Imidazo 1, 2 pyridine is a drug precursor scaffold and has already been successfully utilized to come up with a number of clinical drugs against various diseases. Green synthesis of imidazo1,2apyridines in aqueous medium. The process is tolerant of a variety of functional groups under mild conditions in the absence of catalysts and additives to give nitro functionalized imidazo 1, 2. The ip moiety possesses excellent electrontransporting ability and great thermal stability. The imidazo1,2 apyridine scaffold is a pharmaceutically important drug template, and its derivatives display a broad range of biological activities such as antibacterial, antiviral, antiinflammatory, antitumor, and antihiv. A novel electrontransporting unit, imidazo 1, 2 bpyridazine ip, was first reported for developing host materials. The paper deals with the recent progress realised in the comprehension of the pharmacological properties of this scaffold. Pdf medicinal attributes of imidazo1,2apyridine derivatives. Imidazo 1, 2 apyridine is one of the most potential bicyclic 56 heterocyclic rings that is recognized as a drug prejudice scaffold due to its broad range of applications in medicinal chemistry such as anticancer, antimycobacterial, antileishmanial, anticonvulsant, antimicrobial, antiviral, antidiabetic, proton pump inhibitor, insecticidal activities. A practical and efficient approach to imidazo1,2apyridine.
Abstractin this work, we describe the design, synthesis and pharmacological evaluation of novel. Bactericidal activity of an imidazo 1, 2 apyridine using a mouse m. Advantages of this reaction include short reaction times and the absence of catalyst. Multicomponent reactions mcrs are robust tools for the rapid synthesis of complex, small molecule libraries for use in drug discovery and development. In conclusion, this work represents an efficient synthesis of imidazo1,2 apyridine, pyrido 1,2apyrimidine and pyrido1,2a1,3diazepine derivatives via a onepot, fourcomponent reaction. Discovery, structureactivity relationship and binding mode. Imidazo1,2 apyridine 3carboxamides ipas as new antitb agents targeting qcrb have garnered great interest recently. The so obtained gbb product imidazo 1, 2 apyridine 4a bearing an amino group and an acetylene unit may then undergo a sequential 6exodig cyclizationretroene reaction to form the desired imidazo 1, 2 apyridine fused isoquinoline 6a.
Synthesis of novel imidazo1,2apyridines with potent activity against herpesviruses. Imidazo1,2apyridines that directly interact with hepatitis. A potent irak4 inhibitor was identified through routine project cross screening. A similar family of compounds, the imidazo 1, 2 apyridine 3hydrazones, have been synthesized but are all. Imidazo 1, 2 a pyridines and pyrimidines are important organic fluorophores which have been investigated as biomarkers and photochemical sensors. Synthesis of novel imidazo1,2apyridines with potent activity. Versatile imidazo 1, 2 apyridine carboxylic acid 4 could be prepared in four steps from commercially available 2 amino pyridine 2 scheme 1. Imidazo1,2 apyridine is a bicyclic system with a bridgehead nitrogen atom, of growing interest in medicinal chemistry. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. Imidazo 1, 2 apyridine is a bicyclic system with a bridgehead nitrogen atom, of growing interest in medicinal chemistry. Chapter 5 synthesis of imidazo pyridine derivatives. This invention relates generally to imidazo1,2 apyridine based modulators of liver x receptors lxrs having formula i and related methods. Pdf synthesis of imidazo1,2apyridinechromones by a. Microwaveassisted synthesis of 3formyl substituted imidazo1,2a.
The cost effective, ligand and additive free protocol using koac successfully afforded 3. Tuberculosis is an airborne disease, mostly affecting young adults in their productive years. Introduction the imidazo4,5bpyridine ring system 5, 8 represent a core skeleton of a class of heterocyclic compound analogues of purine with their diversity of biological activity 15, depending on the substituents on the pyridine ring. Multicomponent reaction of imidazo1,5apyridine carbenes. Figure 1 illustrates the shapes of these frontier orbitals. General description in vivo antitrypanosomal activity of imidazo 1, 2 apyridiness in the stib900 mouse model has been investigated packaging 5, 25 g in glass bottle. The effect on the luminescent property by substituents in the heterocycle and phenyl rings, have been studied as well. Imidazo1,2apyridine2carboxaldehyde 97% sigmaaldrich. Imidazo4,5bpyridine has been proved to be a useful scaffold for medicinal agents 6,7.
