153436-54-5

Basic information

• Product Name: PD 153035 HYDROCHLORIDE
• Synonyms: 4-[(3-BROMOPHENYL)AMINO]-6,7-DIMETHOXYQUINAZOLINE HYDROCHLORIDE;PD 153035 HYDROCHLORIDE;PD153035HCl;4-(3-Bromphenylamino)-6,7-bis(methoxy)quinazoline;4-(3-Bromphenylamino)-6,7-dimethylquinazoline;4-Quinazolinamine, N-(3-bromphenyl)-6,7-dimethoxy-;N-(3-bromophenyl)-6,7-dimethoxyquinazolin-4-amine;Zinc00600292
• CAS NO: 153436-54-5
• Molecular Formula: C₁₆H₁₄BrN₃O₂
• Molecular Weight: 396.67
• Product Categories: Inhibitor;Inhibitors
• Mol File: 153436-54-5.mol

Chemical Properties

• Melting Point: 189-190 °C
• Boiling Point: 472.1 °C at 760 mmHg
• Flash Point: 239.3 °C
• Appearance: /
• Density: 1.499g/cm³
• Vapor Pressure: 4.38E-09mmHg at 25°C
• Refractive Index: 1.679
• Storage Temp.: Store at RT
• Solubility: Soluble in DMSO (up to 5 mg/ml).
• PKA: 5.55±0.30(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
• CAS DataBase Reference: PD 153035 HYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: PD 153035 HYDROCHLORIDE(153436-54-5)
• EPA Substance Registry System: PD 153035 HYDROCHLORIDE(153436-54-5)

Safety Data

• Hazardous Substances Data: 153436-54-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
PD 153035 HYDROCHLORIDE is used as an inhibitor for EGFR, competitive with ATP, due to its extremely potent and specific inhibitory effect on EGFR tyrosine kinase activity. This makes it a valuable compound for the development of targeted cancer therapies.
Used in Cancer Research:
PD 153035 HYDROCHLORIDE is used as a research tool for studying the role of EGFR in various cellular processes and its involvement in cancer cell growth. It helps researchers understand the mechanisms of EGF-mediated signaling and the potential of EGFR inhibition in cancer treatment.
Used in Drug Development:
PD 153035 HYDROCHLORIDE is used as a lead compound in the development of new drugs targeting EGFR-related pathways. Its potent and selective inhibition of EGFR tyrosine kinase activity makes it a promising starting point for designing more effective and targeted cancer therapies.
Used in Oncology:
PD 153035 HYDROCHLORIDE is used as an anticancer agent, particularly for inhibiting the growth of various cancer cell lines. Its ability to selectively block EGF-mediated cellular processes makes it a potential therapeutic option for patients with EGFR-driven cancers.

Biological Activity

An extremely potent inhibitor of epidermal growth factor (EGF) receptor tyrosine kinase, with an IC 50 of 25 pM. Inhibits other purified tyrosine kinases only at micromolar or higher concentrations.

References

1) Fry et al. (1994), A specific inhibitor of the epidermal growth factor receptor tyrosine kinase; Science, 265 1093 2) Bos et al. (1997), PD153035, a tyrosine kinase inhibitor, prevents epidermal growth factor receptor activation and inhibits growth of cancer cells in a receptor number-dependent manner; Clin. Cancer Res., 3 2099 3) Tetreault et al. (2008), Specific signaling cascades involved in cell spreading during healing of micro-wounded gastric epithelial monolayers; J. Cell. Biochem., 105 1240

InChI:InChI=1/C16H14BrN3O2/c1-21-14-7-12-13(8-15(14)22-2)18-9-19-16(12)20-11-5-3-4-10(17)6-11/h3-9H,1-2H3,(H,18,19,20)

Upstream product

• 4722-81-0 AG 1693 
• 385784-68-9 N'-(2-cyano-4,5-dimethoxy-phenyl)-N,N-dimethyl-formamidine 
• 591-19-5 m-Bromoaniline 
• 6315-89-5 3,4-dimethoxyaniline 
• 873974-98-2 5,6-dimethoxyindoline-2,3-dione 
• 13794-72-4 3H-6,7-dimethoxyquinazolin-4-one 
• 13794-72-4 6,7-dimethoxy-4-hydroxyquinazoline 
• 5653-40-7 2-Amino-4,5-dimethoxybenzoic acid 
• 26961-27-3 2-amino-4,5-dimethoxybenzonitrile 
• 13790-39-1 6,7-dimethoxy-4-chloroquinazoline 

Downstream Products

• 169205-86-1 4-(3-bromoanilino)-6,7-dihydroxyquinazoline 
• 295330-61-9 4-[(3-bromophenyl)amino]-6-hydroxy-7-methoxyquinazoline 
• 229476-53-3 EBE-A₂₂ 

Relevant articles and documents

Design of a Cyclin G Associated Kinase (GAK)/Epidermal Growth Factor Receptor (EGFR) Inhibitor Set to Interrogate the Relationship of EGFR and GAK in Chordoma

We describe the design of a set of inhibitors to investigate the relationship between cyclin G associated kinase (GAK) and epidermal growth factor receptor (EGFR) in chordoma bone cancers. These compounds were characterized both in vitro and using in cell

Anti-tubercular activity of novel 4-anilinoquinolines and 4-anilinoquinazolines

We screened a series of 4-anilinoquinolines and 4-anilinoquinazolines and identified novel inhibitors of Mycobacterium tuberculosis (Mtb). The focused 4-anilinoquinoline/quinazoline scaffold arrays yielded compounds with high potency and the identification of 6,7-dimethoxy-N-(4-((4-methylbenzyl)oxy)phenyl)quinolin-4-amine (34) with an MIC90 value of 0.63–1.25 μM. We also defined a series of key structural features, including the benzyloxy aniline and the 6,7-dimethoxy quinoline ring, that are important for Mtb inhibition. Importantly the compounds showed very limited toxicity and scope for further improvement by iterative medicinal chemistry.

