803736-83-6

Upstream product

• 1810-72-6 2,6-dichloroquinoline 
• 124-38-9 carbon dioxide 
• 1061222-04-5 2,6-dichloro-5-iodoquinoline 

Relevant academic research and scientific papers

Synthesis and SAR development of quinoline analogs as novel P2X7 receptor antagonists

The P2X7 receptor (P2X7R) plays an important role in diverse conditions associated with tissue damage and inflammation, suggesting that the human P2X7R (hP2X7R) is an attractive therapeutic target. In the present study, the synthesis and structure-activity relationship (SAR) of a novel series of quinoline derivatives as P2X7R antagonists are described herein. These compounds exhibited mechanistic activity (YO PRO) in an engineered HEK293 expressing hP2X7R as well as a functional response (IL-1β) in human THP-1 (hTHP-1) cellular assays. Compound 19 was identified as the most promising compound in this series with excellent cellular potency, low liver microsomal clearance, good permeability and low efflux ratio. In addition, this compound also displayed good pharmacokinetic properties and acceptable brain permeability (Kp,uu of 0.37).

The discovery and preclinical characterization of 6-chloro-N-(2-(4,4-difluoropiperidin-1-yl)-2-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)quinoline-5-carboxamide based P2X7 antagonists

The synthesis, SAR and preclinical characterization of a series of 6-chloro-N-(2-(4,4-difluoropiperidin-1-yl)-2-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)quinoline-5-carboxamide based P2X7 antagonists is described herein. The lead compounds are potent inhibitors in Ca2+flux and whole blood IL-1β P2X7 release assays at both human and mouse isoforms. Compound 1e showed a robust reduction of IL-1β release in a mouse ex vivo model with a 50?mg/kg oral dose. Evaluation of compound 1e in the mouse SNI tactile allodynia, carrageenan-induced paw edema or CIA models resulted in no analgesic or anti-inflammatory effects.

NOVEL QUINOLINE DERIVATIVES AND THEIR USE IN NEURODEGENERATIVE DISEASES

The present invention relates to quinoline compounds, and pharmaceutically acceptable compositions thereof, useful as antagonists of P2X7, and for the treatment of P2X7-related disorders.

QUINOLINE OR ISOQUINOLINE SUBSTITUTED P2X7 ANTAGONISTS

The present invention is related to novel compounds of formula (I) having P2X7 antagonistic properties, pharmaceutical compositions comprising these compounds, chemical processes for preparing these compounds and their use in the treatment or prophylaxis of diseases associated with P2X7 receptor activity in animals, in particular humans. (I)

Novel Compounds 679

The invention provides compounds of formula (I), processes for their preparation, pharmaceutical compositions containing them, a process for preparing the pharmaceutical compositions, and their use in therapy, wherein R1, R2, R3

NOVEL COMPOUNDS

The invention provides compounds of formula (I), or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof, in which A, n, p, q, R1, R2, R3 and R4 are as defined in the specification; a proc

QUINOLINE DERIVATES AND THEIR USE IN THERAPY

The invention provides compounds of formula (I) wherein n, p, q, X, R1, R2, R3, R4, R5 and R6 are as defined in the specification; processes for their preparation, pharmaceutical compositio

NEW P2X7 RECEPTOR ANTAGONISTS AND THEIR USE

The invention provides compounds of formula (IA), processes for their preparation, pharmaceutical compositions containing them, and their use in therapy. [Chemical formula should be inserted here. Please see paper copy] (IA)