26059-83-6

Upstream product

• 91808-64-9 4-nitro-2-bromobenzamide 
• 100-46-9 benzylamine 
• 3011-89-0 Novastat 
• 31930-18-4 2-amino-4-nitrobenzamide 
• 100-51-6 benzyl alcohol 
• 98-88-4 benzoyl chloride 
• 619-17-0 4-Nitroanthranilic acid 
• 591-50-4 iodobenzene 
• 201230-82-2 carbon monoxide 
• 100-52-7 benzaldehyde 
• 87376-25-8 2-amino-4-nitro-benzonitrile 
• 618-39-3 benzamidin 
• 93-97-0 benzoic acid anhydride 
• 618-36-0 rac-methylbenzylamine 

Downstream Products

• 80806-69-5 7-Nitro-2-phenyl-3-carboxymethyl-4(3H)-quinazolinone 

Relevant academic research and scientific papers

Covalent Lipid Pocket Ligands Targeting p38α MAPK Mutants

A chemical genetic approach is presented to covalently target a unique lipid binding pocket in the protein kinase p38α, whose function is not yet known. Based on a series of cocrystal structures, a library of 2-arylquinazolines that were decorated with electrophiles were designed and synthesized to covalently target tailored p38α mutants containing artificially introduced cysteine residues. Matching protein–ligand pairs were identified by MS analysis and further validated by MS/MS studies and protein crystallography. The covalent ligands that emerged from this approach showed excellent selectivity towards a single p38α mutant and will be applicable as suitable probes in future studies of biological systems to dissect the function of the lipid pocket by means of pharmacological perturbations.

Electrochemically induced synthesis of quinazolinonesviacathode hydration ofo-aminobenzonitriles in aqueous solutions

An efficient and practical electrochemically catalyzed transition metal-free process for the synthesis of substituted quinazolinones from simple and readily availableo-aminobenzonitriles and aldehydes in water has been accomplished. I2/base and water play an unprecedented and vital role in the reaction. By electrochemically catalysed hydrolysis ofo-aminobenzonitriles, the synthesis of quinazolinones with benzaldehyde was first proposed. The synthetic utility of this method was demonstrated by gram-scale operation, as well as the preparation of bioactiveN-(2,5-dichlorophenyl)-6-(2,2,2-trifluoroethoxy) pteridin-4-amine, which enables straightforward, practical and environmentally benign quinazolinone formation.

Electro-oxidative cyclization: Access to quinazolinones: Via K2S2O8without transition metal catalyst and base

A K2S2O8-promoted oxidative tandem cyclization of primary alcohols with 2-aminobenzamides to synthesize quinazolinones was successfully achieved under undivided electrolytic conditions without a transition metal and base. The key feature of this protocol is the utilization of K2S2O8 as an inexpensive and easy-to-handle radical surrogate that can effectively promote the reaction via a simple procedure, leading to the formation of nitrogen heterocycles via direct oxidative cyclization at room temperature in a one-pot procedure under constant current. Owing to the use of continuous-flow electrochemical setups, this green, mild and practical electrosynthesis features high efficiency and excellent functional group tolerance and is easy to scale up.

Iridium(III)-Catalyzed Alkynylation of 2-(Hetero)arylquinazolin-4-one Scaffolds via C-H Bond Activation

The directed C-H alkynylation of 2-(hetero)arylquinazolin-4-ones has been explored with the ethynylbenziodoxolone reagent TIPS-EBX employing an Ir(III) catalyst. Complementary conditions for either monoalkynylation or dialkynylation have been developed. Also demonstrated is the broad scope of this reaction and the compatibility of various functional groups such as ?F, ?Cl, ?Br, ?CF3, ?OMe, ?NO2, and alkyl, etc.

A practical synthesis of quinazolinones via intermolecular cyclization between 2-halobenzamides and benzylamines catalyzed by copper(I) immobilized on MCM-41

The heterogeneous tandem N-arylation/oxidative C–H amidation of 2-halobenzamides and benzylamines was achieved in DMSO at 110 or 120 °C by using an MCM-41-immobilized L-proline copper(I) complex [MCM-41-L-Proline-CuBr] as the catalyst and air as the oxidant, yielding a variety of quinazolinone derivatives in good yields. The new MCM-41-L-Proline-CuBr catalyst can easily be prepared from commercially readily available and inexpensive reagents and recovered by filtration of the reaction mixture, and reused up to seven times with almost consistent activity.

