- Design, synthesis and anticancer evaluation of 3-methyl-1H-indazole derivatives as novel selective bromodomain-containing protein 4 inhibitors
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Bromodomain-containing Protein 4 (BRD4), an ‘epigenetic reader’, regulates chromatin structure and gene expression via recognizing and binding acetylated lysine in histones. BRD4 has become a therapeutic target for cancers because it promotes the expression of the tumor genes, such as c-Myc, NF-κB, and Bcl-2. In this study, a new series of 3-methyl-1H-indazole derivatives were designed via virtual screening and structure-based optimization. All compounds were synthesized and evaluated for their inhibitory activities to BRD4-BD1 and their antiproliferative effects in cancer cell lines. Among them, several compounds (such as 9d, 9u and 9w) exhibited strong BRD4-BD1 affinities and inhibition activities, and potently suppressed MV4;11 cancer cell line proliferation. Among them, compound 9d showed excellent selectivity for BRD4 and effectively suppressed c-Myc, the downstream protein of BRD4. This study provided new lead compounds for further biological evaluation on BRD4.
- Dong, Ru,Zhang, Cheng,Wang, Chao,Zhou, Xin,Li, Wen,Zhang, Jin-Yang,Wang, Min,Xu, Yong,Sun, Li-Ping
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- Small molecule microarray identifies inhibitors of tyrosyl-DNA phosphodiesterase 1 that simultaneously access the catalytic pocket and two substrate binding sites
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Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a member of the phospholipase D family of enzymes, which catalyzes the removal of both 3′- and 5′-DNA phosphodiester adducts. Importantly, it is capable of reducing the anticancer effects of type I topoisomerase (TOP1) inhibitors by repairing the stalled covalent complexes of TOP1 with DNA. It achieves this by promoting the hydrolysis of the phosphodiester bond between the Y723 residue of human TOP1 and the 3′-phosphate of its DNA substrate. Blocking TDP1 function is an attractive means of enhancing the efficacy of TOP1 inhibitors and overcoming drug resistance. Previously, we reported the use of an X-ray crystallographic screen of more than 600 fragments to identify small molecule variations on phthalic acid and hydroxyquinoline motifs that bind within the TDP1 catalytic pocket. Yet, the majority of these compounds showed limited (millimolar) TDP1 inhibitory potencies. We now report examining a 21?000-member library of drug-like Small Molecules in Microarray (SMM) format for their ability to bind Alexa Fluor 647 (AF647)-labeled TDP1. The screen identified structurally similarN,2-diphenylimidazo[1,2-a]pyrazin-3-amines as TDP1 binders and catalytic inhibitors. We then explored the core heterocycle skeleton using one-pot Groebke-Blackburn-Bienayme multicomponent reactions and arrived at analogs having higher inhibitory potencies. Solving TDP1 co-crystal structures of a subset of compounds showed their binding at the TDP1 catalytic site, while mimicking substrate interactions. Although our original fragment screen differed significantly from the current microarray protocol, both methods identified ligand-protein interactions containing highly similar elements. Importantly inhibitors identified through the SMM approach show competitive inhibition against TDP1 and access the catalytic phosphate-binding pocket, while simultaneously providing extensions into both the substrate DNA and peptide-binding channels. As such, they represent a platform for further elaboration of trivalent ligands, that could serve as a new genre of potent TDP1 inhibitors.
- Zhao, Xue Zhi,Kiselev, Evgeny,Lountos, George T.,Wang, Wenjie,Tropea, Joseph E.,Needle, Danielle,Hilimire, Thomas A.,Schneekloth, John S.,Waugh, David S.,Pommier, Yves,Burke, Terrence R.
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p. 3876 - 3884
(2021/04/02)
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- Application of proteasome inhibitor in inhibition of novel coronavirus
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The invention provides application of a proteasome inhibitor in inhibition of a novel coronavirus or preparation of novel coronavirus inhibitors. The proteasome inhibitor has a structure represented by a formula (I) or isomers, pharmaceutically acceptable salts thereof and prodrugs thereof. According to the application, by applying the proteasome inhibitor to inhibition of the novel coronavirus, good inhibiting activity is obtained, and a novel treatment way of think is provided for diseases such as pneumonia caused by the novel coronavirus.
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Paragraph 0091; 0110-0112; 0130; 0152-0154
(2021/06/22)
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- Synthesis and Properties of N,N′-Disubstituted Ureas and Their Isosteric Analogs Containing Polycyclic Fragments: XI. 1-[(Adamantan-1 yl)alkyl]-3-arylselenoureas
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Abstract: A series of N,N′-disubstituted selenoureas containing an adamantane fragmenthave been synthesized in 23–75% yields. Procedures for the isolation andpurification of aromatic isoselenocyanates have been improved. The chemicalshift of the C=Se carbon nucleus in the 13C NMRspectra of selenoureas has been refined. The synthesized selenoureas have beenfound to be promising as inhibitors of not only epoxide hydrolase (sEH-H) butalso phosphatase domains (sEH-P) of human soluble epoxide hydrolase.
