Catalystfree synthesis of quinazoline derivatives using low. Scheme 39 a series of quinazoline derivatives 37 and 38 have strong inhibition on human pin1 33 see scheme 40. I 43hquinazolinones 1 and related quinazolines 2 are classes. The binding mode of the compounds at the active site of. Supporting information cuicatalyzed cn bond formation and.
The invention concerns quinazoline derivatives of formula i. It is a light yellow crystalline solid that is soluble in water. 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. Ep 1667992 b1 quinazoline derivatives the lens free. Reactions of organolithium reagents with quinazoline. Owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. Two new synthesized and characterized quinazoline schiff bases 1 and 2 were investigated for anticancer activity against mcf7 human breast cancer cell line. Ajarimb a school of chemistry, cardiff university, main building, park place, cardiff cf10 3at, uk b criminal evidence, ministry of interior, riyadh 11632, p. Quinazolinoneamino acid hybrids as dual inhibitors of egfr. Therapeutical chemistry department, national research centre, dokki, cairo 12622. The rcsb pdb also provides a variety of tools and resources. For instance, three drugs, gefitnib iressa, erlotinib tarceva 23 24and lapatinib tykerb 25have been ap. Insilico design of novel analogues were carried out using acd labs chem sketch 12. Chinazolin was proposed for its compound by weddige, on observing that this was isomeric with the then compound cinnoline and quinaoxaline.
In medical chemistry, quinazoline quinazolinone and its derivatives are an essential building block for many drugs 3 4567 such as albaconazole, raltitrexed, methaqualone, proquazone. Chemical characteristics, synthetic methods, and biological. Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metalfree domino reactions. The egfr wt inhibitors were optimized at b3lyp631g level of theory using density functional theory dft method. Treatment of 2amino5methylbenzoic acid with butyl isothiocyanate resulted in the new 2thioxoquinazolin4one 3. Alkylation and hydrazinolysis of the inherent thioxo group in afforded the corresponding thioethers 423 and hydrazine derivatives.
A simple and efficient, ligandfree coppercatalyzed approach to quinazoline derivatives uses readily available substituted 2bromophenylmethylamines and amides as starting materials. Computational modeling of novel quinazoline derivatives as. Synthesis and anticancer activity of new quinazoline derivatives. 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. Catalystfree synthesis of quinazoline derivatives using. Quinazoline is composed of fused benzene and pyrimidine rings. 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 biological activities of the synthesized quinazoline derivatives also are discussed. Quinazoline derivatives have found applications as antimalarial agents and in cancer treatment.
Few novel 4,6disubstituted quinazoline derivatives 3336 showed good antiinflammatory and anticancer activity cytotoxic against u937 leukemia cell lines 32 see scheme 39. 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. Synthesis of some new quinazolinone derivatives and. Utility of 2methylquinazolin43hone in the synthesis. Molinspiration software was used to analyze lipinski rule of five and drug likeness properties. Buchwald department of chemistry, massachusetts institute of technology, 77 massachusetts avenue, cambridge, massachusetts 029, united states supporting information general reagent information reactions were setup on the bench top and carried out under an argon. 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. Many quinazoline derivatives, such as erlotinib, gefitinib and lapatinib. Subsequent ring closure with acetic anhydride afford corresponding 1,3benzoxazin4one benzoxazinone which will be treated with different amines to give 43hquinazolinone derivatives. Quinazoline is an organic compound with the formula c 8 h 6 n 2. Synthesis of some novel quinazoline derivatives having anti. Reactions of organolithium reagents with quinazoline derivatives gamal a. 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 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.
Synthesis of quinazoline derivatives containing veratrole and. In silico pharmacokinetics studies for quinazolines proposed. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed. 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. Quinazoline derivatives as selective cyp1b1 inhibitors. Synthesis of quinazoline derivatives containing veratrole. The aim of this study was to discover new quinazoline derivatives with preventive effect on lipo polysaccharideinduced acute lung injury via anti inflammatory. Synthesis of some novel quinazoline derivatives having anticancer activity. Quinazolines heterocyclic building blocks sigmaaldrich. Potential of quinazoline and quinazolinone derivatives. The infrared spectra of quinazoline and its derivatives public deposited. A highly employed method for 43hquinazolinone synthesis is based on acylation of anthranilic acid with acyl chloride. Design, synthesis and biological evaluation of spiro cyclohexane1,2 quinazoline derivatives as potent dipeptidyl peptidase iv inhibitors. Quinazolines and quinazolinones are classes of fused het.
