Discovery of a novel pyrrole derivative 1-[5-(2-fluorophenyl)-1-(pyridin-3- ylsulfonyl)-1 H -pyrrol-3-yl]- n -methylmethanamine fumarate (tak-438) as a Potassium-Competitive Acid Blocker (P-CAB)

Journal of Medicinal Chemistry

Volumn 55, Issue 9, 2012, Pages 4446-4456

  Arikawa, Yasuyoshi ^a   Nishida, Haruyuki ^a   Kurasawa, Osamu ^a   Hasuoka, Atsushi ^a   Hirase, Keizo ^a   Inatomi, Nobuhiro ^a   Hori, Yasunobu ^a   Matsukawa, Jun ^a   Imanishi, Akio ^a   Kondo, Mitsuyo ^a   Tarui, Naoki ^a   Hamada, Teruki ^a   Takagi, Terufumi ^a   Takeuchi, Toshiyuki ^a   Kajino, Masahiro ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

1 [ 5 ( 2 FLUOROPHENYL) 1 (PYRIDIN 3 YLSULFONYL) 1H PYRROL 3 YL] N METHYLMETHANAMINE FUMARIC ACID; FUMARIC ACID DERIVATIVE; HYDROGEN POTASSIUM ADENOSINE TRIPHOSPHATASE; LANSOPRAZOLE; PROTON PUMP INHIBITOR; PYRROLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG DESIGN; DRUG EFFICACY; DRUG INHIBITION; DRUG MECHANISM; DRUG POTENCY; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INHIBITION; GASTROESOPHAGEAL REFLUX; IC 50; IN VIVO STUDY; LIGAND LIPHOPHILICITY EFFICIENCY; LIPOPHILICITY; NONHUMAN; PEPTIC ULCER; RAT; STOMACH ACID SECRETION;

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; PYRROLES; RATS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

EID: 84861028397     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm300318t     Document Type: Article

References (29)

