338992-20-4

Usage

Uses

Used in Pharmaceutical Industry:
Tert-butyl 4-((4-(4-bromo-2-fluorophenylamino)-6-methoxyquinazolin-7-yloxy)methyl)piperidine-1-carboxylate is used as a potential drug candidate for [application reason]. Tert-butyl 4-((4-(4-bromo-2-fluorophenylamino)-6-methoxyquinazolin-7-yloxy)methyl)piperidine-1-carboxylate's unique structure, including the piperidine ring and quinazolinone moiety, along with the various substituents, suggests that it may have specific biological activities that could be harnessed for therapeutic purposes. Its use in the pharmaceutical industry is aimed at exploring these potential activities and developing new treatments for various diseases.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry, Tert-butyl 4-((4-(4-bromo-2-fluorophenylamino)-6-methoxyquinazolin-7-yloxy)methyl)piperidine-1-carboxylate serves as a valuable compound for [application reason]. Researchers can use Tert-butyl 4-((4-(4-bromo-2-fluorophenylamino)-6-methoxyquinazolin-7-yloxy)methyl)piperidine-1-carboxylate as a starting point for the design and synthesis of new drugs, leveraging its structural features to create molecules with improved pharmacological properties. Tert-butyl 4-((4-(4-bromo-2-fluorophenylamino)-6-methoxyquinazolin-7-yloxy)methyl)piperidine-1-carboxylate's synthesis and modification can provide insights into the structure-activity relationships of quinazoline derivatives and contribute to the development of more effective drugs.

InChI:InChI=1/C7H7ClN2O/c8-5-1-2-10-6(3-5)4-7(9)11/h1-3H,4H2,(H2,9,11)

Upstream product

• 166815-96-9 N-tert-butoxycarbonyl-4-(4-toluenesulphonyloxymethyl)piperidine 
• 385785-02-4 2-amino-4-(benzyloxy)-5-methoxybenzonitrile 
• 385784-84-9 4-(benzyloxy)-5-methoxy-2-nitrobenzonitrile 
• 52805-34-2 4-(benzyloxy)-3-methoxybenzonitrile 
• 4421-08-3 3-methoxy-4-hydroxybenzonitrile 
• 123855-51-6 tert-butyl 4-(hydroxymethyl)piperidin-1-carboxylate 
• 723283-25-8 (E)-tert-butyl 4-((4-cyano-5-(((dimethylamino)methylene)amino)-2-methoxyphenoxy)methyl)piperidine-1-carboxylate 
• 367-24-8 4-bromo-2-fluoroaniline 
• 2426-87-1 3-methoxy-4-(phenylmethoxy)benzaldehyde 
• 193001-44-4 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride 
• 179688-01-8 7-(benzyloxy)-6-methoxyquinazolin-4(3H)-one 
• 60547-98-0 2-amino-4-benzyloxy-5-methoxybenzamide 
• 196603-96-0 4-(4-bromo-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline 
• 60547-94-6 5-Methoxy-2-nitro-4-(phenylmethoxy)benzamide 

Downstream Products

• 443913-73-3 vandetanib 
• 910298-60-1 4-((4-bromo-2-fluorophenyl)amino)-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-6-ol 
• 1363151-84-1 N-(4-bromo-2-fluorophenyl)-6-methoxy-7-(piperidinyl-4-methoxy)quinazolin-4-amine hydrochloride 
• 1363151-86-3 (S)-(4-((4-bromo-2-fluorophenylamino)-6-methoxyquinazolinyl-7-oxy)methyl)-1-(piperidinyl-2-pyrrolidinyl)methanone hydrochloride 
• 1363153-84-7 C₃₇H₄₈BrFN₆O₆ 
• 1363153-79-0 (S)-N-((S)-1-((S)-2-(4-((4-bromo-2-fluorophenylamino)-6-methoxyquinazolinyl-7-oxy)methyl)piperidine)-1-carbonyl)-1-((pyrrolidinyl)-3,3-dimethyloxobutan-2-yl)-2-(methylamino)propanamide hydrochloride 
• 1363150-67-7 C₄₁H₅₅BrFN₇O₇ 
• 1363153-82-5 C₃₁H₃₇BrFN₅O₅ 
• 338992-12-4 N-Desmethylvandetanib 

Relevant academic research and scientific papers

Tyrosine kinase inhibitors implant he loni and its key intermediate for the preparation of

The invention discloses tyrosine kinase inhibitor implant he loni and its key intermediate of the preparation method, which belongs to the medicine, in the field of fine chemicals. The invention of the preparation method of gefitinib, is a brand-new preparation scheme, from whatever a intermediate starting, can be obtained in accordance with the requirements of the target compound. The method of the invention has short steps, the reaction operation is simple, safe and reliable, high yield, low cost, high purity, pollution little and simple operation and the like.

An alternative synthesis of Vandetanib (Caprelsa) via a microwave accelerated Dimroth rearrangement

Vandetanib is an orally available tyrosine kinase inhibitor used in the treatment of cancer. The current synthesis proceeds via an unstable 4-chloroquinazoline, using harsh reagents, in addition to requiring sequential protection and deprotection steps. In the present work, use of the Dimroth rearrangement in the key quinazoline forming step enabled the synthesis of Vandetanib in nine steps (compared to the previously reported 12–14).

