SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME NOVEL QUINAZOLINE DERIVATIVES AS ACID PUMP ANTAGONISTS

Gastric acid hypersecretion is a major cause of gastric complications like hypergastrinemia, hyperhistaminemia and Zollinger-Ellison syndrome. Out of various drug treatments used, H₂-receptor antagonists possess some limitations, such as the development of tolerance when used for a long period, having a short duration of action, and no complete inhibition of acid secretion in response to a meal. In the case of PPIs they are showing the slow onset of action, short half-life, incomplete acid suppression, and differences in effectiveness in patients due to CYP₂C₁₉ (Cytochrome P₂C₁₉) metabolism To overcome these limitations, other alternative better therapeutic agents should be focused. Potassium-competitive acid blockers (P-CABs) or Acid pump antagonists (APAs) are new H⁺/K⁺-ATPase inhibitors that can exhibit almost complete inhibition of gastric acid secretion through reversible and K⁺-competitive inhibition of the enzyme. In our research work, We are reporting the synthetic methods of novel Quinazoline derivatives and their preliminary gastric acid secretion suppression action. Proposed compounds belong to two Series of N-((3-Benzamido-4-oxo-3, 4-dihydroquinazolin 2-yl) methyl)-N- (substituted) phenyl-benzamides and were prepared, and structural was confirmed using different spectroscopic methods including Infrared spectroscopy, mass spectroscopy, and ¹HNMR. The primary antisecretory activity was evaluated by an in-vitro method using an isolated Hog gastric H⁺/K⁺-ATPase enzyme. All the compounds were found to be potent inhibitors of Isolated Hog stomach H⁺/ K⁺-ATPase enzyme with variant efficacy, and amongst them, compound LMDP-15 was emerged out as a potent inhibitor with IC₅₀ 7 µM. The proposed novel series of N-((3-Benzamido-4-oxo-3, 4-dihydroquinazolin-2-yl) methyl)-N-(substituted) phenylbenzamides (1) provides active and reversible inhibitors of the gastric H⁺/K⁺-ATPase.