The antitumor activity of quinazoline derivatives is wellknown 1217. Chemical characteristics, synthetic methods, and biological. Two new synthesized and characterized quinazoline schiff bases 1 and 2 were investigated for anticancer activity against mcf7 human breast cancer cell line. Reactions of organolithium reagents with quinazoline. The biological activities of the synthesized quinazoline derivatives also are discussed. The invention concerns quinazoline derivatives of formula i. Chinazolin was proposed for its compound by weddige, on observing that this was isomeric with the then compound cinnoline and quinaoxaline. It is a light yellow crystalline solid that is soluble in water. Ajarimb a school of chemistry, cardiff university, main building, park place, cardiff cf10 3at, uk b criminal evidence, ministry of interior, riyadh 11632, p. Design, synthesis, and biological evaluation of quinazoline. Ep 1667992 b1 quinazoline derivatives the lens free. Several biological activities were reported for fused tricyclic quinazoline derivatives 8, 9 among which deoxyvasicinone is highly interesting and has been. Cuicatalyzed cn bond formation and cleavage for the synthesis of benzimidazo1,2aquinazoline derivatives chao li, wenting zhang, xiangshan wang school of chemistry and chemical engineering, jiangsu key laboratory of green synthesis for functional materials, jiangsu normal university, xuzhou jiangsu 221116, p. In silico pharmacokinetics studies for quinazolines proposed.
The heterocyclic fused rings quinazoline and quinazolinone have drawn a huge consideration owing to their expanded applications in the field of pharmaceutical chemistry. Synthesis of some novel quinazoline derivatives having anti. Subsequently, their in vitro anticancer activity against a549, hct116 and mcf7. Also quinazoline derivatives have a therapeutic potential as an antiinvasive agent with potential activity in early and advanced solid tumors, metastatic bone disease and leukemia 35. Recent structures with potent anticancer activity chapter pdf available february 2018 with 55 reads. A simple and efficient, ligandfree coppercatalyzed approach to quinazoline derivatives uses readily available substituted 2bromophenylmethylamines and amides as starting materials. Gefitinib iressa and erlotinib are derivatives of quinazolinones introduced to the market as anticancer agents. The pasty mass obtained was diluted with 50ml of water and treated with aqueous sodium bicarbonate solution.
Though the parent quinazoline molecule is rarely mentioned by itself in technical literature, substituted derivatives have been synthesized for medicinal purposes such as antimalarial and anticancer agents. Synthesis and anticancer activity of new quinazoline. Supporting information cuicatalyzed cn bond formation and. The availability of newly identified quinazoline derivatives as potent cyp1b1 inhibitors would allow further studies on cyp1b1 enzymemediated modulation of xenobiotics. Design, synthesis and biological evaluation of spiro cyclohexane1,2 quinazoline derivatives as potent dipeptidyl peptidase iv inhibitors volume. Catalystfree synthesis of quinazoline derivatives using low. Quinazoline is the main fused heterocyclic ring system reported for their biological activities, compounds with varieties of pharmacophores, which bring together knowledge of a target with understanding of the molecule types that might. According to the main method the authors adopted in their research design, those synthetic methods were divided. The heterocyclic compounds have a great importance in medicinal chemistry.
Synthesis, characterisation and biological evaluation of. The infrared spectra of quinazoline and its derivatives public deposited. Introduction quinazoline 43hone ring system has been consistently regarded as promising privileged structural icon ow ing to its pharmacodynamic versatility in many of its synthetic derivatives as well as in several naturally occur. After intraperitoneal ip injection to albino mice at a dose of 100 mgkg body weight, synthesized quinazolin43hones 124 were examined in the maximal electroshock mes induced seizures and subcutaneous pentylenetetrazole scptz induced seizure models in mice. The cascade reaction includes a sequential ullmanntype coupling and aerobic oxidation and provides a convenient and practical strategy for the synthesis of. In medical chemistry, quinazoline quinazolinone and its derivatives are an essential building block for many drugs 3 4567 such as albaconazole, raltitrexed, methaqualone, proquazone. When the effervescence ceased, the precipitate obtained was filtered and washed with water. Potential of quinazoline and quinazolinone derivatives. Many quinazoline derivatives, such as erlotinib, gefitinib and lapatinib. Computational modeling of novel quinazoline derivatives as.
Synthesis, characterization, and anticancer activity of. Quinazoline is an organic compound with the formula c 8 h 6 n 2. Reactions of organolithium reagents with quinazoline derivatives. Catalystfree synthesis of quinazoline derivatives using.
