It is an aromatic heterocycle with a bicyclic structure consisting of two fused sixmembered aromatic rings, a benzene ring and a pyrimidine ring. Quinazolinediones are particularly attractive pharmacophores because of their wide range of bioactivities. Synthesis of some substituted quinazoline moieties. A simple and efficient, ligandfree coppercatalyzed approach to quinazoline derivatives uses readily available substituted 2bromophenylmethylamines and amides as starting materials. 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 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. The deaminative coupling reaction of 2aminobenzamides with amines provides quinazolinone products.
Use of the information, documents and data from the echa website is subject to the terms and conditions of this legal notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the echa website may be reproduced, distributed andor used, totally or in part, for noncommercial purposes provided that echa is. Gaucher disease is a lysosomal storage disorder lsd caused by deficiency in the enzyme glucocerebrosidase gc. 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. Quinazolines were found to be inhibitors of not just egfr, but many other receptor tyrosine kinases as well. Research has demonstrated that the niementowski quinazoline synthesis could be employed for the creation of potential egfrinhibiting molecules. It is a light yellow crystalline solid that is soluble in water. The molecular manipulation of promising lead compound is still a major line. An efficient cucatalyzed synthesis of quinazolines via the cn bond formation reactions between nh bonds of amidines and csp 3h bonds adjacent to sulfur or nitrogen atoms in the commonly used solvents, such as dmso, dmf, dma, nmp or tmeda, followed by intramolecular cc bond formation reactions was developed for the first time. Synthesis and antimicrobial activity of some new quinazoline. Synthesis, characterization, and anticancer activity of new. Experimental all chemical used of reagent grade and used as supplied. 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. A series of quinazolinone and benzamide derivatives have been efficiently synthesized in good to excellent yields via the reaction of 2aminobenzamide and aromatic benzoyl chlorides under solventfree conditions using sbaprso3h as a nano solid acid catalyst.
Introduction biological importance of drugs containing quinazoline moiety examples of drugs with quinazoline moiety uses of quinazoline. Quinazoline derivatives have a therapeutic benefit as an anti invasive agents with potential activity in early and advanced solid tumors, metastatic bone disease and leukemias610. The cascade reaction includes a sequential ullmanntype coupling and aerobic oxidation and provides a convenient and practical strategy for the synthesis of. The synthesized compounds were characterized by spectral methods. Quinazoline is an organic compound with the formula c 8 h 6 n 2. The ftir spectra in the range 4000 400 cm1 were recorded by shimadzu instrument. These sizeexpanded u analogues exhibit fluorescent emission wavelengths that span 155 nm, from 335 to 490 nm. Synthesis, characterization and antimicrobial studies of. Synthesis and antimicrobial activity of some new quinazoline derivatives dhaval j. Quinazolines quinazoline is composed of fused benzene and pyrimidine rings.
Quinazoline and condensed quinazolines ha ve exhibited a v ariety of biolo gical acti vities lik e analg esic, antiinf lammator y1, antihypertensive2, antihistaminic, anticancer35, sedative, hypnotic and. Reactions of organolithium reagents with quinazoline. Synthesis of chalcone incorporated quinazoline derivatives as. The reaction tolerates a wide range of substitutions on the aromatic and dione rings. The pasty mass obtained was diluted with 50ml of water and treated with aqueous sodium bicarbonate solution. Synthesis of some novel quinazoline derivatives having. This discovery was made by in silico screening of 1. Synthesis of some new quinazolinone derivatives and. Design, synthesis and anticonvulsant evaluation of novel 8. The numbering of the quinazoline ring system which is currently used was suggested by paal and busch. Websters timeline history, 1906 2007 icon group international on. A novel domino synthesis of quinazolinediones by palladium. Supporting information highly efficient coppercatalyzed cascade. A brief survey about biological importance of quinazoline and thier derivatives revealed that a large number of publications began to appear after 1960s.
Recently, many efforts have been focused by chemists on the modification of quinazoline ring for development of pharmaceutical and clinical compounds. Evaluation of quinazoline analogues as glucocerebrosidase. Some of the known quinazoline derivative are reported to exhibit remarkable anticancer activity11. Quinazoline is an aza derivative of the quinoline, it is also known as 1,3diazanaphthalene. These metrics are regularly updated to reflect usage leading up to the last few days. Small molecule chaperones of protein folding and translocation have been proposed as a promising therapeutic approach to this lsd. In 1968 only two derivatives were used, methaqualone as. An efficient onepot approach to multiple substituted quinazolines with diaryliodonium salt 1, and two nitriles 2 has been presented. Coppercatalyzed annulation of amidines for quinazoline. The bioactive assays showed that most of the compounds exhibited moderate antimicrobial activities against the tested strains. Quinazoline is a compound made up of two fused sixmembered simple aromatic rings, a benzene ring and a pyrimidine ring. Quinazoline derivatives have found applications as antimalarial agents and in cancer treatment.
