5174-90-3

Usage

Uses

Used in Pharmaceutical Research and Drug Development:
2-OXO-1,2-DIHYDRO-[1,8]NAPHTHYRIDINE-3-CARBOXYLIC ACID ETHYL ESTER is used as a potential candidate for new drug discovery due to its unique structure and diverse biological activities.
Used in Anti-Inflammatory Applications:
In the medical field, 2-OXO-1,2-DIHYDRO-[1,8]NAPHTHYRIDINE-3-CARBOXYLIC ACID ETHYL ESTER is used as an anti-inflammatory agent, leveraging its pharmacological properties to potentially treat conditions characterized by inflammation.
Used in Anti-Cancer Applications:
2-OXO-1,2-DIHYDRO-[1,8]NAPHTHYRIDINE-3-CARBOXYLIC ACID ETHYL ESTER is also used as an anti-cancer agent, being studied for its potential to target and treat various types of cancer, based on its observed biological effects.
Used in Future Therapeutic Applications:
Given its promising pharmacological profile, 2-OXO-1,2-DIHYDRO-[1,8]NAPHTHYRIDINE-3-CARBOXYLIC ACID ETHYL ESTER is under investigation for potential therapeutic applications, which may include the development of new treatments for a range of diseases and conditions.

InChI:InChI=1/C11H10N2O3/c1-2-16-11(15)8-6-7-4-3-5-12-9(7)13-10(8)14/h3-6H,2H2,1H3,(H,12,13,14)

Upstream product

• 7521-41-7 2-Aminonicotinaldehyde 
• 105-53-3 diethyl malonate 
• 1071-46-1 hydrogen ethyl malonate 
• 2033-24-1 cycl-isopropylidene malonate 
• 64-17-5 ethanol 
• 7521-27-9 2-(3-pyridyl)-1,3,8-triazanaphthalene 
• 98-92-0 nicotinamide 
• 86847-59-8 2-(pivaloylamino)pyridine 
• 86847-64-5 N-(3-formyl-2-pyridinyl)-2,2-dimethylpropanamide 

Downstream Products

• 1160012-33-8 N-(4-fluorophenethyl)-1,8-naphthyridin-2(1H)-on-3-carboxamide 
• 1160012-25-8 N-cyclohexyl-1,8-naphthyridin-2(1H)-on-3-carboxamide 
• 1160012-31-6 N-phenethyl-1,8-naphthyridin-2(1H)-on-3-carboxamide 
• 1160012-27-0 N-(4-methylcyclohexyl)-1,8-naphthyridin-2(1H)-on-3-carboxamide 
• 1239164-04-5 3-(2-hydroxy-6-oxo-1-cyclohexenecarbonyl)-1-methyl-1,8-naphthyridin-2(1H)-one 
• 1239164-56-7 3-oxo-1-cyclohexenyl 1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-carboxylate 
• 1239164-12-5 1-benzyl-3-(2-hydroxy-6-oxo-1-cyclohexenecarbonyl)-1,8-naphthyridin-2(1H)-one 
• 1239164-60-3 3-oxo-1-cyclohexenyl 1-benzyl-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylate 

Relevant academic research and scientific papers

Ferric Chloride-catalyzed Synthesis of 2-Oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylate Derivatives and Their Biological Evaluation

A new methodology has been developed for the synthesis of novel 2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylates from 2-aminonicotinaldehyde, Meldrum’s acid, and the corresponding alcohols in the presence of anhydrous iron(III) chloride as a cheap and readily available catalyst. The structure of the synthesized compounds was established by IR, 1H NMR, and mass spectral data and elemental analyses. All the synthesized compounds were evaluated for their in vitro antibacterial and antifungal activity, and the activity of some derivatives was comparable with the activity of Ciprofloxacin and Nystatin used as reference drugs.

