1315308-11-2

Upstream product

• 273727-44-9 4-(4-bromo-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 1315308-10-1 C₃₇H₃₀F₃NO₄ 
• 1160271-34-0 tert-butyl 4-(4-(3-(ethoxycarbonyl)-6-(4-(trifluoromethyl)phenyl)naphthalen-1-yl)phenyl)piperidine-1-carboxylate 
• 1160271-32-8 ethyl 4-(4-(piperidin-4-yl)phenyl)-7-(4-(trifluoromethyl)phenyl)-2-naphthoate 
• 1160270-14-3 ethyl 7-(4-(trifluoromethyl)phenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthoate 

Relevant academic research and scientific papers

Applying the pro-drug approach to afford highly bioavailable antagonists of P2Y14

Our series of competitive antagonists against the G-protein coupled receptor P2Y14 were found to be highly shifted in the presence of serum (>99% protein bound). A binding assay using 2% human serum albumin (HSA) was developed to guide further SAR studies and led to the identification of the zwitterion 2, which is substantially less shifted (18-fold) than our previous lead compound 1 (323-fold). However, as the bioavailability of 2 was low, a library of ester pro-drugs was prepared (7a-7j) and assessed in vitro. The most interesting candidates were then profiled in vivo and led to the identification of the pro-drug 7j, which possesses a substantially improved pharmacokinetic profile.