4640-66-8

Usage

Uses

Used in Pharmaceutical Industry:
4-Chlorobenzoylacetonitrile is used as an intermediate in the synthesis of various pharmaceutical compounds. Its presence in the molecular structure can contribute to the development of new drugs with improved efficacy and reduced side effects.
Used in Agrochemical Industry:
In the agrochemical industry, 4-Chlorobenzoylacetonitrile is utilized as a key component in the production of pesticides and other crop protection agents. Its incorporation into these products can enhance their effectiveness in controlling pests and diseases, leading to increased crop yields and better food security.
Used in Dye Industry:
4-Chlorobenzoylacetonitrile is also used as a starting material for the synthesis of various dyes and pigments. The resulting dyes can be employed in a wide range of applications, including textiles, plastics, and printing inks, due to their vibrant colors and excellent lightfastness.
Used in Organic Synthesis:
As a versatile building block, 4-Chlorobenzoylacetonitrile is used in the synthesis of a wide array of organic compounds. Its unique chemical properties allow for various functional group transformations, enabling the creation of complex molecules with diverse applications in different industries.

InChI:InChI=1/C9H6ClNO/c10-8-3-1-7(2-4-8)9(12)5-6-11/h1-4H,5H2

Upstream product

• 99-91-2 para-chloroacetophenone 
• 17197-20-5 3-amino-3-(4-chlorophenyl)acrylonitrile 
• 98-88-4 benzoyl chloride 
• 7335-27-5 ethyl 4-chlorobenzoate 
• 75-05-8 acetonitrile 
• 143-33-9 sodium cyanide 
• 536-38-9 4-chlorobenzoylmethyl bromide 
• 17059-59-5 1-(4-chloro-phenyl)-3-phenyl-propane-1,3-dione 
• 623-03-0 4-Cyanochlorobenzene 
• 74-11-3 para-chlorobenzoic acid 
• 873-76-7 para-Chlorobenzyl alcohol 
• 1116-98-9 cyanoacetic acid tert-butyl ester 
• 122-01-0 4-chloro-benzoyl chloride 
• 83392-36-3 methyl 3-(4-chlorophenyl)-3-oxopropanedithioate 

Downstream Products

• 64646-26-0 2-(4-chloro-benzoyl)-3-phenyl-acrylonitrile 
• 54295-36-2 2-(4-chloro-phenyl)-6-morpholin-4-yl-4-phenyl-nicotinonitrile 
• 54295-35-1 2,4-bis-(4-chloro-phenyl)-6-morpholin-4-yl-nicotinonitrile 
• 74101-10-3 5-(4-chloro-phenyl)-2-(4-phenyl-thiazol-2-yl)-2H-pyrazol-3-ylamine 
• 68775-20-2 5-amino-1-(benzothiazol-2-yl)-3-(p-chlorophenyl)-1-H-pyrazole 
• 337467-32-0 2-[2-(4-chlorophenyl)-2-oxoethylidene]-1,3-thiazolidin-4-one 
• 74101-20-5 5-(4-chloro-phenyl)-2-[4-(4-chloro-phenyl)-thiazol-2-yl]-2H-pyrazol-3-ylamine 
• 74114-54-8 2-[4-(4-bromo-phenyl)-thiazol-2-yl]-5-(4-chloro-phenyl)-2H-pyrazol-3-ylamine 
• 69316-19-4 3-(4-chlorophenyl)-2-hydroxyimino-3-oxopropanenitrile 
• 33866-48-7 3-(4-chloro-phenyl)-isoxazol-5-ylamine 
• 81072-15-3 2-<α-(p-chlorobenzoyl)-α-cyanomethylene>-1-methylhexahydropyrimidine 
• 205595-39-7 2-amino-5-cyano-6-(4'-chlorophenyl)-4-thioxo-4H-pyran-3-ylphosphonic acid dimethyl ester 
• 205595-44-4 [2-Amino-6-(4-chloro-phenyl)-5-cyano-4-thioxo-4H-pyran-3-yl]-phosphonic acid diethyl ester 
• 208726-32-3 2-amino-5-cyano-6-(4'-chlorophenyl)-4-thioxo-4H-pyran-3-ylphosphonic acid diisopropyl ester 

Relevant academic research and scientific papers

Pyrolytic behavior of substituted N-aminoheteroaromatics: Synthesis of pyrazolo[1,5-a]pyridine and 3-substituted 3-oxo-propionitrile derivatives

(Chemical Equation Presented) Flash vacuum pyrolysis (FVP) of 1,7-bis-(3-aroylideneamino)-4,6,10,12-tetramethyl-2,8-dioxo-1, 7-diazacyclododeca-3,5,9,11-tetraene-3,9-dicarbonitriles 11a-c at 650°C and 0.02 Torr yielded 5,7-dimethyl-3-(4-methylbenzoyl)-pyrazolo[1,5-a]pyridine-4- carbonitrile 14, 4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile 16 and 3-aryl-3-oxo-propionitriles 17a,b. A plausible mechanism is suggested to account for the formation of the products.

