380844-22-4

Upstream product

• 645-08-9 Isovanillic acid 
• 621-59-0 isovanillin 
• 929683-54-5 3-(3-chloropropoxy)-4-methoxybenzaldehyde 
• 67-56-1 methanol 
• 6702-50-7 3-hydroxy-4-methoxybenzoate 
• 109-70-6 1.3-chlorobromopropane 
• 632-02-0 3-chloropropyl p-toluenesulfonate 

Downstream Products

• 1259017-55-4 3-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-7-methoxyquinazolin-6-yloxy)propyl 4-(bis(4-fluorophenyl)methyl)piperazine-1-carbodithioate 
• 1259017-73-6 N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-(3-chloropropoxy)-7-methoxyquina-zolin-4-amine 
• 1259017-72-5 N-(3-bromophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine 
• 1259017-50-9 3-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-7-methoxyquinazolin-6-yloxy)propyl 4-methylpiperazine-1-carbodithioate 
• 1259017-48-5 3-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)propyl 4-methylpiperazine-1-carbodithioate 
• 1259017-46-3 3-(4-(3-bromophenylamino)-7-methoxyquinazolin-6-yloxy)propyl 4-methylpiperazine-1-carbodithioate 
• 1259017-51-0 3-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-7-methoxyquinazolin-6-yloxy)propyl piperazine-1-carbodithioate 
• 1259017-53-2 3-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-7-methoxyquinazolin-6-yloxy)propyl morpholine-4-carbodithioate 
• 1259017-54-3 3-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-7-methoxyquinazolin-6-yloxy)propyl thiomorpholine-4-carbodithioate 
• 1006609-38-6 ethyl 3-(7-methoxy-6-(3-(4-phenylpiperazin-1-yl)propoxy)quinazolin-4-ylamino)-1H-pyrrole-2-carboxylate 
• 214472-17-0 4-methoxy-5-[3-(4-morpholinyl)propoxy]benzoic acid methyl ester 
• 1456070-15-7 C₂₃H₂₄ClFN₄O₂S 
• 1456070-14-6 C₂₃H₂₄ClFN₄O₃ 
• 1445860-67-2 4-(3'-chloro-4'-fluorophenylamino)-6-[3-(2-oxa-6-azaspiro[3.3]heptane-6-yl)propoxy]-7-methoxyquinazoline 

Relevant academic research and scientific papers

Novel anti-tumor compounds

The present invention provides a novel anti-tumor compound. The compound is a compound shown in formula (I) or pharmaceutically accepted salt or a solvate of the salt. Further provided is a pharmaceutical composition. The pharmaceutical composition compri

Four-membered heterocycles-containing 4-anilino-quinazoline derivatives as epidermal growth factor receptor (EGFR) kinase inhibitors

We report herein the design and synthesis of novel azaspirocycle or azetidine substituted 4-anilinoquinazoline derivatives. The EGFR inhibitory activities and in vitro antitumor potency of these newly synthesized compounds against two lung cancer cell lines HCC827 and A549 were evaluated. Most of the target compounds possess good inhibitory potency. In particular, compounds 21g with 2-oxa-6-azaspiro[3.4]octane substituent was found to possess higher EGFR inhibitory activities and similar antitumor potency comparing to the lead compound gefitinib with improved water solubility.

Design, synthesis, and in vitro antitumor activity evaluation of novel 4-pyrrylamino quinazoline derivatives

Here, we describe the design and synthesis of two series of 4-pyrrylamino quinazolines as new analogs of the epidermal growth factor receptor inhibitor gefitinib. In vitro antitumor activity of these novel compounds against pancreatic (Miapaca2) and prostate (DU145) cancer cell lines was evaluated. Compared with the parental gefitinib, all 18 derivatives show a greatly increased cytotoxicity to cancer cells. In vitro kinase inhibitory activity on epidermal growth factor receptor was also investigated. Among them, compounds GI-6, GII-4, GII-6, GII-8, and GII-9 are more potential receptor tyrosine kinase (RTK) inhibitors. Based on these results, we propose simple structure-activity relationship to provide information for designing and developing more potent antitumor agents.

