testing, and molecular model study of some new 4(3H)-quinazolinone analogs. Bioorganic & Medicinal Chemistry Letters. 2006;14:8608-8621
  41. 41. Forsch RA, Wright JE, Rosowsky A. Synthesis and in-vitro antitumor activity of thiophene analogues of 5-chloro-5,8-dideazafolic acid. Bioorganic & Medicinal Chemistry. 2002;10:2067-2076
  42. 42. Sirisoma N, Pervin A, Zhang H, Jiang S, Adam Willardsen J, Anderson MB, et al. Discovery of N-methyl-4-(4-methoxyanilino)-quinazolines as potent apoptosis inducers: Structure activity relationship of the quinazoline ring. Bioorganic & Medicinal Chemistry Letters. 2010;20(7):2330-2334
  43. 43. Hour MJ, Huang LJ, Kuo SC, Xia Y, Bastow K, Nakanishi Y, et al. 6-Alkylamino and 2,3-dihydro-3′-methoxy-2-phenyl-4-quinazolinones and related compounds: Their synthesis, cytotoxicity, and inhibition of tubulin polymerization. Journal of Medicinal Chemistry. 2000;43(23):4479-4487
  44. 44. Lehner RS, Norris T, Santafianos DP. Synthesis and anticancer activity of 4-(3-ethylphenylamino)-quinazolines. Chemical Abstracts. 2000;133(20):769
  45. 45. Sherbeny EL, Magda A. Synthesis of certain pyrimido-[2,1-b] benzothiazole and benzothiazolo[2,3-b]-quinazoline derivatives forin-vitroantitumor and antiviral activities. Arzneimittel Forschung. 2000;50(II):848-853
  46. 46. El-Hiti GA, Abdel-Megeed MF, Zied TMM. Synthesis and reaction of some 3-aryl-2-thioxo quinazolin-4(3H)-ones. Indian Journal of Chemistry. 2002;41B:1519-1522
  47. 47. Spirkova K, Stankovsky S, Mrvova A, Cipak L. Synthesis and biological activity of some 2-substituted quinazolin-4-ones. Chemical Papers. 1999;53(4):272-275
  48. 48. Mang J, Mielcke TR, Mascarello A, Filippi-Chiela E, Zanin RF, Lenz G. Synthesis and anticancer activities of some new 2,4-diamino-6-substituted quinazoline derivatives. European Journal of Medicinal Chemistry. 1994;48:255
  49. 49. Li HZ, He HY, Han YY, Gu X, He L, Qi QR, et al. A general synthetic procedure for 2-chloromethyl-4(3H)-quinazolinone derivatives and their utilization in the preparation of novel anticancer agents with 4-anilinoquinazoline scaffolds. Molecules. 2010;15(12):9473-9485
  50. 50. Wang YD, Miller K, Boschelli DH, Ye F, Wu B, Floyd MB, et al. Inhibitors of tyrosine kinase: The preparation and structure activity relationship of 4-anilino-3-cyanoquinolines and 4-anilino quinazolines. Bioorganic & Medicinal Chemistry Letters. 2000;10(21):2477-2480
  51. 51. Papoulis AT, Rosowsky A, Forsch RA, Queener SF. Synthesis, anti-parasitic, and antitumor activity of 2,4-diamino-6-(arylmethyl)-5,6,7,8-tetrahydroquinazoline analogues of piritrexim. Journal of Medicinal Chemistry. 1999;42(6):1007-1017
  52. 52. Cao SL, Feng YP, Jiang YY, Liu SY, Ding GY, Li RT. Synthesis and in-vitro antitumor activity of 4(3H)-quinazolinone derivatives with dithiocarbamate side chains. Bioorganic & Medicinal Chemistry Letters. 2005;15:1915-1917
  53. 53. Sirisoma N, Pervin A, Zhang H, Jiang S, Willardsen JA, Anderson MB, et al. Discovery of N-(4-methoxyphenyl)-N-2-dimethylquinazolin-4-amine: A potent apoptosis inducer and efficacious anticancer agent with high blood brain barrier penetration. Journal of Medicinal Chemistry. 2009;52(8):2341-2351
