6629-04-5

Usage

Uses

Used in Pharmaceutical Industry:
N-Cyanoacetylurethane is used as a synthetic intermediate for the development of inhibitors targeting the PDZ domain of PICK1. This protein-protein interaction domain is a potential target for the treatment of brain ischemia, pain, and addiction-related illnesses. By inhibiting the PDZ domain of PICK1, these inhibitors can modulate the underlying signaling pathways and provide therapeutic benefits in these conditions.
Additionally, N-Cyanoacetylurethane is used in the synthesis of cathepsin K inhibitors. Cathepsin K is a cysteine protease enzyme implicated in various pathological conditions, including osteoporosis and arthritis. Inhibiting cathepsin K activity can help in managing these diseases by reducing bone resorption and inflammation.

InChI:InChI=1/C6H8N2O3/c1-2-11-6(10)8-5(9)3-4-7/h2-3H2,1H3,(H,8,9,10)

Upstream product

• 372-09-8 cyanoacetic acid 
• 51-79-6 urethane 

Downstream Products

• 1187-34-4 α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide 
• 30615-95-3 (2-cyano-2-(2-phenylhydrazino)acetyl)carbamic acid ethyl ester 
• 30615-96-4 N-(p-Tolylhydrazono-cyanacetyl)-carbamidsaeure-aethylester 
• 30615-98-6 N-<(4-brom-phenylhydrazono)-cyanacetyl>-carbamidsaeure-ethylester 
• 30487-53-7 ((E)-3-p-Tolylamino-acryloyl)-carbamic acid ethyl ester 
• 30487-54-8 C₁₃H₁₆N₂O₄ 
• 4260-38-2 (3-anilino-acryloyl)-carbamic acid ethyl ester 
• 83132-66-5 Ethyl 2-(2-carboxybenzoyl)phenylhydrazonocyanacetylcarbamate 
• 133568-70-4 ethyl 4-(3,5-dioxo-6-cyano-2,3,4,5-tetrahydro-1,2,4-triazin-2-yl)-phenylhydrazonocyanoacetylcarbamate 
• 133568-69-1 ethyl 3-(3,5-dioxo-6-cyano-2,3,4,5-tetrahydro-1,2,4-triazin-2-yl)-phenylhydrazonocyanoacetylcarbamate 
• 77442-00-3 4-(2-Thio-6-azauracil-5-yl-methyl)phenylhydrazonocyanacetylcarbamidsaeureethylester 
• 74875-28-8 ethyl N-<<methyl>carbonyl>carbamate 
• 77441-99-7 4-(6-Azauracil-5-yl-methyl)phenylhydrazonocyanacetylcarbamidsaeureethylester 
• 74875-23-3 ethyl N-<<hydrazinylidene>methyl>carbonyl>carbamate 

Relevant academic research and scientific papers

Determinants of the Inhibition of DprE1 and CYP2C9 by Antitubercular Thiophenes

Mycobacterium tuberculosis (Mtb) DprE1, an essential isomerase for the biosynthesis of the mycobacterial cell wall, is a validated target for tuberculosis (TB) drug development. Here we report the X-ray crystal structures of DprE1 and the DprE1 resistant mutant (Y314C) in complexes with TCA1 derivatives to elucidate the molecular basis of their inhibitory activities and an unconventional resistance mechanism, which enabled us to optimize the potency of the analogs. The selected lead compound showed excellent in vitro and in vivo activities, and low risk of toxicity profile except for the inhibition of CYP2C9. A crystal structure of CYP2C9 in complex with a TCA1 analog revealed the similar interaction patterns to the DprE1–TCA1 complex. Guided by the structures, an optimized molecule was generated with differential inhibitory activities against DprE1 and CYP2C9, which provides insights for development of a clinical candidate to treat TB.

Exploring disordered loops in DprE1 provides a functional site to combat drug-resistance in Mycobacterium strains

As an anti-tuberculosis target, DprE1 contains two flexible loops (Loop I and Loop II) which have never been exploited for developing DprE1 inhibitors. Here Leu317 in Loop II was discovered as a new functional site to combat drug-resistance in Mycobacterium strains. Based on TCA1, LZDT1 was designed to optimize the hydrophobic interaction with Leu317. A subsequent biochemical and cellular assay displayed increased potency of LZDT1 in inhibiting DprE1 and killing drug-sensitive/-resistant Mycobacterium strains. The improved activity of LZDT1 and its analogue LZDT2 against multidrug resistant tuberculosis was particularly highlighted. For LZDT1, its enhanced interaction with Leu317 also impaired the drug-insensitivity of DprE1 caused by Cys387 mutation. A new nonbenzothiazole lead (LZDT10) with reduced Cys387-dependence was further produced by optimizing interactions with Leu317, improvement directions for LZDT10 were discussed as well. Our research underscores the value of potential functional sites in disordered loops, and affords a feasible way to develop these functional sites into opportunities for drug-resistance management.

