4‐(Nitro, amino, acetylamino)‐2‐aminobenzoic acid were allowed to react with PPh3(SCN)2 and gave the crossholding 7‐nitro, 7‐acetylamino‐ and 7‐amino‐2‐thioxo quinazolin‐4‐ones respectively. The nature of the substituent at position 4 of the 2‐aminobenzoic acids has significant influence on the outcome of the cyclisation reaction with PPh3(SCN)2. Similarly, the nature of the substituent at position 7 of the 2‐substituted quinazolin‐4‐ones significantly affected the ease with which alkylation reactions could be performed. The alkylation selectivity of the 7‐ substiuted‐2‐thioxo quinazolin‐4‐ones was found to depend on the nature of the alkyl halide and the nature of the substituent at position 2.

A series of novel 8‐aryl‐2‐morpholino quinazolines (11a–n, 12a–d, 14a–f, and 15) were synthesized from the precursor 2‐thioxo quinazolin‐4‐ones 8. The 8‐aryl‐2‐morpholino quinazolines compounds were assayed for DNA‐PK and PI3K. All compounds showed low DNA‐PK % inhibition activity at 10 μM compound concertation, and the most active was 8‐(dibenzo[b,d]thiophen‐4‐yl) 12d with 38% inhibition. Similar pattern of PI3K α, β, γ, and δ isoforms inhibition activity at 10 μM were observed. The most active isoform was PI3K δ of 41% inhibition for 8‐(dibenzo[b,d]furan‐4‐yl) compound 11. Most compounds were less active than expected in spite of the strong structural resemblance to known inhibitors (NU7441, 3, 4, and 6). Loss of activity could be attributed to the tautomerization to the aromatic enol (4‐OH), which could specify that the important functional group for the activity is the 4‐carbonyl (C=O) group. Alternatively, the aromatization of the pyrimidine heterocyclic ring could alter the conformation, and thus binding site, of the 2‐morpholine ring, which could reduce the compound‐receptor hydrogen bonding to the morpholine 4‐oxygen. Selected compounds displayed appreciable cytotoxicity with 6‐chloro‐8‐(dibenzo[b,d]thiophen‐4‐yl)‐2‐morpholinoquinazolin‐4(1H)‐one 11j exhibiting the greatest activity with an IC50 of 9.95 μM. Therefore, the mechanism of the cytotoxicity of compound 11j were not through DNA‐PK or PI3K inhibition activity.

in Wiley Online Library (wileyonlinelibrary.com).2-amino-3, 4, 5, or 6-nitrobenzoic acids were reacted with PPh 3 (SCN) 2 and alkyl isothiocyanates to give 5, 6, 7, or 8-nitro-2-thioxo-3-substituted quinazolin-4-ones, respectively. The position of the nitro group was found to have significant influence on the outcome of the reactions. Similarly, the nature of the substituent at position 8 (NO 2 , NH 2 , NH(C═O)CH 3 ) in 8-substituted-2-methylthio quinazolin-4-ones was also found to significantly influence their reactivity towards morpholine. A selection of the products were also tested for in vitro antibacterial activity but little activity was observed. Scheme 3. Synthesis of 8-amino-2-morpholino quinazolines. (i) = morpholine, reflux, 3-72 h. (ii) = K 2 CO 3 , CH 3 I or benzyl bromide, acetone, reflux, 1.5 h. (iii) = SnCl 2 .

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The synthesis of (E)-10-hydroxy-2-decenoic acid ethyl ester (10H2DA-EE) (3) was achieved via a one-pot, tandem oxidation-Wittig process from commercially available 1,8-octanediol (1), Wittig reagent (Ph3P=CHCO2Et) (2) and activated MnO2. Subsequent hydrolysis with sodium hydroxide gave (E)-10-hydroxy-2-decenoic acid (10H2DA) (4).