2. Academic Validation
  3. Discovery of a novel pyrrole derivative 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine fumarate (TAK-438) as a potassium-competitive acid blocker (P-CAB)

Discovery of a novel pyrrole derivative 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine fumarate (TAK-438) as a potassium-competitive acid blocker (P-CAB)

  • J Med Chem. 2012 May 10;55(9):4446-56. doi: 10.1021/jm300318t.
Yasuyoshi Arikawa 1,  Haruyuki Nishida,  Osamu Kurasawa,  Atsushi Hasuoka,  Keizo Hirase,  Nobuhiro Inatomi,  Yasunobu Hori,  Jun Matsukawa,  Akio Imanishi,  Mitsuyo Kondo,  Naoki Tarui,  Teruki Hamada,  Terufumi Takagi,  Toshiyuki Takeuchi,  Masahiro Kajino
Affiliations

Affiliation

  • 1 Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1, Muraokahigashi-2-chome, Fujisawa, Kanagawa 251-8555, Japan. yasuyoshi.arikawa@takeda.com
PMID: 22512618 DOI: 10.1021/jm300318t
Abstract

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.

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