fumarates and Peptic-Ulcer

Topics: Cholelithiasis; Clinical Trials as Topic; Cycloheptanes; Fumarates; Humans; Kidney Calculi; Morphine; Muscles; Papaverine; Peptic Ulcer; Preoperative Care; Spasm

In our pursuit of developing a novel and potent potassium-competitive acid blocker (P-CAB), we synthesized pyrrole derivatives focusing on compounds with low log D and high ligand-lipophilicity efficiency (LLE) values. Among the compounds synthesized, the compound 13e exhibited potent H(+),K(+)-ATPase inhibitory activity and potent gastric acid secretion inhibitory action in vivo. Its maximum efficacy was more potent and its duration of action was much longer than those of proton pump inhibitors (PPIs). Therefore, compound 13e (1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine fumarate, TAK-438) was selected as a drug candidate for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer, and other acid-related diseases.

Topics: Animals; Anti-Ulcer Agents; Dogs; Enzyme Inhibitors; Fumarates; Gastric Mucosa; H(+)-K(+)-Exchanging ATPase; Humans; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Male; Molecular Structure; Peptic Ulcer; Proton Pump Inhibitors; Pyrroles; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Sulfonamides

Topics: Animals; Bromides; Electric Stimulation; Fumarates; Gastric Juice; Gastrointestinal Motility; Guinea Pigs; Muscle, Smooth; Parasympathetic Nervous System; Parasympatholytics; Peptic Ulcer; Piperidines; Rats; Salivation; Stomach; Valerates

Topics: Cycloheptanes; Fumarates; Lymphatic System; Muscles; Peptic Ulcer; Vasodilator Agents

Topics: Absorption; Anemia; Anemia, Hypochromic; Biomedical Research; Blood; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Fumarates; Gastrectomy; Humans; Iron; Iron Chelating Agents; Peptic Ulcer