5453-65-6

Usage

Uses

Used in Pharmaceutical Industry:
2-Chloro-N-naphthalen-2-yl-acetamide is used as a chemical intermediate for the synthesis of various pharmaceuticals. Its unique structure and functional groups make it a valuable building block in the development of new drugs with potential therapeutic applications.
Used in Agrochemical Industry:
In the agrochemical industry, 2-Chloro-N-naphthalen-2-yl-acetamide is utilized as an intermediate in the production of various agrochemicals. Its properties contribute to the development of effective pesticides and other agricultural chemicals that help protect crops and enhance agricultural productivity.
Safety Precautions:
It is important to handle 2-Chloro-N-naphthalen-2-yl-acetamide with care, as it may be harmful if ingested, inhaled, or comes into contact with skin or eyes. Proper safety precautions and handling procedures should be followed when working with this chemical to avoid any potential health risks.

InChI:InChI=1/C12H10ClNO/c13-8-12(15)14-11-6-5-9-3-1-2-4-10(9)7-11/h1-7H,8H2,(H,14,15)

Upstream product

• 79-04-9 chloroacetyl chloride 
• 91-59-8 naphthalen-2-ylamine 

Downstream Products

• 84327-89-9 2-[5-(4-Chloro-phenyl)-[1,3,4]oxadiazol-2-ylsulfanyl]-N-naphthalen-2-yl-acetamide 
• 326913-77-3 C₂₈H₂₄N₆S 
• 125983-80-4 2-(4-Amino-phenylamino)-N-naphthalen-2-yl-2-thioxo-acetamide 
• 125983-81-5 2-(4-Acetylamino-phenylamino)-N-naphthalen-2-yl-2-thioxo-acetamide 
• 17172-55-3 2-(4-formylphenoxy)-N-(naphthalen-2-yl)acetamide 
• 1392572-97-2 C₂₀H₁₃N₃O₃S 
• 374771-83-2 5-cyano-4-(2-furyl)-2-methyl-N-(2-methylphenyl)-6-{[2-(2-naphthylamino)-2-oxoethyl]thio}-1,4-dihydropyridine-3-carboxamide 
• 374914-85-9 N-(4-chlorophenyl)-5-cyano-2-methyl-6-{[2-(2-naphthylamino)-2-oxoethyl]thio}-4-phenyl-1,4-dihydropyridine-3-carboxamide 
• 1002934-74-8 C₂₀H₁₇NO₃ 
• 1310561-71-7 N-(naphthalen-2-yl)-2-(4-((2,4,6-trioxotetrahydropyrimidin-5(6H)-ylidene)methyl)phenoxy)acetamide 
• 1310561-86-4 2-(4-((4,6-dioxo-2-thioxotetrahydropyrimidin-5(6H)-ylidene)methyl)phenoxy)-N-(naphthalen-2-yl)acetamide 
• 1266715-62-1 (Z)-2-(4-((2,4-dioxothiazolidin-5-ylidene)methyl)phenoxy)-N-(naphthalen-2-yl)acetamide 
• 326913-73-9 C₂₆H₁₈ClN₅S 
• 326913-75-1 C₂₇H₂₁N₅OS 

Relevant academic research and scientific papers

Novel selective ido1 inhibitors with isoxazolo[5,4-d]pyrimidin-4(5h)-one scaffold

Indoleamine 2,3-dioxygenase 1 (IDO1) is a promising target in immunomodulation of several pathological conditions, especially cancers. Here we present the synthesis of a series of IDO1 inhibitors with the novel isoxazolo[5,4-d]pyrimidin-4(5H)-one scaffold. A focused library was prepared using a 6-or 7-step synthetic procedure to allow a systematic investigation of the structure-activity relationships of the described scaffold. Chemistry-driven modifications lead us to the discovery of our best-in-class inhibitors possessing p-trifluoromethyl (23), p-cyclohexyl (32), or p-methoxycarbonyl (20, 39) substituted aniline moieties with IC50 values in the low micromolar range. In addition to hIDO1, compounds were tested for their inhibition of indoleamine 2,3-dioxygenase 2 and tryptophan dioxygenase, and found to be selective for hIDO1. Our results thus demon-strate a successful study on IDO1-selective isoxazolo[5,4-d]pyrimidin-4(5H)-one inhibitors, defining promising chemical probes with a novel scaffold for further development of potent small-molecule immunomodulators.