One-pot three-component synthesis of novel pyrazolo[3,4-b]pyridines as potent antileukemic agents

In the current study, we report on the development of novel series of pyrazolo[3,4-b]pyridine derivatives (8a-u, 11a-n, and 14a,b) as potential anticancer agents. The prepared pyrazolo[3,4-b]pyridines have been screened for their antitumor activity in vitro at NCI-DTP. Thereafter, compound 8a was qualified by NCI for full panel five-dose assay to assess its GI50, TGI and LC50 values. Compound 8a showed broad-spectrum anti-proliferative activities over the whole NCI panel, with outstanding growth inhibition full panel GI50 (MG-MID) value equals 2.16 μM and subpanel GI50 (MG-MID) range: 1.92–2.86 μM. Furthermore, pyrazolo[3,4-b]pyridines 8a, 8e-h, 8o, 8u, 11a, 11e, 11h, 11l and 14a-b were assayed for their antiproliferative effect against a panel of leukemia cell lines (K562, MV4-11, CEM, RS4;11, ML-2 and KOPN-8) where they possessed moderate to excellent anti-leukemic activity. Moreover, pyrazolo[3,4-b]pyridines 8o, 8u, 14a and 14b were further explored for their effect on cell cycle on RS4;11 cells, in which they dose-dependently increased populations of cells in G2/M phases. Finally we analyzed the changes of selected proteins (HOXA9, MEIS1, PARP, BcL-2 and McL-1) related to cell death and viability in RS4;11 cells via Western blotting. Collectively, the obtained results suggested pyrazolo[3,4-b]pyridines 8o, 8u, 14a and 14b as promising lead molecules for further optimization to develop more potent and efficient anticancer candidates.

Synthesis and in vitro antiproliferative activity of certain novel pyrazolo[3,4-b]pyridines with potential p38α MAPK-inhibitory activity

Novel series of pyrazolo[3,4-b]pyridines 9a–j and 14a–f were prepared via a one-pot three-component reaction. Compounds 9a–j were synthesized by the reaction of 3-(4-chlorophenyl)?1-phenyl-1H-pyrazol-5-amine (4) with benzoyl acetonitriles 3a,b and aldehydes 5a–e, whereas the spiro derivatives 14a–f were synthesized by the reaction of pyrazole derivative 4 with 3a–c and indoline-2,3-diones 10a,b. Screening of the antiproliferative activity of 9a–j and 14a–f revealed that 14a and 14d were the most potent analogues against HepG2 and HeLa cells, with IC50 = 4.2 and 5.9 μM, respectively. Moreover, compounds 9c and 14a could promote cell cycle disturbance and apoptosis in HepG2 cells, as evidenced by DNA flow cytometry and Annexin V-FITC/PI assays. Cell cycle analysis of 9c and 14a indicated a reduction in HepG2 cells in the G1 phase, with arrest in the S phase and the G2/M phase, respectively. Also, 9c and 14a are good apoptotic inducers in the HepG2 cell line. Furthermore, compounds 9h and 14d stood out as the most efficient antiproliferative agents in the NCI 60-cell line panel screening, with mean GI % equal to 60.3% and 55.4%, respectively. Additionally, 9c, 9h, 14a, and 14d showed good inhibitory action against the cellular pathway regulator p38α kinase, with IC50 = 0.42, 0.41, 0.13, and 0.64 μM, respectively. A docking study was carried out on the p38α kinase active site, showing a binding mode comparable to that of reported p38 mitogen-activated protein kinase inhibitors. These newly discovered pyrazolo[3,4-b]pyridines could be considered as potential candidates for the development of newly targeted anticancer agents.

Modular synthesis and antiproliferative activity of new dihydro-1H-pyrazolo[1,3-b]pyridine embelin derivatives

A set of new dihydro-1H-pyrazolo[1,3-b]pyridine and pyrazolo[1,3-b]pyridine embelin derivatives was synthesized through a multicomponent reaction from natural embelin, 3-substituted-5-aminopyrazoles and aldehydes. The synthesized compounds were evaluated against three hematologic tumor cell lines, HEL (acute erythroid leukemia), K-562 (chronic myeloid leukemia) and HL-60 (acute myeloid leukemia), and five breast cancer cell lines (SKBR3, MCF-7, MDA-MB-231, BT-549, HS-578T). The primate non-malignant kidney Vero cell line was used as the control of cytotoxicity. From the obtained results, some structure–activity relationships were out-lined. Furthermore, in silico prediction of physicochemical properties and ADME parameters were determined for the derivatives with the best antiproliferative values.

