WO Other References Rewcastle et al. Patents5 8: Bridges, "The current status of tyrosine kinase inhibitors:
Chemical Properties of Quinazolines The chemistry of quinazoline was reviewed by Williamson in and then by Lindquist in and brought up to date by Armarego in Quinazolines is stable in cold dilute acid and alkaline solutions, but it is destroyed when these solutions are boiled.
O-Aminobenzaldehyde, ammonia, and formic acid are formed when quinazoline is boiled with hydrochloric acid. Hydrolysis, Oxidation, and Reduction Oxidation of quinazoline in dilute aqueous acid with two equivalents of hydrogen peroxide at room temperature gave 3,4-dihydrooxo quinazoline.
In alkaline medium, the anhydrous neutral species of quinazoline were predominantly undergo oxidation with KMnO4 and yielded 3,4-dihydro-6 4-oxo quinazoline. Oxidation Catalytic hydrogenation of quinazoline stopped after the absorption of one molecule of hydrogen and gave 3,4-dihydro quinazoline see Scheme 3 Scheme 3 3.
Reduction Reduction with sodium amalgam gave 1,2,3,4-tetrahydroquinazoline. Lithium aluminum hydride and sodium borohydride gave 3,4-dihydro and 1,2,3,4-tetrahydroquinazoline see Scheme 4 Scheme 4 3.
Nucleophilic and Electrophilic Substitution Reactions The two known nucleophilic substitution reactions of quinazoline are sodamide and hydrazine most probably proceed via the intermediate addition products, and gave 4-amino and 4-hydrazine quinazoline see Scheme 5 Scheme 5 3.
Electrophilic Substitution Reaction of Quinazoline Nitration is the only known electrophilic substitution reaction of quinazoline. Quinazoline gives 6-nitroquinazoline with fuming nitric acid in concentrated H2SO4. No oxidation of the heterocyclic ring can occur under these conditions because the hydrated cation is not present see Scheme 6 Scheme 6 3.
Alkylation Reactions Alkylation of quinazoline takes place on N atom, 3-methyl, 3-ethylalkyl, and 3-benzylquinazolinium salts that readily take up a molecule of alcohol to form the corresponding 4-alkoxyalkyl-3,4-dihydro quinazolinium salts.
These salts gave the pseudo bases, 3-alkyl-3,4-dihydrohydroxy quinazolines on treatment with strong alkali see Scheme 7 Scheme 7 3. Addition Reactions Quinazoline is highly reactive towards anionic reagents which attack on position 4.
Sodium bisulphate, hydrogen cyanide, acetone, 2-butanone, acetophenone, and cyclohexanone add across the 3,4-double bond of quinazoline. Methyl, ethyl, isopropyl, benzyl, t-butyl, and phenyl magnesium halides and phenyl lithium also add across the 3,4-double bond to give the corresponding 4-substituted 3,4-dihydroquinazolines.
Synthesis of Quinazoline Compounds Various methods were reported for the synthesis of oxoquinazolines. From Isatoic Anhydride Isatoic anhydride was readily reacted with amines to dihydrooxoquinazolines by refluxing ethyl orthoformate for 1—6 hrs without isolating the intermediate amides see Scheme 10 Scheme 10 4.
From 3,1,4-Benoxazones Acylanthranils and Amines 3,1,4-Benoxazones react with amines to give 3,4-dihydrooxoquinazolines. Primary aliphatic amines and anilines react with 2-methylnitrooxoquinazolines see Scheme of the stated derivatives with the scheme and also prepared derivatives were with promising cytotoxic effect.
Keywords: anti-cancer, benzo[d]thiazole, IC 50, 7-methoxy(3-morpholinopropoxy)3,4-dihydroquinazoline ANTI-CANCER ACTIVITY OF SOME NOVEL DERIVATIVES OF 2-AMINO BENZOTHIAZOLES: IN VITRO AND IN VIVO STUDIES.
M. Pharm Dissertation Protocol.
Submitted to the. for derivatives of anti-inflammatory activity. A series of 2-substituted quinazolinone derivatives (11) was synthesized and their biological studies were done by Kiruthiga et al.
. Synthesis of novel 4,6-disubstituted quinazoline derivatives, their anti-inflammatory and anti-cancer activity (cytotoxic) against U leukemia cell lines. Maarouf A, El-Bendary E, Goda F. Synthesis and evaluation of some novel quinazolinone derivatives as diuretic agents.
Arch Pharm., (10) (). Mendoza C, Correa J, Nieto R, Marquez A, Aguilar R.
Design, synthesis and biological evaluation of quinazoline derivatives as anti-trypanosomatid and anti-plasmodial agents. Some novel 2,3-disubstituted-3H-Quinazolinone derivatives with the aim and to get more potent drug for the treatment of Anti tumor and microbial infectious diseases.
The structure of the compounds was confirmed by spectral analysis.