557770-90-8

Usage

Uses

Used in Pharmaceutical Research and Drug Development:
7-(3-Chloropropoxy)-4-chloroquinazoline is utilized as a key component in pharmaceutical research and drug development due to its potential biological activities. It serves as a building block for the synthesis of new medicinal compounds, particularly those with antitumor and antimalarial properties.
Used in Antitumor Applications:
In the field of oncology, 7-(3-Chloropropoxy)-4-chloroquinazoline is used as an antitumor agent, targeting various types of cancer. Its potential biological activities make it a promising candidate for the development of new cancer therapies.
Used in Antimalarial Applications:
7-(3-Chloropropoxy)-4-chloroquinazoline also exhibits potential antimalarial properties, making it a valuable resource in the development of new treatments for malaria.
Used in Agricultural Chemicals:
7-(3-CHLOROPROPOXY)-4-CHLOROQUINAZOLINE has potential applications in the agricultural chemical sector, where it can be used to develop new pesticides or herbicides to improve crop yield and protect against pests.
Used in Industrial Processes:
7-(3-Chloropropoxy)-4-chloroquinazoline also serves as a specialty chemical in various industrial processes, where its unique properties can be harnessed for specific applications, such as in the synthesis of other chemicals or materials.

InChI:InChI=1/C11H10Cl2N2O/c12-4-1-5-16-8-2-3-9-10(6-8)14-7-15-11(9)13/h2-3,6-7H,1,4-5H2

Upstream product

• 557770-89-5 4-(3-phenylpropylamino)-7-(2-chloroethoxy)quinazoline 
• 16499-57-3 7-fluoro-3H-quinazolin-4-one 
• 446-32-2 4-fluoroanthranilic acid 

Downstream Products

• 722544-46-9 2-(5-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-2H-pyrazol-3-yl)-N-(3-fluorophenyl)acetamide 
• 557770-91-9 2-(3-((7-(3-chloropropoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)acetic acid 
• 786681-63-8 2-(4-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-1-yl)-N-(2,3-difluorophenyl)acetamide 
• 1253969-55-9 C₂₇H₂₄ClN₇O 
• 1253969-34-4 C₃₁H₃₂N₈O₂ 
• 1253969-35-5 C₃₂H₃₄N₈O 
• 1253969-36-6 C₃₁H₃₄N₈O 
• 1253969-37-7 C₃₁H₃₂N₈O 
• 1383952-16-6 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3-(7-(3-chloropropoxy)quinazolin-4-ylamino)phenyl)urea 
• 1383952-17-7 1-(3-chloro-4-fluorophenyl)-3-(3-(7-(3-chloropropoxy)quinazolin-4-ylamino)phenyl)urea 
• 957881-03-7 2-{ethyl[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)proplyl]amino}ethyl dihydrogen phosphate 
• 722544-50-5 di-tert-butyl 2-[[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)propyl](ethyl)amino]ethyl phosphate 
• 722544-37-8 di-tert-butyl {(2R)-1-[3-({4-[(5-{2-[(2,3-difluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)propyl]pyrrolidin-2-yl}methyl phosphate 
• 722544-51-6 N-(3-fluorophenyl)-2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide 

Relevant academic research and scientific papers

As Aurora kinase inhibitors of the substituted quinazoline derivatives

The invention relates to a substituted quinazoline derivative as an aurora kinase inhibitor, which is shown as structural formula (I) or (Ia), tautomers, hydrates, solvates or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the tautomers, hydrates, solvates and pharmaceutically acceptable salts as drug active ingredients, and application of the compounds and the pharmaceutical compositions in preparation of medicines for protection, treatment, curing or alleviation of proliferative diseases of patients.

Rational Design of Bisubstrate-Type Analogues as Inhibitors of DNA Methyltransferases in Cancer Cells

Aberrant DNA hypermethylation of promoter of tumor suppressor genes is commonly observed in cancer, and its inhibition by small molecules is promising for their reactivation. Here we designed bisubstrate analogues-based inhibitors, by mimicking each substrate, the S-adenosyl-l-methionine and the deoxycytidine, and linking them together. This approach resulted in quinazoline-quinoline derivatives as potent inhibitors of DNMT3A and DNMT1, some showing certain isoform selectivity. We highlighted the importance of (i) the nature and rigidity of the linker between the two moieties for inhibition, as (ii) the presence of the nitrogen on the quinoline group, and (iii) of a hydrophobic group on the quinazoline. The most potent inhibitors induced demethylation of CDKN2A promoter in colon carcinoma HCT116 cells and its reactivation after 7 days of treatment. Furthermore, in a leukemia cell model system, we found a correlation between demethylation of the promoter induced by the treatment, chromatin opening at the promoter, and the reactivation of a reporter gene.