A novel strategy to the synthesis of 4-anilinoquinazoline derivatives

A novel approach to prepare 4-anilinoquinazoline derivatives based on the transformation of indoline-2,3-dione to formamidine was developed. The processes with this approach are simple, efficient, and environmentally friendly. The efficiency of this approach was evaluated by synthesizing 17 4-anilinoquinazolines and comparing the obtained yields with those achievable through conventional synthetic methods. It was the first time that compounds 8d, 8e, 8h, and 13b-f were synthesized. The characteristics of the IR and the UV spectra of these compounds and the effects of their substituents on the spectra were observed.

Investigation of quinazolines as inhibitors of breast cancer resistance protein (ABCG2)

Chemotherapy is one of the major forms of cancer treatment. Unfortunately, tumors are prone to multidrug resistance leading to failure of treatment. Breast cancer resistance protein (BCRP), the second member of ABC transporter subfamily G, has been found to play a major role in drug efflux and hence multidrug resistance. Until now, very few potent and selective BCRP inhibitors like Ko143 have been identified. In the search for more potent and selective BCRP inhibitors, we synthesized and investigated a series of differently substituted quinazoline compounds. Several variations at positions 2, 4, 6 and 7 of the quinazoline scaffold were carried out to develop a structure-activity- relationship analysis for these compounds. It was found that compounds bearing a phenyl substituent at position 2 of the 4-anilinoquinazoline scaffold were most potent. On the aniline ring at position 4 of the quinazoline moiety substituents like NO2, CN, CF3 led to very high BCRP inhibition potencies. The most potent compounds were further investigated for their intrinsic cytotoxicity and their ability to reverse the multidrug resistance. Compound 20, an anilinoquinazoline bearing a phenyl ring at position 2 and meta-nitro substitution on the 4-anilino ring, was found to have the highest therapeutic ratio. The most active compounds from each variation were also investigated for their effect on BCRP expression. It was found that compound 20 has no significant effect on BCRP expression, while compound 31 decreased the surface BCRP expression. The only difference in the two compounds was the presence of a 3,4-dimethoxyphenyl ring in compound 31 instead of phenyl substitution at position 2 of the quinazoline moiety. From the study of all target compounds, compound 20 was the most prominent compound having inhibitory potency even higher than Ko143, the most potent BCRP inhibitor known. Compound 20 was also found to be selective towards BCRP with a very high therapeutic ratio.

Impact of aryloxy-linked quinazolines: A novel series of selective VEGFR-2 receptor tyrosine kinase inhibitors

Three series of 6,7-dimethoxyquinazoline derivatives substituted in the 4-position by aniline, N-methylaniline and aryloxy entities, targeting EGFR and VEGFR-2 tyrosine kinases, were designed and synthesized. Pharmacological activities of these compounds

A novel approach to quinazolin-4(3H)-one via quinazoline oxidation: an improved synthesis of 4-anilinoquinazolines

A novel strategy to prepare 4-anilinoquinazoline derivatives based on the oxidation of the quinazoline ring is described. Quinazoline oxidation has been investigated and improved, thus leading to an efficient and high yielding method to quinazolin-4(3H)-ones. Efficiency of this approach has been evaluated synthesizing four well known tyrosine kinase inhibitors and comparing the obtained yields with those achievable through conventional synthetic methods.

Synthesis and biological evaluation of substituted 6-alkynyl-4-anilinoquinazoline derivatives as potent EGFR inhibitors

A series of C-6 or C-3′ alkynyl-substituted 4-anilinoquinazoline derivatives was prepared straightforwardly by a Sonogashira reaction of the corresponding bromo-substituted 4-anilinoquinazolines. Bioactive assay of these compounds for in vitro EGFR kinase inhibition demonstrated that the novel 6-hydroxypropynyl-4-anilinoquinazoline 5e was a very potent EGFR kinase inhibitor with an IC50 of 14 nM.

Efficient synthesis of 4-aminoquinazoline and thieno[3,2-d]pyrimidin-4- ylamine derivatives by microwave irradiation

(Chemical Equation Presented) A simple, efficient, and high-yielding synthesis of quinazolin-4-ylamine and thieno[3,2-d]pyrimidin-4-ylamine derivatives is reported under microwave irradiation conditions. Reaction conditions including temperature, solvent,

Quinazoline formulations and therapeutic use thereof

Pharmaceutical compositions for parenteral administration of poorly soluble quinazoline compounds in the form of microemulsions or micellar solutions are described. The compositions are useful in treating patients suffering from cancer or having allergic

Synthesis and anti-tumor activity of 6,7-dialkoxy-4-phenylamino-quinazolines

Compounds of the formula: wherein: Rais iodo, (C1-C4)hydroxyalkyl, benzyloxy, OCF3, SCF3, SO3H, SO2F, SO2NR2R3where R2is hydrogen or (