Discovery of Novel Thiophene-arylamide Derivatives as DprE1 Inhibitors with Potent Antimycobacterial Activities

In this study, we report the design and synthesis of a series of novel thiophene-arylamide compounds derived from the noncovalent decaprenylphosphoryl-β-d-ribose 2′-epimerase (DprE1) inhibitor TCA1 through a structure-based scaffold hopping strategy. Systematic optimization of the two side chains flanking the thiophene core led to new lead compounds bearing a thiophene-arylamide scaffold with potent antimycobacterial activity and low cytotoxicity. Compounds 23j, 24f, 25a, and 25b exhibited potent in vitro activity against both drug-susceptible (minimum inhibitory concentration (MIC) = 0.02-0.12 μg/mL) and drug-resistant (MIC = 0.031-0.24 μg/mL) tuberculosis strains while retaining potent DprE1 inhibition (half maximal inhibitory concentration (IC50) = 0.2-0.9 μg/mL) and good intracellular antimycobacterial activity. In addition, these compounds showed good hepatocyte stability and low inhibition of the human ether-à-go-go related gene (hERG) channel. The representative compound 25a with acceptable pharmacokinetic property demonstrated significant bactericidal activity in an acute mouse model of tuberculosis. Moreover, the molecular docking study of template compound 23j provides new insight into the discovery of novel antitubercular agents targeting DprE1.

SUBSTITUTED TRIAZINONES AS THYROID HORMONE RECEPTOR AGONISTS

The application relates to a compound of Formula (I') or (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which modulates the activity of thyroid hormone receptors, a pharmaceutical composition comprising a compound of Formula (I') or (I), and a method of treating or preventing a disease or disorder regulated by thyroid hormone.

Liposomal encapsulated FSC231, a PICK1 inhibitor, prevents the ischemia/reperfusion-induced degradation of GluA2-containing AMPA receptors

Strokes remain one of the leading causes of disability within the United States. Despite an enormous amount of research effort within the scientific community, very few therapeutics are available for stroke patients. Cytotoxic accumulation of intracellular calcium is a well-studied phenomenon that occurs following ischemic stroke. This intracellular calcium overload results from excessive release of the excitatory neurotransmitter glutamate, a process known as excitotoxicity. Calcium-permeable AMPA receptors (AMPARs), lacking the GluA2 subunit, contribute to calcium cytotoxicity and subsequent neuronal death. The internalization and subsequent degradation of GluA2 AMPAR subunits following oxygen-glucose deprivation/reperfusion (OGD/R) is, at least in part, mediated by protein-interacting with C kinase-1 (PICK1). The purpose of the present study is to evaluate whether treatment with a PICK1 inhibitor, FSC231, prevents the OGD/R-induced degradation of the GluA2 AMPAR subunit. Utilizing an acute rodent hippocampal slice model system, we determined that pretreatment with FSC231 prevented the OGD/R-induced association of PICK1-GluA2. FSC231 treatment during OGD/R rescues total GluA2 AMPAR subunit protein levels. This suggests that the interaction between GluA2 and PICK1 serves as an important step in the ischemic/reperfusion-induced reduction in total GluA2 levels.

Diaryl 2- amide-substituted thiophene imide ester compound as well as preparation method and application thereof (by machine translation)

The invention also discloses a 2 - synthesis method thereof, and an application of the compound as an antibacterial agent, in the phthisis-caused by the bacterium, in particular to the, mycobacterium-induced infectious disease (especially (Tuberculosis,TB), mycobacterium- induced mycobacterium, tuberculosis), and (I) the invention, specifically relates to a pharmaceutical composition containing the compound of the present invention or, a R pharmaceutical composition comprising the compound of the present invention. 1 , R2 , R3 , R4 , R5 As described Y in the present invention. as described in the specification, the present invention is directed, to the preparation of novel compounds, having an anti-mycobacterial activity as potential, new drug (s) for the treatment (TB) or preventative treatment of infectious diseases, consisting of M. tuberculosis, in particular phthisis- caused by tubercular mycobacteria, while being useful in overcoming the problems associated with drug resistance. (by machine translation)

NANOMATERIAL COMPOSITIONS, SYNTHESIS, AND ASSEMBLY

Compositions or an assembly of a series of biomimetic compounds include chemical structures that mimic or structurally resemble a nucleic acid base pair. Complexes of nanotubes and agents are useful to deliver agents into the cells or bodily tissues of individuals for therapeutic and diagnostic purposes. Exemplary compounds include those of Formula (I), (III), (V) or (VII), or of Formula (II), (IV), (VI) or (VIII).

COMPOUNDS FOR TREATMENT OF DRUG RESISTANT AND PERSISTENT TUBERCULOSIS

Described herein are compounds and compositions for treating drug resistant and persistent tuberculosis. Also described herein is a method of screening for identifiying biofilm formation inhibitors.

QUINOLINE COMPOUND COMPOSING 1,2,4-TRIAZINE-DIONE AND USE THEREOF

The present invention relates to a quinoline deravative represented by general formula (I) or a pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof, wherein Ar, R1, R2, R3, X, Y and n have the meanings given in the description. The present invention also relates to the comparatively strong effect of the compound represented by general formula (I) on inhibiting c-Met kinase. The present invention further relates to the use of this compound or a pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof in the manufacturing of a medicament for treating the disease caused by abnormally over-expressing c-Met kinase, in particular, for treating or preventing cancer.

Structure-activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1

Recently, we described the first small-molecule inhibitor, (E)-ethyl 2-cyano-3-(3,4-dichlorophenyl)acryloylcarbamate (1), of the PDZ domain of protein interacting with Cα-kinase 1 (PICK1), a potential drug target against brain ischemia, pain and cocaine addiction. Herein, we explore structure-activity relationships of 1 by introducing subtle modifications of the acryloylcarbamate scaffold and variations of the substituents on this scaffold. The configuration around the double bond of 1 and analogues was settled by a combination of X-ray crystallography, NMR and density functional theory calculations. Thereby, docking studies were used to correlate biological affinities with structural considerations for ligand-protein interactions. The most potent analogue obtained in this study showed an improvement in affinity compared to 1 and is currently a lead in further studies of PICK1 inhibition.