Novel EGFR inhibitors prepared by combination of dithiocarbamic acid esters and 4-anilinoquinazolines

On the basis of combination strategy, a novel series of EGFR inhibitors were designed and synthesized by combination of dithiocarbamic acid esters and 4-anilinoquinazolines. The effect of the synthesized compounds on cell proliferation was evaluated by MTT assay in three human cancer cell lines: MDA-MB-468, SK-BR-3 and HCT-116. Two compounds (11d and 11f) were found more potent against all three cell lines and five compounds (11a, 11d-11g) were found more potent against both MDA-MB-468 and SK-BR-3 than Lapatinib. SAR studies revealed that the substituents on C6 and C7 positions of quinazoline, the amine component of dithiocarbamate moiety and the linker greatly affected the activity. This work provides a promising new strategy for the preparation of potent tyrosine kinase inhibitors.

4-Quinazolinyloxy-diaryl ureas as novel BRAFV600E inhibitors

Aryl phenyl ureas with a 4-quinazolinoxy substituent at the meta-position of the phenyl ring are potent inhibitors of mutant and wild type BRAF kinase. Compound 7 (1-(5-tert-butylisoxazol-3-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy) phenyl)urea hydrochloride) exhibits good pharmacokinetic properties in rat and mouse and is efficacious in a mouse tumor xenograft model following oral dosing.

Design and synthesis of novel Gefitinib analogues with improved anti-tumor activity

There is an urgent need to design and develop new and more potent EGFR inhibitors with improved anti-tumor activity. Here we describe the design and synthesis of two series of 4-benzothienyl amino quinazolines as new analogues of the EGFR inhibitor Gefiti

QUINAZOLINE DERIVATIVES AS RAF KINASE MODULATORS AND METHODS OF USE THEREOF

Compounds according to formula (I), compositions and methods are provided for modulating the activity of RAF kinases, including BRAF kinase and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by RAF kinases. Formula (I): or a pharmaceutically acceptable salt, solvate, clathrate of hydrate thereof, wherein X is O or S(O)t; Ra is O or S.

Synthesis of gefitinib from methyl 3-hydroxy-4-methoxy-benzoate

This paper reports a novel synthesis of gefitinib starting from methyl 3-hydroxy-4-methoxybenzoate. The process starts with alkylation of the starting material, followed by nitration, reduction, cyclization, chlorination and two successive amination reactions. The intermediates and target molecule were characterized by 1H-NMR, 13C-NMR, MS and the purities of all these compounds were determined by HPLC. This novel synthetic route produced overall yields as high as 37.4%.

Fluorine-18 labeling of 6,7-disubstituted anilinoquinazoline derivatives for positron emission tomography (PET) imaging of tyrosine kinase receptors: Synthesis of18F-Iressa and related molecular probes

Inhibitors of tyrosine kinase enzymatic activity represent a promising new class of antineoplastic agents. Although clinical studies performed over the last decade give more insight on the potential therapeutic applications of such drugs, identification of the individual patients who might benefit from them remains a major challenge. We have developed a synthetic strategy for the production of a wide variety of radiolabeled 6,7-disubstituted 4-anilinoquinazolines suitable for noninvasive imaging of tyrosine kinase receptors to predict therapy effectiveness. Three new F-18 labeled radiopharmaceuticals based on the therapeutic agents Tarceva, Iressa, and ZD6474 were synthesized. Decay-corrected yields varied between 25 and 40% for a total synthesis time of 120 min, thus providing F-18 labeled tyrosine kinase inhibitors in quantities and times practical for use as PET radiopharmaceuticals. Copyright

PROCESS FOR PRODUCING QUINAZOLIN-4-ONE DERIVATIVE

A process for producing a quinazolin-4-one compound having the formula: [wherein R1, R2, R3 and R4 each represents a group not participating in the below-mentioned reaction, and R1, R2, R3 and R4 can be combined together to form a ring] which comprises reacting an anthranilic acid derivative having the formula: [wherein R5 is a hydrogen atom or a hydrocarbyl group] with a formic acid derivative in the presence of an ammonium carboxylate.