- Kuznetsov, Ya. P.,Rasskazova,Pitushkin,Eshtukov,Vasipov,Burmistrov,Butov
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p. 1036 - 1046
(2021/09/08)
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- Silver-Catalyzed Selective Multicomponent Coupling Reactions of Arynes with Nitriles and Isonitriles
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Pathway selective aryne-based novel multicomponent coupling reactions with isonitriles and nitriles are described. Crucial to these reactions is the formation of a silver-aryne complex, which shows differential reactivity toward isonitriles and nitriles to form two different forms of ortho-nitrilium organosilver arene species. Interception of the nitrilium of an aryne-isonitrile adduct with another isonitrile leads to the formation of benzocyclobutene-1,2-diimines, whereas the nitrilium of an aryne-nitrile adduct renders selective formation of 3H-indol-3-imines or 3-iminoindolin-2-ol depending on the structure of the nitrile employed.
- Ghorai, Sourav,Lin, Yongjia,Xia, Yuanzhi,Wink, Donald J.,Lee, Daesung
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supporting information
p. 642 - 647
(2020/01/31)
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- Bis-Selenoureas for Anion Binding: A 1H NMR and Theoretical Study
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The anion binding ability of a family of bis-selenoureas L1-L3 obtained by the reaction of 1,3-bis(aminomethyl)-benzene and phenylisoselenocyanate, p-methoxyphenylisoselenocyanate and naphtylisoselenocyanate, for L1, L2, and L3, respectively, has been tested and compared to that of previously described bis-urea analogues. Results suggest that the introduction of selenium leads to an increase in the acidity of the urea NH hydrogen atoms, and therefore to a stronger affinity (more than three-fold higher) towards anion species, in particular dihydrogen phosphate, in DMSO-d6. Theoretical calculations allowed for the optimization of the adducts receptors corroborating the experimental results.
- Caltagirone, Claudia,Ciancaleoni, Gianluca,Lippolis, Vito,Mocci, Rita,Picci, Giacomo,Zielińska-B?ajet, Mariola
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p. 1389 - 1395
(2020/08/05)
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- Multicomponent Ugi Reaction of Indole- N-carboxylic Acids: Expeditious Access to Indole Carboxamide Amino Amides
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A novel multicomponent Ugi-type reaction for the synthesis of indole carboxamide amino amides from aldehydes, amines, isocyanides, and indole-N-carboxylic acids, which were simply prepared from indoles and CO2, is described. This method provides an expeditious and practical access to indole tethered peptide units, along with the achievement of remarkable structural diversity and brevity. Gram-scale reaction was conducted to demonstrate the scalability, and the products could be transformed to new indole derivatives.
- Zeng, Linwei,Sajiki, Hironao,Cui, Sunliang
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supporting information
p. 5269 - 5272
(2019/07/03)
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- Synthesis of Imides, Imidates, Amidines, and Amides by Intercepting the Aryne-Isocyanide Adduct with Weak Nucleophiles
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New aryne-based multicomponent coupling reactions for the formation of functionalized aromatic compounds have been developed. Arynes generated from triynes or tetraynes through the hexadehydro Diels-Alder reaction readily react with isocyanide to generate nitrilium intermediate. Intercepting this nitrilium species with various weak nucleophile including carboxylic acids, alcohols, sulfonamides, or water generated the corresponding imides, imidates, amidines, or amides. The high regioselectivity of these transformations was mainly controlled by the substituents of the arynes.
- Ghorai, Sourav,Lee, Daesung
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supporting information
p. 7390 - 7393
(2019/10/02)
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- Selective Gold-Catalysed Synthesis of Cyanamides and 1-Substituted 1H-Tetrazol-5-Amines from Isocyanides
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The newly discovered gold-catalysed reaction of isocyanides with hydrazoic acid generated in situ from trimethylsilyl azide and methanol (or, alternatively, from NaN3/AcOH) produces either cyanamides or 1-substituted 1H-tetrazol-5-amines, depending on the amount of available HN3. The reaction proceeds selectively and in generally high yields of either product, thus providing a particularly convenient access to a wide range of substituted 1H-tetrazol-5-amines that are rather difficult to access otherwise.
- ?koch, Karel,Císa?ová, Ivana,?těpni?ka, Petr
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supporting information
p. 13788 - 13791
(2018/09/14)
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- Dramatically Enhanced Solubility of Halide-Containing Organometallic Species in Diiodomethane: The Role of Solvent???Complex Halogen Bonding
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In the current study, we evaluated the solubility of a number of organometallic species and showed that it is noticeably improved in diiodomethane when compared to other haloalkane solvents. The better solvation properties of CH2I2 w
- Kinzhalov, Mikhail A.,Kashina, Mariya V.,Mikherdov, Alexander S.,Mozheeva, Ekaterina A.,Novikov, Alexander S.,Smirnov, Andrey S.,Ivanov, Daniil M.,Kryukova, Mariya A.,Ivanov, Aleksandr Yu.,Smirnov, Sergej N.,Kukushkin, Vadim Yu.,Luzyanin, Konstantin V.
