524955-09-7

Basic information

• Product Name: AKOS B033273
• Synonyms: AKOS B033273;3-CHLORO-4-(PYRIDIN-2-YLMETHOXY)-BENZENAMINE;3-CHLORO-4-(PYRIDIN-2-YLMETHOXY)-PHENYLAMINE;ART-CHEM-BB B033273;UKRORGSYN-BB BBV-019513;3-chloro-4-(2-pyridinylMethoxy)- BenzenaMine;3-Chloro-4-[(pyridin-2-yl)Methoxy]benzenaMine [3-Chloro-4-(pyridin-2-ylMethoxy)phenyl]aMine;BenzenaMine, 3-chloro-4-(2-pyridinylMethoxy)-
• CAS NO: 524955-09-7
• Molecular Formula: C₁₂H₁₁ClN₂O
• Molecular Weight: 234.685
• EINECS: 1592732-453-0
• Mol File: 524955-09-7.mol

Chemical Properties

• Melting Point: 91.0 to 95.0 °C
• Boiling Point: 402.5±35.0 °C(Predicted)
• Appearance: /
• Density: 1.292±0.06 g/cm3(Predicted)
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 3.88±0.10(Predicted)
• CAS DataBase Reference: AKOS B033273(CAS DataBase Reference)
• NIST Chemistry Reference: AKOS B033273(524955-09-7)
• EPA Substance Registry System: AKOS B033273(524955-09-7)

Safety Data

• Hazardous Substances Data: 524955-09-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
AKOS B033273 is used as a key intermediate in the synthesis of disubstituted (arylamino)quinolinecarbonitriles. These compounds have demonstrated potent and selective inhibition of human epidermal growth factor receptor-2 (HER2) kinase activity, making them promising candidates for the development of orally active antitumor agents.
In the context of cancer treatment, AKOS B033273 contributes to the development of novel therapeutics that target the HER2 receptor, which is overexpressed in various types of cancer, including breast, ovarian, and gastric cancers. By inhibiting the HER2 receptor, these agents can potentially halt tumor growth and progression, offering a new treatment option for patients with HER2-overexpressing cancers.
Furthermore, the use of AKOS B033273 in the synthesis of disubstituted (arylamino)quinolinecarbonitriles highlights its potential in the development of targeted therapies, which aim to minimize side effects and improve the overall efficacy of cancer treatment.

Upstream product

• 6959-47-3 2-chloromethylpyridine hydrochloride 
• 4377-33-7 2-chloromethylpyridine 
• 55401-97-3 2-(Bromomethyl)pyridine 
• 619-08-9 2-chloro-4-nitrophenol 
• 586-98-1 2-Hydroxymethylpyridine 
• 350-30-1 3-chloro-4-fluoronitrobenzene 
• 3964-52-1 2-chloro 4-aminophenol 
• 179687-79-7 2-((2-chloro-4-nitrophenoxy)methyl)pyridine 

Downstream Products

• 1439373-52-0 C₂₃H₁₉ClN₄O₄ 
• 697299-93-7 4-[3-Chloro-4-(pyridin-2-ylmethoxy)-phenylamino]-7-methoxy-quinazolin-6-ol 
• 1260402-49-0 3-chloro-4-(N-oxidepyridine-2-methoxyl)-phenylamine TFA salt 
• 1351942-60-3 4-(3-chloro-4(pyridin-2-yl-methoxy)phenylamino)-6-nitro-7-(tetrahydrofuran-3-yl-oxy)quinoline-3-carbonitrile 
• 1351943-50-4 6-amino-4-(3-chloro-4-(pyridin-2-yl-methoxy)phenylamino)-7-(tetrahydrofuran-3-yl-oxy)quinoline-3-carbonitrile 
• 1351940-20-9 (E)-4-bromo-N-(4-(3-chloro-4-(pyridin-2-yl-methoxy)phenylamino)-3-cyano-7-(tetrahydrofuran-3-yl-oxy)quinolin-6-yl)-but-2-enamide 
• 1351940-21-0 (E)-N-(4-(3-chloro-4-(pyridin-2-yl-methoxy)phenylamino)-3-cyano-7-(tetrahydrofuran-3-yl-oxy)quinolin-6-yl)-4-(dimethylamino)-but-2-enamide 
• 1351940-22-1 (E)-N-(4-(3-chloro-4-(pyridin-2-yl-methoxy)phenylamino)-3-cyano-7-(tetrahydrofuran-3-yl-oxy)quinolin-6-yl)-4-(dimethylamino)-but-2-enamide hydrochloride 
• 1351940-53-8 N-(4-(3-chloro-4-(pyridin-2-yl-methoxy)phenylamino)-3-cyano-7-(tetrahydrofuran-3-yl-oxy)quinolin-6-yl)acrylamide 
• 1351940-60-7 tert-butyl 4-(2-(4-(3-chloro-4-(pyridin-2-yl-methoxy)phenylamino)-3-cyano-7-(tetrahydrofuran-3-yl-oxy)quinolin-6-yl-amino)-2-oxoethylidene)piperidine-1-carboxylate 
• 1351940-61-8 N-(4-(3-chloro-4-(pyridin-2-yl-methoxy)phenylamino)-3-cyano-7-(tetrahydrofuran-3-yl-oxy)quinolin-6-yl)-2-(piperidin-4-ylidene)acetamide 
• 1351940-63-0 N-(4-(3-chloro-4-(pyridin-2-yl-methoxy)phenylamino)-3-cyano-7-(tetrahydrofuran-3-yl-oxy)quinolin-6-yl)-2-(1-methylpiperidin-4-ylidene)acetamide 
• 1351940-72-1 N-(4-(3-chloro-4-(pyridin-2-yl-methoxy)phenylamino)-3-cyano-7-(tetrahydrofuran-3-yl-oxy)quinolin-6-yl)-2-(1-(2-(2-(2-hydroxyethoxy)ethylamino)acetyl)piperidin-4-ylidene)acetamide 
• 1351941-65-5 4-(3-chloro-4-(pyridin-2-yl-methoxy)phenylamino)-6-(piperidin-1-yl)-7-(tetrahydrofuran-3-yl-oxy)quinoline-3-carbonitrile 

