- Highly Cytotoxic Palladium(II) Pincer Complexes Based on Picolinylamides Functionalized with Amino Acids Bearing Ancillary S-Donor Groups
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The reactions of picolinyl and 4-chloropicolinyl chlorides with methyl esters of S-methyl-l-cysteine, l- and d-methionine, and l-histidine afforded a series of functionalized carboxamides, which readily formed pincer-type complexes upon interaction with PdCl2(NCPh)2 in solution under mild conditions. The direct cyclopalladation of the ligands derived was also accomplished in the solid phase, in particular, mechanochemically, although it was complicated by the partial deactivation of the starting amides. The resulting complexes with 5,5- and 5,6-membered fused metallocycles were fully characterized by IR and NMR spectroscopy, including variable-temperature and 2D-NMR studies. In the case of some cysteine- and methionine-based derivatives, the realization of κ3-N,N,S-coordination was supported by X-ray diffraction. The cytotoxic effects of these complexes were examined on HCT116, MCF7, and PC3 human cancer cell lines as well as HEK293 as a representative of normal cells. The comparative studies allowed us to determine that the presence of the sulfide ancillary donor group is crucial for cytotoxic activity of this type of Pd(II) complexes. The main structure-activity relationships and the most promising palladocycles were outlined. The additional studies by gel electrophoresis revealed that 4-chloropicolinyl derivatives, despite the nature of an amino acid, can bind with DNA and inhibit topoisomerase I activity.
- Churusova, Svetlana G.,Aleksanyan, Diana V.,Rybalkina, Ekaterina Yu.,Susova, Olga Yu.,Brunova, Valentina V.,Aysin, Rinat R.,Nelyubina, Yulia V.,Peregudov, Alexander S.,Gutsul, Evgenii I.,Klemenkova, Zinaida S.,Kozlov, Vladimir A.
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- N-(4-[18F]-fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl) piperazin-1-yl]ethyl}carboxamides as analogs of WAY100635. New PET tracers of serotonin 5-HT1A receptors
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N-(4-[18F]-Fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl) piperazin-1-yl]ethyl}-carboxamides were prepared by labeling their 4-nitropyridin-2-yl precursors through nitro substitution by the 18F anion. In vitro and in vivo tests showed
- García, Gonzalo,Abet, Valentina,Alajarín, Ramón,álvarez-Builla, Julio,Delgado, Mercedes,García-García, Luis,Bascu?ana-Almarcha, Pablo,Pe?a-Salcedo, Carmen,Kelly, James,Pozo, Miguel A.
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- A new colorimetric and fluorescent bifunctional probe for Cu2+ and F- ions based on perylene bisimide derivatives
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A perylene bisimide derivative (PBI) based colorimetric and fluorescent bifunctional probe PAM-PBI was designed and synthesized. It was highly selective and sensitive for distinguishing both Cu2+ and F- from other ions through a conspicuous change of UV-vis and fluorescence spectra. The recognition of Cu2+ by PAM-PBI showed an obvious color change from rose red to purple in aqueous solution, while the sensing of F- gave a marked color change from rose red to light green in THF.
- Wang, Yefeng,Zhang, Liang,Zhang, Guanjun,Wu, Yue,Wu, Shengying,Yu, Jianjun,Wang, Limin
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- Surface modification of silica nanoparticles: A new strategy for the realization of self-organized fluorescence chemosensorst
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The self-organization of the proper subunits of a fluorescence chemosensor on the surface of silica nanoparticles allows the easy design and realization of new effective sensing systems. Commercially available silica particles (20 nm diameter) were functionalized with triethoxysilane derivatives of selective Cu(II) ligands and fluorescent dyes. Grafting of the sensor components to the particle surface ensures the spatial proximity between the sensor components and, as a consequence, binding of Cu(II) ions by the ligand subunits leads to quenching of the fluorescent units emission. In 9:1 DMSO-water solution, the coated silica nanoparticles (CSNs) selectively detect copper ions down to nanomolar concentrations. The operative range of the sensors can be tuned either by switching the ligand units or by modification of the components ratio. Sensors with the desired photophysical properties can be easily prepared by using different fluorescent dyes. Moreover, the organization of the network of sensor components gives rise to cooperative and collective effects: on one hand, the ligand subunits bound to the particle surfaces cooperate to form multivalent binding sites with an increased affinity for the Cu(II) ions; on the other hand, binding of a single metal ion leads to the quenching of several fluorescent groups producing a remarkable signal amplification. The Royal Society of Chemistry 2005.