Highly Potent and Selective Butyrylcholinesterase Inhibitors for Cognitive Improvement and Neuroprotection

Butyrylcholinesterase (BChE) has been considered as a potential therapeutic target for Alzheimer's disease (AD) because of its compensation capacity to hydrolyze acetylcholine (ACh) and its close association with Aβ deposit. Here, we identified S06-1011 (hBChE IC50 = 16 nM) and S06-1031 (hBChE IC50 = 25 nM) as highly effective and selective BChE inhibitors, which were proved to be safe and long-acting. Candidate compounds exhibited neuroprotective effects and the ability to improve cognition in scopolamine- and Aβ1-42 peptide-induced cognitive deficit models. The best candidate S06-1011 increased the level of ghrelin, a substrate of BChE, which can function as improving the mental mood appetite. The weight gain of the S06-1011-treated group remarkably increased. Hence, BChE inhibition not only plays a protective role against dementia but also exerts a great effect on treating and nursing care.

Hydrophobic substituents on isatin derivatives enhance their inhibition against bacterial peptidoglycan glycosyltransferase activity

Moenomycin A, the well-known natural product inhibitor of peptidoglycan glycosyltransferase (PGT), is a large amphiphilic molecule of molecular mass of 1583 g/mol and its bioavailablity as a drug is relatively poor. In searching for small-molecule ligands

Cink4T, a quinazolinone-based dual inhibitor of Cdk4 and tubulin polymerization, identified via ligand-based virtual screening, for efficient anticancer therapy

Inhibition of cyclin dependent kinase 4 (Cdk4) prevents cancer cells from entering the early G0/G1 phase of the cell division cycle whereas inhibiting tubulin polymerization blocks cancer cells’ ability to undergo mitosis (M) late in the cell cycle. We had reported earlier that two non-planar and relatively non-toxic fascaplysin derivatives, an indole and a tryptoline, inhibit Cdk4 with IC50 values of 6.2 and 10 μM, respectively. Serendipitously, we had also found that they inhibited tubulin polymerization. The molecules were efficacious in mouse tumor models. We have now identified Cink4T in a 59-compound quinazolinone library, designed on the basis of ligand-based virtual screening, as a compound that inhibits Cdk4 and tubulin. Its IC50 value for Cdk4 inhibition is 0.47 μM and >50 μM for inhibition of Cdk1, Cdk2, Cdk6, Cdk9. Cink4T inhibits tubulin polymerization with an IC50 of 0.6 μM. Molecular modelling studies on Cink4T with Cdk4 and tubulin crystal structures lend support to these observations. Cancer cell cycle analyses confirm that Cink4T blocks cells at both G0/G1 and M phases as it should if it were to inhibit both Cdk4 and tubulin polymerization. Our results show, for the very first time, that virtual screening can be used to design novel inhibitors that can potently block two crucial phases of the cell division cycle.

CYP enzymes, expressed within live human suspension cells, are superior to widely-used microsomal enzymes in identifying potent CYP1A1/CYP1B1 inhibitors: Identification of quinazolinones as CYP1A1/CYP1B1 inhibitors that efficiently reverse B[a]P toxicity and cisplatin resistance

Microsomal cytochrome P450 (CYP) enzymes, isolated from recombinant bacterial/insect/yeast cells, are extensively used for drug metabolism studies. However, they may not always portray how a developmental drug would behave in human cells with intact intracellular transport mechanisms. This study emphasizes the usefulness of human HEK293 kidney cells, grown in ‘suspension’ for expression of CYPs, in finding potent CYP1A1/CYP1B1 inhibitors, as possible anticancer agents. With live cell-based assays, quinazolinones 9i/9b were found to be selective CYP1A1/CYP1B1 inhibitors with IC50 values of 30/21 nM, and > 150-fold selectivity over CYP2/3 enzymes, whereas they were far less active using commercially-available CYP1A1/CYP1B1 microsomal enzymes (IC50, >10/1.3–1.7 μM). Compound 9i prevented CYP1A1-mediated benzo[a]pyrene-toxicity in normal fibroblasts whereas 9b completely reversed cisplatin resistance in PC-3/prostate, COR-L23/lung, MIAPaCa-2/pancreatic and LS174T/colon cancer cells, underlining the human-cell-assays’ potential. Our results indicate that the most potent CYP1A1/CYP1B1 inhibitors would not have been identified if one had relied merely on microsomal enzymes.