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supporting information
p. 12785 - 12789
(2018/09/11)
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- Silver-catalyzed [3+2+1] annulation of aryl amidines with benzyl isocyanide
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A silver-catalyzed [3+2+1] annulation of amidines with benzyl isocyanide toward 2,4-diaryl-1,3,5-triazines was developed. A variety of symmetrical and unsymmetrical products were obtained in moderate to good yields. This work also features an oxidant-free approach to 2,4-disubstituted triazines.
- Lu, Xiaodong,Xin, Xiaoyi,Wan, Boshun
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supporting information
p. 361 - 364
(2018/01/08)
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- Visible-Light-Induced Radical Cascade Cyclization: Synthesis of the ABCD Ring Cores of Camptothecins
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A new strategy for constructing indolizino[1,2-b]quinolin-9(11H)-ones (ring cores of camptothecins) from readily available isocyanoarenes and N-(alkyl-2-yn-1-yl)pyridin-2(1H)-ones has been developed through a visible-light-induced radical cascade cyclization process. The reaction proceeds under mild conditions with fair to excellent yields. The easy introduction of substituents for both reactants and the broad functional group tolerance of the reaction make it a straightforward route to the cores of the marketed camptothecins and their derivatives.
- Yuan, Yao,Dong, Wuheng,Gao, Xiaoshuang,Gao, Huang,Xie, Xiaomin,Zhang, Zhaoguo
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supporting information
p. 2840 - 2846
(2018/03/09)
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- 4-phenoxyl substituted quinoline compound containing 2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one and imidazole and application of compound
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The invention relates to a quinoline derivative shown as the general formula I and containing 2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one and imidazole, and pharmaceutically acceptable salt, hydrate, solvate or prodrug of the quinoline derivative. In the general formula I, Ar, R1, R2, L, and n have meanings as the description defined. The invention further relates to a great c-Met kinase inhibiting effect of the compound shown as the general formula I, and applications of pharmaceutically acceptable salt, hydrate, solvate or prodrug of the compound to prepare medicines for treating and/or preventing diseases caused by abnormal high expression of c-Met kinase, particularly an application of preparing a medicine for treating and/or preventing cancer.
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-
Paragraph 0189; 0220; 0221
(2018/01/09)
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- An isocyanide based multi-component reaction under catalyst- and solvent-free conditions for the synthesis of unsymmetrical thioureas
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A new and efficient method for the synthesis of thiourea derivatives by a sequential one-pot, three-component reaction between aromatic isocyanides, amines, and 1,2-di-tert-butyldisulfane (DTBS) was developed and 27 different examples were synthesized in good to excellent yields. DTBS was identified as an effective sulfur surrogate without the use of both catalysts and solvents. This protocol does not employ any transition metal catalyst or special experimental setup.
- Singh, Karandeep,Sharma, Siddharth
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p. 197 - 201
(2016/12/28)
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- Discovery of New Selenoureido Analogues of 4-(4-Fluorophenylureido)benzenesulfonamide as Carbonic Anhydrase Inhibitors
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A series of benzenesulfonamides bearing selenourea moieties was obtained considering the ureido-sulfonamide SLC-0111, in Phase I clinical trials as antitumor agent, as a lead molecule. All compounds showed interesting inhibition potencies against the physiologically relevant human (h) carbonic anhydrase (hCAs, EC 4.2.1.1) isoforms I, II, IV, and IX. The most flexible analogues in the series 14-19 showed low nanomolar inhibition constants against hCA I, II, and IX. We assessed selected compounds on the in vitro antioxidant properties and binding modes and evaluated ex vivo human prostate (PC3), breast (MDA-MB-231), and colon-rectal (HT-29) cancer cell lines both in normoxic and hypoxic conditions.
- Angeli, Andrea,Tanini, Damiano,Peat, Thomas S.,Di Cesare Mannelli, Lorenzo,Bartolucci, Gianluca,Capperucci, Antonella,Ghelardini, Carla,Supuran, Claudiu T.,Carta, Fabrizio
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supporting information
p. 963 - 968
(2017/09/22)
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- Revisited Mechanistic Implications of the Joullié-Ugi Three-Component Reaction
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The effect of the solvent on the diastereoselectivity of the Joullié-Ugi three-component reaction (JU-3CR) using an α-substituted five-membered cyclic imine is revisited. The cis and trans isomers were generated in toluene and HFIP, respectively. Hammett
- Katsuyama, Akira,Matsuda, Akira,Ichikawa, Satoshi
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supporting information
p. 2552 - 2555
(2016/07/06)
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- Radical perfluoroalkylation - Easy access to 2-perfluoroalkylindol-3-imines-via electron catalysis
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Arylisonitriles (2 equivalents) react with alkyl and perfluoroalkyl radicals to form 2-alkylated indole-3-imines via two sequential additions to the isonitrile moiety followed by homolytic aromatic substitution. The three component reaction comprises three C-C bond formations. The endocyclic imine functionality in the products is more reactive in follow up chemistry and hydrolysis of the exocyclic imine leads to 3-oxindoles that show fluorescence properties.