- Rampazzo, Enrico,Brasola, Elena,Marcuz, Silvia,Mancin, Fabrizio,Tecilla, Paolo,Tonellato, Umberto
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- Acid-induced molecular-structural transformation of N-methyl aromatic oligoamides bearing pyridine-2-carboxamide
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Amide oligomers composed of pyridine-2-carboxamide as the repeating unit were synthesized in a stepwise manner and their structures were examined by means of 1H NMR, NOE measurements, and DFT calculations. All the synthesized oligomers adopted a folded conformation, but became partially unfolded at the C-terminal upon addition of acid. A characteristic long-range hydrogen bond, which stabilizes local folding, was present in oligomers with a long main chain.
- Yamasaki, Ryu,Fujikake, Saori,Ito, Ai,Migita, Kentaro,Morita, Nobuyoshi,Tamura, Osamu,Okamoto, Iwao
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- Chiral Helicity Induced by Hydrogen Bonding and Chirality of Podand Histidyl Moieties
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figure presented The single-crystal X-ray structure determination of N,N′-bis{(S)-(+)-1-methoxycarbonyl-2-(4-imidazolyl)ethyl}-2,6- pyridinedicarboxamide (L-BHisPA) and the D-isomer (D-BHisPA) derived from the corresponding chiral histidine revealed a left- and right-handed helical conformation, respectively, through intramolecular hydrogen bonding and chirality of the podand histidyl moieties. Furthermore, each helical molecule is connected by continuous intermolecular hydrogen bonds to afford a left- or right-handed helical assembly, respectively, in the crystal packing.
- Moriuchi, Toshiyuki,Nishiyama, Masahito,Yoshida, Kazuhiro,Ishikawa, Takuji,Hirao, Toshikazu
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- Planar-chiral metal complexes comprised of square-planar metal and achiral tetradentate ligands: Design, optical resolution, and thermodynamics
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Planar-chiral palladium complexes {[[N,N′-[1,4-butanediylbis(oxy-7,1- naphthalenediyl)]bis(2-pyridinecarboxamidato)](2-)-κN1, κN1′,κN2,κN2′] palladium (PdL4) and [[2,2′-[1,4-butanediylbis[[(oxy-7,1- naphthalenediyl)imino]methyl]]dipyrrolato](2-)-κN1, κN1′,κN2,κN2′] palladium (PdL5)} were synthesized from achiral tetradentate ligands N,N′-[1,4-butanediylbis(oxy-7,1-naphthalenediyl)]bis(2- pyridinecarboxamide) (H2L4) and N,N′-bis[(1H-pyrrol- 2-yl)methylidene]-7,7′-(1,4-butanediyldioxy)bis(1-naphthalenamine) (H 2L5) bearing two dissymmetric bidentate units at both ends and a PdII ion, respectively. The palladium complexes were crystallized in the monoclinic space group P21/n with the unit cell parameters a = 16.5464(6) A, b = 11.3534(4) A, c = 17.6697(7) A, α = 115.5300(10)°, and Z = 4 for PdL4 and a = 17.2271(8) A, b = 10.1016(5) A, c = 17.9361(9) A, α = 105.6310(10)°, and Z = 4 for PdL5. The planar-chiral structures of PdL4 and PdL5 were confirmed by single-crystal X-ray analyses, resulting in the fact that the crystals were racemic mixtures. The racemic mixtures were successfully resolved by using chiral high-performance liquid-chromatography techniques. Racemizations of the complexes were found to be drastically dependent on the arrangement of the charged or uncharged metal-binding N atoms of the ligands.
