1152597-56-2Relevant academic research and scientific papers
Potent, Orally Bioavailable, and Efficacious Macrocyclic Inhibitors of Factor XIa. Discovery of Pyridine-Based Macrocycles Possessing Phenylazole Carboxamide P1 Groups
Corte, James R.,Pinto, Donald J. P.,Fang, Tianan,Osuna, Honey,Yang, Wu,Wang, Yufeng,Lai, Amy,Clark, Charles G.,Sun, Jung-Hui,Rampulla, Richard,Mathur, Arvind,Kaspady, Mahammed,Neithnadka, Premsai Rai,Li, Yi-Xin Cindy,Rossi, Karen A.,Myers, Joseph E.,Sheriff, Steven,Lou, Zhen,Harper, Timothy W.,Huang, Christine,Zheng, Joanna J.,Bozarth, Jeffrey M.,Wu, Yiming,Wong, Pancras C.,Crain, Earl J.,Seiffert, Dietmar A.,Luettgen, Joseph M.,Lam, Patrick Y. S.,Wexler, Ruth R.,Ewing, William R.
, p. 784 - 803 (2020/02/04)
Factor XIa (FXIa) inhibitors are promising novel anticoagulants, which show excellent efficacy in preclinical thrombosis models with minimal effects on hemostasis. The discovery of potent and selective FXIa inhibitors which are also orally bioavailable has been a challenge. Here, we describe optimization of the imidazole-based macrocyclic series and our initial progress toward meeting this challenge. A two-pronged strategy, which focused on replacement of the imidazole scaffold and the design of new P1 groups, led to the discovery of potent, orally bioavailable pyridine-based macrocyclic FXIa inhibitors. Moreover, pyridine-based macrocycle 19, possessing the phenylimidazole carboxamide P1, exhibited excellent selectivity against relevant blood coagulation enzymes and displayed antithrombotic efficacy in a rabbit thrombosis model.
Tetrahydroisoquinoline amide compounds containing quaternary ammonium ion and pharmaceutical use thereof
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Paragraph 0311-0315, (2019/07/11)
The invention relates to tetrahydroisoquinoline amide compounds containing quaternary ammonium ion, a preparation method of the compounds, and a use of the compounds in the treatment or prevention ofthromboembolic diseases.
Tetrahydroisoquinoline compound and its preparation method, pharmaceutical composition and use
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Paragraph 0105, (2018/03/24)
The invention relates to a tetrahydroisoquinoline compound and its preparation method, pharmaceutical composition and use. The tetrahydroisoquinoline compound is shown by the general formula (1). In the general formula (1), the symbols have the same definitions as in the specification.
TETRAHYDROISOQUINOLINES CONTAINING SUBSTITUTED AZOLES AS FACTOR XIA INHIBITORS
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Page/Page column 116-117, (2014/10/15)
The present invention provides compounds of Formula (I), or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.
NOVEL MACROCYCLES AS FACTOR XIA INHIBITORS
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Paragraph 00318, (2013/03/26)
The present invention provides compounds of Formula (Ia): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.