Deadly KCN and pricey metal free track for accessing β-ketonitriles employing mild reaction conditions

A one pot synthesis of β-ketonitriles from readily accessible 3-chloropropenals using economically benign iodine, aqueous ammonia and sodium hydroxide solution, employing mild reaction conditions have been described. This report presents a convenient, inexpensive, highly toxic-matter-free and eco-friendly approach for β-ketonitriles.

Selective Synthesis of β-Ketonitriles via Catalytic Carbopalladation of Dinitriles

A practical, convenient, and highly selective method of synthesizing β-ketonitriles from the Pd-catalyzed addition of organoboron reagents to dinitriles has been developed. This method provides excellent functional-group tolerance, a broad scope of substrates, and the convenience of using commercially available substrates. The method is expected to show further utility in future synthetic procedures.

Antitumor properties of certain spirooxindoles towards hepatocellular carcinoma endowed with antioxidant activity

In the current medical era, spirooxindole motif stands out as a privileged heterospirocyclic scaffold that represents the core for a wide range of bioactive naturally isolated products (such as Strychnofoline and spirotryprostatins A and B) and synthetic compounds. Interestingly, no much attention has been paid to develop spirooxindole derivatives with dual antioxidant and anticancer activities. In this context, a series of spirooxindoles 6a-p was examined for their anticancer effect towards HepG2 hepatocellular carcinoma and PC-3 prostate cancer cell lines. Spirooxindole 6a was found to be an efficient anti-proliferative agent towards both HepG2 and PC-3 cells (IC50 = 6.9 and 11.8 μM, respectively). Afterwards, spirooxindole 6a was assessed for its apoptosis induction potential in HepG2 cells, where its pro-apoptotic impact was approved via the significant elevation in the Bax/Bcl-2 ratio and the expression levels of caspase-3,.

Structure guided design of potent indole-based ATX inhibitors bearing hydrazone moiety with tumor suppression effects

ATX was capable of catalyzing the hydrolysis of LPC to the lipid mediator LPA which attracted considerable attention on the development of potent ATX inhibitors. Herein, driven by the HTS product indole-based lead 1, a hybridization strategy was utilized to construct the trifluoroacetyl hydrazone moiety through assembling the phenyl thiazole fragment to the indole skeleton of lead 1. After a systematic structure guided optimization, by cycling the phenyl thiazole to the compacted benzothiazole or decreasing the lipophilicity, two promising ATX inhibitors (9j and 25a) were identified with IC50 values of 2.1 nM and 19.0 nM, respectively. All compounds were tested a panel of cancer cell lines and a preliminary affinity on breast cancer cell lines (SI > 16.5) were observed which shed a light on their potential application of breast cancer relevant cases. Through a dedicated docking study, the intramolecular pseudo-ring within the trifluoroacetylhydrazone moiety played a significant role in constraining the binding poses of 9j and 25a. Finally, a binding free energy calculation was conducted to examine the contribution of different interactions in binding affinity.

Identification of diphenylalkylisoxazol-5-amine scaffold as novel activator of cardiac myosin

To identify novel potent cardiac myosin activator, a series of diphenylalkylisoxazol-5-amine compounds 4–7 have been synthesized and evaluated for cardiac myosin ATPase activation. Among the 37 compounds, 4a (CMA at 10 μM = 81.6%), 4w (CMA at 10 μM = 71.2%) and 6b (CMA at 10 μM = 67.4%) showed potent cardiac myosin activation at a single concentration of 10 μM. These results suggested that the introduction of the amino-isoxazole ring as a bioisostere for urea group is acceptable for the cardiac myosin activation. Additional structure–activity relationship (SAR) studies were conducted. Para substitution (-Cl, –OCH3, -SO2N(CH3)2) to the phenyl rings or replacement of a phenyl ring with a heterocycle (pyridine, piperidine and tetrahydropyran) appeared to attenuate cardiac myosin activation at 10 μM. Additional hydrogen bonding acceptor next to the amino group of the isoxazoles did not enhance the activity. The potent isoxazole compounds showed selectivity for cardiac myosin activation over skeletal and smooth muscle myosin, and therefore these potent and selective isoxazole compounds could be considered as a new series of cardiac myosin ATPase activators for the treatment of systolic heart failure.

Synthesis and Structure-Activity Relationship of Dual-Stage Antimalarial Pyrazolo[3,4- b]pyridines

Malaria remains one of the most deadly infectious diseases, causing hundreds of thousands of deaths each year, primarily in young children and pregnant mothers. Here, we report the discovery and derivatization of a series of pyrazolo[3,4-b]pyridines targeting Plasmodium falciparum, the deadliest species of the malaria parasite. Hit compounds in this series display sub-micromolar in vitro activity against the intraerythrocytic stage of the parasite as well as little to no toxicity against the human fibroblast BJ and liver HepG2 cell lines. In addition, our hit compounds show good activity against the liver stage of the parasite but little activity against the gametocyte stage. Parasitological profiles, including rate of killing, docking, and molecular dynamics studies, suggest that our compounds may target the Qo binding site of cytochrome bc1.