- Goto, Hidetoshi,Hayakawa, Teppei,Furutachi, Kanako,Sugimoto, Hiroshi,Inoue, Shohei
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- A pyrene-based highly selective turn-on fluorescent sensor for copper(II) ion and its application in live cell imaging
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A new pyrene derivative (chemosensor 1) containing a picolinohydrazide moiety exhibits high selectivity for Cu2+ ion detection in mixed aqueous media (CH3OH:H2O= 7:3). Significant fluorescence enhancement was observed with chemosensor 1 in the presence of Cu2+. However, the metal ions Ag+, Ca2+, Cd2+, Co2+, Cu 2+, Fe2+, Fe3+, Hg2+, K+, Mg 2+, Mn2+, Ni2+, Pb2+, and Zn 2+ produced only minor changes in fluorescence for the system. The apparent association constant (Ka) of Cu2+ binding in chemosensor 1 was found to be 2.75103 M-1. The maximum fluorescence enhancement caused by Cu2+ binding in chemosensor 1 was observed over the pH range 5-8. Moreover, by means of fluorescence microscopy experiments, it is demonstrated that 1 can be used as a fluorescent probe for detecting Cu2+ in living cells.
- Wu, Shu-Pao,Huang, Zhen-Ming,Liu, Shi-Rong,Chung, Peter Kun
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- A fluorescence nanosensor for Cu2+ on silica particles
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A fluorescence nanosensor for Cu2+ ions has been obtained by surface functionalization of silica particles with trialk-oxysilane derivatized ligand and fluorescent dye.
- Brasola, Elena,Mancin, Fabrizio,Rampazzo, Enrico,Tecilla, Paolo,Tonellato, Umberto
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- ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 (ENPP1) MODULATORS AND USES THEREOF
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Provided herein are small molecule modulators of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.
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Paragraph 00278; 00355; 00370
(2021/07/02)
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- Pseudocryptand Hosts for Paraquats and Diquats
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H-bonding interaction of acidic moieties (CH2OH, COOH) at the 5- and 5′-positions of bis(1,3-phenylene)-32-crown-10 (1) with di- or tritopic anions leads to enhanced formation of inclusion complexes with N,N′-dialkyl-4,4′-bipyridinium salts ("paraquats", 2); the enforced folding of the crown ethers into pseudocryptands thus leads to pseudo-pseudorotaxanes. Strikingly, in the presence of the most effective anion (trifluoroacetate, TFA), the apparent bimolecular association constants for crown-paraquat complexation increase by more than an order of magnitude and approach those for covalent cryptands derived from the crown ether. Even though they may form pseudocryptands, the picolinate, nicotinate, and isonicotinate diesters 6 of cis-(4,4')-bis(hydroxymethyl)dibenzo-30-crown-10 do not exhibit enhanced binding of either diquat or paraquat relative to the starting diol in contrast to the picolinate ester of isomeric 5,5′-bis(hydroxymethyl)bis(m-phenylene)-32-crown-10, which displayed a higher binding constant than the starting diol. The results for the analogous reverse esters 7 derived from cis-(4,4')-dicarboxydibenzo-30-crown-10 and pyridylmethanols reveal weaker complexes with diquat than the normal esters 6; however, surprisingly, two reverse esters 7 complex paraquat more strongly than isomers 6.
- Jones, Jason W.,Price, Terry L.,Huang, Feihe,Zakharov, Lev,Rheingold, Arnold L.,Slebodnick, Carla,Gibson, Harry W.
