Method Optimization for Synthesis of Trisubstitued Quinazoline Derivatives

Main Article Content

Zahra Haghighijoo Masoomeh Eskandari Soghra Khabnadideh

Abstract

A series of new 4-anilinoquinazoline derivatives (IV-XVI) were synthesized in convenient pathway with desirable yields. 4-Aminoquinazoline derivatives corresponding Erlotinib are more active compounds for inhibition of the epidermal growth factor receptor (EGFR) which are used as anticancer agents. Although these categories of compounds have widespread clinical use, most of the reported syntheses protocol for them require multistep and low-yielding reaction pathways. Here we tried a new method with only 3 or 4 steps to prepare 4-anilinoquinazoline derivatives. We synthesized our new compounds in two parts (part I with 3 steps and part II with 4 steps). In the first step of part I, we used ortho-diflouro or ortho-dimethoxy anthranilic acid to get the quinazoline ring with a carbonyl group at its 4 position. Then, in the second and third steps of this part, we replaced the carbonyl group of quinazoline ring by chlorine and amine group respectively (IV-X). In part II, we used dichloro anthranilic acid to get the quinazoline ring with a carbonyl group at its 4 position. In these cases, after synthesis of the quinazoline ring we could etherify it via its substitutions on the starting anthranilic acid (XI-XVI), in order to mimic the erlotinib structure as a tyrosine kinase inhibitor. The next steps of this part (replacing the carbonyl group by chlorine and then by amine) were the same as part I. Our new compounds contain different substitutions at orto (6,7) or meta (5,7) positions of the quinazoline ring.

Article Details

How to Cite
HAGHIGHIJOO, Zahra; ESKANDARI, Masoomeh; KHABNADIDEH, Soghra. Method Optimization for Synthesis of Trisubstitued Quinazoline Derivatives. Medical Research Archives, [S.l.], v. 5, n. 5, may 2017. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/1199>. Date accessed: 09 dec. 2023.
Keywords
4–aminoquinazoline, Erlotinib, anti-cancer, EGFR
Section
Research Articles

References

1. Myangar KN, Raval JP. Design, synthesis, and in vitro antimicrobial activities of novel azetidinyl-3-quinazolin-4-one hybrids. Medicinal Chemistry Research. 2012;21(10):2762-2771.

2. Ouyang G, Zhang P, Xu G, Song B, Yang S, Jin L, Xue W, Hu D, Lu P, Chen Z. Synthesis and antifungal bioactivities of 3-alkylquinazolin-4-one derivatives. Molecules. 2006;11(6):383-392.

3. Kumar KS, Ganguly S, Veerasamy R, De Clercq E. Synthesis, antiviral activity and cytotoxicity evaluation of Schiff bases of some 2-phenyl quinazoline-4 (3) H-ones. European journal of medicinal chemistry. 2010;45(11):5474-5479.

4. Wu J, Bai S, Yue M, Luo L, Shi Q, Ma J, Du X, Kang S, Hu D, Yang S. Synthesis and insecticidal activity of 6, 8-dichloro-quinazoline derivatives containing a sulfide substructure. Chemical Papers. 2014;68(7):969-975.

5. Tiwari VK, Kale RR, Mishra BB, Singh A. A facile one-pot MW approach for 3-heteroaryl-2-thioxo-2,3-dihydroquinazolin-4 (1H)-one. Arkivoc. 2008;14:27-36.

6. Chandrika PM, RAO ARR, NARSAIAH B, RAJU MB. Quinazoline Derivatives With Potent Anti-Inflammatory And Anti-Allergic Activities. International Journal of Chemical Science. 2008;6(3):1119-1146.

7. Alafeefy AM, Kadi AA, El-Azab AS, Abdel-Hamide SG, Daba MH. Synthesis, Analgesic and AntiInflammatory Evaluation of Some New 3H Quinazolin-4-one Derivatives. Archiv der Pharmazie. 2008;341(6):377-385.

8. Wang SB, Deng XQ, Zheng Y, Yuan YP, Quan ZS, Guan LP. Synthesis and evaluation of anticonvulsant and antidepressant activities of 5-alkoxytetrazolo[1,5-c]thieno[2,3-e]pyrimidine derivatives. European journal of medicinal chemistry. 2012;56:139-144.

9. Usifoh CO, Scriba GK. Synthesis and anticonvulsant activity of acetylenic quinazolinone derivatives. Archiv der Pharmazie. 2000;333(8):261-266.

