1160269-99-7

Upstream product

• 128796-39-4 4-trifluoromethylphenylboronic acid 
• 178876-99-8 7-Bromo-4-hydroxynaphthalene-2-carboxylic acid ethyl ester 

Downstream Products

• 1160270-01-8 ethyl 7-(4-(trifluoromethyl)phenyl)-4-(((trifluoromethyl)sulfonyl)oxy)-2-naphthoate 
• 1160271-34-0 tert-butyl 4-(4-(3-(ethoxycarbonyl)-6-(4-(trifluoromethyl)phenyl)naphthalen-1-yl)phenyl)piperidine-1-carboxylate 
• 1160271-35-1 4-(4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)-7-(4-(trifluoromethyl)phenyl)-2-naphthoic acid 
• 1160271-30-6 4-[4-(4-piperidinyl)phenyl]-7-[4-(trifluoromethyl)phenyl]-2-naphthalenecarboxylic acid 
• 1160270-14-3 ethyl 7-(4-(trifluoromethyl)phenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthoate 
• 1160269-96-4 4-{4-[(1R)-2,2-difluoro-1-hydroxyethyl]phenyl}-7-[4-(trifluoromethyl)phenyl]-2-naphthoic acid 
• 1160270-20-1 4-{4-[(1S)-2,2,2-trifluoro-1-hydroxyethyl]phenyl}-7-[4-(trifluoromethyl)phenyl]-2-naphthoic acid 
• 1160270-18-7 4-{4-[(1R)-2,2,2-trifluoro-1-hydroxyethyl]phenyl}-7-[4-(trifluoromethyl)phenyl]-2-naphthoic acid 
• 1160270-12-1 4-[4-(2,2,2-trifluoro-1-hydroxyethyl)phenyl]-7-[4-(trifluoromethyl)phenyl]-2-naphthoic acid 
• 1310579-79-3 C₂₅H₁₇F₃O₄S 
• 1310579-78-2 C₂₃H₁₅F₃O₄S₂ 

Relevant academic research and scientific papers

A selective high-Affinity antagonist of the P2Y14 receptor inhibits udp-glucose-stimulated chemotaxis of human neutrophilss

The nucleotide-sugar-Activated P2Y14 receptor (P2Y 14-R) is highly expressed in hematopoietic cells. Although the physiologic functions of this receptor remain undefined, it has been strongly implicated recently in immune and inflammatory responses. Lack of availability of receptor-selective high-Affinity antagonists has impeded progress in studies of this and most of the eight nucleotide-Activated P2Y receptors. A series of molecules recently were identified by Gauthier et al. (Gauthier et al., 2011) that exhibited antagonist activity at the P2Y14-R. We synthesized one of these molecules, a 4,7-disubstituted 2- naphthoic acid derivative (PPTN), and studied its pharmacological properties in detail. The concentration-effect curve of UDP-glucose for promoting inhibition of adenylyl cyclase in C6 glioma cells stably expressing the P2Y14-R was shifted to the right in a concentration-dependent manner by PPTN. Schild analyses revealed that PPTN-mediated inhibition followed competitive kinetics, with a KB of 434 pM observed. In contrast, 1 mM PPTN exhibited no agonist or antagonist effect at the P2Y1, P2Y2, P2Y4, P2Y6, P2Y 11, P2Y12, or P2Y13 receptors. UDP-glucose-promoted chemotaxis of differentiated HL-60 human promyelocytic leukemia cells was blocked by PPTN with a concentration dependence consistent with the KB determined with recombinant P2Y14-R. In contrast, the chemotactic response evoked by the chemoattractant peptide fMetLeuPhe was unaffected by PPTN. UDP-glucose-promoted chemotaxis of freshly isolated human neutrophils also was blocked by PPTN. In summary, this work establishes PPTN as a highly selective high-Affinity antagonist of the P2Y14-R that is useful for interrogating the action of this receptor in physiologic systems.

The identification of 4,7-disubstituted naphthoic acid derivatives as UDP-competitive antagonists of P2Y14

A weak, UDP-competitive antagonist of the pyrimidinergic receptor P2RY 14 with a naphthoic acid core was identified through high-throughput screening. Optimization provided compounds with improved potency but poor pharmacokinetics. Acylglucuronidation was determined to be the major route of metabolism. Increasing the electron-withdrawing nature of the substituents markedly reduced glucuronidation and improved the pharmacokinetic profile. Additional optimization led to the identification of compound 38 which is an 8 nM UDP-competitive antagonist of P2Y14 with a good pharmacokinetic profile.

SUBSTITUTED 2-NAPHTHOIC ACIDS AS ANTAGONISTS OF GPR105 ACTIVITY

Substituted 2-naphthoic acids of structural formula I are effective as antagonists of the biological activity of GPR105 protein. They are useful for the treatment, control or prevention of disorders responsive to antagonism of this receptor, such as diabe