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p. 823 - 834
(2018/01/28)
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- Investigating Structural Requirements for the Antiproliferative Activity of Biphenyl Nicotinamides
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A number of trimethoxybenzoic acid anilides, previously studied as permeability glycoprotein (P-gp) modulators, were screened with the aim of identifying new anticancer agents. One of these compounds, which showed antiproliferative activity against resist
- Majellaro, Maria,Stefanachi, Angela,Tardia, Piero,Vicenti, Chiara,Boccarelli, Angelina,Pannunzio, Alessandra,Campanella, Federica,Coluccia, Mauro,Denora, Nunzio,Leonetti, Francesco,de Candia, Modesto,Altomare, Cosimo Damiano,Cellamare, Saverio
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p. 1380 - 1389
(2017/09/01)
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- The light-emitting compound and use this light-emitting compound of the organic light emitting diode device
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An embodiment of the present invention provides an emitting compound of following formula: wherein “A” is represented by and “B” is represented by
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Paragraph 0074-0077
(2017/04/11)
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- Synthesis and evaluation of neuroprotective 4-O-substituted chrysotoxine derivatives as potential multifunctional agents for the treatment of Alzheimer's disease
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A series of 4-O-substituted chrysotoxine (CTX) derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). In vitro assays indicated that four ring substituted compounds (2a, 2b, 3i and 3j)
- Guan, Li,Hao, Yanfeng,Chen, Lei,Wei, Meng-Lin,Jiang, Qin,Liu, Wen-Yuan,Zhang, Yan-Bo,Zhang, Jie,Feng, Feng,Qu, Wei
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p. 22827 - 22838
(2016/03/12)
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- Regio- and stereoselective Pd-catalyzed direct arylation of unactivated sp3 C(3)-H bonds of tetrahydrofuran and 1,4-benzodioxane systems
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An auxiliary-enabled Pd-catalyzed highly regio- and stereoselective sp3 C-H activation and the direct arylation of the C3-position of oxygen heterocycles, such as tetrahydrofuran and 1,4-benzodioxane systems, are reported. An efficient stereoselective construction of cis 2,3-disubstituted tetrahydrofuran derivatives (analogues of norlignans) and cis 2,3-disubstituted 1,4-benzodioxane derivatives (analogues of neolignans) is described. The direct C(sp3)-H arylation of the C3-position of (R)- or (S)- tetrahydrofuran-2-carboxamides furnished the corresponding (2R,3R) and (2S,3S) C3-arylated THF scaffolds as major compounds with very high regio- and diastereoselectivities. The stereochemistry of the products obtained in this work were unambiguously assigned on the basis of the X-ray structure analyses of representative compounds 3b, 3e, 4p, and 7.
- Parella, Ramarao,Babu, Srinivasarao Arulananda
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p. 2339 - 2355
(2015/06/01)
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- Rilyazine Derivatives and Compositions for The Treatment of Cancer
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The present application discloses Rilyazine analogs, methods for their preparation, and the treatment of cancer by the administration of an effective amount of the Rilyazine analogs to a patient in need thereof.
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Paragraph 0126; 0127
(2015/03/16)
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- Design, synthesis and antitubercular evaluation of new 2-amino-5-(4-(benzyloxy)benzyl)thiophene-3-carboxylic acid derivatives. Part 3
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A series of 2-amino-5-(4-(benzyloxy)benzyl)thiophene-3-carboxylic acid derivatives was designed and synthesized. The derivatives were evaluated for antitubercular activity against M. tuberculosis ATCC 27294 using the Microplate Alamar Blue Assay (MABA). Among them, compound 8b exhibited the most potent activity with MIC value of 1.9 μM.
- Lu, Xiaoyun,Tang, Jian,You, Qidong,Wan, Baojie,Franzblau, Scott G.
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- Amide-tethered organosilatranes: Syntheses, structural characterization and photophysical properties
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A series of trimethoxysilanes and silatranes coupled with distinct aromatic moieties (biphenyl, thiophene, pyrazine and pyridine) through amide linkage are reported. The synthetic approach involved the amidation of 3-aminopropyltrimethoxysilane (APTMS) with various carboxylic acids via acid chlorides (1a-1g) to generate amidopropylsilanes (2a-2g). Transesterification of the resultant silanes with triethanolamine and tris(isopropanolamine) yielded unsubstituted (3a-3g) and 3,7,10-trimethylsubstitued organosilatranes (4a-4g), respectively. The compounds were successfully characterized by various spectroscopic techniques [IR, NMR (1H, 13C) and Mass] and elemental analysis. The complete structure elucidation for compounds 3a, 3c·H2O and 3f was carried out using single crystal X-ray diffraction analysis. The photophysical response was studied by UV-Vis absorption and fluorescence spectroscopy. These organosilatranes possess metal ion binding sites and can be put forth for advanced analytical applications.
