The Proton-Sensing GPR4 Receptor Regulates Paracellular Gap Formation and Permeability of Vascular Endothelial Cells

be activated by protons in the inflamed tissue microenvironment. Herein, we report that acidosis-induced GPR4 activation increases paracellular gap formation and permeability of vascular endothelialcells through the Ga12/13/Rho GTPase signaling pathway. Evaluation of GPR4 in the inflammatoryresponse using the acute hindlimb ischemia-reperfusion mouse model revealed that GPR4 mediatestissue edema, inflammatory exudate formation, endothelial adhesion molecule expression, and leuko-cyte infiltration in the inflamed tissue. Genetic knockout and pharmacologic inhibition of GPR4alleviate tissue inflammation. These results suggest GPR4 is a pro-inflammatory receptor and couldbe targeted for therapeutic intervention

Synthesis of 3-chloro-4-fluoro-7,8-dihydro-6H-isoquinolin-5-one and its derivatives.

Synthesis of novel 3-Chloro-4-fluoro-7,8-dihydro-6H-isoquinolin-5-one and its derivatives using sequentional ortho-formylation/ortho-allylation reaction of 2-chloro-3-fluoropyridine and ring-closing metathesis is described

Palladium-Catalyzed Cyanomethylation of Aryl Halides through Domino Suzuki Coupling-Isoxazole Fragmentation.

A one-pot protocol for the cyanomethylation of aryl halides through a palladium-catalyzed reaction with isoxazole-4-boronic acid pinacol ester was developed. Mechanistically, the reaction proceeds through (1) Suzuki coupling, (2) base-induced fragmentation, and (3) deformylation as shown by characterization of all postulated intermediates. Under optimized conditions (PdCl(2)dppf, KF, DMSO/H(2)O, 130 °C) a broad spectrum of aryl bromides could be converted into arylacetonitriles with up to 88% yield