872017-92-0Relevant academic research and scientific papers
Phenylimidazoles as potent and selective inhibitors of coagulation factor XIa with in vivo antithrombotic activity
Hangeland, Jon J.,Friends, Todd J.,Rossi, Karen A.,Smallheer, Joanne M.,Wang, Cailan,Sun, Zhong,Corte, James R.,Fang, Tianan,Wong, Pancras C.,Rendina, Alan R.,Barbera, Frank A.,Bozarth, Jeffrey M.,Luettgen, Joseph M.,Watson, Carol A.,Zhang, Ge,Wei, Anzhi,Ramamurthy, Vidhyashankar,Morin, Paul E.,Bisacchi, Gregory S.,Subramaniam, Srinath,Arunachalam, Piramanayagam,Mathur, Arvind,Seiffert, Dietmar A.,Wexler, Ruth R.,Quan, Mimi L.
, p. 9915 - 9932 (2015/02/05)
Novel inhibitors of FXIa containing an (S)-2-phenyl-1-(4-phenyl-1H-imidazol-2-yl)ethanamine core have been optimized to provide compound 16b, a potent, reversible inhibitor of FXIa (Ki = 0.3 nM) having in vivo antithrombotic efficacy in the rabbit AV-shunt thrombosis model (ID50 = 0.6 mg/kg + 1 mg kg-1 h-1). Initial analog selection was informed by molecular modeling using compounds 11a and 11h overlaid onto the X-ray crystal structure of tetrahydroquinoline 3 complexed to FXIa. Further optimization was achieved by specific modifications derived from careful analysis of the X-ray crystal structure of the FXIa/11h complex. Compound 16b was well tolerated and enabled extensive pharmacologic evaluation of the FXIa mechanism up to the ID90 for thrombus inhibition.
ARYLPROPIONAMIDE, ARYLACRYLAMIDE, ARYLPROPYNAMIDE, OR ARYLMETHYLUREA ANALOGS AS FACTOR XIA INHIBITORS
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Page/Page column 107; 121-122, (2008/06/13)
The present invention provides compounds of Formula (I): Formula (I) or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L1, M and R11 are as defined herein. The compounds of Formula (I) are selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.
FIVE-MEMBERED HETEROCYCLES USEFUL AS SERINE PROTEASE INHIBITORS
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Page/Page column 154, (2008/06/13)
The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): (I) [INSERTCHEMICAL STRUCTURE HERE] (V)[INSERT CHEMICAL STRUCTURE HERE] or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R3, R4, R6, R11, X1, X2, and X3 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.