10. White DC, Greenwood TD, Downey AL, Bloomquist JR, Wolfe JF. Synthesis and anticonvulsant evaluation of some new 2-substituted-3-arylpyrido[2,3-d]pyrimidinones. Bioorganic & medicinal chemistry. 2004;12(21):5711-5717.

11. Farag AA, Khalifa EM, Sadik NA, Abbas SY, Al-Shemi AG, Ammar AA. Synthesis, characterization, and evaluation of some novel 4 (3H)-quinazolinone derivatives as anti-inflammatory and analgesic agents. Medicinal Chemistry Research. 2013;22(1):440-452.

12. Wu X, Li M, Tang W, Zheng Y, Lian J, Xu L, Ji M.. Design, Synthesis, and In vitro Antitumor Activity Evaluation of Novel 4-pyrrylamino Quinazoline Derivatives. Chemical biology & drug design. 2011;78(6):932-940.

13. Marzaro G, Guiotto A, Chilin A. Quinazoline derivatives as potential anticancer agents: a patent review (2007-2010). Expert opinion on therapeutic patents. 2012;22(3):223-252.

14. Singh K, Sharma PP, Kumar A, Chaudhary A, Roy RK. 4-Aminoquinazoline Analogs: A Novel Class of Anticancer Agents. Mini reviews in medicinal chemistry. 2013;13(8):1177-1194.

15. Harris CS, Kettle JG, Williams EJ. Facile synthesis of 7-amino anilinoquinazolines via direct amination of the quinazoline core. Tetrahedron letters. 2005; 46(43):7381-7384.

16. Marzaro G, Guiotto A, Pastorini G, Chilin A. A novel approach to quinazolin-4(3H)-one via quinazoline oxidation: an improved synthesis of 4-anilinoquinazolines. Tetrahedron. 2010;66(4):962-968.

17. Szczepankiewicz W. Suwiński J. Bujok R. Synthesis of 4-arylaminoquinazolines and 2-aryl-4-arylaminoquinazolines from 2-aminobenzonitrile, anilines and formic Acid or benzaldehydes. Tetrahedron. 2000;56(47):9343-9349.

18. Chilin A, Marzaro G, Zanatta S, Guiotto A. A microwave improvement in the synthesis of the quinazoline scaffold. Tetrahedron letters. 2007;48(18):3229-3231.

19. Cao R, Mi N, Zhang H. 3D-QSAR study of c-Src kinase inhibitors based on docking. Journal of molecular modeling. 2010;16(2):361-375.

20. Makino S, Suzuki N, Nakanishi E, Tsuji T. Efficient solid-phase synthesis of quinazoline-2-thioxo-4-ones with SynPhase™ lanterns. Tetrahedron Letters. 2000;41(43):8333-8337.

21. Rivero IA, Espinoza K, Somanathan R. Syntheses of Quinazoline-2, 4-dione Alkaloids and Analogues from Mexican Zanthoxylum Species†. Molecules. 2004;9(7):609-616.

22. Shao H, Colucci M, Tong S, Zhang H, Castelhano AL. A practical solid phase synthesis of quinazoline-2,4-diones. Tetrahedron Letters. 1998;39(40):7235-7238.

23. Khalifa M, Osman AN, Ibrahim MG, el Rahman A, Ossman E, Ismail MA. Synthesis and biological activity of certain derivatives of 2, 4-dioxo-1, 2, 3, 4-tetrahydroquinazoline. Part 2. Die Pharmazie. 1982;37(2):115-117.

24. Palop JA, Planoa D, Morenoa E, Sanmartín, C. Novel quinazoline and pyrido [2, 3-d] pyrimidine derivatives and their hydroselenite salts as antitumoral agents. ARKIVO. 2014;2:187-206.

25. Azev YA, Golomolzin BV, Shorshnev SV. Reactions of quinazoline and its 4-oxo- and 4-chloro-substituted derivatives with nucleophiles. Pharmaceutical Chemistry Journal. 2011;44(12):687-690.

26. Li S, Guo C, Sun X, Li Y, Zhao H, Zhan D, Lan M, Tang Y.. Synthesis and biological evaluation of quinazoline and quinoline bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors and EPR bio-probe agents. European Journal of Medicinal Chemistry. 2012;49(0):271-278.