80650-46-0

Usage

Uses

Used in Agricultural Industry:
Acetamide, 2-chloro-N-4-pyridinylis used as a herbicide for controlling weeds and grasses in various crops. It functions by inhibiting a crucial enzyme in the plant's growth process, which results in the death of the targeted plants. Its selective nature allows it to be an effective tool in agricultural practices without causing widespread harm to non-targeted plant species.
It is important to handle Acetamide, 2-chloro-N-4-pyridinylwith care due to its potential toxicity to humans and the environment if not used properly. Proper application and safety measures are essential to minimize any adverse effects.

Upstream product

• 504-24-5 4-aminopyridine 
• 79-04-9 chloroacetyl chloride 

Downstream Products

• 1196090-97-7 (R)-3-(1-Phenyl-cycloheptanecarbonyloxy)-1-(pyridin-4 ylcarbamoylmethyl)-1-azonia-bicyclo[2.2.2]octane chloride 
• 936632-78-9 1-deoxy-1-(6-{4-[(pyridin-4-ylcarbamoyl)methoxy]phenylamino}-9H-purin-9-yl)-N-ethyl-2,3-O-(1-methylethylidene)-β-D-ribofuranuronamide 
• 936633-18-0 2-(4-aminophenoxy)-N-pyridin-4-ylacetamide 
• 303225-67-4 2-(4-nitrophenoxy)-N-pyridin-4-ylacetamide 

Relevant academic research and scientific papers

Synthesis and Structure–Activity Relationship of Thioacetamide-Triazoles against Escherichia coli

Infections due to Gram-negative bacteria are increasingly dangerous due to the spread of multi-drug resistant strains, emphasizing the urgent need for new antibiotics with alternative modes of action. We have previously identified a novel class of antibacterial agents, thioacetamide-triazoles, using an antifolate targeted screen and determined their mode of action which is dependent on activation by cysteine synthase A. Herein, we report a detailed examination of the anti-E. coli structure–activity relationship of the thioacetamide-triazoles. Analogs of the initial hit compounds were synthesized to study the contribution of the aryl, thioacetamide, and triazole sections. A clear structure–activity relationship was observed generating compounds with excellent inhibition values. Substitutions to the aryl ring were generally best tolerated, including the introduction of thiazole and pyridine heteroaryl systems. Substitutions to the central thioacetamide linker section were more nuanced; the introduction of a methyl branch to the thioacetamide linker substantially decreased antibacterial activity, but the isomeric propionamide and N-benzamide systems retained activity. Changes to the triazole portion of the molecule dramatically decreased the antibacterial activity, further indicating that 1,2,3-triazole is critical for potency. From these studies, we have identified new lead compounds with desirable in-vitro ADME properties and in-vivo pharmacokinetic properties.

Microwave-assisted synthesis, structural characterization and assessment of the antibacterial activity of some new aminopyridine, pyrrolidine, piperidine and morpholine acetamides

A series of new acetamide derivatives 22–28 of primary and secondary amines and para-toluene sulphinate sodium salt have been synthesized under microwave irradiation and assessed in vitro for their antibacterial activity against one Gram-positive and two Gram-negative bacterial species such as S. pyogenes, E. coli, and P. mirabilis using the Mueller-Hinton Agar diffusion (well diffusion) method. The synthesized compounds with significant differences in inhibition diameters and MICs were compared with those of amoxicillin, ampicillin, cephalothin, azithromycin and doxycycline. All of the evaluated acetamide derivatives were used with varying inhibition concentrations of 6.25, 12.5, 37.5, 62.5, 87.5, 112.5 and 125 μg/mL. The results show that the most important antibacterial properties were displayed by the synthetic compounds 22 and 24, both of bear a para-chlorophenyl moiety incorporated into the 2-position moiety of acetamide 1. The molecular structures of the new compounds were determined using the FT-IR and1H-NMR techniques.

NEW COMPOUNDS FOR TREATMENT OF DISEASES RELATED TO DUX4 EXPRESSION

The present invention relates to compounds for the treatment of diseases related to DUX4 expression, such as muscular dystrophies. It also relates to use of such compounds, or to methods of use of such compounds.