- Leifert, Dirk,Artiukhin, Denis G.,Neugebauer, Johannes,Galstyan, Anzhela,Strassert, Cristian Alejandro,Studer, Armido
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supporting information
p. 5997 - 6000
(2016/05/24)
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- Synthesis of Isoselenocyanates
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Isoselenocyanates were synthesized by two methods under phase-transfer conditions (50% aq NaOH, CH2Cl2, Aliquat 336); the first started from isocyanides and selenium and gave isoselenocyanates in 61-89% yields, while the second started from amines and used chloroform and selenium, by applying sequentially the Hofmann isonitrile synthesis and the addition of selenium, in 4-70% yields.
- Zakrzewski, Jerzy,Huras, Bogumi?a,Kie?czewska, Anna
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- Synthesis and structure–activity relationship of α-keto amides as enterovirus 71 3C protease inhibitors
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α-Keto amide derivatives as enterovirus 71 (EV71) 3C protease (3Cpro) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. structure–activity relationship (SAR) study indicated that small moieties were primarily tolerated at P1' and the introduction of para-fluoro benzyl at P2 notably improved the potency of inhibitor. Inhibitors 8v, 8w and 8x exhibited satisfactory activity (IC50= 1.32 ± 0.26 μM, 1.88 ± 0.35 μM and 1.52 ± 0.31 μM, respectively) and favorable CC50values (CC50> 100 μM). α-Keto amide may represent a good choice as a warhead for EV71 3Cproinhibitor.
- Zeng, Debin,Ma, Yuying,Zhang, Rui,Nie, Quandeng,Cui, Zhengjie,Wang, Yaxin,Shang, Luqing,Yin, Zheng
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supporting information
p. 1762 - 1766
(2016/12/22)
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- The including benzene seleno-D quinoxaline compound, and its preparation and use
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The invention discloses a benzeneselenenyl quinoxaline compound and preparation and application thereof, the benzeneselenenyl quinoxaline compound has a structure shown as the formula (V), and the synthetic route is shown as the following reaction equatio
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-
Paragraph 0030
(2017/02/28)
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- Palladium-catalyzed direct coupling of 2-vinylanilines and isocyanides: An efficient synthesis of 2-aminoquinolines
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Palladium-catalyzed oxidative coupling of 2-vinylanilines and isocyanides constitutes a direct, facile, and efficient approach to 2-aminoquinolines. The procedure, employing palladium acetate and silver carbonate, is attractive in terms of assembly efficiency, functional group tolerance, and operational simplicity. A variety of 2-aminoquinolines were prepared in good to excellent yields.
- Wang, Lijie,Ferguson, Jamie,Zeng, Fanlong
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supporting information
p. 11486 - 11491
(2015/12/04)
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- Synthesis of selenazolopyridine derivatives with capability to induce apoptosis in human breast carcinoma MCF-7 cells through scavenge of intracellular ROS
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A series of selenazolopyridine derivatives have been synthesized and characterized by X-ray diffraction, high resolution NMR and Mass spectrum. The in vitro anticancer activities of the synthetic compounds were screened against a panel of human cancer cell lines, human breast carcinoma MCF-7 cells, human liver carcinoma HepG2 cells and L02 normal cell line by MTT assay. By analyzing the structure-activity relationship among the synthetic compounds, it was found that 2-(phenylamino) selenazolo [5,4-b] pyridine, (PSeD, 7) had higher growth inhibitory effect on MCF-7 cells. The intracellular mechanism of cell death was evaluated by flow cytometric analysis and ROS assay, which revealed that PSeD could induce MCF-7 cells apoptosis by scavenging intracellular ROS. Taken together, we regard PSeD as an antioxidant which could inhibit cancer cell growth through induction of apoptosis.
- Zhou, Meiyun,Ji, Shengbin,Wu, Zhaojun,Li, Yiqun,Zheng, Wenjie,Zhou, Hua,Chen, Tianfeng
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- Regioselective one-pot three component synthesis of chiral 2-iminoselenazolines under sonication
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A one-pot multi component reaction of selenoureas, which are in situ generated from l-amino esters and isoselenocyanates, with α-bromoketone under ultrasonication. Selenourea and α-bromoketones formed 2-iminoselenazoles through a Hantzsch selenazole-type reaction. The steric effect of the α-substituted bromoketones on the rate of the tandem reaction was studied to understand the reaction mechanism by isolating the key reaction intermediate, 2-iminoselenol.
- Chang, Wong-Jin,Kulkarni, Manohar V.,Sun, Chung-Ming
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p. 97113 - 97120
(2015/12/01)
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- A general simple methodology for synthesis of isonitriles using benzene-1,3-disulfonyl dichloride
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Isonitrile derivatives have been synthesized in good to high yields by dehydration of aliphatic and aromatic formamides in the presence of benzene-1,3-disulfonyl dichloride as easy and efficient reagent.