- Singh, Gurjaspreet,Rani, Sunita,Saroa, Amandeep,Promila,Arora, Aanchal,Choquesillo-Lazarte, Duane
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supporting information
p. 78 - 91
(2015/06/02)
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- Pyridine-oxazoline and quinoline-oxazoline ligated cobalt complexes: Synthesis, characterization, and 1,3-butadiene polymerization behaviors
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A series of cobalt complexes supported by pyridine-oxazoline (Pyox) and quinoline-oxazoline (Quox) were synthesized. Determined by single crystal X-ray crystallography, complexes 6a and 7c adopted distorted octahedron and trigonal bipyramid geometries, re
- Guo, Jun,Liu, Heng,Bi, Jifu,Zhang, Chunyu,Zhang, Hexin,Bai, Chenxi,Hu, Yanming,Zhang, Xuequan
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p. 305 - 312
(2015/08/06)
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- C-H bond oxidation catalyzed by an imine-based iron complex: A mechanistic insight
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A family of imine-based nonheme iron(II) complexes (LX)2Fe(OTf)2 has been prepared, characterized, and employed as C-H oxidation catalysts. Ligands LX (X = 1, 2, 3, and 4) stand for tridentate imine ligands resulting from spontaneous condensation of 2-pycolyl-amine and 4-substituted-2-picolyl aldehydes. Fast and quantitative formation of the complex occurs just upon mixing aldehyde, amine, and Fe(OTf)2 in a 2:2:1 ratio in acetonitrile solution. The solid-state structures of (L1)2Fe(OTf)(ClO4) and (L3)2Fe(OTf)2 are reported, showing a low-spin octahedral iron center, with the ligands arranged in a meridional fashion. 1H NMR analyses indicate that the solid-state structure and spin state is retained in solution. These analyses also show the presence of an amine-imine tautomeric equilibrium. (LX)2Fe(OTf)2 efficiently catalyze the oxidation of alkyl C-H bonds employing H2O2 as a terminal oxidant. Manipulation of the electronic properties of the imine ligand has only a minor impact on efficiency and selectivity of the oxidative process. A mechanistic study is presented, providing evidence that C-H oxidations are metal-based. Reactions occur with stereoretention at the hydroxylated carbon and selectively at tertiary over secondary C-H bonds. Isotopic labeling analyses show that H2O2 is the dominant origin of the oxygen atoms inserted in the oxygenated product. Experimental evidence is provided that reactions involve initial oxidation of the complexes to the ferric state, and it is proposed that a ligand arm dissociates to enable hydrogen peroxide binding and activation. Selectivity patterns and isotopic labeling studies strongly suggest that activation of hydrogen peroxide occurs by heterolytic O-O cleavage, without the assistance of a cis-binding water or alkyl carboxylic acid. The sum of these observations provides sound evidence that controlled activation of H2O2 at (LX)2Fe(OTf)2 differs from that occurring in biomimetic iron catalysts described to date.
- Olivo, Giorgio,Nardi, Martina,Vìdal, Diego,Barbieri, Alessia,Lapi, Andrea,Gómez, Laura,Lanzalunga, Osvaldo,Costas, Miquel,Di Stefano, Stefano
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supporting information
p. 10141 - 10152
(2015/11/16)
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- Copper-catalyzed ortho-C-H amination of protected anilines with secondary amines
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A practical Cu-catalyzed picolinamide-directed o-amination of anilines showing excellent mono-substitution selectivity and high functional group tolerance has been developed.
