22208-39-5

Usage

Uses

Used in Pharmaceutical Industry:
2-cyano-N-(4-nitrophenyl)acetamide is used as a chemical intermediate for the synthesis of various pharmaceuticals and organic compounds. Its unique functional groups, including the nitro and cyanide groups, make it a valuable component in the development of new drugs and medicinal agents.
Used in Organic Synthesis:
In the field of organic synthesis, 2-cyano-N-(4-nitrophenyl)acetamide serves as a key intermediate for the preparation of a wide range of organic compounds. Its reactivity and chemical properties allow it to be used in various chemical reactions, contributing to the synthesis of diverse organic molecules with potential applications in various industries.

Upstream product

• 6674-22-2 1,8-diazabicyclo[5.4.0]undec-7-ene 
• 100-01-6 4-nitro-aniline 
• 36140-83-7 1-cyanoacetyl-3,5-dimethylpyrazole 
• 372-09-8 cyanoacetic acid 

Downstream Products

• 608519-82-0 2-amino-4-methylsulfanyl-1-(4-nitro-phenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile 
• 73536-40-0 6-hydroxy-4-methyl-1-(4-nitrophenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile 
• 1263303-91-8 2-hydroxyimino-3-(4-nitrophenyl)amino-3-oxopropionitrile 
• 136186-29-3 (Z)-2-Cyano-3-hydroxy-N-(4-isothiocyanato-phenyl)-3-(4-trifluoromethyl-phenyl)-acrylamide 
• 24522-55-2 N-(4-nitro phenyl)-4,6-dimethyl-3-cyano-2-pyridone 
• 4452-08-8 cyanoketene 
• 100-01-6 4-nitro-aniline 
• 146494-84-0 2-Amino-4-(4-nitro-phenyl)-3-oxo-1,4-diaza-spiro[4.5]decane-2-carboxylic acid amide 
• 136186-26-0 (Z)-2-Cyano-3-hydroxy-N-(4-nitro-phenyl)-3-(4-trifluoromethyl-phenyl)-acrylamide 

Relevant academic research and scientific papers

Identification of Novel Fused Heteroaromatics-Based MALT1 Inhibitors by High-Throughput Screening to Treat B Cell Lymphoma

Development of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitors is of great value and significance in the treatment of neoplastic disorders and inflammatory and autoimmune diseases. However, there is a lack of effective MALT1 inhibitors in clinic. Herein, a novel class of potent 5-oxo-1-thioxo-4,5-dihydro-1H-thiazolo[3,4-a]quinazoline-based MALT1 inhibitors and their covalent derivatives were first identified and designed through high-throughput screening. We demonstrated that compounds 15c, 15e, and 20c effectively inhibited the MALT1 protease and displayed selective cytotoxicity to activated B cell-like diffuse large B cell lymphoma with low single-digit micromolar potency. Furthermore, compound 20c specifically repressed NF-κB signaling and induced cell apoptosis in MALT1-dependent TMD8 cells in a dose-dependent manner. More importantly, 20c showed good pharmacokinetic properties and antitumor efficacy with no significant toxicity in the TMD8 xenograft tumor model. Collectively, this study provides valuable lead compounds of MALT1 inhibitors for further structural optimization and antitumor mechanism study.

Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal function

Ion selectivity is a defining feature of a given ion channel and is considered immutable. Here we show that ion selectivity of the lysosomal ion channel TPC2, which is hotly debated (Calcraft et al., 2009; Guo et al., 2017; Jha et al., 2014; Ruas et al., 2015; Wang et al., 2012), depends on the activating ligand. A high-throughput screen identified two structurally distinct TPC2 agonists. One of these evoked robust Ca2+-signals and non-selective cation currents, the other weaker Ca2+-signals and Na+-selective currents. These properties were mirrored by the Ca2+- mobilizing messenger, NAADP and the phosphoinositide, PI(3,5)P2, respectively. Agonist action was differentially inhibited by mutation of a single TPC2 residue and coupled to opposing changes in lysosomal pH and exocytosis. Our findings resolve conflicting reports on the permeability and gating properties of TPC2 and they establish a new paradigm whereby a single ion channel mediates distinct, functionally-relevant ionic signatures on demand.

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).

Novel anion receptors for selective recognition of dimethyl phosphinate and carboxylate

We have designed and synthesized new anion receptors 1 and 2, which have amide N[sbnd]H, pyrrole N[sbnd]H and vinyl C[sbnd]H as hydrogen bond donors. These receptors are selective for dimethyl phosphinate and carboxylates. Due to electron withdrawing effect of the cyano group which is trans to the vinyl hydrogen with respect to carbon-carbon double bond, receptor 1 has higher binding constants for phosphinate and carboxylate than those of receptor 2. Modeling studies shows that cyano group polarized all three hydrogens through planar π-electron network. In addition, receptor 1 gave orange colored 1,4-addition product for cyanide.