Discovery of 4-aminoquinazoline - Urea derivatives as Aurora kinase inhibitors with antiproliferative activity

Two series of 20 novel 4-aminoquinazoline - urea derivatives have been designed and synthesized. The entire target compounds were investigated for their in vitro antiproliferative activity against six human cancer cell lines (K562, U937, A549, NCI-H661, HT29 and LoVo) using the MTT-based assay. Most compounds showed significant antiproliferative activities against four solid tumor cell lines, but no or poor activities against two leukemia cell lines. Furthermore, the target compounds were screened for Aurora A/B kinases inhibitory activity. Among them, 7c, 7d, 8c, and 8d are more potent against Aurora A kinase than ZM447439. Docking study of compounds 7d and ZM447439 revealed that they bound strongly to the ATP-binding sites of Aurora A and B. Thus, they may be promising lead compounds for the development of novel anti-tumor drug potentially via inhibiting Aurora kinases.

Synthesis and Quantum Chemical Studies of New 4-aminoquinazoline Derivatives as Aurora A/B Kinase Inhibitors

Nine novel 4-aminoquinazoline derivatives were designed and synthesized. Biochemical and cellular analyses demonstrated that most of the derivatives exhibited a strong activity to inhibit Aurora A and B kinases and to suppress the proliferation of a panel of human tumor cell lines (U937, K562, A549, LoVo, and HT29). Quantum chemical studies were also carried out to determine the structural features of these compounds engaged in the inhibition of Aurora kinases.

Switching the Chemoselectivity in the Amination of 4-Chloroquinazolines with Aminopyrazoles

[Chemical equation presented] The chemoselectivity in the amination of 4-chloroquinazolines with 3-amino-1H-pyrazoles was studied. Under the conditions of Pd2(dba)3/ Xantphos/Na2CO3, 4-chloroquinazolines underwent selective amination with the cyclic secondary amino group of 3-amino-1H-pyrazoles. whereas 4-chloroquinazolines were exclusively aminated with the primary amino group of 3-amino-1H-pyrazoles via SNAr substitution In the presence of HCl.

MALEATE CO-CRYSTAL OF AZD1152

The present invention relates to a novel co-crystal of 2-{cthyl[3-( {4-[(5- {2-[(3-fluorophenyl)amino]-2-oxoethyl}-IH-pyrazol-3-yl)amino]quinazolin-7- yl}oxy)propyl]amino} ethyl dihydrogen phosphate (AZDl 152) which is an aurora kinase inhibitor that is useful in the treatment of hyperproliferative diseases such as cancer.

COMBINATION THERAPY FOR THE TREATMENT OF CANCER

A combination comprising an aurora kinase inhibitor and an efflux transporter inhibitor wherein the aurora kinase inhibitor is a compound of formula (I) or pharmaceutically acceptable salt thereof for use in the treatment of hyperproliferative diseases such as cancer.

Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase

The Aurora kinases have been the subject of considerable interest as targets for the development of new anticancer agents. While evidence suggests inhibition of Aurora B kinase gives rise to the more pronounced antiproliferative phenotype, the most clinically advanced agents reported to date typically inhibit both Aurora A and B. We have discovered a series of pyrazoloquinazolines, some of which show greater than 1000-fold selectivity for Aurora B over Aurora A kinase activity, in recombinant enzyme assays. These compounds have been designed for parenteral administration and achieve high levels of solubility by virtue of their ability to be delivered as readily activated phosphate derivatives. The prodrugs are comprehensively converted to the des-phosphate form in vivo, and the active species have advantageous pharmacokinetic properties and safety pharmacology profiles. The compounds display striking in vivo activity, and compound 5 (AZD1152) has been selected for clinical evaluation and is currently in phase 1 clinical trials.

PROCESS AND INTERMEDIATE

The invention relates to a new process useful in the preparation of pharmaceutical compounds such as 2-{ethyl[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)propyl]amino}ethyl dihydrogen phosphate (AZD1152) and intermediates used therein.

(3- ((QUINAZOLIN-4-YL) AMINO )-1H-PYRAZOL-1-YL) ACETAMIDE DERIVATIVES AND RELATED COMPOUNDS AS AURORA KINASE INHIBITORS FOR THE TREATMENT OF PROLIFERATIVE DISEASES SUCH AS CANCER

Quinazoline derivatives of formula (I) for use in the treatment of proliferative diseases such as cancer and in the preparation of medicaments for use in the treatment of proliferative diseases, and to processes for their preparation, as well as pharmaceutical compositions containing, them as active ingredient. X is O or NR 6 ;R 5 is aryl or heteroaryl optionally substituted by 1, 2 or 3 substituents independently selected from halo, hydroxy, cyano, nitro, amino,C 1-4 alkylamino, bis(C1-4 alkyl)amino, C 1-4 alkyl, C 2-4 alkenyl,C 2-4 alkynyl, C 1-4 alkoxy, C(O)NHR17 , NHC(0)R 18 and S(O) p R 19where p is 0,1 or 2;The other substituents are as defined in claim 1.