Discovery of a tetrahydropyrimidin-2 (1 H)-one derivative (TAK-442) as a potent, selective, and orally active factor Xa inhibitor

T Fujimoto, Y Imaeda, N Konishi, K Hiroe…

Index: Fujimoto, Takuya; Imaeda, Yasuhiro; Konishi, Noriko; Hiroe, Katsuhiko; Kawamura, Masaki; Textor, Garret P.; Aertgeerts, Kathleen; Kubo, Keiji Journal of Medicinal Chemistry, 2010 , vol. 53, # 9 p. 3517 - 3531

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Citation Number: 27

Abstract

Coagulation enzyme factor Xa (FXa) is a particularly promising target for the development of new anticoagulant agents. We previously reported the imidazo [1, 5-c] imidazol-3-one derivative 1 as a potent and orally active FXa inhibitor. However, it was found that 1 predominantly undergoes hydrolysis upon incubation with human liver microsomes, and the human specific metabolic pathway made it difficult to predict the human pharmacokinetics. ...