The Development of a New Proton-Pump Inhibitor: The Case History of Pantoprazole

Analogue-based Drug Discovery

Volumn , Issue , 2006, Pages 115-136

  Senn Bilfinger, Jörg ^a   Sturm, Ernst ^a  

^a ALTANA PHARMA AG   (Germany)

Author keywords

Analogue based drug discovery; Benefits; Benzimidazole moiety; First PPI project candidates; Gastrointestinal research at Byk Gulden; Internal competition with SK F95601; Mechanism of action of PPIs; New proton pump inhibitor (PPI); Optimizing pyridine moiety; Pantoprazole; Toxicological problems

Indexed keywords

EID: 34250884109     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/3527608001.ch6     Document Type: Chapter

References (51)

1. Modlin IM, Sachs G. Acid related diseases: Biology and treatment. 2nd edn. Lippincot, Williams & Wilkins, Philadelphia, 2004.
2. Black JW, Duncan WA, Durant CJ, Ganellin CR, Parsons EM. Definition and antagonism of histamine H2-receptors. Nature, 1972; 236, 385-390.
3. Cooper DG, Young RC, Durant GJ, Ganellin CR. ComprehensiveMedicinal Chemistry. Pergamon Press, Oxford, 1990, pp. 323-421.
4. Colin-Jones DG. The role and limitations of H2-receptor antagonists in the treatment of gastro-oesophageal reflux disease. Aliment. Pharmacol. Ther., 1995, 9(Suppl. 1), 9-14.
5. Forte JG, Lee HC. Gastric adenosine triphosphatases: a review of their possible role in HCl secretion. Gastroenterology, 1977, 73(4 Pt. 2), 921-926.
6. Sachs G, Chang H, Rabon E, Shackman R, Sarau HM, Saccomani G. Metabolic and membrane aspects of gastric H+ transport. Gastroenterology, 1977, 73(4 Pt. 2), 931-940.
7. Sjostrand SE, Ryberg B, Olbe L. Analysis of the actions of cimetidine and metiamide on gastric acid secretion in the isolated guinea pig gastric mucosa. Naunyn Schmiedebergs Arch. Pharmacol., 1977, 296(2), 2-139.
8. Saccomani G. Acta Physiol. Scand. Suppl., 1978, 293-305.
9. Figala V, Klemm K, Kohl B, Krüger U, Rainer G, Schaefer H, et al. Acid activation of (H+-K+)-ATPase inhibiting 2-(2-pyridylmethyl-sulphinyl) benzimidazoles: Isolation and characterization of the thiophilic 'active principle' and its reactions. J. Chem. Soc., Chem. Commun., 1986, 125-127.
10. Lindberg P, Nordberg P, Alminger T, Brandstrom A, Wallmark B. The mechanism of action of the gastric acid secretion inhibitor omeprazole. J. Med. Chem., 1986, 29(8), 8-1327.
11. Berglindh T, Obrink KJ. A method for preparing isolated glands from the rabbit gastric mucosa. Acta Physiol. Scand., 1976, 96(2), 2-150.
12. Kohl B, Sturm E, Senn-Bilfinger J, Simon WA, Krüger U, Schaefer H et al. (H+-K+)-ATPase inhibiting 2-[(2-pyridylmethyl) sulfinyl]benzimidazoles. 4. A novel series of dimethoxypyridyl substituted inhibitors with enhanced selectivity. The selection of pantoprazole as a clinical candidate. J. Med. Chem., 1992, 35(6), 6-1049.
13. Huber R, Kohl B, Sachs G, Senn-Bilfinger J, Simon WA, Sturm E. Review article: the continuing development of proton pump inhibitors with particular reference to pantoprazole. Aliment. Pharmacol. Ther., 1995, 9(4), 4-363.
14. Kurtz W. [A layered lattice antacid with long-term effectiveness. Profile of action and safety exemplified by magaldrate]. Fortschr. Med., 1993, 111(6), 6-93.
15. Magaldrate and almasilate - complex buffering antacids. Drug Ther. Bull., 1985, 23(10), 10-39.
