194423-15-9

Usage

Uses

Used in Pharmaceutical Industry:
4-[(3-BROMOPHENYL)AMINO]-6-ACRYLAMIDOQUINAZOLINE is used as an irreversible epidermal growth factor receptor (EGFR) inhibitor for its ability to effectively target and inhibit the EGFR, a protein that plays a crucial role in cell growth and proliferation. This inhibition can be beneficial in the treatment of various cancers, as the overexpression or mutation of EGFR is often associated with tumor growth and progression.
Used in Oncology Research:
In the field of oncology, PD 168393 is used for the acute inhibition of ErbB4, a receptor tyrosine kinase that is part of the HER family. ErbB4 is involved in cell growth, differentiation, and survival, and its dysregulation has been implicated in various cancers. By inhibiting ErbB4, PD 168393 can potentially disrupt cancer cell signaling pathways and hinder tumor growth.
Used in Drug Development:
4-[(3-BROMOPHENYL)AMINO]-6-ACRYLAMIDOQUINAZOLINE serves as a valuable compound in the development of novel therapeutic agents targeting EGFR and ErbB4. Its unique chemical structure allows for the design and synthesis of new drugs with improved potency, selectivity, and pharmacokinetic properties. These new drugs can be tailored to address specific cancer types or patient populations, offering more personalized treatment options.
Used in Biotechnology Applications:
In addition to its pharmaceutical applications, PD 168393 can also be utilized in biotechnology for the development of diagnostic tools and research reagents. Its ability to specifically target EGFR and ErbB4 makes it a promising candidate for the creation of targeted imaging agents, which can help visualize and monitor cancer progression in patients. Furthermore, PD 168393 can be employed in the development of high-throughput screening assays to identify new compounds with similar or improved inhibitory properties.

Biochem/physiol Actions

PD168393 is a 6-acrylamido-4-anilinoquinazoline compound. It increases apoptosis in malignant peripheral nerve sheath tumor cells, stimulated by lysosomal dysfunction.

Upstream product

• 79-10-7 acrylic acid 
• 169205-78-1 6-amino-4-[(3-bromophenyl)amino]quinazoline 
• 17420-30-3 5-nitroanthranilonitrile 
• 256409-22-0 4-(3-bromo phenyl amine)-6-(3-methylthio propionyl amine)-quinazoline 
• 256409-24-2 4-(3-bromophenylamine)-6-(3-methylsulfoxidopropionylamide)-quinazoline 
• 256409-20-8 4-(3-bromophenylamino)-6-(3-methoxypropionylamide)-quinazoline 
• 169205-77-0 6-nitro-4-(3-bromophenylaniline)quinazoline 
• 814-68-6 acryloyl chloride 

Downstream Products

• 198961-89-6 N⁴-(3-bromophenyl)-N⁶-[3-(4-morpholinyl)propyl]-4,6-quinazolinediamine 
• 198961-88-5 N-[4-[(3-bromophenyl)-amino]-quinazolin-6-yl]-3-morpholino-propylamide 

Relevant academic research and scientific papers

Synthesis and biological evaluation of 4-anilinoquinolines as potent inhibitors of epidermal growth factor receptor

The mutant receptor tyrosine kinase EGFR is a validated and therapeutically amenable target for genotypically selected lung cancer patients. Here we present the synthesis and biological evaluation of a series of 6- and 7-substituted 4-anilinoquinolines as potent type I inhibitors of clinically relevant mutant variants of EGFR. Quinolines 3a and 3e were found to be highly active kinase inhibitors in biochemical assays and were further investigated for their biological effect on EGFR-dependent Ba/F3 cells and non-small cell lung cancer (NSCLC) cell lines.

QUINAZOLINE AND QUINOLINE DERIVATIVES AS IRREVERSIBLE PROTEIN TYROSINE KINASE INHIBITORS

A compound of formula (I), a pharmaceutically acceptable salt, or hydrate thereof, and a method of preparing the same. A method of treating or preventing a physiological disorder caused by abnormal protein tyrosine kinase activity in a mammal comprising administering to said mammal a pharmaceutical composition comprising a compound of formula (I).

