Quinazoline is an organic compound with the formula c 8 h 6 n 2. Griess apparently recognized the bicylic nature of the product. The quinazoline nucleus and its derivatives are a class of heterocyclic compounds that are considered to be the basic framework of biologically active compounds that exist in a number of drug. A quinazoline derivative represented by the following general formula 1a or a salt thereof.
Synthesis of some novel quinazoline derivatives having anticancer activity. Its 4chloro analog has recently revealed much superior activity to it. In this study, a new series of quinazoline derivatives 326 was synthesized and characterized via physicochemical and spectral means. The approach is widely applicable to 2fluoro, 2chloro, 2bromo and 2nitrosubstituted aryl aldehyde and ketone substrates. Systematic structureactivity relationship studies resulted in lead. 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. Design, synthesis and biological evaluation of spiro cyclohexane1,2 quinazoline derivatives as potent dipeptidyl peptidase iv inhibitors.
Chinazolin was proposed for its compound by weddige, on observing that this was isomeric with the then compound cinnoline and quinaoxaline. Inflammation mediators, substituted quinazolines, phospho diesterase inhibitors, carrageenininduced paw oedema, percent inhibition, adenosine. Insights into the photobehavior of fluorescent oxazinone, quinazoline, and difluoroboron derivatives. The antitumor activity of quinazoline derivatives is wellknown. Pyrrolo 3,2f quinazoline 1,3diamine derivatives, containing a novel tricyclic heterocycle compared with trimetrexate, were further explored and shown to be inhibitors of parasitic dhfrs 12. Synthesis of some novel quinazoline derivatives having anti. The synthesis of derivatives of this system has been accomplished by means of three kinds of methods, starting from 43hquinazolinones, 2,5piperazinediones or openchain tripeptides, where anthranilic acid can be at the cterminal, the nterminal or the intermediate. Synthesis and evaluation of some new 4, 6 disubstituted. 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. Ajarimb a school of chemistry, cardiff university, main building, park place, cardiff cf10 3at, uk b criminal evidence, ministry of interior, riyadh 11632, p. Unfortunately, classic chemical synthesis does not provide. The biosynthesis modulation of proinflammatory cytokines pics has become an important strategy for pharmacological intervention in a variety of inflammatory and fibrotic disease states. 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.
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 interact with the target family. R 3 is a alkyl, hydroxy, alkoxy, phenyl the phenyl may be substituted with alkoxy. Reactions of organolithium reagents with quinazoline derivatives gamal a. It has been used for the treatment of high blood pressure as adrenergic blockers, anxiety, and panic disorder prazosin and has also been found useful for. Novel series of spiro2h,3h quinazoline 2,1cyclohexane derivatives ixvi were synthesized and biologically evaluated as cytotoxic agents against human breast carcinoma cell lines mcf7 using doxorubicin as a reference drug. It is a mancude organic heterobicyclic parent, a member of quinazolines, an azaarene and an orthofused heteroarene. Synthesis of some novel quinazoline derivatives having. It is an aromatic heterocycle with a bicyclic structure consisting of two fused sixmembered aromatic rings, a benzene ring and a pyrimidine ring. Synthesis and thermal decomposition kinetics of some. Synthesis, characterization, and anticancer activity of. Quinazolines quinazoline is composed of fused benzene and pyrimidine rings. Review article chemical characteristics, synthetic methods. A new series of quinazoline43hones are evaluated for anticonvulsant activity.
The nature of the oxidant exhibited a considerable effect on the reaction, and tert. Other way to obtain quinazoline 43hthiones is the ring closure of 2acylaminothiobenzamides in basic medium 28,42. The numbering of the quinazoline ring system which is currently used was suggested by paal and busch. This simple and efficient method furnished the corresponding quinazolines in high yields via onepot threecomponent reaction of 2aminoaryl ketones. Scheme 40 a series of quinazoline derivatives 3942 were evaluated for their biological activity as potential antitumor agents 34 see schemes 41 and 42. Jun 03, 20 for instance, quinazoline derivatives with imidazole substituted at the 2position of side chain own potent antiinflammatory function. The photophysical properties of the compounds are described. New antitubercular drugs are needed for the treatment of tb. Rao a a quinazoline and pyrido3,2dpyrimidine based compound library was designed, synthesized and evaluated as multitargeting agents aimed at alzheimers disease ad. Systematic structureactivity relationship studies resulted in lead compounds 23 and 36. According to the main method the authors adopted in their research design, those synthetic methods were divided. Quinazoline is a bicyclic compound earlier known as benzo 1, 3diazine was prepared in the laboratory by gabriel in 1903 although one of its derivative was known much earlier. The cascade reaction includes a sequential ullmanntype coupling and aerobic oxidation and provides a convenient and practical strategy for the synthesis of. Introduction in 1869 griess prepared the first quinazoline derivative, 2 cyano 3, 4dihydro4oxoquinazoline, by the reaction of cyanogens with anthranilic acid.
