15029-36-4

Basic information

• Product Name: N1-ETHYL-2-CYANOACETAMIDE
• Synonyms: N1-ETHYL-2-CYANOACETAMIDE;TIMTEC-BB SBB000040;2-cyano-n-ethylacetamide;3-(Ethylamino)-3-oxopropanenitrile;2-cyano-N-ethyl-ethanamide
• CAS NO: 15029-36-4
• Molecular Formula: C₅H₈N₂O
• Molecular Weight: 112.12982
• Product Categories: Aliphatics
• Mol File: 15029-36-4.mol

Chemical Properties

• Melting Point: 73 °C
• Boiling Point: 320.8 °C at 760 mmHg
• Flash Point: 147.8 °C
• Appearance: /
• Density: 1.015 g/cm³
• Vapor Pressure: 0.00031mmHg at 25°C
• Refractive Index: 1.434
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 9.40±0.10(Predicted)
• CAS DataBase Reference: N1-ETHYL-2-CYANOACETAMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: N1-ETHYL-2-CYANOACETAMIDE(15029-36-4)
• EPA Substance Registry System: N1-ETHYL-2-CYANOACETAMIDE(15029-36-4)

Safety Data

• Hazard Codes: Harmful:
• Hazardous Substances Data: 15029-36-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
N1-ETHYL-2-CYANOACETAMIDE is used as a chemical intermediate for the synthesis of various pharmaceutical compounds. Its unique molecular structure and properties make it a valuable building block in the development of new drugs and therapeutic agents.
Used in Research Applications:
In the field of scientific research, N1-ETHYL-2-CYANOACETAMIDE is employed as a research tool to study the interactions and mechanisms of various biological systems. Its chemical properties allow researchers to investigate its potential applications in drug discovery and development, as well as its effects on cellular processes.
Used in Chemical Synthesis:
N1-ETHYL-2-CYANOACETAMIDE is utilized as a key component in the synthesis of complex organic molecules and compounds. Its versatility in chemical reactions enables the creation of a wide range of products, from specialty chemicals to advanced materials.
Used in Analytical Chemistry:
In analytical chemistry, N1-ETHYL-2-CYANOACETAMIDE is employed as a reference compound or a standard for various analytical techniques. Its well-defined properties make it suitable for calibration and quality control purposes in laboratories.

InChI:InChI=1/C5H8N2O/c1-2-7-5(8)3-4-6/h2-3H2,1H3,(H,7,8)

Upstream product

• 75-04-7 ethylamine 
• 105-56-6 ethyl 2-cyanoacetate 
• 372-09-8 cyanoacetic acid 
• 16130-58-8 cyanoacetic acid chloride 

Downstream Products

• 87074-23-5 (Z)-2-Cyano-3-(3,5-di-tert-butyl-4-hydroxy-phenyl)-N-ethyl-acrylamide 
• 103409-17-2 2-amino-N-ethyl-7-phenyl-1,8-naphthyridine-3-carboxamide 
• 64686-89-1 4-amino-3-phenyl-2-thioxo-2,3-dihydro-thiazole-5-carboxylic acid ethylamide 
• 60598-65-4 2-amino-N-ethyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide 

Relevant articles and documents

Multicomponent Petasis Reaction for the Synthesis of Functionalized 2-Aminothiophenes and Thienodiazepines

Multicomponent Petasis reaction has been widely applied for the synthesis of functionalized amine building blocks and biologically active compounds. Employing primary aromatic amines that are not typical reactive substrates contributes to expand the application scope of the Petasis reaction. In this study, we demonstrated the synthesis of functionalized 2-aminothiophenes using Gewald-reaction-derived 2-aminothiophenes as the amine substrates, whose low reactivity in the Petasis reaction was overcome using hexafluoro-2-propanol as the solvent in a mild condition. The obtained Petasis products are amenable for further transformations owing to the presence of multiple functional handles. A following intramolecular cyclization of selected Petasis products afforded substituted tricyclic heterocycles that incorporate a pharmaceutically interesting thienodiazepine moiety.

Synthesis and Docking Study of Novel Pyranocoumarin Derivatives

Abstract: A new series of fused tricyclic coumarin derivatives were designed, synthesized by a simple and convenient method, starting from 4-hydroxycoumarin and virtually screened by molecular docking on the target protein 3FRZ (PDB ID: 3FRZ), a HCV RNA-dependent RNA polymerase, for potency against hepatitis C virus (HCV). Efficient binding to the target protein was found for most of the synthesized compounds.

