477721-50-9Relevant academic research and scientific papers
Discovery of a Parenteral Small Molecule Coagulation Factor XIa Inhibitor Clinical Candidate (BMS-962212)
Pinto, Donald J. P.,Orwat, Michael J.,Smith, Leon M.,Quan, Mimi L.,Lam, Patrick Y. S.,Rossi, Karen A.,Apedo, Atsu,Bozarth, Jeffrey M.,Wu, Yiming,Zheng, Joanna J.,Xin, Baomin,Toussaint, Nathalie,Stetsko, Paul,Gudmundsson, Olafur,Maxwell, Brad,Crain, Earl J.,Wong, Pancras C.,Lou, Zhen,Harper, Timothy W.,Chacko, Silvi A.,Myers, Joseph E.,Sheriff, Steven,Zhang, Huiping,Hou, Xiaoping,Mathur, Arvind,Seiffert, Dietmar A.,Wexler, Ruth R.,Luettgen, Joseph M.,Ewing, William R.
supporting information, p. 9703 - 9723 (2017/12/26)
Factor XIa (FXIa) is a blood coagulation enzyme that is involved in the amplification of thrombin generation. Mounting evidence suggests that direct inhibition of FXIa can block pathologic thrombus formation while preserving normal hemostasis. Preclinical studies using a variety of approaches to reduce FXIa activity, including direct inhibitors of FXIa, have demonstrated good antithrombotic efficacy without increasing bleeding. On the basis of this potential, we targeted our efforts at identifying potent inhibitors of FXIa with a focus on discovering an acute antithrombotic agent for use in a hospital setting. Herein we describe the discovery of a potent FXIa clinical candidate, 55 (FXIa Ki = 0.7 nM), with excellent preclinical efficacy in thrombosis models and aqueous solubility suitable for intravenous administration. BMS-962212 is a reversible, direct, and highly selective small molecule inhibitor of FXIa.
GUANIDINE SUBSTITUTED TETRAHYDROISOQUINOLINE COMPOUNDS AS FACTOR XIA INHIBITORS
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Paragraph 00240, (2014/05/07)
The present invention provides compounds of Formula (I): or stereoisomers, pharmaceutically acceptable salts thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of factor XIa and/or plasma kallikrein which may be us
GUANIDINE AND AMINE SUBSTITUTED TETRAHYDROISOQUINOLINE COMPOUNDS AS FACTOR XIA INHIBITORS
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Paragraph 00230, (2014/05/07)
The present invention provides compounds of Formula (I): (Formula (I)) or stereoisomers, pharmaceutically acceptable salts thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of factor XIa and/or plasma kallikrein which may be used as medicaments.
TETRAHYDROISOQUINOLINES CONTAINING SUBSTITUTED AZOLES AS FACTOR XIA INHIBITORS
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Page/Page column 106-107, (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.
SUBSTITUTED TETRAHYDROISOQUINOLINE COMPOUNDS AS FACTOR XIA INHIBITORS
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Paragraph 00241, (2013/04/25)
The present invention provides compounds of Formula (I): or stereoisomers, pharmaceutically acceptable salts thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of factor XIa and/or plasma kallikrein which may be used as medicaments.
SUBSTITUTED TETRAHYDROISOQUINOLINE COMPOUNDS AS FACTOR XIA INHIBITORS
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Paragraph 00227, (2013/04/25)
The present invention provides compounds of Formula (I): or stereoisomers, pharmaceutically acceptable salts thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of factor XIa and/or plasma kallikrein which may be used as medicaments.
SUBSTITUTED TETRAHYDROISOQUINOLINE COMPOUNDS AS FACTOR XIA INHIBITORS
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Paragraph 00218, (2013/04/25)
The present invention provides compounds of Formula (I) or stereoisomers, pharmaceutically acceptable salts thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of factor XIa and/or plasma kallikrein which may be used as medicaments.
4-HYDROXPIPERIDINE DERIVATIVE WITH ANALGETIC ACTIVITY
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Page 29, (2010/11/30)
A compound represented by the following Formula (I): (wherein A represents oxygen atom or -NR3- (R3 represents hydrogen atom or lower alkyl group); R1 represents nitro group, lower alkoxycarbonyl group, carbamoyl group unsubstituted or mono- or di-substituted by lower alkyl group, unprotected or protected hydroxyl group, unprotected or protected carboxyl group, lower alkyl group substituted by unprotected or protected hydroxyl group, or tetrazolyl group; and R2 represents hydrogen atom, cyano group or lower alkylsulfonyl group, provided that when A is - NR3-, it is excluded that R1 represents unprotected or protected hydroxyl group or lower alkyl group substituted by unprotected or protected hydroxyl group) or its salt, and method for producing the compound, and a pharmaceutical composition containing the compound as active ingredient.