- Ghorbani-Vaghei, Ramin,Amiri, Mostafa,Veisi, Hojat
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- Odorless isocyanide chemistry: An integrated microfluidic system for a multistep reaction sequence
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Can't smell this: An integrated continuous-flow microfluidic setup enables in situ generation, extraction, separation, and reaction of foul-smelling isocyanides with little exposure to the surroundings. Isocyanides were generated by dehydration of the corresponding N-substituted formamides, and several representative isocyanide-based organic reactions were successfully performed. DIPEA=N,N-diisopropylethylamine. Copyright
- Sharma, Siddharth,Maurya, Ram Awatar,Min, Kyoung-Ik,Jeong, Guan-Young,Kim, Dong-Pyo
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supporting information
p. 7564 - 7568
(2013/07/26)
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- One-pot synthesis of 1-substituted-5-alkylselanyl-1H-tetrazoles from isoselenocyanates: Unexpected formation of N-alkyl-N-arylcyanamides and (Z)-Se-alkyl-N-cyano-N,N′-diarylisoselenoureas
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1-Substituted-5-alkylsulfanyl-1H-tetrazoles are well known class of organic substances with various applications in medicinal chemistry or photographic industry. Their selenium analogues, 1-substituted-5-alkylselanyl-1H-tetrazoles are, however, much less explored because of the lack of suitable methods for their preparation. In this work we investigated the synthesis of 1-alkyl/aryl-5-alkylselanyl-1H-tetrazoles from synthetically available alkyl/arylisoselenocyanates. One-pot reactions of arylisoselenocyanates with sodium azide and alkylating agent led to the target 5-alkylselanyl-1-aryl-1H- tetrazoles but also to interesting side products, namely N-alkyl-N- arylcyanamides and (Z)-Se-alkyl-N-cyano-N,N′-diarylisoselenoureas. Nevertheless, when alkylisoselenocyanates were utilized as the substrates, the reactions led exclusively to the formation of 1-alkyl-5-alkylselanyl-1H- tetrazoles in good yields. This simple one-pot procedure brings new possibilities for the preparation of variously substituted selenium compounds. It also opens the way to further investigations of selenium isosteres of the widely utilized 5-thiotetrazole moiety in biomedical applications.
- Karabanovich, Galina,Roh, Jaroslav,Padělková, Zdeňka,Novák, Zdeněk,Vávrová, Kate?ina,Hrabálek, Alexandr
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p. 8798 - 8808
(2013/09/23)
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- On the reaction of carboxylic acids and isonitriles with conventional heating
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Control over the formation of N-formylamides versus the formation of captodative alkenes from the reaction of arylacetic acids with isonitriles has been achieved. Low temperatures and high concentrations favor alkenes, and high temperatures and low concen
- Polisar, Jason G.,Norton, Jack R.
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supporting information
p. 10236 - 10240,5
(2020/09/02)
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- Facile reaction of carboxylic acids with isonitriles in toluene
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Isonitriles react with low concentrations of carboxylic acids in toluene at 110 °C to give N-formylamides in yields generally above 70%. These concentrations can be obtained either by syringe pump addition of a toluene solution of the acid, or by using a suspension of the acid if it has limited solubility in toluene at room temperature.
- Polisar, Jason G.,Li, Ling,Norton, Jack R.
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supporting information; experimental part
p. 2933 - 2934
(2011/06/23)
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- Silver hexafluoroantimonate-catalyzed three-component [2+2+1]cycloadditions of allenoates, dual activated olefins, and isocyanides
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The intermolecular [2+2+1]multicomponent cycloadditions from readily available allenoates, dual activated olefins and isocyanides catalyzed by silver hexafluoroantimonate were studied. This protocol allowed the syntheses of highly functionalized five-membered carbocycles with exclusive regioselectivity and stereoselectivity in an efficient and atom-economical manner.
- Li, Jian,Liu, Yuejin,Li, Chunju,Jia, Xueshun
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supporting information; experimental part
p. 913 - 917
(2011/06/18)
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- Syntheses of spirocyclic oxindole-butenolides by using three-component cycloadditions of isocyanides, allenoates, and isatins
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Spiro workflow! Efficient syntheses of spirocyclic oxindole-butenolides from readily available isocyanides, allenoates, and isatins are disclosed (see scheme; R1=alkyl, aryl; R2=halide, nitro, methoxy; PG=protecting group). This protocol also allows the insertion of carbon monoxide into organic molecules without the aid of a transition-metal catalyst after the hydrolysis process. Copyright
- Li, Jian,Liu, Yuejin,Li, Chunju,Jia, Xueshun
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supporting information; experimental part
p. 7409 - 7413
(2011/08/05)
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- A practical synthesis of 5-aroyl-1-aryltetrazoles using an Ugi-like 4-component reaction followed by a biomimetic transamination
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Multicomponent reactions (MCRs), followed by subsequent transformations, are fascinating tools for the rapid and effective synthesis of molecular scaffolds with potential pharmacological relevance. We became interested in the preparation of novel 5-aroyl-1-aryltetrazoles as (1) they still represent challenging structures not easily accessible through the methods described in literature, and (2) the -ketotetrazolic framework may be considered as a potential bioisostere of the enonic linker of chalcones. In the present work, a novel, simple, effective and general synthesis for this class of compounds is described. Georg Thieme Verlag Stuttgart - New York.