QUINOLINE OR QUINAZOLINE DERIVATIVES WITH APOPTOSIS INDUCING ACTIVITY ON CELLS

Provided is a pharmaceutical composition comprising, as an active ingredient, a quinoline or quinazoline derivative of formula (I), a pharmaceutically acceptable salt, an isomer, a hydrate, and a solvate thereof, which is effective in the prevention and treatment of a cancer, inflammation, autoimmune diseases or neurodegenerative disorders which are induced by the overexpression of inhibitor of apoptosis proteins (IAPs).

Radiosynthesis of [11C]Vandetanib and [11C]chloro- Vandetanib as new potential PET agents for imaging of VEGFR in cancer

Vandetanib (ZD6474) and its chlorine analogue chloro-Vandetanib are potent and selective vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors with low nanomolar IC50 values. [ 11C]Vandetanib and [11C]chloro-Vandetanib, new potential PET agents for imaging of VEGFR in cancer, were first designed, synthesized and labeled at nitrogen and oxygen positions from their corresponding N- and O-des-methylated precursors, in 40-50% decay corrected radiochemical yield and 370-555 GBq/μmol specific activity at end of bombardment (EOB).

SUBSTITUTED QUINAZOLINE INHIBITORS OF GROWTH FACTOR RECEPTOR TYROSINE KINASES

The present invention relates to new substituted quinazoline inhibitors of vascular endothelial growth factor receptor tyrosine kinase, epidermal growth factor receptor tyrosine kinase, and/or REarranged during Transfection tyrosine kinase, pharmaceutical compositions thereof, and methods of use thereof.

CHEMICAL PROCESS

The present invention relates to chemical processes for the manufacture of certain quinazoline derivatives, or pharmaceutically acceptable salts thereof. The invention also relates to processes for the manufacture of certain intermediates useful in the manufacture of the quinazoline derivatives and to processes for the manufacture of the quinazoline derivatives utilising said intermediates. In particular, the present invention relates to chemical processes and intermediates useful in the manufacture of the compound 4-(4- bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline.

QUINAZOLINE DERIVATIVES AS VEGF INHIBITORS

The invention relates to quinazoline derivatives of the formula I:- wherein: m is an integer from 1 to 3; R 1 represents halogeno or C 1-3 alkyl; X 1 represents -O-; R 2 is selected from one of the following three groups: 1) C 1-5 alkylR 3 (wherein R 3 is piperidin-4-yl which may bear one or two substituents selected from hydroxy, halogeno, C 1-4 alkyl, C 1-4 hydroxyalkyl and C 1-4 alkoxy; 2) C 2-5 alkenylR 3 (wherein R 3 is as defined hereinbefore); 3) C 2-5 alkynylR 3 (wherein R 3 is as defined hereinbefore); and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

Novel 4-anilinoquinazolines with C-7 basic side chains: Design and structure activity relationship of a series of potent, orally active, VEGF receptor tyrosine kinase inhibitors

We have previously shown that 4-anilinoquinazolines can be potent inhibitors of vascular endothelial growth factor (VEGF) receptor (Flt-1 and KDR) tyrosine kinase activity. A novel subseries of 4-anilinoquinazolines that possess basic side chains at the C-7 position of the quinazoline nucleus have been synthesized. This subseries contains potent, nanomolar inhibitors of KDR (median IC50 0.02 μM, range 0.001-0.04 μM), which are comparatively less potent vs Flt-1 tyrosine kinase (median IC50 0.55 μM, range 0.02-1.6 μM). The compounds also retain some inhibitory activity against the tyrosine kinase associated to the endothelial growth factor receptor (EGFR) (median IC50 0.2 μM, range 0.075-0.8 μM) but demonstrate selectivity vs that associated to the FGF receptor 1 (median IC50 2.5 μM, range 0.9-19 μM). This selectivity profile is also evident in a growth factor-stimulated human endothelial cell (HUVEC) proliferation assay (i.e., inhibition of VEGF > EGF > FGF), with inhibition of VEGF-induced proliferation being achieved at nanomolar concentrations (median IC50 0.06 μM). Further examination of compound 2 (ZD6474) in recombinant enzyme assays revealed excellent selectivity for the inhibition of KDR tyrosine kinase (IC50 0.04 μM) vs the kinase activity of erbB2, MEK, CDK-2, Tie-2, IGFR-1R, PDK, PDGFRβ, and AKT (IC50 range: 1.1 to > 100 μM). Anilinoquinazolines possessing basic C-7 side chains exhibited markedly improved aqueous solubility over previously described anilinoquinazolines possessing neutral C-7 side chains (up to 500-fold improvement at pH 7.4). In addition, aqueous solubility of the neutral fraction present at pH 7.4 of the basic subseries of anilinoquinazoline proved to be higher than that of the neutral analogue 1 (ZD4190). Oral administration of representative compounds to mice (50 mg/kg) produced plasma levels between 0.2 and 3 μM at 24 h after dosing. Our development candidate 2 demonstrated a very attractive in vitro profile combined with excellent solubility (330 μM at pH 7.4) and good oral bioavailability in rat and dog (> 80 and > 50%, respectively). This compound demonstrated highly significant, dose-dependent, antitumor activity in athymic mice. Once daily oral administration of 100 mg/kg of compound 2 for 21 days inhibited the growth of established Calu-6 lung carcinoma xenografts by 79% (P 0.001, Mann Whitney rank sum test), and substantial inhibition (36%, P 0.02) was evident with 12.5 mg/kg/day.