524743-46-2Relevant academic research and scientific papers
Orally active factor Xa inhibitors: Investigation of a novel series of 3-amidinophenylsulfonamide derivatives using an amidoxime prodrug strategy
Uchida, Masahiko,Okazaki, Kosuke,Mukaiyama, Harunobu,Isawa, Hidetoshi,Kobayashi, Hiroaki,Shiohara, Hiroaki,Muranaka, Hideyuki,Kai, Yuichiro,Kikuchi, Norihiko,Takeuchi, Hideki,Yokoyama, Kenji,Tsuji, Eiichi,Ozawa, Tomonaga,Hoyano, Yuji,Koizumi, Takashi,Misawa, Keiko,Hara, Kiyoto,Nakano, Shigeru,Murakami, Yasuoki,Okuno, Hiroaki
scheme or table, p. 4682 - 4687 (2009/04/08)
A series of novel and potent 3-amidinophenylsulfonamide derivatives of factor Xa inhibitors were designed and synthesized using an amidoxime prodrug strategy. We focused on systemic clearance of parent compounds in rats, and performed in vivo pharmacokinetic screening. Incorporation of a carboxymethoxy group markedly improved systemic clearance (compound 43), and the related amidoxime 44 showed sufficient prodrug conversion. Compound 45, the double prodrug of 43, exhibited practicable bioavailability after oral administration in rats. Among the various compounds under investigation, KFA-1982 was selected for clinical development.
5-AMIDINO-2-HYDROXYBENZENESULFONAMIDE DERIVATIVES, MEDICINAL COMPOSITIONS CONTAINING THE SAME, MEDICINAL USE THEREOF AND INTERMEDIATES IN THE PRODUCTION THEREOF
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Page 27, (2010/02/07)
The present invention relates to a 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the general formula: wherein R1 is an optionally substituted lower alkyl group, an optionally substituted lower alkoxy group, an optionally substituted lower alkenyl group, a cycloalkyl group or a lower acyl group etc.; Q is a hydrogen atom or an optionally substituted lower alkyl group; and Z is a hydrogen atom or a hydroxy group etc., or a pharmaceutically acceptable salt thereof, which exert a potent and selective activated blood coagulation factor X inhibitory activity and is useful as an agent for the prevention or treatment of a disease occurred associating an activated blood coagulation factor X, a pharmaceutical composition comprising the same and an intermediate thereof. These compounds are useful as preventives or remedies for various diseases such as brain infarction, cerebral thrombosis, cerebral embolism, TIA, cerebral vascular jerk, Alzheimer's diseases, myocardial infarction, heart attack, heart failure, thrombosis, pulmonary infarction and pulmonary embolism.
