133747-67-8Relevant articles and documents
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.
supporting information, 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.
TETRAHYDROISOQUINOLINES CONTAINING SUBSTITUTED AZOLES AS FACTOR XIA INHIBITORS
-
Page/Page column 123-124, (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
-
Paragraph 00338, (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.
Synthesis of 4-methyloxybenzoic acids and related compounds, and their inhibitory capacities toward fatty-acid and sterol biosynthesis
Watanabe, S.,Ogawa, K.,Ohno, T.,Yano, S.,Yamada, H.,Shirasaka, T.
, p. 675 - 686 (2007/10/02)
The synthesis of a series of 4-methyloxybenzoic acids and related compounds, and their evaluation for inhibitory capacity toward fatty-acid and sterol biosyntheses using rats' liver slices in vitro and rabbits
Phenylcarboxylic acid derivatives having hetero ring
-
, (2008/06/13)
Phenylcarboxylic acid derivatives having a hetero ring in the substituent of the formula: STR1 wherein R1 is halogen, alkyl, cycloalkyl, hydroxy, alkoxy, phenoxy which has a substituent selected from halogen and alkyl, carboxyl, alkylsulfonyloxy, phenylsulfonyloxy optionally substituted by halogen, alkylsulfonyloxyalkoxy, amino, alkanoylamino, benzoylamino, alkenyloxy, phenylalkoxyalkoxy, hydroxyalkoxy, phenylalkoxy having optionally 1 to 3 substituents selected from halogen, alkyl and alkoxy, halogenoalkyl, cycloalkyloxy optionally substituted by hydroxy, alkoxy substituted by cycloalkyl having optionally hydroxy substituent, imidazolylalkyl or imidazolylalkoxy; k is 0 or 1 to 3; or (R1)k is alkylenedioxy; A is alkylene or alkylenoxy; l is 0 or 1; B is methylene or carbonyl; m is 0 or 1; D is alkylene; E is alkylene or alkenylene; n is 0 or 1; and R2 is hydrogen or alkyl, or a salt thereof, which have fatty acid synthesis-inhibitory activity, cholesterol synthesis-inhibitory activity and are useful as antilipidemic agent, prophylactic and treating agent of arteriosclerosis, prophylactic and treating agent of obesity, antidiabetics.