23915-78-8

Upstream product

• 38322-74-6 7-methoxy-4-oxo-4H-chromene-2-carboxylic acid ethyl ester 
• 150-19-6 O-methylresorcine 
• 552-41-0 1-(2-hydroxy-4-methoxyphenyl)ethanone 
• 95-92-1 oxalic acid diethyl ester 
• 23866-72-0 ethyl 7-hydroxy-4-oxo-4H-chromen-2-carboxylate 

Downstream Products

• 79480-10-7 N-phenyl-7-methoxy-4(H)-oxo-1-benzopyran-2-carboxamide 

Relevant academic research and scientific papers

SUBSTITUTED CYCLOLAKYLS AS MODULATORS OF THE INTEGRATED STRESS PATHWAY

Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases, disorders and conditions.

Optimizing the synthetic route of chromone-2-carboxylic acids: A step forward to speed-up the discovery of chromone-based multitarget-directed ligands

6-Bromochromone-2-carboxylic acid (3) was synthesized by a microwave-assisted process. The optimization of the reaction was performed varying parameters, such as type of base/number of reagent equivalents, solvent, temperature and reaction time. The yield of the reaction was improved to 87%. The new synthetic route is versatile as several chromone-2-carboxylic acids (compounds 4B-10B) were obtained with good yields (54-93%). Only in the case of the nitro substituent (compound 11B), an ester was obtained instead of the desired carboxylic acid. Following this synthetic route chromone carboxylic acids can be attained with a high degree of purity, without the need of the tedious and expensive purification processes through column chromatography. The reaction is safe, cost-effective, fast and robust, and can be used in the development of concise and diversity-oriented libraries based on chromone scaffold. The overall study can be looked as a step forward to speed-up the discovery of chromone-based multitarget-directed ligands.

Neurogenic and neuroprotective donepezil-flavonoid hybrids with sigma-1 affinity and inhibition of key enzymes in Alzheimer's disease

In this work we describe neurogenic and neuroprotective donepezil-flavonoid hybrids (DFHs), exhibiting nanomolar affinities for the sigma-1 receptor (σ1R) and inhibition of key enzymes in Alzheimer's disease (AD), such as acetylcholinesterase (AChE), 5-lipoxygenase (5-LOX), and monoamine oxidases (MAOs). In general, new compounds scavenge free radical species, are predicted to be brain-permeable, and protect neuronal cells against mitochondrial oxidative stress. N-(2-(1-Benzylpiperidin-4-yl)ethyl)-6,7-dimethoxy-4-oxo-4H-chromene-2-carboxamide (18) is highlighted due to its interesting biological profile in σ1R, AChE, 5-LOX, MAO-A and MAO-B. In phenotypic assays, it protects a neuronal cell line against mitochondrial oxidative stress and promotes maturation of neural stem cells into a neuronal phenotype, which could contribute to the reparation of neuronal tissues. Molecular modelling studies of 18 in AChE, 5-LOX and σ1R revealed the main interactions with these proteins, which will be further exploited in the optimization of new, more efficient DFHs.

Synthesis, spectroscopic characterization and X-ray structure of novel 7-methoxy-4-oxo-N-phenyl-4H-chromene-2-carboxamides

The chromone scaffold has been found to be an important tool in the drug discovery process through its relevant pharmacological activities. Chromone carboxamide derivatives synthesized within our group have shown noteworthy results as inhibitors of monoam

Optimization of chromone-2-carboxamide melanin concentrating hormone receptor 1 antagonists: Assessment of potency, efficacy, and cardiovascular safety

Evaluation of multiple structurally distinct series of melanin concentrating hormone receptor 1 antagonists in an anesthetized rat cardiovascualar assay led to the identification of a chromone-2-carboxamide series as having excellent safety against the chosen cardiovascular endpoints at high drug concentrations in the plasma and brain. Optimization of this series led to considerable improvements in affinity, functional potency, and pharmacokinetic profile. This led to the identification of a 7-fluorochromone-2-carboxamide (22) that was orally efficacious in a diet-induced obese mouse model, retained a favorable cardiovascular profile in rat, and demonstrated dramatic improvement in effects on mean arterial pressure in our dog cardiovascular model compared to other series reported by our group. However, this analogue also led to prolongation of the QT interval in the dog that was linked to affinity for hERG channel and unexpectedly potent functional blockade of this ion channel.

Antagonists of melanin concentrating hormone effects on the melanin concentrating hormone receptor

The present invention is directed to compounds of formula (I), which antagonize of the effects of melanin-concentrating hormone (MCH) through the melanin concentrating hormone receptor which is useful for the prevention or treatment of eating disorders, weight gain, obesity, abnormalities in reproduction and sexual behavior, thyroid hormone secretion, diuresis and water/electrolyte homeostasis, sensory processing, memory, sleeping, arousal, anxiety, depression, seizures, neurodegeneration and psychiatric disorders.

SUBSTITUTED PIPERIDINE AND PIPERAZINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR MODULATORS

The present invention relates to novel substituted piperidine and piperazine derivatives as melanocortin-4 receptor (MC-4R) modulators. MC-4R agonists of the invention can be used for the treatment of disorders and diseases such as obesity, diabetes and s

Use of polyphosphoric acid in the hydrolysis of chromone esters

Hydrolysis of esters was achieved in fairly high yield (59-98%) using polyphosphoric acid (PPA). The reagent was particularly useful for the hydrolysis of chromone side chain esters without ring opening.

A Selective and Versatile Synthesis of Substituted Chromones via Addition of Phenols to Dimethyl Acetylenedicarboxylate

Despite many published syntheses of chromones, none has been reported to be both selective for chromones and tolerant of ring substitution.The addition of substituted phenols to dimethyl acetylenedicarboxylate is now reported as a versatile high yield initial step in a simple three-step synthesis of chromone 2-carboxylic acids.Triethylamine being used to deprotonate the substituted phenol, the addition to dimethyl acetylenedicarboxylate proceeds under mild conditions and tolerates a wide range of functional groups on the phenol.Although not stereoselective, both fumarate and maleate aryloxy products of this addition can then be cyclized, according to a known method, to chromones without contamination by isomeric coumarins.Thus the addition reaction is a valuable component of a versatile and selective synthesis of substituted chromones.