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