557770-89-5

Usage

Uses

Used in Pharmaceutical Industry:
7-(3-HYDROXY-PROPOXY)-3H-QUINAZOLIN-4-ONE is used as an intermediate in the preparation of the aurora kinase inhibitor AZD1152 (A808100). Aurora kinases are a family of serine/threonine protein kinases that play a crucial role in cell division and are often overexpressed or mutated in various types of cancer. By inhibiting these kinases, AZD1152 can help prevent uncontrolled cell division and potentially treat cancer.
Application Reason:
The use of 7-(3-HYDROXY-PROPOXY)-3H-QUINAZOLIN-4-ONE as an intermediate in the synthesis of AZD1152 is due to its unique chemical structure, which can be further modified and functionalized to produce the desired aurora kinase inhibitor. 7-(3-HYDROXY-PROPOXY)-3H-QUINAZOLIN-4-ONE serves as a key building block in the development of targeted cancer therapies, offering a promising avenue for the treatment of various malignancies.

InChI:InChI=1/C11H12N2O3/c14-4-1-5-16-8-2-3-9-10(6-8)12-7-13-11(9)15/h2-3,6-7,14H,1,4-5H2,(H,12,13,15)

Upstream product

• 16499-57-3 7-fluoro-3H-quinazolin-4-one 
• 504-63-2 trimethyleneglycol 
• 446-32-2 4-fluoroanthranilic acid 
• 16499-57-3 7-fluoro-1H-quinazolin-4-one 

Downstream Products

• 557770-90-8 4-chloro-7-(3-chloropropoxy)quinazoline 
• 1253969-55-9 C₂₇H₂₄ClN₇O 
• 1253969-34-4 C₃₁H₃₂N₈O₂ 
• 1253969-35-5 C₃₂H₃₄N₈O 
• 1253969-36-6 C₃₁H₃₄N₈O 
• 1253969-37-7 C₃₁H₃₂N₈O 
• 557770-91-9 2-(3-((7-(3-chloropropoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)acetic acid 
• 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 
• 557770-93-1 N-(2,3-difluorophenyl)-2-{3-[(7-{3-[(2R)-2-(2-hydroxymethyl)pyrrolidin-1-yl]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide 

Relevant academic research and scientific papers

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.

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.

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.

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.

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.

QUINAZOLINE DERIVATIVES AS SRC TYROSINE KINASE INHIBITORS

The invention concerns quinazoline derivatives of Formula (I): (A chemical formula should be inserted here - please see paper copy enclosed herewith) wherein Z is an O, S, SO, SO2, N(R2) or C(R2)2 group wherein each R2 group is hydrogen or (1-8C) alkyl, m is 0, 1, 2 or 3, each R1 group is selected from halogeno, (1-8C) alkyl, (1-6C) alkoxy and any of the other meanings defined in the description, n is 0, 1, 2 or 3, and each R3 group is selected from halogeno, (1-8C) alkyl, (1-6C) alkoxy and any of the other meanings defined in the description, or pharmaceutically-acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an anti-invasive agent in the containment and/or treatment of solid tumour disease.

PHOSPHONOOXY QUINAZOLINE DERIVATIVES AND THEIR PHARMACEUTICAL USE

Quinazoline derivatives of formula (I) wherein A is 5-membered heteroaryl containing a nitrogen atom and one or two further nitrogen atoms; compositions containing them, processes for their preparation and their use in therapy.

QUINAZOLINE COMPOUNDS

Quinazoline derivatives of formula (I) wherein A is 5-membered heteroaryl containing a sulphur atom and optionally containing one or more nitrogen atoms; compositions containing them, processes for their preparation and their use in therapy.