- Giustiniano, Mariateresa,Pirali, Tracey,Massarotti, Alberto,Biletta, Beatrice,Novellino, Ettore,Campiglia, Pietro,Sorba, Giovanni,Tron, Gian Cesare
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experimental part
p. 4107 - 4118
(2011/03/17)
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- Oxidation of arylthiourea by cetyltrimethylammonium dichromate
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With a view to investigate the oxidation behaviors of cetyltrimethylammonium dichromate on multifunctional groups, some arylthioureas were subjected to oxidation, both in neutral and in acidic conditions. In neutral conditions, the products were found to be a mixture of corresponding urea and isonitrile. In acidic conditions, the products were corresponding ureas only. A probable mechanism was proposed for the formation of the product, wherein the first step involves coupling of-NH2 and-SH of one molecule to the-NH2 and-SH of another molecule, respectively, which is followed by removal of nitrogen and sulfur. The microwave irradiation resulted in great yield of isonitrile than urea in neutral conditions. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
- Sahu, Sandhyamayee,Sahoo, Prangya Rani,Patel, Sabita,Mishra
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experimental part
p. 3268 - 3273
(2010/12/24)
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- Synthesis of sugar-derived isoselenocyanates, selenoureas, and selenazoles
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Aryl, alkyl, and sugar-derived isoselenocyanates were prepared by a one-pot procedure starting from the corresponding formamides, using triphosgene as a dehydrating agent, triethylamine, and black selenium powder. The preparation of sugar selenoureas by coupling of O-protected sugar-derived isoselenocyanates with different amines, and by coupling of unprotected glycopyranosyl amines with phenyl isoselenocyanate was also accomplished. The synthesis of a glucopyranos-2-yl-selenazole starting from O-protected 2-amino-2-deoxy-d-glucose by coupling with benzoyl isoselenocyanate, Se-alkylation with phenacyl bromide, and acid-catalyzed dehydration is also reported. Unprotected N-(β-d-glucopyranosyl)-N′-phenylselenourea was transformed into a 1,2-trans-fused bicyclic isourea upon treatment with aqueous hydrogen peroxide; the same isourea was prepared by a one-pot three-step procedure from β-d-glycopyranosylamine by thiophosgenation, coupling with aniline, and HgO-mediated desulfurization.
- López, óscar,Maza, Susana,Ulgar, Víctor,Maya, Inés,Fernández-Bola?os, José G.
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experimental part
p. 2556 - 2566
(2009/08/08)
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- Discovery of novel analgesic and anti-inflammatory 3-arylamine-imidazo[1,2-a]pyridine symbiotic prototypes
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We describe herein the design, synthesis and pharmacological evaluation of novel 3-arylamine-imidazo[1,2-a]pyridine derivatives structurally designed as novel symbiotic prototypes presenting analgesic and anti-inflammatory properties. The derivatives obtained were submitted to in vivo assays of nociception, hyperalgesia and inflammation, and to in vitro assays of human PGHS-2 inhibition. These assays allowed the identification of compound LASSBio-1135 (3a) as an anti-inflammatory and analgesic symbiotic prototype. This compound inhibited moderately the human PGHS-2 enzyme activity (IC50 = 18.5 μM) and reverted the capsaicin-induced thermal hyperalgesia (100 μmol/kg, po) similarly to p38 MAPK inhibitor SB-203580 (2). Additionally, LASSBio-1135 (3a) presented activity similar to celecoxib (1) regarding the reduction of the carrageenan-induced rat paw edema (33% of inhibition at 100 μmol/kg, po). We also discovered derivatives LASSBio-1140 (3c) and LASSBio-1141 (3e) as analgesic and anti-inflammatory prototypes, which were able to attenuate the capsaicin-induced thermal hyperalgesia (100 μmol/kg, po) and reduce the carrageenan-induced paw edema (ED50 = 11.5 μmol/kg (3.3 mg/kg) and 14.5 μmol/kg (4.1 mg/kg), respectively), being both more active than celecoxib (1), despite the fact that their effects involve a different mechanism of action. Additionally, derivative LASSBio-1145 (3j) showed remarkable analgesic (ED50 = 22.7 μmol/kg (8.9 mg/kg)) and anti-inflammatory (ED50 = 8.7 μmol/kg (3.4 mg/kg)) profile in vivo (100 μmol/kg; po), in AcOH-induced abdominal constrictions in mice and carrageenan-induced rat paw edema models, respectively, being a novel orally-active anti-inflammatory drug candidate that acts as a selective PGHS-2 inhibitor (IC50 = 2.8 μM).
- Lacerda, Renata B.,de Lima, Cleverton K.F.,da Silva, Leandro L.,Romeiro, Nelilma C.,Miranda, Ana Luisa P.,Barreiro, Eliezer J.,Fraga, Carlos A.M.
