100501-57-3Relevant articles and documents
BICYCLIC BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION
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Page/Page column 57, (2018/09/08)
The present invention relates to certain bicyclic bis-heteroaryl compounds of Formula (I), pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and
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.
, 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.
PRMT5 INHIBITORS AND USES THEREOF
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, (2016/04/20)
Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof:wherein Y1 is of formula (?) or formula (y):Ring Y is a 5- to 6-membered heteroaryl ring; and V4, V5, Rx, x, y, and n are as defined herein. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
N-Alkylhydrazones of aliphatic ketones in the synthesis of 1,3,4-trisubstituted non-symmetric pyrazoles
Ivonin, Sergey P.,Kurpil', Bohdan B.,Rusanov, Eduard B.,Grygorenko, Oleksandr O.,Volochnyuk, Dmitry M.
, p. 2187 - 2189 (2014/04/17)
Reactions of N-alkylhydrazones of aliphatic ketones with the Vilsmeier-Haack reagent (DMF-POCl3) were evaluated as a promising approach toward the synthesis of trisubstituted non-symmetric pyrazoles. It was found that either 1,3,4-trialkylpyrazoles or 1,3-dialkylpyrazole-4-carbaldehydes could be obtained in these transformations in high yields (72-83%), in a regioselective manner.
TETRAHYDROISOQUINOLINES CONTAINING SUBSTITUTED AZOLES AS FACTOR XIA INHIBITORS
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Page/Page column 135, (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 00417, (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.
