**9. Quinazolines**

Quinazolines are interesting targets for new method development due to their importance in a broad range of therapeutic areas [51, 52]. Quinazoline derivatives, which possess a wide range of biological activities contain the 4-oxo-2-thioxo-1,2,3,4 tetrahydropyrimidine structural moiety in their heterocyclic rings [53–58].

The synthetic methods available for the preparation of quinazolines involved the amidation of 2-aminobenzoic acid or its derivatives, i.e. 2-aminobenzonitrile, 2-aminobenzoate, and 2-arylnitrilium salts, followed by oxidative ring closure [59–63]. Other synthetic pathways include the cyclization of anthranilamides with aldehydes [64], and with ketones or acid chlorides under acidic or basic conditions [65–67]. These methods involved multistep processes, poor yields, toxic reagents and

**Figure 11.** *Quinazolines.*

time-consuming experimental procedures. Moreover, very few methods are reported for the synthesis of 2-thioxoquinazoline-4-ones, as most of the methods reported are of quinazoline-2,4(1*H*,3*H*)-diones, from various sources [61, 62, 68–75].

Recently, Saeed *et al*. [76] reported the base catalysed intramolecular nucleophilic cyclization of substituted thioureas in the presence of DMF to afford the 2-thioxoquinazoline-4-ones. The solid-phase synthesis for the preparation of2 thioxoquinazoline-4-one had been reported [77–80]. Treatment of 5-ethoxymethylene-1,3-diaryl-2-thiobarbituric acids (**2**) with malononitrile in presence of NH4OAc and acetic acid with ZnCl2 as catalyst in refluxing condition gave the corresponding 2-thioxoquinazolin-4-ones, **21** in 78–85% overall yields [81] (**Figure 11**). However, the reaction of **2** with ethyl cyanoacetate in presence of ammonium acetate and acetic acid with ZnCl2 as a catalyst gave 7-hydroxy-2,3-dihydro-2-thioxo-1,3-diarylquinazolin-4(*1H*)-ones, **22** in 76–87% overall yields [81].

The synthesized compounds **21** and **22** were screened *in vitro* for their antimicrobial activities [82, 83]. Cytotoxicity studies were performed for the compounds on human lung cancer cell line A549 using an MTT assay. The A549 cells were grown at 37°C, 5% CO2 and 100% relative humidity.