16. Riedel R, Bohnenkamp W, Eltze M, Heintze K, Prinz W, Kromer W. Comparison of the gastric antisecretory and antiulcer potencies of telenzepine, pirenzepine, ranitidine and cimetidine in the rat. Digestion, 1988, 40(1), 1-25.
17. Bell NJ, Burget D, Howden CW, Wilkinson J, Hunt RH. Appropriate acid suppression for the management of gastro-oesophageal reflux disease. Digestion, 1992, 51 (Suppl. 1), 59-67.
18. Bertaccini G, Coruzzi G. Control of gastric acid secretion by histamine H2 receptor antagonists and anticholinergics. Pharmacol. Res., 1989, 21(4), 4-339.
19. Feldman M. Inhibition of gastric acid secretion by selective and nonselective anticholinergics. Gastroenterology, 1984, 86(2), 2-361.
20. Sjostrand SE, Olbe L, Fellenius E. The discovery and development of the proton pump inhibitor. In: Olbe L (Ed.). Proton Pump Inhibitors. Birkhäuser, Basel, 1999.
21. Sundell G, Sjostrand SE, Olbe L. Gastric antisecretory effects of H83/69, a benzimidazolyl- pyridyl-methyl-sulfoxide. Acta Pharmacol. Toxicol., 1977, Suppl. 4, 77.
22. Kilian U, Beume R, Eltze M, Häfner D, Hanauer G, Schudt C. Telenzepine and its enantiomers, M1-selective antimuscarinics, in guinea pig lung function tests. Agents Actions Suppl., 1991, 34, 131-147.
23. Stockbrügger RW. Antimuscarinic drugs. Methods Fund. Exp. Clin. Pharmacol., 1989, 11 (Suppl. 1), 79-86.
24. Olbe L, Haglund U, Leth R, Lind T, Cederberg C, Ekenved G, et al. Effects of substituted benzimidazole (H 149/94) on gastric acid secretion in humans. Gastroenterology, 1982, 83(1 Pt. 2), 193-198.
25. Wallmark B, Sachs G, Mardh S, Fellenius E. Inhibition of gastric (H+/K+)- ATPase by the substituted benzimidazole, picoprazole. Biochim. Biophys. Acta, 1983, 728(1), 1-31.
26. Fellenius E, Berglindh T, Sachs G, Olbe L, Elander B, Sjostrand SE, et al. Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+/K+)- ATPase. Nature, 1981, 290, 159-161.
27. Junggren UK, Sjöstrand SE, Eur Pat 005129, 1979.
28. Senn-Bilfinger J, Schaefer H, Figala V, Klemm K, Rainer G, Riedel R. European Patent 080602, 1981.
29. Larsson H, Carlsson E, Junggren U, Olbe L, Sjostrand SE, Skanberg I, et al. Inhibition of gastric acid secretion by omeprazole in the dog and rat. Gastroenterology, 1983, 85(4), 4-900.
30. Rainer G, Riedel R, Senn-Bilfinger J, Klemm K, Schaefer H, Figala V. European Patent 134400, 1984.
31. Olbe L, Carlsson E, Lindberg P. A proton- pump inhibitor expedition: the case histories of omeprazole and esomeprazole. Nat. Rev. Drug Discov., 2003, 2(2), 2-132.
32. Senn-Bilfinger J, Krüger U, Sturm E, Figala V, Klemm K, Kohl B et al. (H+-K+)-ATPase inhibiting 2-[(2-pyridylmethyl) sulfinyl]benzimidazoles. 2. The reaction cascade induced by treatment with acids. Formation of 5H-pyriodo [1′,2′:4,5] [1,2,4] thiadiazino benzimidazole-13-ium salts and their reactions with thiols. J. Org. Chem., 1987, 52(20), 20-4582.
33. Sturm E, Krüger U, Senn-Bilfinger J, Figala V, Klemm K, Kohl B, et al. (H+-K+)-ATPase inhibiting 2-[(2-pyridylmethyl) sulfinyl]benzimidazoles. 1. Their reaction with thiols under acidic conditions. Disulfide containing 2-pyridiniobenzimidazolides as mimics for the inhibited enzyme. J. Org. Chem., 1987, 52(20), 20-4573.
