- An Efficient Access to Pyrimidine-based Polyfunctional Heterocycles with Anticipated Antibacterial Activity
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6-Amino-2-thioxotetrahydropyrimidine-5-carbonitrile derivative 2 was synthesized in a good yield via refluxing a mixture of arylidene 1 and thiourea in a highly basic sodium ethoxide solution. Subsequently, the synthesized pyrimidine-2-thione derivative 2 was allowed to interact with diversified nucleophiles and electrophiles under various reaction conditions in order to have a feasible access to further new and assorted fused heterocycles. Finally, the biological activity of the newly synthesized fused pyrimidines was screened in vitro against four different Gram-positive and Gram-negative bacterial strains. All the developed heterocycles were adequately characterized utilizing 1H-NMR, 13C-NMR, Fourier transform infrared, elemental analysis, and electrospray ionization–mass spectrum and tested for their antibacterial activity.
- Mourad, Asmaa Kamal,Mohammed, Fatehia K.,Tammam, Gamal Hassan,Mohammed, Shimaa Rabie
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Read Online
- Metal-free multicomponent synthesis of novel macrocyclic tetrathiadienes with cyano and amino groups
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The first synthesis of 5,12-diamino-7,14-bis(aryl)-1,4,8,11-tetrathiacyclotetradeca-5,12-diene-6,13-dicarbonitriles was performed as a multicomponent macroheterocyclization of malononitrile, aryl aldehydes, and 1,2-ethanedithiol in the presence of a catal
- Akhmadiev, Nail S.,Akhmetova, Vnira R.,Ibragimov, Askhat G.,Mescheryakova, Ekaterina S.
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p. 18768 - 18775
(2021/06/03)
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- Discovery of Highly Potent Adenosine A1Receptor Agonists: Targeting Positron Emission Tomography Probes
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Adenosine receptor (AR) radiotracers for positron emission tomography (PET) have provided knowledge on the in vivo biodistribution of ARs in the central nervous system (CNS), which is of therapeutic interest for various neuropsychiatric disorders. Additio
- Guo, Min,Bakhoda, Abolghasem,Gao, Zhan-Guo,Ramsey, Joseph M.,Li, Yang,O'Conor, Kelly A.,Kelleher, Andrew C.,Eisenberg, Seth M.,Kang, Yeona,Yan, Xuefeng,Javdan, Cameron,Fowler, Joanna S.,Rice, Kenner C.,Hooker, Jacob M.,Jacobson, Kenneth A.,Kim, Sung Won,Volkow, Nora D.
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- Rapid and efficient uncatalyzed knoevenagel condensations from binary mixture of ethanol and water
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This paper presents a new green protocol for Knoevenagel condensations of aldehydes and compounds with an active methylene group in a binary mixture of ethanol/water (3:7, v/v). This medium favored the uncatalyzed Knoevenagel reactions and easy workup pro
- Ferreira, Jo?o M. G. O.,De Resende Filho, Jo?o B. M.,Batista, Poliane K.,Teotonio, Ercules E. S.,Vale, Juliana A.
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p. 1382 - 1387
(2018/06/12)
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- Contemporary development in sequential Knoevenagel, Michael addition multicomponent reaction for the synthesis of 4-Aryl-5-oxo-5H-indeno[1,2-b]pyridine-3-carbonitrile
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An uncatalyzed efficient synthesis of bioactive pyridine derivatives has been investigated for the first time by a three-component sequential multicomponent reaction tackled with aromatic aldehydes, malononitrile, and 1,3-indandione via Knoevenagel condensation followed by Michael addition. The difference between the domino multicomponent and sequential multicomponent reaction is emphasized by this methodology. The reaction proceeds at ambient temperature without frequently useful N-source like ammonium salt for the construction of N-heterocycles, which makes this protocol a novel synthetic route for the preparation of the indenopyridine skeleton.
- Patravale, Ajinkya A.,Gore, Anil H.,Patil, Dipti R.,Kolekar, Govind B.,Deshmukh, Madhukar B.,Choudhari, Prafulla B.,Bhatia, Manish S.,Anbhule, Prashant V.
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p. 2919 - 2935
(2016/04/05)
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- Fluorous bispidine: A bifunctional reagent for copper-catalyzed oxidation and knoevenagel condensation reactions in water
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Fluorous bispidine-type ligands have been developed to facilitate its recovery and reusability and to demonstrate its bifunctional property as a ligand and base in copper-catalyzed aerobic oxidation, the Knoevenagel condensation and tandem oxidation/Knoevenagel condensation in water under mild conditions. Application of the fluorous ligand was also extended to the surfactant-free copper-catalyzed allylic and benzylic sp3 C-H oxidation reaction in water. The fluorous ligands could be recovered using F-SPE with recovery ranging from 91-97% and could be reused five times with little loss of activity.
