14228-23-0

Usage

Uses

Used in Pharmaceutical Research:
2-(4-Pyridinyl)-4-quinolinecarboxylic acid is used as a research compound for investigating its neurotoxic properties and its potential role in the development and progression of neurodegenerative diseases. The study of its interaction with the NMDA receptor aids in understanding the underlying mechanisms of diseases like Alzheimer's and Huntington's.
Used in Drug Development:
In the pharmaceutical industry, 2-(4-Pyridinyl)-4-quinolinecarboxylic acid is utilized as a lead compound in the development of new drugs targeting neurodegenerative and inflammatory conditions. Its ability to modulate NMDA receptor activity and induce oxidative stress and neuroinflammation makes it a promising candidate for therapeutic intervention strategies.
Used in Neuroprotective Therapies:
2-(4-Pyridinyl)-4-quinolinecarboxylic acid is explored as a component in neuroprotective therapies aimed at mitigating the effects of oxidative stress and neuroinflammation, which are common pathological features in multiple sclerosis and other inflammatory diseases of the central nervous system.
Used in Diagnostic Tools:
2-(4-Pyridinyl)-4-quinolinecarboxylic acid's impact on neurodegenerative processes makes it a valuable tool in the development of diagnostic assays and tests to assess the presence and severity of neurodegenerative diseases, potentially leading to earlier and more accurate diagnoses.

InChI:InChI=1/C15H10N2O2/c18-15(19)12-9-14(10-5-7-16-8-6-10)17-13-4-2-1-3-11(12)13/h1-9H,(H,18,19)/p-1

Upstream product

• 1122-54-9 methyl (4-pyridyl) ketone 
• 91-56-5 indole-2,3-dione 
• 98-86-2 acetophenone 

Downstream Products

• 1351929-56-0 N-(4-(hydroxymethyl)phenyl)-2-(pyridin-4-yl)quinoline-4-carboxamide 
• 1351929-55-9 N-(4-(methylamino)phenyl)-2-(pyridin-4-yl)quinoline-4-carboxamide 
• 1144460-63-8 N-(4-hydroxyphenyl)-2-(pyridin-4-yl)quinoline-4-carboxamide 
• 863670-33-1 2-(pyridin-4-yl)-N-p-tolylquinoline-4-carboxamide 
• 1351929-43-5 N-(4-(dimethylamino)phenyl)-2-(pyridin-4-yl)quinoline-4-carboxamide 
• 879921-23-0 N-(4-methoxyphenyl)-2-(pyridin-4-yl)quinoline-4-carboxamide 
• 879921-41-2 N-phenyl-2-(pyridin-4-yl)quinoline-4-carboxamide 
• 1165797-18-1 tert-butyl {[trans-4-({[(2-(pyridin-4-yl)quinolin-4-yl)carbonyl]amino}methyl)cyclohexyl]methyl}carbamate 

Relevant academic research and scientific papers

Synthesis, structure evaluation, spectroscopic and antibacterial investigation of metal complexes with 2-(pyridin-4-yl)quinoline-4-carboxylic acid

Four metal complexes based on quinoline carboxylate ligand from 2-(pyridin-4-yl)quinoline-4-carboxylic acid (HL), {[ML2(H2O)2]·2H2O}n (M = MnII, 1; M = CoII, 2; M = CdII, 3) and {[Ag2L2(H2O)2]·3H2O}n (4) have been synthesized under hydrothermal conditions. Their structures were determined by elemental analyses, IR spectra, and further characterized by single-crystal X-ray diffraction analysis. Complexes 1-3 feature a 1D chain structure which is further linked together to construct the 3D supramolecular network through hydrogen bonds. Complex 4 exhibits a 3D configuration. The fluorescent behavior and antibacterial activities of these compounds have been investigated.

Comparative study of the affinity and metabolism of type i and type II binding quinoline carboxamide analogues by cytochrome P450 3A4

Compounds that coordinate to the heme-iron of cytochrome P450 (CYP) enzymes are assumed to increase metabolic stability. However, recently we observed that the type II binding quinoline carboxamide (QCA) compounds were metabolically less stable. To test if the higher intrinsic clearance of type II binding compounds relative to type I binding compounds is general for other metabolic transformations, we synthesized a library of QCA compounds that could undergo N-dealkylation, O-dealkylation, benzylic hydroxylation, and aromatic hydroxylation. The results demonstrated that type II binding QCA analogues were metabolically less stable (2- to 12-fold) at subsaturating concentration compared to type I binding counterparts for all the transformations. When the rates of different metabolic transformations between type I and type II binding compounds were compared, they were found to be in the order of N-demethylation > benzylic hydroxylation> O-demethylation > aromatic hydroxylation. Finally, for the QCA analogues with aza-heteroaromatic rings, we did not detect metabolism in aza-aromatic rings (pyridine, pyrazine, pyrimidine), indicating that electronegativity of the nitrogen can change regioselectivity in CYP metabolism.

Design of small molecule inhibitors of acetyl-CoA carboxylase 1 and 2 showing reduction of hepatic malonyl-CoA levels in vivo in obese Zucker rats

Inhibition of acetyl-CoA carboxylases has the potential for modulating long chain fatty acid biosynthesis and mitochondrial fatty acid oxidation. Hybridization of weak inhibitors of ACC2 provided a novel, moderately potent but lipophilic series. Optimization led to compounds 33 and 37, which exhibit potent inhibition of human ACC2, 10-fold selectivity over inhibition of human ACC1, good physical and in vitro ADME properties and good bioavailability. X-ray crystallography has shown this series binding in the CT-domain of ACC2 and revealed two key hydrogen bonding interactions. Both 33 and 37 lower levels of hepatic malonyl-CoA in vivo in obese Zucker rats.