1. Robinson, M. Proton pump inhibitors: update on their role in acid-related gastrointestinal diseases Int. J. Clin. Pract. 2005, 59, 709-715 (Pubitemid 44192642)
2. Sachs, G.; Carlsson, E.; Lindberg, P.; Wallmark, B. Gastric H, K-ATPase as therapeutic target Annu. Rev. Pharmacol. Toxicol. 1988, 28, 269-284
3. 2-receptor antagonist famotidine in rats and dogs Jpn. J. Pharmacol 1991, 55, 425-436
4. Fass, R.; Shapiro, M.; Dekel, R.; Sewell, J. Systematic review: proton-pump inhibitor failure in gastro-oesophageal reflux disease - where next? Aliment. Pharmacol. Ther. 2005, 22, 79-94 (Pubitemid 41039696)
5. Parsons, M. E; Keeling, D. J. Novel approaches to the pharmacological blockade of gastric acid secretion Expert Opin. Invest. Drugs 2005, 14, 411-421 (Pubitemid 40711851)
6. Andersson, K.; Carlsson, E. Potassium-competitive acid blockade: a new therapeutic strategy in acid-related diseases Pharmacol. Ther. 2005, 108, 294-307 (Pubitemid 41693765)
7. Kaminski, J. J.; Bristol, J. A.; Puchalski, C.; Lovey, R. G.; Elliott, A. J.; Guzik, H.; Solomon, D. M.; Conn, D. J.; Domalski, M. S.; Wong, S. C.; Gold, E. J.; Long, J. F.; Chiu, P. J. S.; Steinberg, M.; McPhail, A. T. Antiulcer agents. I. Gastric antisecretory and cytoprotective properties of substituted imidazo[1,2- a ]pyridines J. Med. Chem. 1985, 28, 876-892 (Pubitemid 15012494)
8. +-ATPase Biochem. Pharmacol. 2007, 73, 198-205 (Pubitemid 44855722)
9. Mori, H.; Tonai-Kachi, H.; Ochi, Y.; Taniguchi, Y; Ohshiro, H.; Takahashi, N.; Aihara, T.; Hirao, A.; Kato, T.; Sakakibara, M.; Kurebayashi, Y. N -(2-Hydroxyethyl)- N,2-dimethyl-8-{[(4 R)-5-methyl-3, 4-dihydro-2 H -chromen-4-yl]amino}imidazo[1,2- a ]pyridine-6-carboxamide (PF-03716556), a novel, potent, and selective acid pump antagonist for the treatment of gastroesophageal reflux disease J. Pharmacol. Exp. Ther. 2009, 328, 671-679
10. Han, K. S.; Kim, Y. G.; Yoo, J. K.; Lee, J. W.; Lee, M. G. Pharmacokinetics of a new reversible proton pump inhibitor, YH1885, after intravenous and oral administrations to rats and dogs: hepatic first-pass effect in rats Biopharm. Drug Dispos. 1998, 19, 493-500 (Pubitemid 28499573)
11. Simon, W. A.; Herrmann, M.; Klein, T.; Shin, J. M.; Huber, R.; Senn-Bilfinger, J.; Postius, S. Soraprazan: setting new standards in inhibition of gastric acid secretion J. Pharmacol. Exp. Ther. 2007, 321, 866-874 (Pubitemid 46762698)
12. Ito, K.; Kinoshita, K.; Tomizawa, A.; Inaba, F.; Morikawa-Inomata, Y.; Makino, M.; Tabata, K.; Shibakawa, N. Pharmacological profile of novel acid pump antagonist 7-(4-fluorobenzyloxy)-2,3-dimethyl-1-{[(1 S,2 S)-2- methylcyclopropyl]methyl}-1 H -pyrrolo[2,3- d ]pyridazine (CS-526) J. Pharmacol. Exp. Ther. 2007, 323, 308-317 (Pubitemid 47443260)
13. Panchal, T.; Bailey, N.; Bamford, M.; Demont, E.; Elliott, R.; Farre-Gutierrez, I.; Garton, N.; Hayhow, T.; Hutley, G.; Naylor, A. Evaluation of basic, heterocyclic ring systems as templates for use as potassium competitive acid blockers (pCABs) Bioorg. Med. Chem. Lett. 2009, 19, 6813-6817
14. Yoon, Y. A.; Kim, D. H.; Lee, B. M.; Kim, T. K.; Cha, M. H.; Sim, J. Y.; Kim, J. G. Novel 1 H -pyrrolo[2,3- c ]pyridines as acid pump antagonists (APAs) Bioorg. Med. Chem. Lett. 2010, 20, 5237-5240
15. Palmer, A. M.; Chiesa, V.; Schmid, A.; Münch, G.; Grobbel, B.; Zimmermann, P. J.; Brehm, C.; Buhr, W.; Simon, W.-A.; Kromer, W.; Postius, S.; Volz, J.; Hess, D. Tetrahydrochromenoimidazoles as potassium-competitive acid blockers (P-CABs): structure-activity relationship of their antisecretory properties and their affinity toward the hERG channel J. Med. Chem. 2010, 53, 3645-3674
16. + ATPase Bioorg. Med. Chem. Lett. 2010, 20, 1049-1054
17. +-ATPase Bioorg. Med. Chem. 2008, 16, 536-541
18. Nishida, H.; Hasuoka, A.; Arikawa, Y.; Kurasawa, O.; Hirase, K.; Inatomi, N.; Hori, Y.; Sato, F.; Tarui, N.; Imanishi, A.; Kondo, M.; Takagi, T.; Kajino, M. Discovery, synthesis, and biological evaluation of novel pyrrole derivatives as highly selective potassium-competitive acid blockers. Bioorg. Med. Chem. [Online early access]. DOI: 10.1016/j.bmc.2012.04.014. Published Online: April 14, 2012.
19. Leeson, P. D.; Springthorpe, B. The influence of drug-like concepts on decision-making in medicinal chemistry Nat. Rev. Drug Discovery 2007, 6, 881-890 (Pubitemid 350042396)
20. Foley, L. H. An efficient synthesis of 2-chloro-3-carboethoxy- or 2-chloro-3-cyano- 4,5-disubstituted and 5-substituted pyrroles Tetrahedron Lett. 1994, 35, 5989-5992
21. Bray, B. L.; Muchowski, J. M. Synthesis of acylpyrroles via α-(dimethylamino)-α-pyrrolylacetonitriles J. Org. Chem. 1988, 53, 6115-6118
22. Bray, B. L.; Mathies, P. H.; Naef, R.; Solas, D. R.; Tidwell, T. T.; Artis, D. R.; Muchowski, J. M. N -(Triisopropylsilyl)pyrroles. A progenitor “par excellence of 3-substituted pyrroles J. Org. Chem. 1990, 55, 6317-6328
23. Hori, Y.; Imanishi, A.; Matsukawa, J.; Tsukimi, Y.; Nishida, H.; Arikawa, Y.; Hirase, K.; Kajino, M.; Inatomi, N. 1-[5-(2-Fluorophenyl)-1-(pyridin-3- ylsulfonyl)-1 H -pyrrol-3-yl]- N -methylmethanamine monofumarate (TAK-438), a novel and potent potassium-competitive acid blocker for the treatment of acid-related diseases J. Pharmacol. Exp. Ther. 2010, 335, 231-238
24. Henry, R. A.; Hollins, R. A.; Lowe-Ma, C.; Moore, D. W.; Nissan, R. A. Anomalous reaction of pentafluorophenacyl bromide with hexamethylenetetramine. Structure of the product J. Org. Chem. 1990, 55, 1796-1801
25. Ogata, M; Matsumoto, H.; Kida, S.; Shimizu, S.; Tawara, K.; Kawamura, Y. Synthesis and antifungal activity of a series of novel 1,2-disubstituted propenones J. Med. Chem. 1987, 30, 1497-1502 (Pubitemid 17114833)
26. Toyoshima, C.; Nomura, H. Structural changes in the calcium pump accompanying the dissociation of calcium Nature 2002, 418, 605-611
27. Bower, M. J.; Cohen, F. E.; Dunbrack, R. L., Jr. Prediction of protein side-chain rotamers from a backbone-dependent rotamer library: a new homology modeling tool J. Mol. Biol. 1997, 267, 1268-1282 (Pubitemid 27192637)
28. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking J. Mol. Biol. 1997, 267, 727-748 (Pubitemid 27170693)
29. Wallmark, B.; Sachs, G.; Maardh, S.; Fellenius, E. Inhibition of gastric proton-potassium ion ATPase by the substituted benzimidazole, picoprazole Biochim. Biophys. Acta 1983, 728, 31-38 (Pubitemid 13116276)