The biological activities of the synthesized quinazoline derivatives also are discussed. Compounds 1 and 2 demonstrated a remarkable antiproliferative effect, with an ic 50 value of 6. Synthesis and applications of quinazolinebased fluorescent. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. The observed dipole moment of quinazoline in benzene is 2. Citations are the number of other articles citing this article, calculated by crossref and updated daily. A novel series of quinazolines were synthesised by cyclisation reaction of anthranilic acid with urea to get 2,4 di hydroxy quinazoline 2. Synthesis of quinazoline derivatives and their biological. It was first prepared by gabriel in 1903 and isolated from the chinese plant aseru. A convenient synthetic pathway to threesubstituted quinazoline 2,4dione derivatives was developed from substituted anthranilamide via carbonylation with boc anhydride and then cyclization in the presence of the base sodium methoxide. Moreover, the quinazoline skeleton is very common in several naturally occurring alkaloids displaying a. Quinazoline definition, a colorless, crystalline, heterocyclic compound, c8h6n2. Synthesis and anticancer activity of new quinazoline. The quinazoline and quinazolinone skeleton is frequently encountered in medicinal chemistry.
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. Haoquan li, wanfang li, anke spannenberg, wolfgang baumann, helfried neumann, matthias beller and xiao. Wide range of quinazolinone biological properties including. Synthesis, characterization, and anticancer activity of. Synthesis and antiinflammatory screening of some quinazoline and. The aim of this work is to synthesize new schiff bases linked to quinazoline moiety.
A family of quinazoline based fluorescent nucleoside analogues is synthesized for photophysical studies and applications in probing nucleic acid structure, dynamics, and recognition. The oxidation of primary amines, such as benzylamine, by singlet oxygen has previously been shown to give products that arise from the rapid nucleophilic addition of amines to imines. Quinazoline antifolates thymidylate synthase inhibitors. Reactions of organolithium reagents with quinazoline derivatives. It has broad spectrum of activity which are antiinflammatory, antibacterial, antimicrobial, antihiv, anticancer, and many more due to these biological effects it has drawn more interest in synthesis and derivatization of this moiety as much as possible. An efficient method for the synthesis of disubstituted quinazoline diones with differential nsubstitution proceeds in high yields under mild conditions. Jun 03, 20 owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. Quinazolinone molecules were the superior lead molecules for the drugs from past immemorial.
Review article undeniable pharmacological potentials of quinazoline motifs in therapeutic medicine 1olayinka oyewale ajani, 1oluwatosin yemisi audu, 1damilola victoria aderohunmu, 1fisayo elizabeth owolabi and 2ayodele ojo olomieja. Websters bibliographic and eventbased timelines are comprehensive in scope, covering virtually all topics. Owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. It is a mancude organic heterobicyclic parent, a member of quinazolines, an azaarene and an orthofused heteroarene. In this study, a new series of quinazoline derivatives 326 was synthesized and characterized via physicochemical and spectral means. The reaction enables great flexibility of the substitution patterns on quinazolines and is applicable to two different nitriles to give a regioselective product. For example, one reversible inhibitor with the quinazoline core scaffold potently inhibits both egfr and vegfr in addition to the rearranged during transfection ret receptor tyrosine kinase hennequin et al. Quinazoline nucleus has attracted attention of medicinal chemists, due to wide spectr um of biological activities exhibited by them. Enhancement of different biomedical activities of newly. Analgesics, antibacterial and locomotor activity of. Synthesis and reactivity of some novel quinazoline. A new series of 8substituted43h quinazoline derivatives were synthesized, evaluated for their anticonvulsant activity against chemically ptz, picrotoxin and strychnine and electrically mes induced seizures and compared with the reference drugs valproate and methaqualone. Melting points were determined with an electrical thermal melting point apparatus and are uncorrected.