For instance, quinazoline derivatives with imidazole substituted at the 2position of side chain own potent antiinflammatory function. Synthesis and reactivity of some novel quinazoline derivatives. Isbn 97818388097, eisbn 9781838801403, pdf isbn 9781838800536, published 20200506. Quinazolinone and quinazoline derivatives intechopen. The data from antibacterial examinations indicated that the substituent on the phenyl ring exerted significant influence on. Compounds 1 and 2 demonstrated a remarkable antiproliferative effect, with an ic 50 value of 6. Owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. The biological results showed that most of quinazoline derivatives exhibited potent antiproliferative activities against a panel of three tumor cell lines and a good inhibitory effect against the adhesion and migration of human umbilical vein endothelial cells huvecs. Ep 1667992 b1 quinazoline derivatives the lens free. Synthesis and anticancer activity of new quinazoline. Quinazoline definition of quinazoline by medical dictionary. Synthesis scheme of pyrazolo quinazoline derivatives. Nowadays, the efficacy of mainstay antitb drugs is jeopardized due to the emergence of drugresistant tb. A simple and efficient, ligand free coppercatalyzed approach to quinazoline derivatives uses readily available substituted 2bromophenylmethylamines and amides as starting materials.
Therapeutical chemistry department, national research. Design, synthesis, and biological evaluation of 4methyl. Design, synthesis and biological evaluation of novel. Synthesis and biological evaluation of quinazoline4thiones. 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.
Facile access to potent antiviral quinazoline heterocycles. Quinazoline was used to study the electrochemical behaviour of quinazoline using modern polarographic and voltammetric methods. Earlier, quinazoline 4 ones has been a subject of extensive pharmacological evaluation, as well as, toxicological studies for antimicrobial and antifungal activities. The pyrazino2,1 bquinazoline 3,6dione system is the key structural fragment of a group of alkaloids. Treatment of 2amino5methylbenzoic acid with butyl isothiocyanate resulted in the new 2thioxoquinazolin4one 3. Pdf uses of 2ethoxy4 3h quinazolinone in synthesis. Synthesis and photophysical studies of a series of. A series of 2,4disubstituted quinazoline derivatives were designed and synthesized. A 3 represents a 31a 32 a 33, a 31, a 32 and a 33 represent a single bond. Results and discussion the physical constants of the studied compounds are given in table 1.
Alkylation and hydrazinolysis of the inherent thioxo group in afforded the corresponding thioethers 423 and hydrazine derivatives. Potential of quinazoline and quinazolinone derivatives. A variety of c1 sources could be used, affording 4. The invention concerns quinazoline derivatives of formula i. Synthesis and evaluation of 2,4disubstituted quinazoline. Quinazoline and thiazoloquinazoline a biologically active. Low melting mixture of maltosedimethylurea dmunh 4 cl was found to be an inexpensive, nontoxic, easily biodegradable and effective reaction medium in the catalyst free synthesis of quinazoline derivatives. The main alkaloid components are derivatives of quinazoline and betacarboline 10, which have exhibited anticancer and antibacterial activities in pharmacological studies 4, 10. Synthesis and antimicrobial evaluation of novel 2chloromethyl34methyl6oxo5e phenyldiazenyl 2 thioxo 5,6 dihydropyrimidine 12h yl quinazoline 43hones derivatives were carried out by kumar and coworkers fig. Two new synthesized and characterized quinazoline schiff bases 1 and 2 were investigated for anticancer activity against mcf7 human breast cancer cell line. The data from antibacterial examinations indicated that the substituent on the phenyl ring exerted significant influence on the antibacterial. Derivatives of 2,2dimethyl1,2dihydroquinazoline43hthione can be prepared by condensation of 2aminothiobenzamides with acetone under mild conditions 41. Molecular design based on the structureproperty relationships.
Onepot synthesis of benzo4,5imidazo1,2aquinazoline. Scheme 7 solventcatalystfree microwaveassisted synthesis of quinazolines. The invention concerns quinazoline derivatives of the formula i wherein m is 1, 2 or 3 and each r. Design, synthesis and biological evaluation of spiro cyclohexane1,2 quinazoline derivatives as potent dipeptidyl peptidase iv inhibitors volume. The fluorescence properties of target compounds were studied. Jan 24, 2007 the invention concerns quinazoline derivatives of formula i. Application of quinazoline and pyrido3,2d pyrimidine templates to design multitargeting agents in alzheimers disease tarek mohamed,ab mandeep k. In this study, we decipher the mechanism of action of a new potent series of 2ethylthio4methylaminoquinazoline derivatives. Most quinazoline derivatives were synthesized in five chemical steps from substituted 2fluorobenzoic acid or their chloroanhydride which reacted with isothiourea to give nbenzoylimidothiocarbamate. In the formula, r 1 represents a hydrogen atom or alkyl. Design, synthesis and biological evaluation of spiro. Quinazolines heterocyclic building blocks sigmaaldrich. A simple and efficient approach for the synthesis of 2. A cellpermeable quinazoline compound that augments the cytostatic effects of rapamycin and acts as an autophagy stimulator both in mammalian cultures in vitro and in a drosophila melanogaster hd model in vivo.