Relevant articles and documents

Novel heteroaryl amide derivatives as MAO-B inhibitors and pharmaceutical compositions for preventing, ameliorating or treating neurodegenerative diseases comprising the same

A novel heteroaryl amide derivative compound useful as MAO-B inhibitors. The present invention relates to a compound selected from a pharmaceutically acceptable salt thereof, a hydrate thereof, or a stereoisomer thereof, and a pharmaceutical composition comprising the compound as an active ingredient for preventing, alleviating, or treating neurodegenerative diseases such MAO as B's disease, 's disease, 's disease, and the like.

Discovery of novel and potent safinamide-based derivatives as highly selective hMAO-B inhibitors for treatment of Parkinson's disease (PD): Design, synthesis, in vitro, in vivo and in silico biological studies

Up to date, the current clinical practice employs only symptomatic treatments for management of Parkinson's disease (PD) but unable to stop disease progression. The discovery of new chemical entities endowed with potent and selective human monoamine oxidase B (hMAO-B) inhibitory activity is a clinically relevant subject. Herein, a structural optimization strategy for safinamide (a well-known second generation hMAO-B inhibitor) afforded a series of thirty-six safinamide-derived new analogs (4aa–bj). Most compounds showed promising inhibitory activities against hMAO-B (>70% inhibition at a single dose concentration of 10 μM), with no apparent effect on hMAO-A at 100 μM. Moreover, while six compounds (4ak, 4as, 4az, 4be, 4bg, and 4bi) exhibited potent double-digit nanomolar activities over hMAO-B with IC50 values of 29.5, 42.2, 22.3, 18.8, 42.2, and 33.9 nM, respectively, three derivatives (4aq, 4at, and 4bf), possessing the same carboxamide moiety (2-pyrazinyl), showed the most potent single-digit nanomolar activities (IC50 = 9.7, 5.1, and 3.9 nM, respectively). Compound 4bf revealed an excellent selectivity index (SI > 25641) with a 29-fold increase compared to safinamide (SI > 892). A structure activity relationship along with molecular docking simulations provided insights into enzyme ? inhibitor interactions and a rational for the observed activity. In an in vivo MPTP-induced mouse model of PD, oral administration of compound 4bf significantly protected nigrostriatal dopaminergic neurons as revealed by tyrosine hydroxylase staining and prevented MPTP-induced Parkinsonism as revealed by motor behavioral assays. Accordingly, we present compound 4bf as a novel, highly potent, and selective hMAO-B inhibitor with an effective therapeutic profile for relieving PD.

Targeting Her2-insYVMA with Covalent Inhibitors - A Focused Compound Screening and Structure-Based Design Approach

Mutated or amplified Her2 serves as a driver of non-small cell lung cancer or mediates resistance toward the inhibition of its family member epidermal growth factor receptor with small-molecule inhibitors. To date, small-molecule inhibitors targeting Her2 which can be used in clinical routine are lacking, and therefore, the development of novel inhibitors was undertaken. In this study, the well-established pyrrolopyrimidine scaffold was modified with structural motifs identified from a screening campaign with more than 1600 compounds, which were applied against wild-type Her2 and its mutant variant Her2-A775_G776insYVMA. The resulting inhibitors were designed to covalently target a reactive cysteine in the binding site of Her2 and were further optimized by means of structure-based drug design utilizing a set of obtained complex crystal structures. In addition, the analysis of binding kinetics and absorption, distribution, metabolism, and excretion parameters as well as mass spectrometry experiments and western blot analysis substantiated our approach.

