103029-79-4Relevant articles and documents
SUBSTITUTED BICYCLIC COMPOUNDS AS FARNESOID X RECEPTOR MODULATORS
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Page/Page column 106, (2020/08/28)
Disclosed are compounds of Formula (I): or a stereoisomer, a tautomer, or a salt or solvate thereof, wherein Q is C2-6 alkenyl or C2-6 alkynyl, each substituted with zero to 2 R1; and the other variables are as defined herein. These compounds modulate the activity of farnesoid X receptor (FXR), for example, as agonists. Also disclosed are pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
Discovery of a nonpeptidic small molecule antagonist of the human platelet thrombin receptor (PAR-1)
Nantermet, Philippe G,Barrow, James C.,Lundell, George F.,Pellicore, Janetta M.,Rittle, Kenneth E.,Young, MaryBeth,Freidinger, Roger M.,Connolly, Thomas M.,Condra, Cindra,Karczewski, Jerzy,Bednar, Rodney A.,Gaul, Stanley L.,Gould, Robert J.,Prendergast, Kris,Selnick, Harold G.
, p. 319 - 323 (2007/10/03)
The synthesis and biological evaluation of a series of nonpeptidic small molecule antagonists of the human platelet thrombin receptor (PAR-1) are described. Optimization of the 5-amino-3-arylisoxazole lead resulted in an approximate 100-fold increase in potency. The most potent of these compounds (54) inhibits platelet activation with IC50s of 90 nM against the thrombin receptor agonist peptide (TRAP) and 510 nM against thrombin as the agonist. Further, antagonist 54 fully blocks platelet aggregation stimulated by 1 nM thrombin for 10 min.