- Ang, Wei Jie,Chng, Yong Sheng,Lam, Yulin
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p. 81415 - 81428
(2015/10/06)
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- A new and efficient ZnCl2-catalyzed synthesis and biological evaluation of novel 2-amino-3,5-dicyano-4-aryl-6-aryl-aminopyridines as potent antibacterial agents against Helicobacter pylori (HP)
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Here a new and efficient method via ZnCl2-catalyzed direct cyclization of diverse benzylidenemalononitriles and arylamines has been developed. With this method, a variety of novel 2-amino-3,5-dicyano-4-aryl-6-aryl-aminopyridines (2a-2v) could be easily prepared under the mild conditions with board substrate/functional group tolerance and decent product yields. The biological activities of the selected compounds (2c, 2e, 2g, 2i, 2k, 2m, 2n and 2o) has also been evaluated as new antibacterial agents. The results demonstrated that almost all of the compounds had more potent antibacterial activities against HP than that of clinically used drugs, Ornidazole, Metronidazole, Nitrimidazine and Clarithromycin, suggesting that further development of such compounds might be of great interest.
- Huang, Jijun,Zhou, Jie,Song, Senchuan,Song, Huacan,Chen, Zhiyong,Yi, Wei
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p. 8628 - 8636
(2015/10/19)
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- Ammonium fluoride as an inexpensive catalyst for Knoevenagel condensation in solvent-free conditions under microwave irradiation
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Ammonium fluoride (NH4F) has been found to be an inexpensive catalyst for Knoevenagel condensation between aromatic aldehydes 1 and active methylene compounds 2 to afford arylidene derivatives 3 in excellent yields.
- Mogilaiah,Vinay Chandra,Jagadeeshwar,Kavitha
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p. 694 - 697
(2013/07/05)
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- Design, synthesis, docking study and biological evaluation of some novel tetrahydrochromeno [3′,4′:5,6]pyrano[2,3-b]quinolin-6(7H)-one derivatives against acetyl- and butyrylcholinesterase
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Novel hybrid derivatives of two known scaffolds; tetrahydroaminoquinoline and coumarin were synthesized and evaluated for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities. By means of an efficient nanocatalyst, the reaction time for the syntheses of the target compounds was reduced. Subsequently, Ellman's modified method was used to evaluate the enzyme inhibitory activity of the synthesized structures. It was observed that most hybrid structures were moderate to potent inhibitors of AChE compared to Tacrine as the reference drug among which 7f with 4-fluorophenyl substituent was the most active compound (IC50 = 5 nM).
- Khoobi, Mehdi,Alipour, Masoumeh,Moradi, Alireza,Sakhteman, Amirhossein,Nadri, Hamid,Razavi, Seyyede Faeze,Ghandi, Mehdi,Foroumadi, Alireza,Shafiee, Abbas
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p. 291 - 300
(2013/10/01)
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- On-column solvent-free oxidative cleavage reactions of vicinal diols by silica gel and paraperiodic acid: Application to in-situ sequential oxidation and Knoevenagel reactions
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An on-column solvent-free oxidative cleavage reaction of vicinal diols by paraperiodic acid supported on silica gel at room temperature is described. The resulting pure carbonyl compounds are prepared in good to excellent yields with short reaction times. The cleavage reactions proceed under mild conditions, which avoids further cyclization reactions of the product dialdehydes. This method is also used for sequential oxidation and Knoevenagel reactions to prepare condensation products in good yields by using paraperiodic acid on a mixed bed of alumina and silica gel. The on-column solvent-free oxidative cleavage reaction of vicinal diols by paraperiodic acid supported on silica gel at room temperature is investigated. This approach is applied to an oxidation andKnoevenagel reaction sequence by using a mixed bed of alumina and silica gel to give condensation products in good yields. Copyright
- Dakdouki, Saada C.,Villemin, Didier,Bar, Nathalie
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supporting information; experimental part
p. 780 - 784
(2012/03/11)
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- A facile route to the synthesis of 1,4-pyranonaphthoquinone derivatives under microwave irradiation without catalyst
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(Chemical Equation Presented) A series of 1,4-pyranonaphthoquinone derivatives were synthesized via the reaction of arylidenemalononitrile and 2-hydroxynaphthalene-1,4-dione in the mixed solvent of N,N-dimethylformamide and glacial acetic acid (HOAc) under microwave irradiation without catalyst. This protocol has the notable advantages of short reaction time, high yield, and convenient operation.