Development of potent dual PDK1/AurA kinase inhibitors for cancer therapy: Lead-optimization, structural insights, and ADME-Tox profile

We report the synthesis of novel first-in-class 2-oxindole-based derivatives as dual PDK1-AurA kinase inhibitors as a novel strategy to treat Ewing sarcoma. The most potent compound 12 is suitable for progression to in vivo studies. The specific attributes of 12 included nanomolar inhibitory potency against both phosphoinositide-dependent kinase-1 (PDK1) and Aurora A (AurA) kinase, with acceptable in vitro ADME-Tox properties (cytotoxicity in 2 healthy and 14 hematological and solid cancer cell-lines; inhibition of PDE4C1, SIRT7, HDAC4, HDAC6, HDAC8, HDAC9, AurB, CYP1A2, CYP2C9, CYP2C19, CYP2D6, and hERG). X-ray crystallography and docking studies led to the identification of the key AurA and PDK1/12 interactions. Finally, in vitro drug-intake kinetics and in vivo PK appear to indicate that these compounds are attractive lead-structures for the design and synthesis of PDK1/AurA dual-target molecules to further investigate the in vivo efficacy against Ewing Sarcoma.

Development of [18f]lu14 for pet imaging of cannabinoid receptor type 2 in the brain

Cannabinoid receptors type 2 (CB2R) represent an attractive therapeutic target for neurodegenerative diseases and cancer. Aiming at the development of a positron emission tomography (PET) radiotracer to monitor receptor density and/or occupancy during a CB2R-tailored therapy, we herein describe the radiosynthesis of cis-[18F]1-(4-fluorobutyl-N-((1s,4s)-4-methylcyclohexyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide ([18F]LU14) starting from the corresponding mesylate precursor. The first biological evaluation revealed that [18F]LU14 is a highly affine CB2R radioligand with >80% intact tracer in the brain at 30 min p.i. Its further evaluation by PET in a well-established rat model of CB2R overexpression demonstrated its ability to selectively image the CB2R in the brain and its potential as a tracer to further investigate disease-related changes in CB2R expression.

Structure-activity relationship of spop inhibitors against kidney cancer

Speckle-type POZ protein (SPOP) is overexpressed in the nucleus and misallocated in the cytoplasm in almost all the clear-cell renal cell carcinomas (ccRCCs), which leads to kidney tumorigenesis. Previously, we elucidated that the oncogenic SPOP-signaling pathway in ccRCC could be suppressed by 6b that inhibits SPOP-mediated protein interactions. Herein, we have established a structure-activity relationship for 6b analogues as SPOP inhibitors. Compound 6lc suppresses the viability and inhibits the colony formation of ccRCC cell lines driven by cytoplasmic SPOP, superior to 6b. Compound 6lc binds to the SPOP protein in vitro and disrupts SPOP binding to phosphatase-and-tensin homologue (PTEN) in HEK293T cells, which causes the observable phenomena: a decline in the ubiquitination of PTEN, elevated levels of both PTEN and dual-specificity phosphatase 7, and decreased levels of phosphorylated AKT and ERK when ccRCC cell lines are exposed to 6lc in a dose-response manner. Taken together, compound 6lc is a potent candidate against kidney tumorigenesis.

5-MEMBERED AND BICYCLIC HETEROCYCLIC AMIDES AS INHIBITORS OF ROCK

The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically-acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective ROCK inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating cardiovascular, smooth muscle, oncologic, neuropathologic, autoimmune, fibrotic, and/or inflammatory disorders using the same.

Anti-proliferative properties and proapoptotic function of new CB2 selective cannabinoid receptor agonist in jurkat leukemia cells