Small molecule quantification by liquid chromatography-mass spectrometry for metabolites of drugs and drug candidates

Identification and quantification of the metabolites of drugs and drug candidates are routinely performed using liquid chromatography-mass spectrometry (LC-MS). The best practice is to generate a standard curve with the metabolite versus the internal standard. However, to avoid the difficulties in metabolite synthesis, standard curves are sometimes prepared using the substrate, assuming that the signal for substrate and the metabolite will be equivalent. We have tested the errors associated with this assumption using a series of very similar compounds that undergo common metabolic reactions using both conventional flow electrospray ionization LC-MS and low-flow captive spray ionization (CSI) LC-MS. The differences in standard curves for four different types of transformations (O-demethylation, N-demethylation, aromatic hydroxylation, and benzylic hydroxylation) are presented. The results demonstrate that the signals of the substrates compared with those of the metabolites are statistically different in 18 of the 20 substrate-metabolite combinations for both methods. The ratio of the slopes of the standard curves varied up to 4-fold but was slightly less for the CSI method. Copyright

NEW ACETYL COENZYME A CARBOXYLASE (ACC) INHIBITORS AND USES IN TREATMENTS OF OBESITY AND DIABETES MELLITUS - 087

The present invention relates to Acetyl Coenzyme A Carboxylase (ACC) inhibitors according to formula (I), or an enantiomer thereof, or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, E, L, Z and n are as defined herein, to processes for preparing such compounds, to pharmaceutical compositions containing them, to the use of such inhibitors and to methods for th eir therapeutic use, particularly in the treatments of obesity and diabetes mellitus.

Cytochrome P450 2C9 type II binding studies on quinoline-4-carboxamide analogues

CYP2C9 is a significant P450 protein responsible for drug metabolism. With the increased use of heterocyclic compounds in drug design, a rapid and efficient predrug screening of these potential type II binding compounds is essential to avoid adverse drug

Discovering novel chemical inhibitors of human cyclophilin A: Virtual screening, synthesis, and bioassay

Cyclophilin A (CypA) is a member of cyclophilins, a family of the highly homologous peptidyl prolyl cis-trans isomerases (PPIases), which can bind to cyclosporin A (CsA). CypA plays critical roles in various biological processes, including protein folding, assembly, transportation, regulation of neuron growth, and HIV replication. The discovery of CypA inhibitor is now of a great special interest in the treatment of immunological disorders. In this study, a series of novel small molecular CypA inhibitors have been discovered by using structure-based virtual screening in conjunction with chemical synthesis and bioassay. The SPECS_1 database containing 85,000 small molecular compounds was searched by virtual screening against the crystal structure of human CypA. After SPR-based binding affinity assay, 15 compounds were found to show binding affinities to CypA at submicro-molar or micro-molar level (compounds 1-15). Seven compounds were selected as the starting point for the further structure modification in considering binding activity, synthesis difficulty, and structure similarity. We thus synthesized 40 new small molecular compounds (1-6, 15, 16a-q, 17a-d, and 18a-l), and four of which (compounds 16b, 16h, 16k, and 18g) showed high CypA PPIase inhibition activities with IC50s of 2.5-6.2 μM. Pharmacological assay indicated that these four compounds demonstrated somewhat inhibition activities against the proliferation of spleen cells.

A series of quinoline analogues as potent inhibitors of C. albicans prolyl tRNA synthetase

A series of quinoline inhibitors of C. albicans prolyl tRNA synthetase was identified. The most potent analogue, 2-(4bromo-phenyl)-6-chloro-8-methyl-4-quinolinecarboxylic acid, showed IC50=5 nM (Ca. ProRS) with high selectivity over the human enzyme.

Discovery of a novel class of selective non-peptide antagonists for the human neurokinin-3 receptor. 1. Identification of the 4-quinolinecarboxamide framework

A novel class of potent and selective non-peptide neurokinin-3 (NK-3) receptor antagonists, featuring the 4-quinolinecarboxamide framework, has been designed based upon chemically diverse NK-1 receptor antagonists. The novel compounds 33-76, prompted by chemical modifications of the prototype 4, have been characterized by binding analysis using a membrane preparation of chinese hamster ovary (CHO) cells expressing the human neurokinin-3 receptors (hNK-3-CHO), and clear structure-activity relationships (SARs) have been established. From SARs, (R)-N-[α-(methoxycarbonyl)benzyl]-2- phenylquinoline-4-carboxamide (65, SB 218795, hNK-3-CHO binding K(i) = 13 nM) emerged as one of the most potent compounds of this novel class. Selectivity studies versus the other neurokinin receptors (hNK-2-CHO and hNK-1-CHO) revealed that 65 is about 90-fold selective for hNK-3 versus hNK-2 receptors (hNK-2-CHO binding K(i) = 1221 nM) and over 7000-fold selective versus hNK-1 receptors (hNK-1-CHO binding K(i) = >100 μM). In vitro functional studies in rabbit isolated iris sphincter muscle preparation demonstrated that 65 is a competitive antagonist of the contractile response induced by the potent and selective NK-3 receptor agonist senktide with a K(b) = 43 nM. Overall, the data indicate that 65 is a potent and selective hNK-3 receptor antagonist and a useful lead for further chemical optimization.