Novel representative of crown ethers incorporating the quinazoline moiety is synthesized. Scheme 39 a series of quinazoline derivatives 37 and 38 have strong inhibition on human pin1 33 see scheme 40. The invention concerns quinazoline derivatives of the formula i. I 43hquinazolinones 1 and related quinazolines 2 are classes. Insilico design of novel analogues were carried out using acd labs chem sketch 12. Synthesis of quinazoline derivatives containing veratrole and. Qsar modelling on thirty 34 novel quinazoline derivatives egfr wt inhibitors as nonsmall cell lung cancer nsclc agents was performed to develop a model with good predictive power that can predict the activities of newly designed compounds that have not been synthesised. The rcsb pdb also provides a variety of tools and resources. Design, synthesis and biological evaluation of spiro cyclohexane1,2 quinazoline derivatives as potent dipeptidyl peptidase iv inhibitors. Quinazoline is a mancude organic heterobicyclic parent that is naphthalene in which the carbon atoms at positions 1 and 3 have been replaced by nitrogen atoms.
Melanin concentrating hormone receptor 1 mchr1, a crucial regulator of energy homeostasis involved in the control of feeding and energy metabolism, is a promising target for treatment of obesity. In alkaline medium, where the anhydrous neutral species of quinazoline were predominantly undergo oxidation with kmno 4 furnished a high yield of 3,4dihydro4oxo quinazoline was also formed. The quinazoline skeleton appears in many alkaloids, most commonly in the form of 43hquinazolinone moieties. Acidbase interactions in some isoquinoline and quinazoline amino derivatives wojciech zielinski and agnieszka kudelko department of organic technology and petrochemistry silesian university of technology ul. Numerous studies of structureactivity relationships sar involving many series of quinazoline derivatives have led to advances in power, specificity and the pharmacokinetics properties of these inhibitors 22.
Also, some 4anilinoquinazolines represent a new class of. Acidbase interactions in some isoquinoline and quinazoline. Download fulltext pdf quinazolinone and quinazoline derivatives. Treatment of 2amino5methylbenzoic acid with butyl isothiocyanate resulted in the new 2thioxoquinazolin4one 3. A new series of quinazoline43hones are evaluated for anticonvulsant activity. Few novel 4,6disubstituted quinazoline derivatives 3336 showed good antiinflammatory and anticancer activity cytotoxic against u937 leukemia cell lines 32 see scheme 39. Utility of 2methylquinazolin43hone in the synthesis of. Synthesis and antimicrobial evaluation of novel 2chloromethyl34methyl6oxo5e phenyldiazenyl 2 thioxo 5,6 dihydropyrimidine 12h ylquinazoline 43hones derivatives were carried out by kumar and coworkers fig. Cuicatalyzed cn bond formation and cleavage for the synthesis of benzimidazo1,2a quinazoline derivatives chao li, wenting zhang, xiangshan wang school of chemistry and chemical engineering, jiangsu key laboratory of green synthesis for functional materials, jiangsu normal university, xuzhou jiangsu 221116, p. Qsar, molecular docking and in silico pharmacokinetic prediction siddharth jitendrakumar modi, vithal madhvarao kulkarni department of pharmaceutical chemistry, poona college of pharmacy, bharati vidyapeeth deemed to be university, pune 411038, maharashtra, india. The egfr wt inhibitors were optimized at b3lyp631g level of theory using density functional theory dft method. In this study, a new series of quinazoline derivatives 326 was synthesized and characterized via physicochemical and spectral means.
Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. Jan 24, 2007 the invention concerns quinazoline derivatives of formula i. Proposed anticancer mechanisms for quinazoline derivatives include. P h o nh 2 n n ch 2cl ph n n h n ch 3 ph me o nh 2 n n ch 2cl me n n h n ch 3 m e table 1. Design, synthesis, and biological evaluation of novel quinazoline. So the quinazoline ring is considered as one of the major classes of benzoheterocyclic compounds that have drawnmuch attention in. The binding model suggests one to four hydrogen bonding interactions between quinazoline derivatives and. Therapeutical chemistry department, national research centre, dokki, cairo 12622. Review article chemical characteristics, synthetic methods. Quinazoline and quinazolinone are reported for their diversified biological activities and compounds with different substitutions bring together to knowledge of a target with understanding of the molecule types that might. Quinazoline is composed of fused benzene and pyrimidine rings. Quinazolinones benzopyrimidine derivatives, are compounds with wide spectrum of biological activities, including.
Compounds 1 and 2 demonstrated a remarkable antiproliferative effect, with an ic 50 value of 6. These studies are likely to reveal their possible usefulness in the treatment of xenobioticsassociated disorders that lead to hormonal cancers. In silico pharmacokinetics studies for quinazolines. Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metalfree domino reactions.
