Document Type
Article
Language
eng
Publication Date
2019
Publisher
American Chemical Society
Source Publication
ACS Medicinal Chemistry Letters
Source ISSN
1948-5875
Abstract
A novel class of bivalent ligands targeting putative protease-activated receptor (PAR) heteromers has been prepared based upon reported antagonists for the subtypes PAR1 and PAR2. Modified versions of the PAR1 antagonist RWJ-58259 containing alkyne adapters were connected via cycloaddition reactions to azide-capped polyethylene glycol (PEG) spacers attached to imidazopyridazine-based PAR2 antagonists. Initial studies of the PAR1–PAR2 antagonists indicated that they inhibited G alpha q-mediated calcium mobilization in endothelial and cancer cells driven by both PAR1 and PAR2 agonists. Compounds of this novel class hold promise for the prevention of restenosis, cancer cell metastasis, and other proliferative disorders.
Recommended Citation
Majewski, Mark W.; Gandhi, Disha M.; Rosas, Ricardo Jr.; Kodall, Revathi; Arnold, Leggy A.; and Dockendorff, Chris, "Design and Evaluation of Heterobivalent PAR1–PAR2 Ligands as Antagonists of Calcium Mobilization" (2019). Chemistry Faculty Research and Publications. 966.
https://epublications.marquette.edu/chem_fac/966
Comments
Accepted version. ACS Medicinal Chemistry Letters, Vol. 10, No. 1 (2019): 121-126. DOI. © 2019 American Chemical Society. Used with permission.