Improving the solubility of anti-proliferative thieno[2,3-b]quinoline-2-carboxamides

Thieno[2,3-b]pyridines are a class of compounds known for their potent anti-proliferative activities against a range of human cancer cell lines. In this research, a number of strategies to generate analogues that have improved aqueous solubility whilst retaining the potent anti-proliferative actions, compared to previously-explored compounds in this class, were made. Herein we report the synthesis of 80 novel compounds, comprising two series, all based on the thieno[2,3-b]pyridine core structure. Overall, it was found that introducing alternative heterocycles did not notably improve the solubility or retain anti-proliferative activity seen in previously-reported analogues. However, pleasingly it was discovered, that the best strategy for improving the solubility was the alteration of the appended alkyl ring to introduce polar groups such as alcohols, ketones and substituted amine groups. In addition to this finding, we have discovered a thieno[2,3-b]pyridine, 15e, with greater aqueous solubility that has ever been seen for this class of compounds that is also a potent inhibitor of cancer cell growth, with IC50′s in the nanomolar range. This new lead structure will form the basis of future explorations into this class of compounds.

Design, synthesis of novel celastrol derivatives and study on their antitumor growth through HIF-1α pathway

Four series of hypoxia-inducible factor-1 alpha (HIF-1α) functioning derivatives stemming from modifications to the C-29 carboxyl group of celastrol were designed and synthesized, and their anticancer activities were evaluated. To address the structure and activity relationship of each derivative, extensive structural changes were made. HRE luciferase reporter assay demonstrated that 12 modified compounds showed superior HIF-1α inhibitory activity. Among them, compound C6 exhibited the best features: firstly, the strongest HIF-1α inhibitory activity (IC50 = 0.05 μM, 5-fold higher than that of celastrol); secondly, lower cytotoxicity (22-fold lower, C6-16.85 μM vs celastrol-0.76 μM). Thus, the safety factor of C6 was about 112 times higher than that of celastrol. Western blot assay indicated that C6 may inhibit the expression of HIF-1α protein in cells. Additionally, C6 hindered tumor cell cloning, migration and induced cell apoptosis. It is worth mentioning that in the mouse tumor xenograft model, C6 (10 mg/kg) displayed good antitumor activity in vivo, showing a better inhibition rate (74.03%) than the reference compound 5-fluorouracil (inhibition rate, 59.58%). However, the celastrol treatment group experienced collective death after four doses of the drug. Moreover, C6 minimally affected the mouse weight, indicating that its application in vivo has little toxic effect. H&E staining experiments show that it could also exacerbate the degree of tumor cell damage. The results of water solubility experiment show that the solubility of C6 is increased by 1.36 times than that of celastrol. In conclusion, C6 is a promising antitumor agent through HIF-1α pathway.

Design, biological evaluation and X-ray crystallography of nanomolar multifunctional ligands targeting simultaneously acetylcholinesterase and glycogen synthase kinase-3

Both cholinesterases (AChE and BChE) and kinases, such as GSK-3α/β, are associated with the pathology of Alzheimer's disease. Two scaffolds, targeting AChE (tacrine) and GSK-3α/β (valmerin) simultaneously, were assembled, using copper(I)-catalysed azide alkyne cycloaddition (CuAAC), to generate a new series of multifunctional ligands. A series of eight multi-target directed ligands (MTDLs) was synthesized and evaluated in vitro and in cell cultures. Molecular docking studies, together with the crystal structures of three MTDL/TcAChE complexes, with three tacrine-valmerin hybrids allowed designing an appropriate linker containing a 1,2,3-triazole moiety whose incorporation preserved, and even increased, the original inhibitory potencies of the two selected pharmacophores toward the two targets. Most of the new derivatives exhibited nanomolar affinity for both targets, and the most potent compound of the series displayed inhibitory potencies of 9.5 nM for human acetylcholinesterase (hAChE) and 7 nM for GSK-3α/β. These novel dual MTDLs may serve as suitable leads for further development, since, in the micromolar range, they exhibited low cytotoxicity on a panel of representative human cell lines including the human neuroblastoma cell line SH-SY5Y. Moreover, these tacrine-valmerin hybrids displayed a good ability to penetrate the blood-brain barrier (BBB) without interacting with efflux pumps such as P-gp.

