15029-30-8

Usage

Chemical Properties

orange needle-like crystalline powder

InChI:InChI=1/C8H12N2O/c9-5-4-8(11)10-6-2-1-3-7-10/h1-4,6-7H2

Upstream product

• 110-89-4 piperidine 
• 105-56-6 ethyl 2-cyanoacetate 
• 1440-60-4 1-chloroacetyl-piperidine 
• 151-50-8 potassium cyanide 
• 105-34-0 methyl 2-cyanoacetate 
• 372-09-8 cyanoacetic acid 
• 16130-58-8 cyanoacetic acid chloride 
• 36140-83-7 1-cyanoacetyl-3,5-dimethylpyrazole 

Downstream Products

• 141811-04-3 4-cyano-2-ethoxycarbonyl-3-piperidin-1-ylcarbonylbutan-2-one 4-phenylsemicarbazone 
• 141811-03-2 4-cyano-2-methoxycarbonyl-3-piperidin-1-ylcarbonylbutan-2-one 4-phenylsemicarbazone 
• 88059-40-9 (Z)-3-Hydroxy-3-(2-methylamino-phenyl)-2-(piperidine-1-carbonyl)-acrylonitrile 
• 51866-38-7 (Z)-3-(3,5-Di-tert-butyl-4-hydroxy-phenyl)-2-(piperidine-1-carbonyl)-acrylonitrile 
• 81730-52-1 3-(piperidin-1-yl)-3-thioxopropanenitrile 
• 4706-33-6 2-oxo-2-(piperidin-1-yl)acetic acid 

Relevant academic research and scientific papers

Part 1: Experimental and theoretical studies of 2-cyano-2-isonitroso-N- piperidynylacetamide (HPiPCO), 2-cyano-2-isonitroso-N-morpholylacetamide (HMCO) and their Pt- and Pd-complexes

The reaction between substituted cyan-acetamides NC-CH2-C(O)X (X = N-piperidyne or N-morpholyl residues) and gaseous methylnitrite CH 3ONO in isopropanol at room temperature in the presence of a base within minutes leads to colorless cyanoximes 2-cyano-2-isonitroso-N- piperidynylacetamide (further as HPiPCO), and 2-cyano-2-isonitroso-N- morpholylacetamide (HMCO) in 70-90% yield. The deprotonation of HPiPCO and HMCO with a base such as NaOEt affords anionic Na-salts, bright-yellow in color originated from n → π* transitions in the nitroso-chromophore. Anionic cyanoximates react with aqueous solutions of K 2MCl4 (M = Pd, Pt) to form yellow-orange PdL2 and dark blue-green polymeric [PtL2]n (L = PiPCO -, MCO-), which upon treatment with DMSO or DMF breaks down to pale-yellow monomeric PtL2. Synthesized metal complexes were characterized by spectroscopic methods (IR, UV-Vis), measurement of the electric conductivity and the X-ray analysis. Both PdL2 and PtL2 exhibit non-electrolyte behavior in DMSO and DMF. Crystal structures of Pd(PiPCO)2 and Pt(PiPCO)2 were determined and revealed the formation of the cis-complexes with nearly planar geometry around the metal core and an adoption of the cis-anti configuration by anions, in contrast to the trans-anti geometry in structures of uncomplexed HPiPCO and HMCO. Ab initio calculations were performed for all six compounds: two cyanoxime ligands and four Pd and Pt metal complexes. A very satisfactory agreement between the calculated and experimental values of geometrical parameters of all evaluated compounds was attained. The electron densities, energies of HOMO and LUMO orbitals and molecular electrostatic potentials were calculated as well.

Synthesis and characterization of two cyanoxime ligands, their precursors, and light insensitive antimicrobial silver(I) cyanoximates