Synthesis, characterisation and biological evaluation of. Treatment of 2amino5methylbenzoic acid with butyl isothiocyanate resulted in the new 2thioxoquinazolin4one 3. Two new synthesized and characterized quinazoline schiff bases 1 and 2 were investigated for anticancer activity against mcf7 human breast cancer cell line. Dakhil department of chemistry, faculty of science, university of benghazi, benghazi, libya a r t i c l e i n f o a b s t r a c t article history. Quinazoline 4one analogs introduction hetero cyclic chemistry research reached in all areas of drug discovery in recent days. Synthesis of sf5containing benzisoxazoles, quinolines. Chemical characteristics, synthetic methods, and biological. Chinazolin was proposed for its compound by weddige, on observing that this was isomeric with the then compound cinnoline and quinaoxaline. Synthesis, biological evaluation and qsar studies of a. Chemical characteristics, synthetic methods, and biological potential of quinazoline and quinazolinone derivatives mohammad asif department of pharmacy, grd pg institute of management and technology, dehradun, uttarakhand 248009, india.
Lipophilic analogues with modification to the c2methyl substituent. Synthetic method for the preparation of quinazolines by. I 43hquinazolinones 1 and related quinazolines 2 are classes. In this paper, we report the synthesis of nsubstituted3nitrophthalimide derivatives iiiii, the reactions of phthalimide iii with amines, hydrazines, and amino acid derivatives to synthesise a small library of 3. The first structureactivity relationship for this antibacterial scaffold is explored in. Journal of chemical and pharmaceutical research, 20, 57. The research on biological activity of quinazoline compounds started when the compound 2methyl1,3aryl4 quinazoline derivative was synthesized. Anthranilic acid was condensed with chloro acylchloride followed by. Moreover, the quinazoline skeleton is very common in. Acid hydrazide, acetylhydrazine carboxylate and acetylhydrazinecarbodithioate were the most active compounds with.
Facile synthesis of 3substituted quinazoline 2,4dione. Synthesis of some novel quinazoline derivatives having anti. Introduction biological importance of drugs containing quinazoline moiety examples of drugs with quinazoline moiety uses of quinazoline drugs conclusion references 2. The simple synthesis of quinazoline2,4dione derivatives. Review article undeniable pharmacological potentials of. Quinazoline is a bicyclic compound earlier known as benzo 1, 3diazine. The fact that a certain chemical substance is restricted to a specific function, such as sex attraction, does not necessarily mean that it was evolved. Synthesis and antimicrobial evaluation of some new. Concise synthesis of quinazoline alkaloids, luotonins a. A new and facile preparation of quinazoline 2,41h,3hdiones was first reported which was the condensation of aromatic oaminonitriles with dmf or n,ndiethylformamide in the presence of zncl2 0. Enhancement of different biomedical activities of newly synthesized quinazoline derivatives. We recently reported on the discovery of a novel antibacterial 2 with a 43hquinazolinone core. An economical method for the preparation of quinazolines by using singlet oxygen as the sole oxidant has been developed.
More than three fourth of the bioactive drugs available in the market are all hetero cycles. Implication of quinazoline 43hones in medicinal chemistry. Ajarimb a school of chemistry, cardiff university, main building, park place, cardiff cf10 3at, uk b criminal evidence, ministry of interior, riyadh 11632, p. Int j pharm pharm sci, vol 6, issue 5, 567571 568 twenty minutes and then 200 g 5 moles of flaked sodium hydroxide was added slowly in small portions. Article views are the countercompliant sum of full text article downloads since november 2008 both pdf and html across all institutions and individuals. An in situ formed ruthenium catalyst enables a highly selective dehydrogenative coupling reaction of 2aminophenyl ketones with amines to form quinazoline products. Design, synthesis, and evaluation of novel 1methyl3.
Implication of quinazoline43hones in medicinal chemistry. Oct 10, 20 a series of novel 1methyl3substituted quinazoline 2,4dione derivatives was designed, synthesized, and evaluated for their antimicrobial activities against six strains of bacteria and five fungi in vitro. Alkylation and hydrazinolysis of the inherent thioxo group in afforded the corresponding thioethers 423 and hydrazine derivatives. Marvania et al3 synthesized a series of phenyl n mustardquinazoline derivatives and. Reactions of organolithium reagents with quinazoline derivatives gamal a. The propargylated quinazolines 4 and 5 were used in the 1,3dipolar cycloaddition reaction to link. Synthesis of some novel quinazoline derivatives having anticancer activity. Quinazolines are nitrogen containing heterocyclic scaffolds and have showed a wide range biological activities, such as anticancer. Concise synthesis of quinazoline alkaloids, luotonins a and b. In addition several quinazoline derivatives posses diverse. General procedure for coppercatalyzed synthesis of quinazoline derivatives 3aj p2. 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.
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