Acidbase interactions in some isoquinoline and quinazoline. 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. Design, synthesis, and biological evaluation of quinazoline. It is an aromatic heterocycle with a bicyclic structure consisting of two fused sixmembered aromatic rings, a benzene ring and a pyrimidine ring. The pasty mass obtained was diluted with 50ml of water and treated with aqueous sodium bicarbonate solution. 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. 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. Design, synthesis and biological evaluation of spiro cyclohexane1,2 quinazoline derivatives as potent dipeptidyl peptidase iv inhibitors volume. The infrared spectra of quinazoline and its derivatives. 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 and reactivity of some novel quinazoline derivatives.
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. 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. 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. As a member of the wwpdb, the rcsb pdb curates and annotates pdb data according to agreed upon standards. Synthesis and anticancer activity of new quinazoline. Gefitinib iressa and erlotinib are derivatives of quinazolinones introduced to the market as anticancer agents. These studies are likely to reveal their possible usefulness in the treatment of xenobioticsassociated disorders that lead to hormonal cancers.
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. Reactions of organolithium reagents with quinazoline derivatives. In the present work, the uptodate largest set of 181 quinolinequinazoline derivatives as mchr1 antagonists was subjected to both ligand and receptorbased threedimensional quantitative. Compounds 1 and 2 demonstrated a remarkable antiproliferative effect, with an ic 50 value of 6. 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. When the effervescence ceased, the precipitate obtained was filtered and washed with water. Oxidation catalytic hydrogenation of quinazoline stopped after the absorption of one molecules of hydrogen and. Review article chemical characteristics, synthetic methods. In this study, a new series of quinazoline derivatives 326 was synthesized and characterized via physicochemical and spectral means. Synthesis and evaluation of antioxidant properties of some.
Jan 24, 2007 the invention concerns quinazoline derivatives of formula i. The quinazoline skeleton appears in many alkaloids, most commonly in the form of 43hquinazolinone moieties. 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. 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. Among these compounds, the chemical structure of compound 6l was further confirmed via singlecrystal xray diffraction analysis. Utility of 2methylquinazolin43hone in the synthesis of. Synthesis of some novel quinazoline derivatives having. The cascade reaction includes a sequential ullmanntype coupling and aerobic oxidation and provides a convenient and practical strategy for the synthesis of. Quinazolinones benzopyrimidine derivatives, are compounds with wide spectrum of biological activities, including. Substituted quinazolines, as a unique type of heterocycles, have been known for a variety of biological activities, including antibiotic, 1 antidepressant, 2 antiinflammatory, 3,4 antihypertensive, 3 antimalarial, 5 and antitumoral, 6 among others. Subsequently, their in vitro anticancer activity against a549, hct116 and mcf7.
According to the main method the authors adopted in their research design, those synthetic methods were divided. Proposed anticancer mechanisms for quinazoline derivatives include. The antitumor activity of quinazoline derivatives is wellknown 1217. 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. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists. The binding model suggests one to four hydrogen bonding interactions between quinazoline derivatives and. Quinazoline derivatives, which belong to the ncontaining heterocyclic compounds, have caused universal concerns due to their widely and. 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. 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.
Design of novel quinazoline derivatives and related. In silico pharmacokinetics studies for quinazolines. The heterocyclic fused rings quinazoline and quinazolinone have drawn a huge consideration owing to their expanded applications in the field of pharmaceutical chemistry. Synthesis, characterization, and anticancer activity of. 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. Facile access to potent antiviral quinazoline heterocycles. Supporting information cuicatalyzed cn bond formation. A new series of quinazoline43hones are evaluated for anticonvulsant activity. Facile preparation of 4substituted quinazoline derivatives.
Quinazoline is a bicyclic compound earlier known as benzo 1, 3diazine. Quinazoline derivatives, whi ch belong to the ncontaining heterocyclic compounds, have caused universal concerns due to their widely and distinct biopharmaceutical activities. Synthesis, characterisation and biological evaluation of. Also, some 4anilinoquinazolines represent a new class of. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. 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. Palladiumcatalyzed narylation of amidines and a onepot.
To develop a lead antidiabetic compound, a series of 21 novel quinazoline derivatives have been synthesized and screened against. The general synthetic route for the quinazoline compounds is shown in scheme 1, and is illustrated for compounds 3ad and 8ag. Synthesis, characterization, and anticancer activity of new. The data from antibacterial examinations indicated that the substituent on the phenyl ring exerted significant influence on the antibacterial. Novel representative of crown ethers incorporating the quinazoline moiety is synthesized. Original article quinazoline derivatives as anticancer agents. The availability of newly identified quinazoline derivatives as potent cyp1b1 inhibitors would allow further studies on cyp1b1 enzymemediated modulation of xenobiotics. Several biological activities were reported for fused tricyclic quinazoline derivatives 8, 9 among which deoxyvasicinone is highly interesting and has been. The numbering of the quinazoline ring system which is currently used was suggested by paal and busch.