Synthesis and biological evaluation of flavone-8-acrylamide derivatives as potential multi-target-directed anti Alzheimer agents and investigation of binding mechanism with acetylcholinesterase

In a search for novel multifunctional anti-Alzheimer agents, a congeneric set of seventeen flavone-8-acrylamide derivatives (8a─q)were synthesized and evaluated for their cholinesterase inhibitory, antioxidant, neuroprotective and modulation of Aβ aggregation activities. The target compounds showed effective and selective inhibitory activity against the AChE over BuChE. In addition, the target compounds also showed moderate anti-oxidant activity and strong neuroprotective capacities, and accelerated dosage-dependently the Aβ aggregation. Also, we presented here a complete study on the interaction of 8a, 8d, 8e, 8h and 8i with AChE. Through fluorescence emission studies, the binding sites number found to be 1, binding constants were calculated as 2.04 × 104, 2.22 × 104, 1.18 × 104, 9.8 × 103 and 3.2 × 104 M?1 and free energy change as ?5.83, ?5.91, ?5.51, ?5.41 and ?6.12 kcal M?1 at 25 °C which were well agreed with the computational calculations indicating a strong binding affinity of flavones and AChE. Furthermore, the CD studies revealed that the secondary structure of AChE became partly unfolded upon binding with 8a, 8d, 8e, 8h and 8i.

New Flavone-Cyanoacetamide Hybrids with a Combination of Cholinergic, Antioxidant, Modulation of β-Amyloid Aggregation, and Neuroprotection Properties as Innovative Multifunctional Therapeutic Candidates for Alzheimer's Disease and Unraveling Their Mechanism of Action with Acetylcholinesterase

In line with the modern multi-target-directed ligand paradigm of Alzheimer's disease (AD), a series of 19 compounds composed of flavone and cyanoacetamide groups have been synthesized and evaluated as multifunctional agents against AD. Biological evaluation demonstrated that compounds 7j, 7n, 7o, 7r, and 7s exhibited excellent inhibitory potency (AChE, IC50 of 0.271 ± 0.012 to 1.006 ± 0.075 μM) and good selectivity toward acetylcholinesterase, significant antioxidant activity, good modulation effects on self-induced Aβ aggregation, low cytotoxicity, and neuroprotection in human neuroblastoma SK-N-SH cells. Further, an inclusive study on the interaction of 7j, 7n, 7o, 7r, and 7s with AChE at physiological pH 7.2 using fluorescence, circular dichroism, and molecular docking methods suggested that these derivatives bind strongly to the peripheral anionic site of AChE mostly through hydrophobic interactions. Overall, the multifunctional profiles and strong AChE binding affinity highlight these compounds as promising prototypes for further pursuit of innovative multifunctional drugs for AD.

Development of the First Two-Pore Domain Potassium Channel TWIK-Related K+ Channel 1-Selective Agonist Possessing in Vivo Antinociceptive Activity

The TWIK-related K+ channel, TREK-1, has recently emerged as an attractive therapeutic target for the development of a novel class of analgesic drugs, suggesting that activation of TREK-1 could result in pain inhibition. Here, we report the synthesis of a series of substituted acrylic acids (1-54) based on our previous work with caffeate esters. The analogues were evaluated for their ability to modulate TREK-1 channel by electrophysiology and for their in vivo antinociceptive activity (acetic acid-induced writhing and hot plate assays), leading to the identification of a series of novel molecules able to activate TREK-1 and displaying potent antinociceptive activity in vivo. Furyl analogue 36 is the most promising of the series.

Synthesis, pharmacological assessment, molecular modeling and in silico studies of fused tricyclic coumarin derivatives as a new family of multifunctional anti-Alzheimer agents

A series of fused tricyclic coumarin derivatives bearing iminopyran ring connected to various amido moieties were developed as potential multifunctional anti-Alzheimer agents for their cholinesterase inhibitory and radical scavenging activities. In vitro studies revealed that most of these compounds exhibited high inhibitory activity on acetylcholinesterase (AChE), with IC50 values ranging from 0.003 to 0.357 μM which is 2-220 folds more potent than the positive control, galantamine. Their inhibition selectivity against AChE over butyrylcholinesterase (BuChE) has increased about 194 fold compared with galantamine. The developed compounds also showed potent ABTS radical scavenging activity (IC50 7.98-15.99 μM). Specifically, the most potent AChE inhibitor 6n (IC50 0.003 ± 0.0007 μM) has an excellent antioxidant profile as determined by the ABTS method (IC50 7.98 ± 0.77 μM). Moreover, cell viability studies in SK N SH cells showed that the compounds 6m-q have significant neuroprotective effects against H2O2-induced cell death, and are not neurotoxic at all concentrations except 6n and 6q. The kinetic analysis of compound 6n proved that it is a mixed-type inhibitor for EeAChE (Ki1 0.0103 μM and Ki2 0.0193 μM). Accordingly, the molecular modeling study demonstrated that 6m-q with substituted benzyl amido moiety possessed an optimal docking pose with interactions at catalytic active site (CAS) and peripheral anionic site (PAS) of AChE simultaneously and thereby they might prevent aggregation of Aβ induced by AChE. Furthermore, in silico ADMET prediction studies indicated that these compounds satisfied all the characteristics of CNS acting drugs. Most active inhibitor 6n is permeable to BBB as determined in the in vivo brain AChE activity. To sum up, the multipotent therapuetic profile of these novel tricyclic coumarins makes them promising leads for developing anti-Alzheimer agents.