- Wang, Xing-Han,Zhang, Xiao-Hong,Tu, Shu-Jiang,Shi, Feng,Zou, Xiang,Yan, Shu,Han, Zheng-Guo,Hao, Wen-Juan,Cao, Xu-Dong,Wu, Shan-Shan
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experimental part
p. 832 - 836
(2009/12/09)
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- 2-Amino-6-furan-2-yl-4-substituted nicotinonitriles as A2a adenosine receptor antagonists
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A2A adenosine receptor antagonists usually have bi- or tricyclic N aromatic systems with varying substitution patterns to achieve desired receptor affinity and selectivity. Using a pharmacophore model designed by overlap of nonxanthine type of previously known A2A antagonists, we synthesized a new class of compounds having a 2-amino nicotinonitrile core moiety. From our data, we conclude that the presence of at least one furan group rather than phenyl is beneficial for high affinity on the A2A adenosine receptor. Compounds 39 (LUF6050) and 44 (LUF6080) of the series had Ki values of 1.4 and 1.0 nM, respectively, with reasonable selectivity toward the other adenosine receptor subtypes, A1, A 2B, and A3. The high affinity of 44 was corroborated in a cAMP second messenger assay, yielding subnanomolar potency for this compound.
- Mantri, Monica,De Graaf, Olivier,Van Veldhoven, Jacobus,G?bly?s, Aniko,Von Frijtag Drabbe Künzel, Jacobien K.,Mulder-Krieger, Thea,Link, Regina,De Vries, Henk,Beukers, Margot W.,Brussee, Johannes,Ijzerman, Adriaan P.
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supporting information; experimental part
p. 4449 - 4455
(2009/06/06)
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- Knoevenagel condensation catalyzed by 1,1,3,3-tetramethylguanidium lactate
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Knoevenagel condensation between malononitrile or ethyl cyanoacetate and carbonyl compounds could be effectively promoted by 1,1,3,3-tetramethylguanidium lactate, a basic ionic liquid, under mild conditions. Good to high isolated yields could be obtained.
- Zhang, Jicheng,Jiang, Tao,Han, Buxing,Zhu, Anlian,Ma, Xiumin
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p. 3305 - 3317
(2007/10/03)
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- Solvent-free Knoevenagel condensation reaction under microwave irradiation exploiting a new reagent: Antimony trichloride
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A rapid microwave-assisted Knoevenagel condensation exploiting antimony trichloride under solvent-free condition is reported. Several aromatic aldehydes condense with malononitrile and ethyl cyanoacetate within a few minutes in high yields.
- Mitra, Alok Kumar,Karchaudhuri, Nilay,De, Aparna
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p. 177 - 179
(2007/10/03)
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- Synthesis of arylmethylenemalononitriles catalyzed by KF-Al 2O3 under ultrasound
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Knoevenagel condensation of malononitrile with aromatic aldehydes catalyzed by KF-Al2O3 under ultrasound irradiation in anhydrous ethanol results in the formation of arylmethylenemalononitriles in 73-97% yields within 15-60min. CSIRO
- Li, Ji-Tai,Chen, Guo-Feng,Wang, Shu-Xiang,He, Lin,Li, Tong-Shuang
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p. 231 - 233
(2008/02/04)
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- Simple procedure for the synthesis of arylmethylenemalononitrile without catalyst
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Knoevenagel condensation of malononitrile with aromatic aldehydes can be achieved at room temperature in the absence of catalysts in short time, and the products of arylmethylenemalononitriles were isolated in a practically pure form without further purification. Copyright Taylor & Francis, Inc.