Design, synthesis and biological study of potent and covalent HER-2 tyrosine kinase inhibitors with low cytotoxicity in vitro

The discovery and development of a novel HER-2 tyrosine kinase inhibitor for the treatment of HER2-positive breast cancer are presented in this article. EGFR family has been recognized as a crucial meditator in the cancer progression; HER-2 tyrosine kinase was one of the members among them. In the effort to explore potent HER-2 inhibitors, a novel series of 4-anilino-3-cyanoquinoline derivatives have been designed, synthesized and evaluated. Most compounds possessed modest proliferation inhibition on SK-BR-3 cell line and HER-2 kinase. Compound 16 appeared to be the most potent compound (HER-2 kinase IC50: 19.4?nM, SK-BR-3 IC50: 94?nM). In the experiment of cellular cytotoxicity assay, compound 16 shows a much lower cytotoxicity than neratinib on Beas-2b cell line (Human bronchial epithelial cells). In conclusion, compound 16 would be a promising lead compound for further anti-breast cancer drug discovery.

Surmounting the resistance against EGFR inhibitors through the development of thieno[2,3-d]pyrimidine-based dual EGFR/HER2 inhibitors

In light of the emergence of resistance against the currently available EGFR inhibitors, our study focuses on tackling this problem through the development of dual EGFR/HER2 inhibitors with improved enzymatic affinities. Guided by the binding mode of the

Discovery of anilino-furo[2,3-d]pyrimidine derivatives as dual inhibitors of EGFR/HER2 tyrosine kinase and their anticancer activity

Being responsible for the development of many cancer types, EGFR (Epidermal Growth Factor Receptor) and HER2 (Human Epidermal growth factor Receptor 2) were the focus of this study where a series of novel 4-anilino-furo[2,3-d]pyrimidine derivatives was designed, synthesized and biologically evaluated. Modification of the solvent accessible 5-position side chain greatly affected the in-vitro EGFR/HER2 inhibitory activity. Three derivatives bearing 5-carboxylic acid side chain, namely the 3-chloroanilino derivative (8c), the 3-bromoaniline (8d) and the lapatinib analogue (10) demonstrated the most significant submicromolar EGFR inhibition. Surprisingly, the in-vitro assay of the ester 7h and its acid analogue 10 showed a significant variation of results between the antiproliferative activity against A549 cell line (IC50 0.5 and 21.4 μM) respectively and EGFR inhibitory activity (18% and 100%) respectively, suggesting that 7h might be a prodrug for 10. This assumption was also affirmed by the in-vivo results, where the in-vivo antitumor assessment against EAC (Ehrlich Ascites Carcinoma) solid tumor model revealed that 7h and 8d (10 mg/kg dose) exhibited antitumor activity comparable to that of gefitinib at the same dose, exhibiting TGI% of 67%, 71% and 70%, respectively. This effect could be explained, at least partly, via activation of apoptosis, where 7h and 8d caused more than 2-fold increase of caspase 3 and cytochrome c expression than the control group which is comparable to that of gefitinib-treated group. Finally, 7h was the most effective apoptotic inducer, resulting in a significant elevation in annexin V–FITC-positive apoptotic cells (both early and late apoptosis) by 25 and 79-folds, respectively, compared to control, which is higher than that of gefitinib (22 and 61-folds, respectively).

QUINAZOLINE DERIVATIVE, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION AND APPLICATION THEREOF

Disclosed are a quinazoline derivative, a preparation method therefor, and a pharmaceutical composition and an application thereof. The present invention provides a compound represented by general formula I, a stereoisomer thereof and a pharmaceutical acceptable salt or a solvate thereof. The quinazoline derivative of the present invention has a unique chemical structure, is characterized by irreversibly inhibiting EGFR tyrosine kinase, has high biological activity, apparently improves the inhibiting effect on the EGFR tyrosine kinase, has quite strong tumor inhibiting effect on tumor cells and a transplantation tumor pathological model of animal tumors, and has good market developing prospects.

QUINAZOLINE DERIVATIVE AND PREPARATION METHOD THEREFOR

The present invention relates to a quinazoline derivative shown in formula (I) and a preparation method therefor, a pharmaceutical composition comprising the compound shown in formula (I), and an application of the compound in preparing drugs for curing and preventing tumors. The compound of the present invention can irreversibly prevent EGFR phosphorylation, and effectively depress signal transduction of cancer cells, and accordingly has higher anti-tumor activity in vitro and in vivo,

Targeting EGFR/HER2 tyrosine kinases with a new potent series of 6-substituted 4-anilinoquinazoline hybrids: Design, synthesis, kinase assay, cell-based assay, and molecular docking

Coexpression of EGFR and HER2 has been found in many tumors such as breast, ovarian, colon and prostate cancers, with poor prognosis of the patients. Herein, our team has designed and synthesized new eighteen compounds with 6-substituted 4-anilinoquinazol

CYANOQUINOLINE DERIVATIVES

Disclosed is a compound of formula I, a stereoisomer thereof, a cis-trans-isomer thereof, a tautomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, a solvate thereof or a prodrug thereof, wherein R1, R2, R3 and R4 are each as defined in the present application.