Synthesis, Biological Evaluation, and Molecular Docking of 8-imino-2-oxo-2H,8H-pyrano[2,3-f]chromene Analogs: New Dual AChE Inhibitors as Potential Drugs for the Treatment of Alzheimer's Disease

Alzheimer's disease onset and progression are associated with the dysregulation of multiple and complex physiological processes, and a successful therapeutic approach should therefore address more than one target. In line with this modern paradigm, a series of 8-imino-2-oxo-2H,8H-pyrano[2,3-f]chromene analogs (4a–q) were synthesized and evaluated for their multitarget-directed activity on acetylcholinesterase, butyrylcholinesterase (BuChE), 2,2’-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical, and amyloid-β peptide (Aβ) specific targets for Alzheimer's disease therapy. Most of the synthesized compounds showed remarkable acetylcholinesterase inhibitory activities in low nm concentrations and good ABTS radical scavenging activity, however, no evidence of BuChE inhibitory activity. Among them, 3-bromobenzylamide derivative 4m exhibited the best acetylcholinesterase inhibitory activity with IC50 value of 13 ± 1.4 nm which is 51-fold superior to galantamine, a reference drug. Kinetic and molecular docking studies indicated 4m as mixed-type inhibitor, binding simultaneously to catalytic active and peripheral anionic sites of acetylcholinesterase. Five compounds 4e, 4f, 4g, 4j, and 4k have shown 1.4- to 2.5-fold of higher antioxidant activities than trolox. Interestingly, the most active compound 4m demonstrated dosage-dependent acceleration of Aβ1?42 aggregation, which may reduce toxicity of oligomers. Overall, these results lead to discovery of fused tricyclic coumarins as promising dual binding site inhibitors of acetylcholinesterase and afford multifunctional compounds with potential impact for further pharmacological development in Alzheimer's therapy.

Tracing binding modes in hit-to-lead optimization: Chameleon-like poses of aspartic protease inhibitors

Successful lead optimization in structure-based drug discovery depends on the correct deduction and interpretation of the underlying structure-activity relationships (SAR) to facilitate efficient decision-making on the next candidates to be synthesized. Consequently, the question arises, how frequently a binding mode (re)-validation is required, to ensure not to be misled by invalid assumptions on the binding geometry. We present an example in which minor chemical modifications within one inhibitor series lead to surprisingly different binding modes. X-ray structure determination of eight inhibitors derived from one core scaffold resulted in four different binding modes in the aspartic protease endothiapepsin, a well-established surrogate for e.g. renin and β-secretase. In addition, we suggest an empirical metrics that might serve as an indicator during lead optimization to qualify compounds as candidates for structural revalidation.

Novel soluble myeloid cell leukemia sequence 1 (Mcl-1) inhibitor (E,E)-2-(benzylaminocarbonyl)-3-styrylacrylonitrile (4g) developed using a fragment-based approach

Based on a known nanomolar Bcl-2 homology domain 3 (BH3) mimetic 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b] pyrrole-9-carbonitrile (S1, MW: 331), we applied a fragment-based approach to obtain BH3 mimetics with improved affinity and improved solubility in a water-ethanol (9:1) cosolvent. After the deconstruction of 1 (S1), we obtained fragment cyanoacetamide (4), which was determined to be a ligand efficiency (LE) hot part. After a rational optimization through fragment evolution beginning with fragment 4, a smaller Mcl-1 inhibitor (E,E)-2-(benzylaminocarbonyl)-3-styrylacrylonitrile (4g, MW: 288) with a 6-fold increase in affinity compared to 1 was obtained, as predicted by our optimization curve and identified by Mcl-1 protein nuclear magnetic resonance (NMR).

A simple and general approach for the synthesis of highly functionalized 6-oxo-1,6-dihydropyridines

A variety of 5-cyano-4-methylthio-6-oxo-1,6-dihydropyridine-3-carboxylates have been efficiently synthesized in a one-pot reaction from N-alkyl and N-aryl derivatives of 2-cyano-3,3-bis(methylthio)acrylamides and selected β-keto esters. The reaction proceeds via potassium hydrogen carbonate mediated conjugate addition of a β-keto ester to 2-cyano-3,3-bis(methylthio) acrylamide followed by loss of methyl mercaptan and subsequent intramolecular condensation of amide group with the acyl carbonyl group. The mechanism of the reaction has been established by isolation of the 2-acetyl-4-cyano-5-amino-3- (methylthio)-5-oxopent-3-enoate intermediate and its independent cyclization to the desired 6-oxo-1,6-dihydropyridine.