INREVERSIBLE PROTEIN TYROSINE KINASES INHIBITORS AND THE PREPARATION METHODS AND USES THEREOF

The compounds which could inhibit protein tyrosine kinases activity or the pharmaceutical acceptable salts or hydrates thereof. The uses of the compounds in treating or preventing physiological abnormal induced by protein tyrosine kinases overexpression in mammal. The preparation methods of the compounds.

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

This invention provides a process for preparing compounds of formula (1) wherein: X is phenyl optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, hydrox

USE OF QUINAZOLINE COMPOUNDS FOR THE TREATMENT OF POLYCYSTIC KIDNEY DISEASE

This invention provides a method of treating or inhibiting polycystic kidney disease in a mammal in need thereof which comprises administering to said mammal a compound having formula (1) wherein X is phenyl which is optionally substituted; R and R1 are each, independently, hydrogen, halogen, alkyl, alkoxy, hydroxy, or trifluoromethyl; R2 is hydrogen, alkyl, alkoxy, hydroxy, trifluoromethyl; Y is a radical selected from the group consisting of (a), (b), (c), (d), (e), (f) and (g); R3 is independently hydrogen, alkyl, carboxy, carboalkoxy, phenyl, or carboalkyl; n = 2-4; or a pharmaceutically acceptable salt thereof, with the proviso that each R3 of Y may be the same or different.

Irreversible inhibitors of tyrosine kinases

The present invention provides compounds that are irreversible inhibitors of tyrosine kinases. Also provided is a method of treating cancer, restenosis, atherosclerosis, endometriosis, and psoriasis and a pharmaceutical composition that comprises a compound that is an irreversible inhibitor of tyrosine kinases.

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.

Method of treating or inhibiting colonic polyps

This invention provides a method of treating or inhibiting colonic polyps in a mammal in need thereof which comprises administering to said mammal a compound having the formula wherein:X is phenyl which is optionally substituted;R and R1 are each, independently, hydrogen, halogen, alkyl, alkoxy, hydroxy, or trifluoromethyl;R2 is hydrogen, alkyl, alkoxy, hydroxy, trifluoromethyl;Y is a radical selected from the group consisting of R3 is independently hydrogen, alkyl, carboxy, carboalkoxy, phenyl, or carboalkyl;n=2-4;or a pharmaceutically acceptable salt thereof, with the proviso that each R3 of Y may be the same or different.

Tyrosine kinase inhibitors. 15. 4-(Phenylamino)quinazoline and 4- (phenylamino)pyrido[d]pyrimidine acrylamides as irreversible inhibitors of the ATP binding site of the epidermal growth factor receptor

A series of 6- and 7-acrylamide derivatives of the 4- (phenylamino)quinazoline and -pyridopyrimidine classes of epidermal growth factor receptor (EGFR) inhibitors were prepared from the corresponding amino compounds by reaction with either acryloyl chloride/base or acrylic acid/1- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. All of the 6- acrylamides, but only the parent quinazoline 7-acrylamide, were irreversible inhibitors of the isolated enzyme, confirming that the former are better- positioned, when bound to the enzyme, to react with the critical cysteine- 773. Quinazoline, pyrido[3,4-d]pyrimidine, and pyrido[3,2-d]pyrimidine 6- acrylamides were all irreversible inhibitors and showed similar high potencies in the enzyme assay (likely due to titration of the available enzyme). However the pyrido[3,2-d]pyrimidine analogues were 2-6-fold less potent than the others in a cellular autophosphorylation assay for EGFR in A431 cells. The quinazolines were generally less potent overall toward inhibition of heregulin-stimulated autophosphorylation of erbB2 (in MDA-MB- 453-cells), whereas the pyridopyrimidines were equipotent. Selected compounds were evaluated in A431 epidermoid and H125 non-small-cell lung cancer human tumor xenografts. The compounds showed better activity when given orally than intraperitoneally. All showed significant tumor growth inhibition (stasis) over a dose range. The poor aqueous solubility of the compounds was a drawback, requiring formulation as fine particulate emulsions.