229342-58-9Relevant articles and documents
Synthesis and structure-activity relationship of potent, selective and orally active anthranilamide-based factor Xa inhibitors: Application of weakly basic sulfoximine group as novel S4 binding element
Pandya, Vrajesh,Jain, Mukul,Chakrabarti, Ganes,Soni, Hitesh,Parmar, Bhavesh,Chaugule, Balaji,Patel, Jigar,Jarag, Tushar,Joshi, Jignesh,Joshi, Nirav,Rath, Akshyaya,Unadkat, Vishal,Sharma, Bhavesh,Ajani, Haresh,Kumar, Jeevan,Sairam, Kalapatapu V.V.M.,Patel, Harilal,Patel, Pankaj
, p. 136 - 152 (2013/02/21)
A novel series of potent and efficacious factor Xa inhibitors which possesses sulfoximine moiety as novel S4 binding element in anthranilamide chemotype has been identified. Lead optimization at this novel P4 group led to many potent factor Xa inhibitors with excellent anticoagulant activity in human plasma. Selected compounds were dosed orally in rats and checked for their ex vivo prothrombin time prolonging activity, which resulted in identification of compound 5-chloro-N-(5-chloropyridin-2-yl)-2-(4-(N-(2-(diethylamino)acetyl)-S- methylsulfonimidoyl)benzamido)benzamide (18f). The detailed pharmacokinetic evaluation and subsequent metabolism study of 18f suggested the presence of an active metabolite. The compound 18f and its active metabolite 18b demonstrated excellent in vivo efficacy in both arterial and venous thrombosis model in rats and were found to be highly selective against related serine proteases. Based on this promising profile, compound 18f was selected for further evaluation.
Thiophene-anthranilamides as highly potent and orally available factor Xa inhibitors
Ye, Bin,Arnaiz, Damian O.,Chou, Yuo-Ling,Griedel, Brian D.,Karanjawala, Rushad,Lee, Wheeseong,Morrissey, Michael M.,Sacchi, Kama L.,Sakata, Steven T.,Shaw, Kenneth J.,Wu, Shung C.,Zhao, Zuchun,Adler, Marc,Cheeseman, Sarah,Dole, William P.,Ewing, Janice,Fitch, Richard,Lentz, Dao,Liang, Amy,Light, David,Morser, John,Post, Joseph,Rumennik, Galina,Subramanyam, Babu,Sullivan, Mark E.,Vergona, Ron,Walters, Janette,Wang, Yi-Xin,White, Kathy A.,Whitlow, Marc,Kochanny, Monica J.
, p. 2967 - 2980 (2008/02/07)
There remains a high unmet medical need for a safe oral therapy for thrombotic disorders. The serine protease factor Xa (fXa), with its central role in the coagulation cascade, is among the more promising targets for anticoagulant therapy and has been the
AROMATIC AMIDES
-
, (2008/06/13)
This application relates to a compound of formula I (or a pharmaceutically acceptable salt thereof) as defined herein, pharmaceutical compositions thereof, and its use as an inhibitor of factor Xa, as well as a process for its preparation and intermediates therefor.