220699-51-4

Basic information

• Product Name: N-[4-(3-Bromophenylamino)quinazolin-6-yl]-4-(dimethylamino)-2(E)-butenamide
• CAS NO: 220699-51-4
• Molecular Formula: C₂₀H₂₀BrN₅O
• Molecular Weight: 426.3193
• Mol File: 220699-51-4.mol

Chemical Properties

• CAS DataBase Reference: N-[4-(3-Bromophenylamino)quinazolin-6-yl]-4-(dimethylamino)-2(E)-butenamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-[4-(3-Bromophenylamino)quinazolin-6-yl]-4-(dimethylamino)-2(E)-butenamide(220699-51-4)
• EPA Substance Registry System: N-[4-(3-Bromophenylamino)quinazolin-6-yl]-4-(dimethylamino)-2(E)-butenamide(220699-51-4)

Safety Data

• Hazardous Substances Data: 220699-51-4(Hazardous Substances Data)

Upstream product

• 144-55-8 sodium hydrogencarbonate 
• 361392-72-5 (2E)-4-bromo-N-{4-[(3-bromophenyl)amino]-6-quinazolinyl}-2-butenamide 
• 220699-90-1 4-[(3-bromophenyl)amino]-6-[(4-bromo-1-oxo-2-buten-1-yl)amino]-quinazoline 
• 124-40-3 dimethyl amine 
• 216163-53-0 N-[4-(3-Bromo-phenylamino)-quinazolin-6-yl]propanamide 
• 1130155-48-4 (E)-4-(dimethylamino)-2-butenoic acid hydrochloride 
• 169205-77-0 6-nitro-4-(3-bromophenylaniline)quinazoline 
• 17420-30-3 5-nitroanthranilonitrile 
• 99083-25-7 4-bromocrotonyl chloride 
• 169205-78-1 6-amino-4-[(3-bromophenyl)amino]quinazoline 

Downstream Products

• 1245555-20-7 (2E)-4-{[4-(3-bromoanilino)-6-quinazolinyl]amino}-N,N-dimethyl-N-[(1-methyl-4-nitro-1H-pyrazol-5-yl)methyl]-4-oxo-2-buten-1-ammonium bromide 
• 1245555-18-3 (2E)-4-{[4-(3-bromoanilino)-6-quinazolinyl]amino}-N,N-dimethyl-N-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]-4-oxo-2-buten-1-ammonium bromide 
• 1245555-17-2 (2E)-4-{[4-(3-bromoanilino)-6-quinazolinyl]amino}-N,N-dimethyl-N-[(1-methyl-5-nitro-1H-pyrrol-2-yl)methyl]-4-oxo-2-buten-1-ammonium bromide 
• 1245555-16-1 (2E)-4-{[4-(3-bromoanilino)-6-quinazolinyl]amino}-N,N-dimethyl-N-(2-nitrobenzyl)-4-oxo-2-buten-1-ammonium bromide 
• 1245555-15-0 (2E)-4-{[4-(3-bromoanilino)-6-quinazolinyl]amino}-N,N-dimethyl-N-(4-nitrobenzyl)-4-oxo-2-buten-1-ammonium bromide 

Relevant articles and documents

Structural insights into how irreversible inhibitors can overcome drug resistance in EGFR

Resistance to kinase- targeted cancer drugs has recently been linked to a single point mutation in the ATP binding site of the kinase. In EGFR, the crucial Thr790 gatekeeper residue is mutated to a Met and prevents reversible ATP competitive inhibitors from binding. Irreversible 4-(phenylamino)quinazolines have been shown to overcome this drug resistance and are currently in clinical trials. In order to obtain a detailed structural understanding of how irreversible inhibitors overcome drug resistance, we used Src kinase as a model system for drug resistant EGFR-T790M. We report the first crystal structure of a drug resistant kinase in complex with an irreversible inhibitor. This 4-(phenylamino)quinazoline inhibits wild type and drug resistant EGFR in vitro at low nM concentrations. The co-crystal structure of drug resistant cSrc-T338M kinase domain provides the structural basis of this activity.

SUBSTITUTED QUINAZOLINE DERIVATIVES AND THEIR USE AS TYROSINE KINASE INHIBITORS

This invention provides compounds of formula (1) wherein X is C3-7 cycloalkyl, pyridinyl, pyrimidinyl or phenyl ring optionally substituted as described in claim 1, R1, R3 and R4 are chosen from the groups listed in claim 1. R2 is chosen from various unsaturated acyl groups listed in claim 1, with certain compounds being disclaimed. Use as tyrosine kinase inhibitors for the treatment of cancer and certain kidney diseases such as polycystic kidney disease.

Substituted quinazoline derivatives

This invention provides compounds of formula 1 having the structure wherein: X, R1, R2, R3, R4, Z, X, and n are as defined hereinbefore in the specification, which are useful as antineoplastic agents and in the treatment of certain kidney diseases, such as polycystic kidney disease.

6-Substituted-4-(3-bromophenylamino)quinazolines as putative irreversible inhibitors of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases with enhanced antitumor activity

A series of new 6-substituted-4-(3-bromophenylamino)quinazoline derivatives that may function as irreversible inhibitors of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases have been prepared. These inhibitors have, at the C-6 position, butynamide, crotonamide, and methacrylamide Michael acceptors bearing water-solublilizing substituents. These compounds were prepared by acylation of 6-amino-4-(3-bromophenylamino)quinazoline with unsaturated acid chlorides or mixed anhydrides. We show that attaching a basic functional group onto the Michael acceptor results in greater reactivity, due to intramolecular catalysis of the Michael addition and/or an inductive effect of the protonated basic group. This, along with improved water solubility, results in compounds with enhanced biological properties. We present molecular modeling and experimental evidence that these inhibitors interact covalently with the target enzymes. One compound, 16a, was shown to have excellent oral activity in a human epidermoid carcinoma (A431) xenograft model in nude mice.