  54. 54. Jung SY, Lee SH, Kang HB, Park HA, Chang SK, Kim J, et al. Antitumor activity of 3,4-dihydroquinazoline dihydrochloride in A549 xenograft nude mice. Bioorganic & Medicinal Chemistry Letters. 2010;20(22):6633-6636
  55. 55. Murgan V, Thomas CC, Rama Sarma GVS, Kumar EP. Synthesis of 2-substituted quinazolin-4(3H)-ones as a new class of anticancer agents. Indian Journal of Pharmaceutical Sciences. 2003;65(4):386-389
  56. 56. Chinigo GM, Paige M, Grindrod S, Hamel E, Dakshanamurthy S, mChruszcz M, et al. Asymmetric synthesis of 2,3-dihydro-2-arylquinazolin-4-ones: Methodology and application to a potent fluorescent tubulin inhibitor with anticancer activity. Journal of Medicinal Chemistry. 2008;51(15):4620-4631
  57. 57. Rakesh KP, Shantharam CS, Manukumar HM. Synthesis and SAR studies of potent H+/K+-ATPase inhibitors of quinazolinone-Schiff’s base analogues. Bioorganic Chemistry. 2016;68:1-8
  58. 58. Rakesh KP, Manukumar HM, Channe Gowda D. Schiff’s bases of quinazolinone derivatives: Synthesis and SAR studies of a novel series of potential anti-inflammatory and antioxidants. Bioorganic and Medicinal Chemistry. 2015;25(5):1072-1077
  59. 59. Zahedifard M, Faraj FL, et al. Synthesis, characterization and apoptotic activity of quinazolinone Schiff base derivatives toward MCF-7 cells via intrinsic and extrinsic apoptosis pathways. Scientific Reports. 2015;5:11544. DOI: 10.1038/srep11544
  60. 60. Devi KA, Sarangapani M, Sriram. Synthesis and antimicrobial activity of some quinazolinones derivatives. International Journal of Drug Development and Research. 2012;4(3):324-327
  61. 61. Zhang J, Liu J, Ma Y, Ren D, Cheng P, Zhao J, et al. One-pot synthesis and antifungal activity against plant pathogens of quinazolinone derivatives containing an amide moiety. Bioorganic & Medicinal Chemistry Letters. 2016;6(9):2273-2277
  62. 62. Zhan X, Xu Y, Qi Q , Wang Y, Shi H, Mao Z. Synthesis, cytotoxic, and antibacterial evaluation of quinazolinone derivatives with substituted amino moiety. Biodiversitas. 2018;15(3):e1700513
  63. 63. Zhang G-H, Xue W-B, An Y-F, Yuan J-M, Qin J-K, Pan C-X, et al. Distinct novel quinazolinone exhibits selective inhibition in MGC-803 cancer cells by dictating mutant p 53 function. European Journal of Medicinal Chemistry. 2015;95:377-387
  64. 64. Wei M, Chai WM, Wang R, Yang Q , Deng Z, Peng Y. Quinazolinone derivatives: Synthesis and comparison of inhibitory mechanisms on a-glucosidase. Bioorganic and Medicinal Chemistry. 2017;25:1303-1308
  65. 65. Ward A, Dong L, Harris JM, Khanna KK, Al-Ejeh F, Fairlie DP, et al. Quinazolinone derivatives as inhibitors of homologous recombinase RAD51. Bioorganic & Medicinal Chemistry Letters. 2017;27(14):3096-3100
  66. 66. Venkatesh R, Kasaboina S, Gaikwad HK, Janardhan S, Bantu R, Nagarapu L, et al. Design and synthesis of 3-(3-((9H-carbazol-4-yl)oxy)-2-hydroxypropyl)-2-phenylquinazolin-4(3H)-one derivatives to induce ACE inhibitory activity. European Journal of Medicinal Chemistry. 2015;96:22-29

Written By

Satyendra Mishra

Submitted: May 6th, 2019 Reviewed: August 16th, 2019 Published: December 13th, 2019