SMALL MOLECULE ACTIVATORS OF NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE (NAMPT) AND USES THEREOF

Provided herein are small molecule activators of Nicotinamide Phosphoribosyltransferase (NAMPT), compositions comprising the compounds, and methods of using the compounds and compositions.

Steering Siglec–Sialic Acid Interactions on Living Cells using Bioorthogonal Chemistry

Sialic acid sugars that terminate cell-surface glycans form the ligands for the sialic acid binding immunoglobulin-like lectin (Siglec) family, which are immunomodulatory receptors expressed by immune cells. Interactions between sialic acid and Siglecs regulate the immune system, and aberrations contribute to pathologies like autoimmunity and cancer. Sialic acid/Siglec interactions between living cells are difficult to study owing to a lack of specific tools. Here, we report a glycoengineering approach to remodel the sialic acids of living cells and their binding to Siglecs. Using bioorthogonal chemistry, a library of cells with more than sixty different sialic acid modifications was generated that showed dramatically increased binding toward the different Siglec family members. Rational design reduced cross-reactivity and led to the discovery of three selective Siglec-5/14 ligands. Furthermore, glycoengineered cells carrying sialic acid ligands for Siglec-3 dampened the activation of Siglec-3+ monocytic cells through the NF-κB and IRF pathways.

Acetobenzylamide piperazine derivative and application thereof as cranial nerve protective agent

The invention discloses an acetobenzylamide piperazine derivative and an application thereof as a cranial nerve protective agent. Pharmacological experiments verify that the compound disclosed by the invention shows an obvious effect against glutamic acid-induced neuron exitotoxicity in vitro and obvious anti-anoxia activity in a mouse, and a herg test further shows that the compound disclosed by the invention does not have the risk of cardiotoxicity. Therefore, the compound disclosed by the invention has the advantages of being high in activity, less in side effect and good in druggability. The compound and a medicinal preparation thereof have a good curative effect for treating cranial nerve injury diseases, for example, stroke and related diseases and do not have the risk of cardiotoxicity. The acetobenzylamide piperazine derivative is a free alkali or salt of a compound with a chemical structural formula shown in the description.

Tri- and tetranuclear RuII-Gd III 2 and RuII-Gd III 3 d-f heterometallic complexes as potential bimodal imaging probes for MRI and optical imaging

The synthesis of tri- and tetranuclear RuII-GdIII2 and RuII-GdIII3 d-f heterometallic complexes of 4-aminopyridine-appended DO3A (DOTA-AMpy, 4) with 1,10-phenanthroline and 4′-(p-tolyl)-2,2′:6′,2′′-terpyridine ancillary ligands and their relaxometry and in vitro cytotoxicity studies are reported. Complexes [Ru(phen)2{Gd(DOTA-AMpy)(H2O)}2]Cl2 (7) and [Ru(ttpy){Gd(DOTA-AMpy)(H2O)}3]Cl2 (9) exhibit the "per Gd" longitudinal relaxivity of 6.19 and 7.47 mM-1 s-1 and 15.37 and 18.61 mM-1 s-1, respectively, in aqueous solution and in the presence of HSA (20 MHz, pH = 7.4, phosphate buffer saline, 37 °C). Complex 7 exhibits an emission band at 590 nm. The cell viability and cytotoxicity studies of complexes 7 and 9 against the HeLa cell lines by MTT assay demonstrate their cytotoxic activity with the IC50 values of 52.1 and 27.9 μM, respectively. Morphological assessment of apoptosis by acridine orange and ethidium bromide staining and by Hoechst-33342 assay shows marked morphological signs of apoptosis in a dose-dependent manner. Flow cytometric analysis by propidium iodide staining indicates the inhibition of HeLa cell proliferation and DNA ladder assay shows apoptotic cell death, lending support to the antitumor activity of 7 and 9. A molecular docking study reveals that these complexes intercalate with DNA and bind to HSA. Relaxometry and cytotoxicity studies indicate that complexes 7 and 9 could be used as potential bimodal imaging probes and as anticancer agents.