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experimental part
p. 74 - 84
(2011/03/17)
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- Synthesis and pesticidal properties of thio and seleno analogs of some common urea herbicides
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Thio and seleno analogs of fenuron, isoproturon, chlorotoluron, metoxuron, monuron, and diuron were synthesized from the corresponding aryl amines. Their reaction with thiophosgene leads to isothiocyanates. Aryl amines were also converted (via isocyanides) to isoselenocyanates. The reaction of both isothio- and isoselenocyanates with dimethylamine affords the corresponding thio and seleno analogs of the above-mentioned urea herbicides. Herbicidal activity of the synthesized compounds was slightly lower than the activity of the parent urea herbicides. The thio and seleno analogs as well as the parent ureas showed good fungicidal activity at a concentration of 200 ppm against selected fungi.
- Zakrzewski, Jerzy,Krawczyk, Maria
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experimental part
p. 1880 - 1903
(2010/02/28)
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- N-Arylimidazole synthesis by cross-cycloaddition of isocyanides using a novel catalytic system
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A direct catalytic synthesis of N-arylimidazoles starting from the corresponding N-arylformamides and N-formylglycine esters is?described. Application to different aryl substituted electron-withdrawing and -donating groups provided the analogous heterocyc
- Bonin, Marc-André,Giguère, Denis,Roy, René
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p. 4912 - 4917
(2008/02/01)
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- Isonitrile trapping reactions under thermolysis of alkoxyamines for the synthesis of quinolines
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An efficient tandem radical process comprising a thermal alkoxyamine homolysis, an isonitrile trapping reaction, a 5-exo-trig cyclization, and a homolytic aromatic substitution leads to substituted dihydroquinolines. Depending on the substituent R1, oxidation to dihydro-1H-cyclopenta- [b]quinolines (for R1 = aryl) or tautomerization to tetrahydro-1H-cyclopenta[b]quinolines (for R1 = CO2Me, CN) occurs. The heterocycles are obtained in moderate to good yields. Upon using microwave-induced heating, the reaction time can be shortened from 3 days to 30 min.
- Janza, Birgit,Studer, Armido
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p. 1875 - 1878
(2007/10/03)
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- Correlation between HOMO alignment and contact resistance in molecular junctions: Aromatic thiols versus aromatic isocyanides
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Understanding electron transport in metal-molecule-metal (MMM) junctions is of great importance for the advancement of molecular electronics. Critical factors that determine conductivity in a MMM junction include the nature of metal-molecule contacts and
- Kim, Bongsoo,Beebe, Jeremy M.,Jun, Yongseok,Zhu,Frisbie, G. Daniel
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p. 4970 - 4971
(2007/10/03)
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- Solvent effect on the sensitized photooxygenation of cyclic and acyclic α-diimines
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The reaction of singlet molecular oxygen with a series of cyclic and acyclic α-diimines was studied. Time-resolved methods were used to measure total reaction rate constants and steady-state methods were used to determine chemical reaction rate constants. GC-MS was used to tentatively assign the reaction products. 5,6-Disubstituted cyclic α-diimines are singlet oxygen quenchers, but become more effective in polar solvents. A reaction mechanism involving a perepoxide intermediate or transition state leading to a hydroperoxide seems to be a key reaction path for product formation. A replacement of the phenyl substituent for a methyl substituent opens up an additional reaction involving a perepoxide-like exciplex, which increases singlet oxygen quenching of the cyclic α-diimines. The reactivity of 5,6-disubstituted cyclic α-diimines towards singlet oxygen is highly dependent on steric interactions arising from vicinal phenyl rings and from electronic effects. 1,4-Disubstituted acyclic α-diimines are, by comparison, moderate or poor singlet oxygen quenchers. Total rate constants are scarcely dependent on solvent properties, but instead correlate with the Hildebrand parameter. These results are explained in terms of a mechanism involving a dioxetane-like exciplex that gives rise to a charged intermediate leading to products.
- Lemp, Else,Zanocco, Antonio L.,Günther, German,Pizarro, Nancy
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p. 10734 - 10746
(2007/10/03)
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- Microwave-assisted synthesis of isonitriles: A general simple methodology
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(Chemical Equation Presented) A facile conversion of formamides to isonitriles under very mild conditions and microwave irradiation is described. This simple and efficient method has been applied for the synthesis of both aliphatic and aromatic isonitriles in high yields.
- Porcheddu, Andrea,Giacomelli, Giampaolo,Salaris, Margherita
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p. 2361 - 2363
(2007/10/03)
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- Thermal oligomerisation of aryl isocyanides: Formation of pyrazino[1,2-a:4,5-a′]diindoles and indigo diarylimines
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The aryl isocyanides 1-4 are converted at 150°C into the hexameric pyrazino[1,2-a:4,5-a′]diindoles 15-19. 4-Fluorophenyl isocyanide, when heated at 135°C, gave the hexamer 19 and the tetrameric indigo di-arylimine 9, and when kept at ambient temperature g
- Boeyens, Jan C.A.,Cook, Leanne M.,Ding, Yunxiang,Fernandes, Manuel A.,Reid, David H.