Synthesis, characterization, and anticancer activity of new. Ep0520722b1 ep19920305703 ep92305703a ep0520722b1 ep 0520722 b1 ep0520722 b1 ep 0520722b1 ep 19920305703 ep19920305703 ep 19920305703 ep 92305703 a ep92305703 a ep 92305703a ep 0520722 b1 ep0520722 b1 ep 0520722b1 authority ep european patent office prior art keywords chloro quinazoline 4c pharmaceutically formula prior art date 19910628 legal status the. Quinazoline derivatives, whi ch belong to the ncontaining heterocyclic compounds, have caused universal concerns due to their widely and distinct biopharmaceutical activities. The aim of this study was to discover new quinazoline derivatives with preventive effect on lipo polysaccharideinduced acute lung injury via anti inflammatory. Reactions of organolithium reagents with quinazoline derivatives gamal a. Quinazolines and quinazolinones are classes of fused het.
Molecular docking and anticonvulsant activity of newly. Oxidation catalytic hydrogenation of quinazoline stopped after the absorption of one molecules of hydrogen and. Molinspiration software was used to analyze lipinski rule of five and drug likeness properties. Quinazoline derivatives as selective cyp1b1 inhibitors. A highly employed method for 43hquinazolinone synthesis is based on acylation of anthranilic acid with acyl chloride.
These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists. Design of novel quinazoline derivatives and related. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a pdf plugin installed and enabled in your browser. The general synthetic route for the quinazoline compounds is shown in scheme 1, and is illustrated for compounds 3ad and 8ag. The infrared spectra of quinazoline and its derivatives. It is a mancude organic heterobicyclic parent, a member of quinazolines, an azaarene and an orthofused heteroarene. Facile access to potent antiviral quinazoline heterocycles. It is an aromatic heterocycle with a bicyclic structure consisting of two fused sixmembered aromatic rings, a benzene ring and a pyrimidine ring. Quinazolinoneamino acid hybrids as dual inhibitors of egfr. Synthesis of some novel quinazoline derivatives having. Alkylation and hydrazinolysis of the inherent thioxo group in afforded the corresponding thioethers 423 and hydrazine derivatives. Facile preparation of 4substituted quinazoline derivatives.
The data from antibacterial examinations indicated that the substituent on the phenyl ring exerted significant influence on the antibacterial. Quinazoline derivatives, which belong to the ncontaining heterocyclic compounds, have caused universal concerns due to their widely and. Synthesis and anticancer activity of new quinazoline derivatives. Palladiumcatalyzed narylation of amidines and a onepot. For instance, three drugs, gefitnib iressa, erlotinib tarceva 23 24and lapatinib tykerb 25have been ap. Ep0520722b1 therapeutic preparations containing quinazoline. Some of quinazoline derivatives are considered as antifolate thymidylate synthase inhibitors such as nolatrexed 1 5, while 2substituted1,3dihydroquinazolinone derivatives are associated with inhibitory effects on tubulin polymerization such as gmc5193 2 6, 7. Among these compounds, the chemical structure of compound 6l was further confirmed via singlecrystal xray diffraction analysis. Quinazoline derivatives have found applications as antimalarial agents and in cancer treatment. Quinazoline is a bicyclic compound earlier known as benzo 1, 3diazine.
Review article chemical characteristics, synthetic methods, and biological potential of quinazoline and quinazolinone derivatives mohammadasif department of pharmacy, grd pg institute of management and technology, dehradun, uttarakhand, india correspondence should be addressed to mohammad asif. A total of 22 quinazoline thioether derivatives incorporating a 1,2,4triazolo4,3apyridine moiety were designed, synthesized, and evaluated as antimicrobial agents in agriculture. Synthesis of quinazoline derivatives containing veratrole. Synthesis and reactivity of some novel quinazoline derivatives. Subsequent ring closure with acetic anhydride afford corresponding 1,3benzoxazin4one benzoxazinone which will be treated with different amines to give 43hquinazolinone derivatives. Owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. Original article quinazoline derivatives as anticancer agents.
Quinazolines quinazoline is composed of fused benzene and pyrimidine rings. Synthesis and evaluation of antioxidant properties of some. Synthesis of some new quinazolinone derivatives and. Utility of 2methylquinazolin43hone in the synthesis. Coupling of 4aminopyridine with 4chloroquinazoline intermediates 7ad using either standard buchwald conditions pd 2 dba 3, binap in presence of sodium tertbutylate, or in dmf at 150 c, afforded the quinazolines 3ad. The binding mode of the compounds at the active site of. Reported in this paper is a very simple method for direct preparation of 4substituted quinazoline derivatives from a reaction between substituted 2aminobenzophenones and thiourea in the presence of dimethyl sulfoxide dmso. As a member of the wwpdb, the rcsb pdb curates and annotates pdb data according to agreed upon standards. Quinazolines heterocyclic building blocks sigmaaldrich. In the present work, the uptodate largest set of 181 quinolinequinazoline derivatives as mchr1 antagonists was subjected to both ligand and receptorbased threedimensional quantitative.
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