- Wang, Xiang-Shan,Zeng, Zhao-Sen,Li, Yu-Ling,Shi, Da-Qing,Tu, Shu-Jiang,Wei, Xian-Yong,Zong, Zhi-Min
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p. 1915 - 1920
(2007/10/03)
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- A series of ligands displaying a remarkable agonistic-antagonistic profile at the adenosine A1 receptor
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Adenosine receptor agonists are usually variations of the natural ligand, adenosine. The ribose moiety in the ligand has previously been shown to be of great importance for the agonistic effects of the compound. In this paper, we present a series of nonadenosine ligands selective for the adenosine A 1 receptor with an extraordinary pharmacological profile. 2-Amino-4-benzo-[1,3]dioxol-5-yl-6-(2-hydroxyethylsulfanyl)pyridine-3, 5-dicarbonitrile (70, LUF 5853) shows full agonistic behavior comparable with the reference compound CPA, while also displaying comparable receptor binding affinity (Ki = 11 nM). In contrast, compound 58 (2-amino-4-(3- trifluoromethylphenyl)-6-(2-hydroxyethylsulfanyl)pyridine-3,5-dicarbonitrile, LUF 5948) has a binding affinity of 14 nM and acts as an inverse agonist. Also present within this same series are compounds that show neutral antagonism of the adenosine A1 receptor, for example compound 65 (2-amino-4-(4-difluoromethoxyphenyl)-6-(2-hydroxyethylsulfanyl)pyridine-3, 5-dicarbonitrile, LUF 5826).
- Chang, Lisa C. W.,Von Frijtag Drabbe Künzel, Jacobien K.,Mulder-Krieger, Thea,Spanjersberg, Ronald F.,Roerink, Sophie F.,Van Den Hout, Gijs,Beukers, Margot W.,Brussee, Johannes,Ijzerman, Adriaan P.
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p. 2045 - 2053
(2007/10/03)
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- An efficient and environment friendly procedure for the synthesis of arylmethylenemalononitrile catalyzed by strong base anion-exchange resin in water
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Knoevenagel condensation of malononitrile with aromatic aldehydes catalyzed by strong base anion-exchange resin in water results aryl- methylenemalononitrile in 74-98% yield at room temperature.
- Jin, Tong-Shou,Zhang, Jian-She,Wang, Ai-Qing,Li, Tong-Shuang
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p. 2611 - 2616
(2007/10/03)
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- Knoevenagel condensation in the heterogeneous phase using KF-montmorillonite as a new catalyst
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The Knoevenagel condensation of aromatic aldehydes was carried out in DMF as solvent on KF-Montmorillonite catalyst, using malononitrile and ethyl cyanoacetate as the acidic methylene reagents. Only the e isomers of the products were obtained and confirme
- Shi, Da-qing,Wang, Xiang-shan,Yao, Chang-sheng,Mu, Lailong
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p. 344 - 345
(2007/10/03)
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- The Knoevenagel condensation reaction of aromatic aldehydes with malononitrile by grinding in the absence of solvents and catalysts
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An improved Knoevenagel condensation reaction of aldehydes and malononitrile can be achieved by grinding at room temperature in the absence of solvents and catalysts. This process is simple, efficient, economical, and environmentally benign. Compared to r
- Ren, Zhongjiao,Cao, Weigud,Tong, Weiqi
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p. 3475 - 3479
(2007/10/03)
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- Heterocycles synthesis through reactions of nucleophiles with acrylonitriles; VI. A novel and facile one-step synthesis of phthalazines
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Several new phthalazines were synthesized via the reaction of aldehydes with malononitrile and ethyl 5-cyano-1,6-dihydro-4-methyl-6-oxo-1-phenyl-pyridazine-3-carboxylate.
- Abdel-Latif, F. F.
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p. 129 - 131
(2007/10/02)
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- Tyrphostins I: Synthesis and Biological Activity of Protein Tyrosine Kinase Inhibitors
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A novel class of low molecular weight proteine kinase inhibitors is described.These compounds consitute a systematic series of molecules with a progressive increase in affinity toward the substrate site of the EGF receptor kinase domain.These competitive inhibitors also effectively block the EGF-dependent autophosphorylation of the receptor.The potent EGF receptor kinase blockers examined were found to competitively inhibit the homologous insulin receptor kinase at 102-103 higher inhibitor concentrations in spite of the significant homology between these protein tyrosine kinases.These results demonstrate the ability to synthesize selective tyrosine kinase inhibitors.The most potent EGF receptor kinase inhibitors also inhibit the EGF-dependent proliferation of A431/clone 15 cells with little or no effect on EGF independent cell growth.These results demonstrate the potential use of protein tyrosine kinase inhibitors as selective antiproliferative agents for proliferative diseases caused by the hyperactivity of protein tyrosine kinases.We have suggested the name "tyrphostins" for this class of antiproliferative compounds which act as protein tyrosine kinase blockers.
- Gazit, Aviv,Yaish, Pnina,Gilon, Chaim,Levitzki, Alexander
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p. 2344 - 2352
(2007/10/02)
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