The emission wavelengths of imidazo1,2apyridines increase as a function of the electronwithdrawing nature of the substituent on the c5aryl group of imidazo1,2 apyridine as a result of inductive e. Imidazo1,2 a pyridine2carbaldehyde cas number 118000434. The imidazo1,2 apyridine scaffold is recognized as a privileged structure as it represents a promising area for identification of lead structures towards the discovery of new synthetic drug molecules. Imidazo 1, 2 apyridine an example of imidazopyridine and a core structure of zolpidem and some compounds described below. Titration of 1c with purified hcv ns4b protein affords a k app of 76 nm data not shown while an identical experiment with 1d affords a k app of 30 nm figure figure2. Moraski, yong cheng, sanghyun cho, jeffrey w cramer, alexander godfrey, thierry masquelin, scott g franzblau, marvin j miller, and jeffery schorey. The paper deals with the recent progress realised in the comprehension of.
The cyclization reaction could be realized with the aid of. This green chemistry approach is easy to handle, economic, nontoxic and. Fecl3catalyzed c3 functionalization of imidazo1,2a. After cooling to room temperature, the precipitate was filtered off and washed with ethyl acetate. Synthesis of substituted imidazo 1, 2 a pyridine derivatives 28ao substituted imidazo 1, 2 a pyridine derivatives 28ao have been synthesized according to the procedure which is described in chapter 2. Exploration of novel imidazo1,2apyridine3carboxamide.
S1 supporting information discovery, structureactivity relationship and binding mode of an imidazo 1, 2 apyridine series of autotaxin inhibitors agnes joncour, nicolas desroy, christopher housseman, xavier bock, natacha bienvenu, laetitia cherel, virginie labeguere, christophe peixoto, denis annoot, luce lepissier, jorg. In recent years, the synthesis and incorporation of different groups to the imidazo1,2 apyridine unity. Synthesis of some new imidazo1,2 a pyridine derivatives article pdf available in molecules 910 october 2004 with 20 reads how we measure reads. We synthesized imidazo 1, 2 apyridine 3carboxamide derivatives and evaluated them.
Synthesis of fused imidazo1,2apyridines derivatives. Onepot threecomponent synthesis of imidazo1,5apyridines. Us7666879b2 imidazo1,2apyridine compounds as vegfr2. Pdf recent progress in the pharmacology of imidazo1,2a. An aqueous synthesis gives methylimidazo1,2apyridines, imidazo1,2apyrazines, and imidazo2,1aisoquinolines without any deliberate addition of catalyst. The present synthetic protocol provides several advantages like operational simplicity, appreciable atom economy. An imidazopyridine is a nitrogen containing heterocycle that is also a class of drugs that contain this same chemical substructure. 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. Pdf a convenient and efficient synthesis, without any organic solvent or catalyst is described for the preparation of imidazo 1,2a pyridine. Here, ligandbased drug design approach yielded a series of 23 novel 64nitrophenoxy1h imidazo 4,5b pyridine derivatives. We report herein the design and synthesis of a series of novel imidazo 1, 2 apyridine amidecinnamamide hybrids linked via an alkyl carbon chain. Recent progress in the pharmacology of imidazo1,2a. It has long been known that imidazo1,2apyridine derivatives exhibit diverse biological. This invention relates generally to imidazo 1, 2 apyridine based modulators of liver x receptors lxrs having formula i and related methods.
General description in vivo antitrypanosomal activity of imidazo 1, 2 a pyridiness in the stib900 mouse model has been investigated packaging 5, 25 g in glass bottle. Imidazo1,2 apyridine an example of imidazopyridine and a core structure of zolpidem and some compounds described below. Sep 10, 2010 the facile threecomponent reactions of n,nsubstituted imidazo1,5 apyridine carbenes, namely imidazo1,5apyridin3ylidenes, with aldehydes and dmad or allenoates were disclosed. Multicomponent synthesis of imidazo1,2 pyridines using. In this study, a selective, potent cmet inhibitor, 22e was identified, with ic 50 values of 3. Besides showing an interesting functional profile, in terms of activity against the target enzyme and selectivity toward highly.