Identification and characterization of benzo[d]oxazol-2(3H)-one derivatives as the first potent and selective small-molecule inhibitors of chromodomain protein CDYL

Chemical probes of epigenetic ‘readers’ of histone post-translational modifications (PTMs) have become powerful tools for mechanistic and functional studies of their target proteins in physiology and pathology. However, only limited ‘reader’ probes have been developed, which restricted our understanding towards these macromolecules and their roles in cells or animals. Here, we reported a structure-guided approach to develop and characterize benzo [d]oxazol-2(3H)-one analogs as the first potent and selective small-molecule inhibitors of chromodomain Y-like (CDYL), a histone methyllysine reader protein. The binding conformation between the chromodomain of CDYL and the modified peptidomimetics was studied via molecular docking and dynamic simulations, facilitating subsequent virtual screening of tens of hits from Specs chemical library validated by SPR technique (KD values: from 271.1 μM to 5.4 μM). Further design and synthesis of 43 compounds helped to interpret the structure-activity relationship (SAR) that lead to the discovery of novel small-molecule inhibitors of CDYL. Compound D03 (KD: 0.5 μM) was discovered and showed excellent selectivity among other chromodomain proteins, including CDYL2 (>140 folds), CDY1 (no observed binding) and CBX7 (>32 folds). Moreover, we demonstrated that D03 engaged with endogenous CDYL in a dose-dependent manner, and perturbed the recruitment of CDYL onto chromatin, resulting in transcriptional derepression of its target genes. Finally, the results showed that D03 promoted the development and branching of neurodendrites by inhibiting CDYL in hippocampal and cortical cultured neurons. This study not only discovers the first selective small-molecule inhibitors of CDYL, but provids a new chemical tool to intervene the dynamic nature of bio-macromolecules involved in epigenetic mechanism.

A facial protocol for the synthesis of benzofuran derivatives by the reaction of o-hydroxy aryl ketone, amine and chloroacetyl chloride

A facile and effective method has been developed for the synthesis of a novel series of benzofuran derivatives via N-acylation, O-alkylation and intramolecular condensation reactions, starting from readily available substituted o-hydroxy aryl ketone, and

Synthesis of novel 2-iminothiazolidin-4-ones

Thiazolidin-4-ones are known to exhibit diverse biological activities such as antimicrobial, anticancer, antidiarrheal, anticonvulsant, antidiabetic, antihistaminic, and antifungal activities. In the present investigation, a series of 2-haloacetamides was prepared by reacting chloroacetyl chloride with amines in dry benzene under reflux conditions. The formed 2-haloacetamides reacted with potassium thiocyanate in refluxing dry acetone to afford new 2-iminothiazolidin-4-ones. The 5-arylidene-2-imino-3 (napthalen-2yl)- thiazolidin-4-ones were prepared by condensing 2-iminothiazolidin-4-ones with substituted benzaldehydes. All the products were characterized by infrared, mass, and 1H and 13C NMR techniques.

Synthesis and biological evaluation of novel 5-benzylidenethiazolidine-2,4- dione derivatives for the treatment of inflammatory diseases

Twenty-two compounds based on thiazolidine-2,4-dione moiety were synthesized and evaluated for the inhibitory potency on the production of nitric oxide (NO), inducible nitric oxide synthase (iNOS) activity, and the generation of prostaglandin E2 (PEG2). (Z)-N-(3-Chlorophenyl)-2-(4- ((2,4-dioxothiazolidin-5-ylidene) methyl) phenoxy) acetamide (3I), superior to the commercial anti-inflammatory drug indomethacin, significantly inhibited iNOS activity (IC50 = 8.66 μM), iNOS-mediated NO, and cyclooxygenase (COX)-2-derived PGE2 production (IC50 = 4.16 and 23.55 μM, respectively) on lipopolysaccharide (LPS)-induced RAW 264.7 cells. Docking study revealed that 3I was perfectly docking into the active site of murine iNOS and suppressed the expression of iNOS protein as evidenced by Western blot analysis. At the dose of 50 mg/kg, oral administration of 3I possessed protective properties in both carrageenan-induced paw edema and adjuvant-induced arthritis rat models.

Synthesis and biological activity of novel barbituric and thiobarbituric acid derivatives against non-alcoholic fatty liver disease

Forty-four barbituric acid or thiobarbituric acid derivatives were synthesized and evaluated for their effects on adipogenesis of 3T3-L1 adipocytes by measuring the expression of adiponectin in vitro. Four compounds (3a, 3o, 3s, 4t) were found to increase the expression of adiponectin and lower the leptin level in 3T3-L1 adipocytes at respective concentration of 10 μM. Among them, 3s showed the most efficacious. Oral administration of 3s effectively reduced body weight, liver weight, and visceral fat and regulated serum levels of biochemical markers in the high-fat/diet-induced Wistar rats. Histopathological evaluation of liver sections by Oil Red O and H&E staining confirmed 3s as a potent, orally active molecule for reducing fat deposition against non-alcoholic fatty liver disease.