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Part-IResults and Discussionby kinetic measurements in both directions for example starting from 29 and 29c. Theformation of the spiro intermediate 29a via Smile’s rearrangement is a rate limiting stepsupported by kinetic measurements. The rate constant obtained for omeprazole analogs isstrongly dependent on substituents in the pyridine ring, indicating that a positive charge iscreated in the pyridine nitrogen atom in the rate-limiting step. The spiro intermediate 29ais dihyrobenzimidazole with a pronounced tendency to undergo aromatization, thusforming the sulfenic acid 29b by a C-S bond cleavage. This sulfenic acid further loses amolecule of H 2 O to form a sulfenamide, 29c. This sulfenamide 29c represents the activeenzyme inhibitor and binds covalently to the sulfhydryl groups of the cysteines (Cys-813and 822) of the proton pump. The recovery of enzyme’s activity requires de novosynthesis of the enzyme which is consistent with the long duration of action of drug. 56This blocking and deactivating of the H + /K + -ATPase enzyme results in irreversibleinactivation of the proton pump and thus, affects its normal acid production and secretion.This leads to most of side effects associated with these PPI’s usage.However, the pyrimidine ring is less basic than the pyridine ring and therefore thought inthe first step the imidazole gets protonated, it can’t form spiro intermediate 29a as thepyrimidine N 1 nitrogen has no electron available for donation to the nucleophilic centre;the C 2 of the imidazole ring and therefore can’t form the spiro intermediate analogous to29a via Smiles rearrangement (Scheme-29).137