The combination of solvents dichlorobenzenedichloroethane plays a crucial role in achieving quantitative yields of desired products under metalfree conditions. Iucr crystal structure, hirshfeld surface analysis and. The position 3 was functionalized with various terminal alkynes in solution and on solid support to synthesize 3substituted imidazo 1, 2 apyridine derivatives. An efficient and convenient synthesis of diversely substituted naphtho 1. All of the synthesized compounds were characterized by 1h and c nuclear magnetic resonance 1h. Varying the substituent on the c3aryl group imidazo1,2 apyridine changes the homo. Novel potent imidazo1,2apyridinenglycinylhydrazone. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists. Due to similar coordination chemistry of palladium with platinum, a lot of palladium compounds investigated for their anticancer activity after the discovery of cisplatin. Imidazo 1,2a pyridines have already been described in the literature, for example in british pat. This is an open access article distributed under the creative commons attribution license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. May 14, 2015 a series of imidazo1,2 apyridine derivatives against cmet was designed by means of bioisosteric replacement. Discovery, structureactivity relationship and binding.
All structured data from the file and property namespaces is available under the. Pdf bactericidal activity of an imidazo1, 2apyridine. Imidazo1, 2 apyridine, sar, groebkeblackburnbienayme reaction, ugi type, multicomponent reaction, nfused imidazole. The so obtained gbb product imidazo1,2 apyridine 4a bearing an amino group and an acetylene unit may then undergo a sequential 6exodig cyclizationretroene reaction to form the desired imidazo1,2 apyridine fused isoquinoline 6a. Free fulltext pdf articles from hundreds of disciplines, all in one place novel potent imidazo1,2 apyridine nglycinylhydrazone inhibitors of tnf. The physical and spectroscopic data of the reported compounds were comparable with literature. The rcsb pdb also provides a variety of tools and resources. Design, synthesis, and biological evaluation of novel imidazo.
Fluorescent property of 3hydroxymethyl imidazo1,2a. Another inhibitor series found to have antitb activity are the imidazo 1, 2 apyridine 3nitroso compounds, but they exhibit undesirable toxicity in a vero cell line. The cyclization reaction could be realized with the aid of silver or gold catalysts. Scheme 1 synthesis of imidazopyridine derivatives from. In general, they are gaba a receptor agonists, however recently proton pump inhibitors. The sonogashira crosscoupling with terminal alkynes and buchwald coupling with aliphatic alcohols in position 6 of 2 phenylimidazo 1,2apyridines was described. Imidazo 1, 2 apyridine and its derivatives have attracted considerable attention due to their wide applications in medicinal chemistry and material sciences. A denitrogenative transannulation of pyridotriazoles with nitriles using bf 3 et 2 o as catalyst provides imidazo1,5apyridines. Using carbazole as ptype units and ip as ntype units, several bipolar host materials, namely, ip6cz, ip68cz, ip36cz, and ip368cz, were developed through altering the substitution site. A class of 3phenylimidazo1,2 apyridine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a nh linkage, are selective ligands for gabaa receptors, in particular having high affinity for the. Synthesis and newlinefunctionalization of imidazo 1, 2 apyridine with novel methods is desired both from economic and environmental point of view. Using acetonitrile as solvent, agcatalyzed intramolecular aminooxygenation produced imidazo 1, 2 apyridine 3carbaldehydes in good yields. Imidazo 1, 2 apyridine derivatives were also synthesized by solid support 14 and using catalyst such as al 2 o 3 15 and ticl 4. By utilizing mcr chemistry, we developed a protocol to functionalize the c3 position of imidazo 1, 2 apyridine through a three component, decarboxylation r.
To the best of our knowledge, this is the first report catalystfree synthesis of imidazo1,2apyridines in the absence of solvent under mild conditions. Design, synthesis and antimycobacterial activity of novel. Imidazo1,2apyridine synthesis organic chemistry portal. The vaporization enthalpies of 2 and 4 n imidazo 1, 2 apyridine and 1, 2,4triazolo 1,5apyrimidine by correlation gas chromatography dmitry lipkind, nigam rath, and james s. Using acetonitrile as solvent, agcatalyzed intramolecular aminooxygenation produced imidazo1,2 apyridine 3carbaldehydes in good yields. Identification of novel imidazo1,2apyridine inhibitors. In this work, we describe a novel class of imidazo 1, 2 apyridine derivatives as aldehyde dehydrogenase 1a3 inhibitors, reporting the evidence of their significance as novel drug candidates for the treatment of gbm. Iicatalyzed tandem reaction between pyridine ketone and benzylamine proceeded via an efficient condensationaminationoxidative dehydrogenation process, affording 1,3diarylated imidazo 1,5apyridines in excellent yields using clean o 2 as an oxidant. Jul 12, 2012 imidazo1,2apyridines 1ab show significant shifts in ec 50 s for replicons bearing these mutations 20. The candidate q203 is in phase ii clinical trials at present, and many series of new ipas were reported to have potent antimycobacterial activity.