High-yield syntheses of N-piperidine-cyanacetamide (1), N-morpholyl-cyanacetamide (4) and their oxime derivatives N-piperidine-2-cyano- 2-oximino-acetamide (HPiPCO, 2) and N-morpholyc-2-cyano-2-oximino-acetamide (HMCO, 5) were developed using two-step preparations. At first, the reactions of neat cyanoacetic acid esters and the respective cyclic secondary amines such as piperideine and morpholine afforded pure cyan-acetamides, which were converted into cyanoximes at room temperature using the nitrosation reaction with gaseous CH3ONO. The synthesized compounds were investigated by means of IR, 1H, 13C and UV-Vis spectroscopy. Crystal structures of two starting substituted cyan-acetamides and two target cyanoximes were determined. Silver(I) complexes of AgL composition (L = PipCO, 3; MCO, 6) were prepared in high yield. Both metal complexes are thermally stable above 100 C, and remarkably stable to high intensity visible light. The stability of dried AgL compounds towards short wavelength UV-radiation (a frequently used germicidal light) was examined using diffusion reflectance spectroscopy. Both complexes demonstrate slow photoreduction within ～3 h, observable as a gradual color change and darkening due to the formation of fine (nano-scale) particles of metallic silver. The complex Ag(MCO), 6, is about 2.6 times less stable towards UV-radiation than its more lypophyllic analog Ag(PipCO), 3. Antimicrobial and biofilm growth inhibition properties of the prepared solid acrylate-based polymeric composites containing embedded silver(I) cyanoximates were investigated using three human pathogens: Pseudomonas aeruginosa PAO1 (wound isolate), Staphylococcus aureus NRS70 (methicillin resistant respiratory isolate), and Streptococcus mutans UA159 (cariogenic dental isolate). Studies showed that both 3 and 6 compounds completely abolished the growth of PAO1 at 0.5 weight% concentration, and the growth of UA159 and NRS70 at 1% concentration. Thus, the data demonstrate that complexes 3 and 6 inhibit both planktonic and biofilm growth of Gram-positive and Gram-negative bacterial pathogens. The demonstrated thermal stability and pronounced antimicrobial activity of both silver(I) cyanoximates indicates the strong potential for the studied complexes to be used as light insensitive antimicrobial additives to light-curable adhesives that set indwelling devices in place.

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.

Synthesis, cytotoxic characterization, and SAR study of imidazo[1,2-b]pyrazole-7-carboxamides

The synthesis and in vitro cytotoxic characteristics of new imidazo[1,2-b]pyrazole-7-carboxamides were investigated. Following a hit-to-lead optimization exploiting 2D and 3D cultures of MCF-7 human breast, 4T1 mammary gland, and HL-60 human promyelocytic leukemia cancer cell lines, a 67-membered library was constructed and the structure–activity relationship (SAR) was determined. Seven synthesized analogues exhibited sub-micromolar activities, from which compound 63 exerted the most significant potency with a remarkable HL-60 sensitivity (IC50 = 0.183 μM).

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.

FTO INHIBITORS

The invention provides compounds that inhibit FTO (fat mass and obesity), including pharmaceutically acceptable salts, hydrides and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof, particularly obesity, with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.

Cyanoacetamide-based oxime carbonates: An efficient, simple alternative for the introduction of Fmoc with minimal dipeptide formation

Nowadays, most peptides are chemically achieved by using the Fmoc/tBu protection strategy, due to its fully orthogonal character, mild temporary group removal and resin cleavage steps. However, its introduction into N-unprotected amino acids is not exempt of synthetic inconveniences, such as dipeptide formation. Lately, novel oxime carbonates were introduced in the arsenal of reagents for the introduction of Fmoc, presenting almost negligible percentage of side-products. Herein, an enforced version of this family of Fmoc-carbonates is presented, containing stable and highly acidic cyanoacetamide-based oximes as leaving group. Such reactive species, affordable in only two steps from simple, readily available starting materials, show unusual ability to obtain the corresponding Fmoc-protected residues in high yield and minimal impact of detrimental side-products, mainly Fmoc-dipeptides.

Synthesis of new 8-formyl-4-methyl-7-hydroxy coumarin derivatives

8-Formyl-4-Methyl-7-Hydroxy Coumarin Derivatives were synthesized via Penchem condensation followed by Duffs reaction. Treatment of this with N,N-di substituted cyano acetamides in the presence of piperdine afforded New 8- Formyl-4-Methyl-7-Hydroxy Coumarin Derivatives (7a-o). Their structures were characterized by IR, 1H and 13C NMR and Mass spectral and elemental analysis data.

Synthesis of perhydro-N-(2,2-disubstituted- 3-aminopropyl) heterocycles as potentially bioactive compounds and fragments for combinatorial chemistry

A new method for the preparation of perhydro- N - (2,2-disubstituted-3- aminopropyl) heterocycles that allows to obtain a large variety of corresponding derivatives with high to moderate yields using simple procedures is described.

Efficient synthesis of new butenolides by subsequent reactions: Application for the synthesis of original iminolactones, bis-iminolactones and bis-lactones

We have developed the synthesis of twenty four new iminolactones, bis-iminolactones and bis-lactones by subsequent esterification-condensation or addition-condensation reactions according to two strategies from α-hydroxyketones. The X-ray diffraction data of a bis-iminolactone is described and present an interesting helical column packing.