Recent advances in the pharmacological diversification of quinazoline/quinazolinone hybrids

Abstract

Due to the pharmacological activities of quinazoline and quinazolinone scaffolds, it has aroused great interest in medicinal chemists for the development of new drugs or drug candidates. The pharmacological activities of quinazoline and its related scaffolds include anti-cancer, anti-microbial, anti-convulsant, and antihyperlipidaemia. Recently, molecular hybridization technology is used for the development of hybrid analogues with improved potency by combining two or more pharmacophores of bioactive scaffolds. The molecular hybridization of various biologically active pharmacophores with quinazoline derivatives resulted in lead compounds with multi-faceted biological activity wherein specific as well as multiple targets were involved. The present review summarizes the advances in lead compounds of quinazoline hybrids and their related heterocycles in medicinal chemistry. Moreover, the review also helps to intensify the drug development process by providing an understanding of the potential role of these hybridized pharmacophoric features in exhibiting various pharmacological activities.

Fig. 1. Pharmacological importance of quinazolinone-based drugs.

Fig. 2. Pharmacological importance of quinazoline-based drugs.

Scheme 1. Synthetic scheme for quinazolinone-phenylquinoxaline hybrids.

Scheme 2. Synthetic scheme for sulfamide-linked quinazolinone hybrids.

Fig. 3. Designing strategy for oxazoline- and dihydroquinazolinone-based hybrids.

Scheme 3. Synthetic and design strategy for quinazolinone- and benzimidazole-based hybrids as DHFR inhibitors.

Scheme 4. Synthetic scheme for quinazolinone- and thiazole-based hybrids.

Scheme 5. Synthetic and design strategy for quinazolinone-oxadiazole hybrids.

Scheme 6. Synthetic strategy for quinazoline and indolin-2-one hybrids, showing the importance of each structural unit.

Scheme 7. Synthetic scheme for benzoxazinone and quinazolinone hybrids.

Scheme 8. Synthetic and design strategy for the Schiff base hybrids of quinazolinone as PDE-4 inhibitors.

Scheme 9. Synthetic scheme for quinazolinone- and thiazolidinone-based hybrids.

Scheme 10. Synthetic and design strategy for quinazolinone-sulfonamide hybrids.

Scheme 11. Synthetic schemes for quinazolinone-based rhodanine (31) and triazole (32) hybrids.

Scheme 12. Synthetic and design strategy for indole- and quinazolinone-based hybrids for anti-cancer potential.

Scheme 13. Synthetic scheme for luotonin A-inspired quinazolinone-triazole hybrids.

Scheme 14. Synthetic scheme for amino acid-linked quinazolinone hybrids.

Scheme 15. Synthetic and design strategy for quinazoline-hydroxamic acid hybrids.

Scheme 16. Synthetic scheme for 4-aminoquinazoline and triazole hybrids.

Scheme 17. Synthetic scheme for indole and 4-aminoquinazoline hybrids.

Scheme 18. Synthetic and design strategy for isatin and 4-aminoquinazoline hybrids.

Scheme 19. Synthetic and design strategy for benzimidazole and 4-aminoquinazoline hybrids.

Scheme 20. Synthesis of oxazolidinone and 4-aminoquinazolinone hybrids.

Fig. 4. Designing strategy for benzimidazole- and 4-aminoquinazoline-based hybrids.

Scheme 21. Synthetic and design strategy for triazole-linked 4-aminoquinazoline hybrids.

Scheme 22. Synthetic scheme for hydroxamic acid and 4-aminoquinazoline-based hybrids for HDAC and VEGFR inhibition.

Scheme 23. Synthetic scheme for sulfonamide linked 4-aminoquinazoline hybrids.

Scheme 24. Synthetic scheme for quinazolinone- and triazole-based hybrids, showing its key features.

Scheme 25. Synthetic scheme for quinazolinone- and triazole-based hybrids.

Scheme 26. Synthetic strategy for quinazolinone-thiazole hybrids.

Scheme 27. Synthetic scheme for various azolyl ethanol-based quinazolinone hybrids.

Scheme 28. Synthesis and design strategy for quinazolinone-thiazolidinone hybrids, showing the importance of fluorine in the anti-microbial potential.

Scheme 29. Synthesis and design strategy for quinazolinone-thiadiazole hybrids.

Scheme 30. Synthetic scheme for pyrazole-linked quinazolinone hybrids.

Scheme 31. Synthetic scheme for quinazolinone-triazole hybrids, showing the importance of each structural unit.

Scheme 32. Synthetic scheme for quinazolinone- and thiazolidinone-based hybrids.

Scheme 33. Synthesis and design strategy for furan-linked quinazoline hybrids.

Scheme 34. Synthesis and design strategy for quinazoline-linked 1,2,4-triazolopyridine hybrids.

Scheme 35. Synthesis and design strategy for quinazoline and 5-aminotriazole hybrids.

Scheme 36. Synthesis and design strategy for triazole- and styryl quinazoline-based hybrids.

Scheme 37. Synthesis of quinazoline- and triazole-linked hybrids.

Fig. 5. Design strategy for quinazoline-linked thiourea (97), chalcone (98), and thiazolidinone (99) hybrids.

Scheme 38. Synthesis of quinazoline-linked thiourea (97), chalcone (98), and thiazolidinone (99) hybrids.

Scheme 39. Synthetic scheme for β-carboline-quinazolinone hybrids.

Fig. 6. Design strategy for quinazoline hybrids with pyrimidine, triazine, tetrazole, and peptide.

Scheme 40. Synthetic scheme for quinazoline hybrids with pyrimidine, triazine, tetrazole, and peptide.

Scheme 41. Synthesis and design strategy for triazole-linked quinazolinone hybrids, targeting α-glucosidase.

Scheme 42. Synthesis of quinazolinone-thiazolidinone hybrids.

Scheme 43. Synthetic scheme for various amino acid-linked quinazolinone hybrids.

Scheme 44. Synthetic strategy for quinazolinone-benzothiazole hybrids, showing the structural importance.

Scheme 45. Synthesis and design strategy for 4-oxothiazolidine and quinazolinone hybrids.

Scheme 46. Synthetic scheme for artemisinin and 4-aminoquinazoline hybrids.

Scheme 47. Synthesis and design strategy for 1-deoxynojirimycin and 4-aminoquinazoline hybrids as dual inhibitors of EGFR and α-glucosidase enzymes.

Scheme 48. Synthesis and design strategy for quinazoline-triazine hybrids as anti-viral and anti-microbial agents.