34. Krüger U, Senn-Bilfinger J, Sturm E, Figala V, Klemm K, Kohl B, et al. (H+-K+)-ATPase inhibiting 2-[(2-pyridylmethyl) sulfinyl]benzimidazoles. 3. Evidence for the involvement of a sulfenic acid in their reactions. J. Org. Chem., 1990, 55(13), 13-4163.
35. Brandstrom A, Lindberg P, Bergman N-A, Alminger T, Ankner K, Jungren U. Chemical reactions of omeprazole and omeprazole analogues. 1. A survey of the chemical transformations of omeprazole and its analogues. Acta Chim. Scand., 1989, 43, 536-548.
36. Lindberg P, Keeling D, Fryklund J, Andersson T, Lundborg P, Carlsson E. Review article: Esomeprazole - enhanced bio-availability, specificity for the proton pump and inhibition of acid secretion. Aliment. Pharmacol. Ther., 2003, 17(4), 481-488.
37. Kohl B, Klemm K, Riedel R, Rainer G, Schaefer H, Senn-Bilfinger J. Eur Pat 166287, 1985.
38. Kromer W, Postius S, Riedel R, Simon WA, Hanauer G, Brand U. et al. BY 1023/SK&F 96022 INN pantoprazole, a novel gastric proton pump inhibitor, potently inhibits acid secretion but lacks relevant cytochrome P450 interactions. J. Pharmacol. Exp. Ther., 1990, 254(1), 1-129.
39. Ife RJ, Dyke CA, Keeling DJ, Meenan E, Meeson ML, Parsons ME, et al. 2-[[(4-Amino-2-pyridyl)methyl]sulfinyl]- benzimidazole H+/K+-ATPase inhibitors. The relationship between pyridine basicity, stability, and activity. J. Med. Chem., 1989, 32(8), 8-1970.
40. Cheer SM, Prakash A, Faulds D, Lamb HM. Pantoprazole: an update of its pharmacological properties and therapeutic use in the management of acidrelated disorders. Drugs, 2003, 63(1), 1-101.
41. Steinijans VW, Huber R, Hartmann M, Zech K, Bliesath H, Wurst W, et al. Lack of pantoprazole drug interactions in man: an updated review. Int. J. Clin. Pharmacol. Ther., 1996, 34(Suppl. 1), S31-S50.
42. Kliem V, Bahlmann J, Hartmann M, Huber R, Lühmann R, Wurst W. Pharmacokinetics of pantoprazole in patients with end-stage renal failure. Nephrol. Dial. Transplant., 1998, 13, 1189-1193.
43. Malen CE, Danree BH. New thiocarboxamide derivatives with specific gastric antisecretory properties. J. Med. Chem., 1971, 14(3), 3-244.
44. Wurzer H, Hofbauer R, Worm HC, Frass M, Kaye K, Kaye AD. Intravenous administration of pantoprazole. An Austrian multicenter study. Clin. Drug Invest., 2002, 22(8), 8-1173.
45. Pisegna JR. Switching between intravenous and oral pantoprazole. J. Clin. Gastroenterol., 2001, 32(1), 1-27.
46. Bardhan KD. Pantoprazole: a new proton pump inhibitor in the management of upper gastrointestinal disease. Drugs Today, 1999, 35(10), 10-773.
47. Vakil N. Review article: new pharmacological agents for the treatment of gastro- oesophageal reflux disease. Aliment Pharacol Ther 2004, 19, 1041-1049.
48. Kenneth R, McQuaid and Loren Laine. Early heartburn relief with proton pump inhibitors: A systematic review and meta-analysis of clinical trails. Clinical Gastroenterology and Hepatology 2005, 3, 553-563.
49. Crawley J A, Schmitt C M. How satisfied are chronic heartburn suffers with their prescription medications? Results of the Patient Unmet Needs Survey. J Clin Outcomes Management 2000, 7, 29-34.
50. Keeling D J, Laing S M, Senn-Bifinger J. SCH 28080 is a lumenally acting, K+-site inhibitor of the gastric (H+; K+)- ATPase. Biochem Pharmacol 1988, 37, 2231-6.
51. Senn-Bilfinger J, Postius S, Simon W, Grundler G, Hanauer G,Huber R, Kromer W, Sturm E. WO200017200-A1.