2-Imino 2H-chromene and 2-(phenylimino) 2H-chromene 3-aryl carboxamide derivatives as novel cytotoxic agents: synthesis, biological assay, and molecular docking study

The inhibition of AKR1B10 has been recognized as a potential therapeutic approach to the treatment of various types of cancers. A novel series of compounds with imino-2H-chromen and phenylimino-2H-chromen scaffolds were synthesized by Knoevenagel condensation reaction. The in vitro cytotoxic activity of synthesized compounds was evaluated against MOLT-4 and SK-OV-3 cells. Among the tested compounds, N-(3,4-dimethoxyphenyl)-2-(phenylimino)-2H-chromene-3-carboxamide (8g) demonstrated potent inhibitory activity against both examined cell lines. The results of the molecular docking study suggested that this compound is involved in critical hydrogen-bonding interactions with the Val301 and Lue302 of AKR1B10 catalytic site.

Promiscuity and selectivity in covalent enzyme inhibition: A systematic study of electrophilic fragments

Covalent ligand-target interactions offer significant pharmacological advantages. However, off-target reactivity of the reactive groups, which usually have electrophilic properties, must be minimized, and the selectivity of irreversible inhibitors is a crucial requirement. We therefore performed a systematic study to determine the selectivity of several electrophilic groups that can be used as building blocks for covalently binding ligands. Six reactive groups with modulated electrophilicity were combined with 11 nonreactive moieties, resulting in a small combinatorial library of 72 fragment-like compounds. These compounds were screened against a group of 11 enzyme targets to assess their selectivity and their potential for promiscuous binding to proteins. The assay results showed a considerably lower degree of promiscuity than initially expected, even for those members of the screening collection that contain supposedly highly reactive electrophiles.

QUINOLINONE DERIVATIVES

HIV inhibitory compounds of formula (I) including the stereoisomeric forms thereof, the pharmaceutically acceptable salts, and pharmaceutically acceptable solvates thereof; wherein R1 is cyano; R2 is H, C1-6alkyl, trifluoromethyl, amino, mono- or di-C1-6alkylamino, C1-6alkylamino wherein the C1-6alkyl group can be substituted; X1 is CH or N; R3 is phenyl or pyridyl, each unsubstituted or substituted; R4 is H, C1-6alkyl, (C1-6alkylcarbonyla mino)C1-6alkyl-, Ar, potionally substituted thienyl, furanyl, pyridyl, pyrimidyl, pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl, triazo lyl, oxazolyl, thiazolyl, halo, trifluoromethyl, hydroxy, C1-6alkyloxy, -OPO(OH)2, amino, aminocarbonyl, cyano, -Y1-R6, -Y1-Alk-R6, or -Y1-Alk-Y2-R7; R5 is H, halo, hydroxy or C1-6alkyloxy; or R4 and R5 form -O-CH2-O-; Y1 is O or NR8; Y2 is O or NR9; Alk is bivalent C1-6alkyl; R6 is pyrrolidinyl, piperidinyl, morpho linyl, piperazinyl, 4-C1 -6alkylpiperazinyl, 4-(C1-6alkylcarbonyl)piperazinyl, pyridyl, or imidazolyl; R7 is H, C1-6alkyl, hydroxyC1 -6alkyl, C1-6alkylcarbonyl; R8 and R9 are H or C1-6alkyl; Ar is optionally substituted phenyl; pharmaceut ical compositions comprising the above compounds (I) as active ingredient.

Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl- 3-hydroxy. N-[3'-methyl-4'-(trifluoromethyl)phenyl]propenamide and related compounds

The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biological activity determined in rat and mouse delayed type hypersensitivity has been found to correlate well with their in vitro DHODH potency. The most promising compound (3) has shown activity in rat and mouse collagen (II)-induced arthritis models (ED50 = 2 and 31 mg/kg, respectively) and has shown a shorter half-life in man when compared with leflunomide. Clinical studies in rheumatoid arthritis are in progress.

Synthesis and Biological Activity of a Series of Diaryl-Substituted α-Cyano-β-hydroxypropenamides, a New Class of Anthelmintic Agents

A series of α-cyano-β-hydroxypropenamides was prepared and tested for anthelmintic activity. α-Cyano-β-hydroxy-N--3-propenamide (1) showed good activity against the nematode Nematospirodes dubius in a mixed parasite infection in mice; several of the analogues were also effective against the cestode Hymenolepis nana.In sheep trials, 1 caused 100percent reduction of the hematophagous nematode Haemonchus contortus after a single dose of 20 mg/kg but did not show satisfactory control of Trichostrongylus colubriformis or Ostertagia circumcincta.Against the liver fluke Fasciola hepatica, 1 suppressed egg production but only temporarily, suggesting that the adult flukes were not eliminated.Mechanism of action studies on 1 using Ascaris mitochondria showed it to be an uncoupler of oxidative phosphorylation.