Synthesis, biological evaluation and molecular docking. In this investigation, series of 3hydroxymethyl imidazo 1, 2 a pyridines and pyrimidines were synthesized and evaluated in relation. Crystal structure, antitumour and antibacterial activity. Environmentally friendly and fast synthesis of imidazo1,2apyridine. For examples, numerous functionalized imidazo 1, 2 apyridines, especially the c3 substituted ones, are found to possess pharmaceutical and biological activities such as antitumor, antiviral, antiprotozoal, antiapoptotic. An aqueous synthesis gives methylimidazo 1, 2 apyridines, imidazo 1, 2 apyrazines, and imidazo 2, 1 aisoquinolines without any deliberate addition of catalyst. Solution and solid phase functionalization of imidazo1,2. Pdf synthesis of novel imidazo1,5apyridine derivates. Further studies were conducted on the fluorescence behaviour of imidazo1,2 apyridine derivatives. The present invention relates to imidazo 1,2 a pyridine derivatives, useful in therapy and their preparation. In synthesis of imidazo 1,5apyridines, pmethoxyben. The effect of substituents in the ketones and 2 aminopyridine, the reagent molar ratios, the character of the solvents, and replacement of iodine by. The required building block of imidazopyridine was synthesized from commercially available 5,5diaminopyridine3ol followed by four step sequence.
Sds of imidazo1,2apyridine, safety data sheets, cas 274. Structure, properties, spectra, suppliers and links for. Several imidazo1,2 apyridine derivatives were reported to be fluorescent in nature17. Catalyst free, c3 functionalization of imidazo1,2a. Synthesis and evaluation of antituberculosis activity of. Imidazo 1, 2 a pyridines were obtained by direct reaction of acetophenone, propiophenone, and their furan analogs and ringsubstituted derivatives with an equimolar amount of iodine and and excess 2 aminopyridine or its substituted derivatives. S1 supporting information discovery, structureactivity relationship and binding mode of an imidazo1,2 apyridine series of autotaxin inhibitors agnes joncour, nicolas desroy, christopher housseman, xavier bock, natacha bienvenu. As a member of the wwpdb, the rcsb pdb curates and annotates pdb data according to agreed upon standards. In summary, we have described a simple, highly efficient, and facile procedure for the synthesis of imidazo1,2 apyridine derivatives from the readily available starting materials. Parkinson discovery chemistry, biosciences, csir, private bag x2, modderfontein 1645, south africa.
Imidazo 1, 2 apyridines that directly interact with hepatitis c ns4b. Imidazo 1, 2 apyridine 3carboxamides are active antimicrobial agents against mycobacterium avium infection in vivo. Multicomponent synthesis of imidazo1,2apyridines using catalytic zinc chloride amanda l. Dec 19, 2018 tuberculosis is an airborne disease, mostly affecting young adults in their productive years.
Ultrasoundassisted synthesis of imidazo1,2apyridines an d. Novel imidazo1,2 apyridine derivatives with potent autotaxinenpp2 inhibitor activity. Pdf the imidazo1,2apyridine scaffold is recognized as a privileged structure and it represents a promising area for identification of lead. Imidazo 1, 2 apyridine is an important heterocylic motif which is widely present in a range of biological active compounds as well as in compounds with interesting optoelectronic properties. Imidazo1,2a pyridine derivatives and their application as. Medicinal attributes of imidazo1,2apyridine derivatives. Chickos department of chemistry and biochemistry and center for nano science, university of missourist. All 38 new hybrids were evaluated for their antimycobacterial activity against m. The binding mode was inferred using a combination of in silico docking into an irak4 homology model, surrogate crystal structure analysis and chemical analogue sar. Imidazo1,2apyridine scaffold as prospective therapeutic. The method is a simple route for the preparation of bridgehead n heterocycles in water.