Structure-based drug design: Synthesis and biological evaluation of quinazolin-4-amine derivatives as selective Aurora A kinase inhibitors

Aurora kinases play critical roles in the regulation of the cell cycle and mitotic spindle assembly. Aurora A kinase, a member of the Aurora protein family, is frequently highly expressed in tumors, and selective Aurora A inhibition serves as a significant component of anticancer therapy. However, designing highly selective Aurora A inhibitors is difficult because Aurora A and B share high homology and differ only by three residues in their ATP-binding pockets. Through structure-based drug design, we designed and synthesized a series of novel quinazolin-4-amine derivatives. These derivatives act as selective Aurora A kinase inhibitors by exploiting the structural differences between Aurora A and B. The selectivities of most compounds were improved (the best up to >757-fold) when comparing with the lead compound (3-fold). In vitro biochemical and cellular assays revealed that compound 6 potently inhibited Aurora A kinase and most human tumor cells. Furthermore, compound 6 effectively suppressed carcinoma, such as triple-negative breast cancers (TNBC) in an animal model. Therefore, compound 6 might serve as a promising anticancer drug. Moreover, through molecular dynamic (MD) analysis, we have identified that a salt bridge formed in Aurora B is key contributor for the isoform selectivity of the inhibitor. This salt bridge has not been previously detected in the reported crystal structure of Aurora B. These results might provide a crucial basis for the further development of highly potent inhibitors with high selectivity for Aurora A.

A highly efficient heterogeneous palladium-catalyzed carbonylative annulation of 2-aminobenzamides with aryl iodides leading to quinazolinones

The first heterogeneous carbonylative annulation of 2-aminobenzamides with aryl iodides was achieved in N,N-dimethylformamide (DMF) at 120 °C under 10 bar of carbon monoxide by using an MCM-41-immobilized bidentate phosphine palladium(II) complex [MCM-41-2P-Pd(OAc)2] as catalyst and 1,8-diazabicycloundec-7-ene (DBU) as base, yielding a wide variety of quinazolinone derivatives in good to excellent yields. The new heterogeneous palladium catalyst can easily be prepared by a simple procedure from commercially readily available reagents, and recovered by filtration of the reaction solution, and recycled up to eight times without significant loss of activity.

Quinazoline derivative with activity of selectively inhibiting Aurora A kinase, preparation method and application thereof

The invention discloses a quinazoline derivative with activity of selectively inhibiting Aurora A kinase, a preparation method and an application thereof. The invention discloses a compound shown in a formula (I) or (II), or a pharmaceutically-acceptable salt, hydrate, solvate, polymorph, tautomer or prodrug, and simultaneously discloses applications of the compound shown in the formula (I) or (II), or the pharmaceutically-acceptable salt, the hydrate, the solvate, the polymorph, the tautomer or the prodrug in preparing a medicine for inhibiting the Aurora A kinase, and in preparing a medicine for treatment and/or prevention and/or delay and/or auxiliary treatment and/or managing proliferative diseases. The quinazoline derivative disclosed by the invention has better activity and selectivity of inhibiting the Aurora A, simultaneously has obvious inhibiting action for proliferation of tumor cells. The medicine is expected to be combined with the traditional chemotherapeutic drug for use, and has the advantages that the tumor killing effect is enhanced, the recurrence interval is prolonged and the live quality of patients is improved.

Structure-based design, synthesis and crystallization of 2-arylquinazolines as lipid pocket ligands of p38α MAPK

In protein kinase research, identifying and addressing small molecule binding sites other than the highly conserved ATP-pocket are of intense interest because this line of investigation extends our understanding of kinase function beyond the catalytic phosphotransfer. Such alternative binding sites may be involved in altering the activation state through subtle conformational changes, control cellular enzyme localization, or in mediating and disrupting protein-protein interactions. Small organic molecules that target these less conserved regions might serve as tools for chemical biology research and to probe alternative strategies in targeting protein kinases in disease settings. Here, we present the structure-based design and synthesis of a focused library of 2-arylquinazoline derivatives to target the lipophilic C-terminal binding pocket in p38α MAPK, for which a clear biological function has yet to be identified. The interactions of the ligands with p38α MAPK was analyzed by SPR measurements and validated by protein X-ray crystallography.

Mechanistic insights into a catalyst-free method to construct quinazolinones through multiple oxidative cyclization

A novel one-pot benign oxidative cyclization of alcohols with 2-aminobenzamides was successfully developed without catalyst to afford the quinazolinones under O2. This one-pot protocol involved oxidations and cyclizations to construct the skeleton of quinazolinones through possibly three kinds of distinct reaction mechanisms.