58787-26-1

Upstream product

• 64-17-5 ethanol 
• 56162-63-1 6-phenyl-2-hydroxypyridine-3-carboxylic acid 

Downstream Products

• 148638-69-1 [2-Oxo-2-(2-oxo-6-phenyl-1,2-dihydro-pyridin-3-yl)-ethyl]-phosphonic acid diethyl ester 
• 148638-68-0 3-(2-Methanesulfonyl-acetyl)-6-phenyl-1H-pyridin-2-one 
• 31676-61-6 2-chloro-6-phenylnicotinic acid ethyl ester 
• 148638-73-7 6-phenyl-2-mercaptonicotinic acid 
• 148638-71-5 (2-Methyl-4-oxo-7-phenyl-4H-pyrano[2,3-b]pyridin-3-yl)-phosphonic acid diethyl ester 

Relevant academic research and scientific papers

Modification on the 1,2-dihydro-2-oxo-pyridine-3-carboxamide core to obtain multi-target modulators of endocannabinoid system

Several preclinical evidence indicate that the modulation of the endocannabinoid system (ECS) represents a promising therapeutic approach for different diseases. However, only few modulators of this system have reached so far an advanced stage of clinical development, mainly due to limited efficacy and CB1 receptor-dependent side effects. Those limitations might be overcome by multi-target compounds that exert pro-cannabinoid activities through the modulation of two or more targets in the ECS. This approach can offer a safer and more effective pharmacological strategy as compared to the modulation of a single target. In this work, we report the synthesis and biological characterization of new 6-aryl-1,2-dihydro-2-oxo-pyridine-3-carboxamide derivatives. Our results identified several compounds exhibiting interesting multi-target profiles within the ECS. In particular, compound B1 showed moderate-to-high affinity for cannabinoid receptors (Ki CB1R = 304 nM, partial agonist, Ki CB2R = 3.1 nM, inverse agonist) and a potent inhibition of AEA uptake (IC50 = 62 nM) with moderate inhibition of FAAH (IC50 = 2.9 μM). The corresponding 2-alkoxypyridine analogue B14 exhibited significant inhibitor activity on both FAAH (IC50 = 69 nM) and AEA uptake (IC50 = 76 nM) without significantly binding to both cannabinoid receptor subtypes. Molecular docking analysis was carried out on the three-dimensional structures of CB1R and CB2R and of FAAH to rationalize the structure-activity relationships of this series of compounds.

GENERAL ROUTES TO 4-OXO-4H-PYRANOPYRIDINE-3-CARBOXYLATES AND RELATED COMPOUNDS: SYNTHESIS OF THE OXYGEN AND SULFUR ISOSTERES OF NALIDIXIC ACID

Imidazolides of 2-hydroxy- and 2-mercaptonicotinic acids with LiCH2CO2Bu-t gave ketoesters which were cyclised with MeOCH=NMe2+ MeOSO3- and i-Pr2NEt or with (RCO)2O-NEt3-DMAP to the title 2-H or 2-R bicyclic esters; the corresponding