The preparation of arylvinylquinazolines was performed by aldol condensation of the appropriate methylquinazoline and functionalized. Chemical characteristics, synthetic methods, and biological. Packaging 1, 5 g in glass bottle biochemphysiol actions genotoxicity of quinazoline was established by bacterial sos chromotest escherichia coli. Polypharmacology is a promising paradigm in modern drug discovery.
Catalystfree synthesis of quinazoline derivatives using. One of the problems with modern public health is target searching for new highly effective medicinal preparations. In this work, a new series of quinazoline compounds of the general formula represented in scheme 1 were designed in such a way to accommodate phenyl group. Author summary tuberculosis tb is the leading cause of death worldwide due to an infectious agent. S1 table and s3 fig these intermediates were heated to close the pyrimidine ring with the formation of the quinazoline 4one scaffold. Proposed anticancer mechanisms for quinazoline derivatives include. Quinazoline is a bicyclic compound earlier known as benzo 1, 3diazine.
A onepot transition metal free method for synthesizing benzo4,5imidazo1,2a quinazoline and imidazo1,2a quinazoline derivatives has been developed. Ep3181553a4 quinazoline derivative, preparation method. Herein, we have discovered a series of novel pi3k and hdac dual inhibitors in which the hydroxamic acid moiety as the zinc binding functional group was introduced to a quinazoline based pi3k pharmacophore through an appropriate linker. Quinazoline definition, a colorless, crystalline, heterocyclic compound, c8h6n2. Gefitinib iressa and erlotinib are derivatives of quinazolinones introduced to the market as anticancer agents.
Biological activities of quinazolinone derivatives. The biological activities of the synthesized quinazoline derivatives also. An efficient and convenient method for the preparation of pyrimidine and quinazoline derivatives by the one. Low melting mixture of maltosedimethylurea dmunh4cl was found to be an inexpensive, nontoxic, easily biodegradable and effective reaction medium in the catalystfree synthesis of quinazoline derivatives. 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. Scheme 39 a series of quinazoline derivatives 37 and 38 have strong inhibition on human pin1 33 see scheme 40.
Among those medicinal preparations are the natural and. In medical chemistry, quinazoline quinazolinone and its derivatives are an essential building block for many drugs 3 4567 such as albaconazole, raltitrexed, methaqualone, proquazone. A new series of quinazoline 43hones are evaluated for anticonvulsant activity. The journal of physical chemistry c 2017, 121 14, 80918108. The molecular manipulation of promising lead compound is still a major line of approach for the discovery of new drugs. Quinazoline and thiazoloquinazoline a biologically.
Study of methanol extracts from different parts of peganum harmala l. Jp45566b2 quinazoline derivatives and pharmaceuticals. The present invention is substituted phenylamino quinazoline acceptable derivatives and pharmaceutically acceptable salts and prodrugs thereof on the formula 4m. Unfortunately, classic chemical synthesis does not provide an opportunity for the formation of n. Synthesis, characterization, and anticancer activity of new. Quinazoline derivatives, whi ch belong to the ncontaining heterocyclic compounds, have caused universal concerns due to their widely and distinct biopharmaceutical activities. The synthesis of a series of pushpull arylvinyl styryl, aryl, and arylethynyl quinazoline derivatives by means of different straightforward protocols is reported. Application of quinazoline and pyrido3,2dpyrimidine. Reactions of organolithium reagents with quinazoline derivatives. It is a light yellow crystalline solid that is soluble in water. The heterocyclic fused rings quinazoline and quinazolinone have drawn a huge consideration owing to their expanded applications in the field of pharmaceutical chemistry.
Quinazoline is the main sixmembered heterocyclic ring system reported for their biological activities, compounds with multiple pharmacophores, which bring together knowledge of a target with understanding of the molecule types that might interact with the target family. An efficient and convenient method for the preparation of 5,6. Solvent catalystfree microwaveassisted synthesis of quinazolines. Pdf owing to the significant biological activities, quinazoline derivatives have. Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metal free domino reactions. Quinazoline derivatives are one of the most important sixmembered nitrogencontaining heterocyclic compounds as many naturally occurring and pharmaceutical compounds contain quinazoline moiety as the core unit. Quinazoline derivatives are well known to have a diverse array of therapeutic activities. Uses of 2ethoxy4 3h quinazolinone in synthesis of quinazoline and quinazolinone derivatives of antimicrobial activity.
Quinazoline derivatives have found applications as antimalarial agents and in cancer treatment. Thus, inhibition of pics will provide the basis f or an effective choice of treatment in inflammatory disorders like rheumatoid arthritis ra, chronic obstructive pulmonary disease copd, asthma. Catalystfree synthesis of quinazoline derivatives using low. The molecular manipulation of promising lead compound is still a major line of approach for the discovery of. Also known as 1,3diazanaphthalene, quinazoline received its name from being an aza derivative of quinoline.
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