Quinazolin-4-One: A Varsatile Molecule

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.

Consecutive Utilization of Mechanochemical and Microwave Methods for the Synthesis of Boc‐2‐amino‐quinazolin‐4(3H)‐ones and DFT Study of Mechanism 6π‐Diazaelectrocyclization Process

“…to rearomatization by [1,5]H shift into the most stable product 17. Relative Gibbs free energies for saddle points on the reaction path from reactant 4 to product 17 are 51.9, 31.9 and 58.2 kcal mol À 1 (TS2, TS3 and TS4, respectively) indicating that the activation energies for the first step (t-butanol elimination) and for the third step ( [1,4]H shift) are unrealistically high (forbidding). This result is not supported experimentally, since the heterocycle product was obtained and none of the intermediates between TS2 and TS4 was detected in the reaction mixture.…”

“…The activation energy for this process (TS7) is the highest and it is the step in the reaction mechanism that determines the reaction rate. By shifting the H atom intermediate 38 from the anthracene C 2 position to adjacent carbonyl group via t-butanol that solvates the molecule (formal [1,5]-H shift, transition state TS8), a keto-enol tautomeric form 39 of the final product is obtained. This species is considerably stabilized, and the energy barrier for H-shift via TS8 is very small (3.7 kcal mol À 1 ).…”

“…Quinazolin-4(3H)-ones are an important class of biologically active molecules [1] which show anticancer, antimalarial, antiviral, anticonvulsant, analgesic, anti-inflammatory and antimicrobial activity. [2] Different synthetic routes were used for their preparation and the reaction sequences employed in synthesis of 2-amino-quinazolin-4(3H)-ones starting from readily available aromatic amines which include Me 3 SiCl [3] and CDI [4] catalyzed reactions are depicted in Scheme 1.…”

“…Comparison of activation energies for t-butanol elimination, 6πdiazaelectrocyclization and[1,5]H-shift for H 2 O solvated 1-anthryl, 1naphthyl and phenyl guanidine to Boc-2-amino-quinazolin-4(3H)-ones[a] …”

Pyridyl Glycosyl Triazole/CuI-Mediated Domino/Tandem Synthesis of Quinazolinones

“…Other than natural products, a number of quinazolinone-based scaffolds are also well known for their potent biological activities such as antihypertensive, antibacterial, and antidiabetic, and other bioactivities. In addition, 3- N -substituted quinazolinones, 2-amino-3-substituted quinazolinone-containing free additional amino functionality, extensively constitute a privileged category of potential drug conjugates, which showed a wide range of pharmacological activities, for example, antihyperglycemic, anticancer, − anti-hypertensive, , antimalarial, antimicrobial, and anti-inflammatory activities. − Some of the representative biologically potent quinazolinone analogues ( V-VII ) are shown in Figure .…”