Several studies demonstrated that cannabinoids reduce tumor growth, inhibit angiogenesis, and decrease cancer cell migration. As these molecules are well tolerated, it would be interesting to investigate the potential benefit of newly synthesized compounds, binding cannabinoid receptors (CBRs). In this study, we describe the synthesis and biological effect of 2-oxo-1,8-naphthyridine-3-carboxamide derivative LV50, a new compound with high CB2 receptor (CB2R) affinity. We demonstrated that it decreases viability of Jurkat leukemia cells, evaluated by Trypan Blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), but mainly induces a proapoptotic effect. We observed an increase of a hypodiploid peak by propidium iodide staining and changes in nuclear morphology by Hoechst 33258. These data were confirmed by a significant increase of Annexin V staining, cleavage of the nuclear enzyme poly(ADP-ribose)-polymerase (PARP), and caspases activation. In addition, in order to exclude that LV50 non-specifically triggers death of all normal leukocytes, we tested the new compound on normal peripheral blood lymphocytes, excluding the idea of general cytotoxicity. To characterize the involvement of CB2R in the anti-proliferative and proapoptotic effect of LV50, cells were pretreated with a specific CB2R antagonist and the obtained data showed reverse results. Thus, we suggest a link between inhibition of cell survival and proapoptotic activity of the new compound that elicits this effect as selective CB2R agonist.

The Discovery and Hit-to-Lead Optimization of Tricyclic Sulfonamides as Potent and Efficacious Potentiators of Glycine Receptors

Current pain therapeutics suffer from undesirable psychotropic and sedative side effects, as well as abuse potential. Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels expressed in nerves of the spinal dorsal horn, where their activation is believed to reduce transmission of painful stimuli. Herein, we describe the identification and hit-to-lead optimization of a novel class of tricyclic sulfonamides as allosteric GlyR potentiators. Initial optimization of high-throughput screening (HTS) hit 1 led to the identification of 3, which demonstrated ex vivo potentiation of glycine-activated current in mouse dorsal horn neurons from spinal cord slices. Further improvement of potency and pharmacokinetics produced in vivo proof-of-concept tool molecule 20 (AM-1488), which reversed tactile allodynia in a mouse spared-nerve injury (SNI) model. Additional structural optimization provided highly potent potentiator 32 (AM-3607), which was cocrystallized with human GlyRα3cryst to afford the first described potentiator-bound X-ray cocrystal structure within this class of ligand-gated ion channels (LGICs).

PYRROLO PYRIMIDINE DERIVATIVE

The compound represented by general formula (I) has strong Axl inhibition activity by means of a pyridone ring structure being introduced into a pyrrolo pyrimidine skeleton, and so the result can serve as a treatment agent for Axl-related diseases, for example cancers such as acute myeloid leukemia, melanoma, breast cancer, pancreatic cancer, and glial tumors, renal disease, immune system disorders, and cardiovascular disease.

Indium(Iii) Chloride as an efficient catalyst for friedlander synthesis 1,8-Naphthyridines under solventfree conditions

InCl3 catalyzed Friedlander condensation of 2-aminonicotinaldehyde 1 with carbonyl compounds containing methylene group 2 has been achieved in solvent-free grinding conditions to give 1,8-naphthyridines 3 in high yields. The method is simple an

Piperazine analogs of naphthyridine-3-carboxamides and indole-2-carboxamides: Novel 5-HT3 receptor antagonists with antidepressant-like activity

Series of piperazine analogs of naphthyridine-3-carboxamides and indole-2-carboxamides were designed using a ligand-based approach with consideration of the pharmacophoric requirements for 5-HT3 receptor antagonists. The title carboxamides were synthesized using appropriate synthetic routes. Initially, the 5-HT3 receptor antagonistic activity of all the compounds was determined on isolated guinea pig ileum tissue against the 5-HT3 agonist, 2-methyl-5-hydroxytryptamine, which was denoted in the form of pA2 values. The structure-activity relationship regarding the influence of the aromatic part and basic moiety as features in the 5-HT3 pharmacophore was derived. Among all the compounds screened, the piperazine derivatives of indole-2-carboxamide 13i and naphthyridine-3-carboxamide 8h exhibited prominent 5-HT3 receptor antagonism with pA2 values of 7.5 and 7.3, respectively. Subsequent investigation of the antidepressant activities of selected compounds in the mouse forced swim test (FST) led to the identification of the piperazine analogs of indole-2-carboxamide 13i and naphthyridine-3-carboxamide 8h as the most promising compounds. Both 13i and 8h demonstrated significant reduction in the duration of immobility as compared to the control. Importantly, none of the tested compounds affected the baseline locomotion of mice at the tested dose levels.