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p. 2168 - 2172
(2007/10/03)
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- Electrochemical reduction of diheteroaryl-1,2-diketones in the presence of carbonimidoyl dichlorides. First synthesis of 2-arylimino-4,5-di-2-furyl-1,3-dioxoles and (E)-1,2-di-2-furylvinylene bis(N-arylchloroformimidates)
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Selective cathodic reductions of 2,2′-furil in an aprotic medium, under constant potential, in the presence of equimolecular amounts of N-arylcarbonimidoyl dichlorides provide previously unknown 2-arylimino-4,5-di-2-furyl-1,3-dioxoles in high yields. Thes
- Guirado, Antonio,Zapata, Andrés,Andreu, Raquel,Martiz, Bruno
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p. 1405 - 1408
(2007/10/03)
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- Electrochemical generation of alkyl and aryl isocyanides
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An efficient and widely applicable reagent-free method for the synthesis of alkyl and aryl isocyanides has been established. The electrochemical reduction of alkyl and aryl carbonimidoyl dichlorides under constant cathode potential leads to the corresponding isocyanides in almost quantitative yields. The availability of the starting materials, the mildness of the reaction conditions as well as the easy isolation of products are noteworthy, advantageous features of the procedure.
- Guirado, Antonio,Zapata, Andres,Gomez, Jesus L.,Trabalon, Luis,Galvez, Jesus
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p. 9631 - 9640
(2007/10/03)
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- 2-Chloro-1,3-dimethylimidazolinium chloride. 1. A powerful dehydrating equivalent to DCC
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2-Chloro-1,3-dimethylimidazolinium chloride (DMC) (3) can act as a powerful dehydrating agent, replacing DCC (1) under nearly neutral conditions. Its application to acylation and dehydration is described.
- Isobe, Toshio,Ishikawa, Tsutomu
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p. 6984 - 6988
(2007/10/03)
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- The cheletropic ene-reaction and its reversal; additions to 1,2,3,4-tetrachloro-5-methylenecyclohexa-1,3-diene
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The cheletropic ene-reaction is presented as an extension of the known pericyclic additions. No example of this process is known but some decarbonylations have been discussed as its reverse. The scope of these reactions is extended by the facile decarbonylation of the alicyclic trienal 11 to give o-xylene. The dramatic lowering of the activation energy when an arene is formed and the finding that in this system phenyl isocyanide can also act as a chelefuge underline the pericyclic character of this reaction. In quest of a cheletropic addition to an ene 1,2,3,4-tetrachloro-5-methylenecyclohexa-1,3-diene was reacted with CO under pressure but to no avail. The reactive ene however readily adds an electron deficient ketone and molecular oxygen.
- Grimme, Wolfram,Haerter, Michael W.,Sklorz, Christoph A.
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p. 1959 - 1966
(2007/10/03)
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- Dehydration of formamides using the Burgess Reagent: A new route to isocyanides
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The Burgess Reagent readily converts formamides into isocyanides in high yields and is particularly effective for substrates containing halide sensitive trimethylsilyl ether groups.
- Creedon, Siobhan M.,Crowley, H. Kevin,McCarthy, Daniel G.
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p. 1015 - 1017
(2007/10/03)
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- A novel rearrangement of 2-amino-3-phenacyl-1,3,4-oxadiazolium halides with hydroxylamine
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The reaction of 2-amino-3-phenacyl-1,3,4-oxadiazolium bromides 1 with hydroxylamine at various pH values is investigated. The intermediate oximes 6 undergo both BECKMANN rearrangement to the semicarbazide derivatives 7 and BECKMANN fragmentation to the benzonitriles 9. The structure of the compounds 7 was elucidated by special decoupling techniques of the 13C-1H NMR. spectra. Johann Ambrosius Barth 1996.
- Koeckritz,Hetzheim,Radeglia
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p. 436 - 440
(2007/10/03)
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- A Convenient and High Yielding Procedure for the Preparation of Isoselenocyanates. Synthesis and Reactivity of O-Alkylselenocarbamates.
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A high yielding one pot procedure for the preparation of isoselenocyanate from the corresponding formamide is reported.Various aromatic and aliphatic primary amines were employed in order to prepare the isoselenocyanates to establish the generality of the procedure.O-Alkylselenocarbamates of various primary, secondary and tertiary alcohols were synthesized and their stability and comparative reactivity were studied.Radical deoxygenation of the selenocarbamate of a secondary and a tertiary alcohol was accomplished under various conditions.
- Barton, Derek H. R.,Parekh, Shyamal I.,Tajbakhsh, Mahmoud,Theodorakis, Emmanouil A.,Tse, Chi-Lam
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p. 639 - 654
(2007/10/02)
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- ELECTROCHEMICAL REDUCTION OF CARBONIMIDOYL DICHLORIDES. A NEW METHOD FOR THE PREPARATION OF ISOCYANIDES
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The cathodic reduction of carbonimidoyl dichlorides provides a new, mild and free-reagent method for the preparation of isocyanides in almost quantitative yields.
- Guirado, Antonio,Zapata, Andres,Fenor, Manuel
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p. 4779 - 4782
(2007/10/02)
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