PHAR3819 Lecture Notes - Lecture 3: Proton-Pump Inhibitor, Thioamide, Benzimidazole
23 Jul 2018
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Document Summary
Proton pump inhibitors: h+, k+-atpase located in parietal cells. Responsible for transferring gastric acid from canaliculus to the stomach lumen. Secretes acid in response to all stimulators: histamine, acetylcholine, gastrin. Cmn 131- pyridyl-2-thioacetamide: originally an antiviral drug. Potent anti secretory properties over long periods of time: no toxic side effects on the thyroid by putting functional groups on the ring. Pyridine is weakly basic so adding substituents chages basicity: methyl substituents at the meta position have an +ve inductive effect, methoxy substituent are more effective at para position than meta position. Resonance effect increases electron density on the nitrogen. Launches 1988 by astra: worlds biggest selling drug. Vary in different substituents on pyridine and benzimidazole ring. The s-enantiomer has better potency and pharmacokinetic profile. Sulfinic acid intermediate and that in itself can directly act with the cysteine in the pp: Irreversible disulfide bonds form between sulfur-containing ppi and sh group of atpase cys.