- Martinez, Angel Manu,Rodriguez, Nuria,Arrayas, Ramon Gomez,Carretero, Juan C.
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supporting information
p. 2801 - 2803
(2014/03/21)
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- Rhodium(III)-catalyzed oxidative olefination of picolinamides: Convenient synthesis of 3-alkenylpicolinamides
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A rhodium(III)-catalyzed selective olefination of picolinamide derivatives has been developed. The reaction shows high regioselectivity, low catalyst loading (0.5 mol%), high yield and good functional group tolerance, providing a convenient strategy for the synthesis of 3-alkenylpicolinamides.
- Zhou, Jun,Li, Bo,Qian, Zhen-Chao,Shi, Bing-Feng
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supporting information
p. 1038 - 1046
(2014/04/03)
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- C-H activation by amide chelation control: Ruthenium-catalyzed direct synthesis of 2-Aryl-3-furanamides
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A new, catalytic methodology for the synthesis of heterobiaryls by the ruthenium-catalyzed C-H activation/cross-coupling of heterocyclic amides with aryl boroneopentylates is surveyed. From this survey, the highly regioselective reaction of furan-3-carboxamide to give 2-aryl-3-furanamides is optimized and generalized in scope with respect to the aryl boroneopentylate coupling partners. Established thereby is a one-step synthetic method which may supercede the broadly applied two-step directed ortho metalation (DoM)-cross coupling reaction involving cryogenic and strong base conditions and which has potential for further ortho and remote metalation chemistry.
- Zhao, Yigang,Snieckus, Victor
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supporting information
p. 1527 - 1532
(2014/06/09)
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- Rh(III)-catalyzed cascade oxidative olefination/cyclization of picolinamides and alkenes via C-H activation
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Rh(III)-catalyzed cascade oxidative alkenylation/cyclization of picolinamides and alkenes to furnish pyrido pyrrolone derivatives is described, in which three C-H bonds and one N-H bond broke, while one C-C bond and one C-N bond formed. The reaction proceeded with high yield and high regioselectivity and stereoselectivity. Moreover, copper acetate can also be used in catalytic amounts with O2 serving as the terminal oxidant.
- Cai, Shangjun,Chen, Chao,Shao, Peng,Xi, Chanjuan
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supporting information
p. 3142 - 3145
(2014/06/23)
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- Investigation of a novel series of 2-hydroxyisoquinoline-1,3(2 H,4 H)-diones as human immunodeficiency virus type 1 integrase inhibitors
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We report herein further insight into the biological activities displayed by a series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs). Substitution of the N-hydroxyimide two-metal binding pharmacophore at position 4 by carboxamido side chains was previously shown by us to be fruitful for this scaffold, since strong human immunodeficiency virus type 1 integrase (HIV-1 IN) inhibitors in the low nanomolar range associated with low micromolar anti-HIV activities were obtained. We investigated the influence of substitution at position 7 on biological activity. Introduction of electron-withdrawing functional groups such as the nitro moiety at position 7 led to a noticeable improvement of antiviral activity, down to low nanomolar anti-HIV potencies, with advantageous therapeutic indexes going close to those of the clinically used raltegravir and retained potencies against a panel of IN mutants.
- Suchaud, Virginie,Bailly, Fabrice,Lion, Cedric,Calmels, Christina,Andreola, Marie-Line,Christ, Frauke,Debyser, Zeger,Cotelle, Philippe
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p. 4640 - 4660
(2014/07/07)
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- Radiosynthesis and evaluation of an 18F-labeled positron emission tomography (PET) radioligand for metabotropic glutamate receptor subtype 4 (mGlu4)
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Four 4-phthalimide derivatives of N-(3-chlorophenyl)-2-picolinamide were synthesized as potential ligands for the PET imaging of mGlu4 in the brain. Of these compounds, N-(3-chloro-4-(4-fluoro-1,3-dioxoisoindolin-2-yl)phenyl)-2-picolinamide (3,
- Kil, Kun-Eek,Poutiainen, Pekka,Zhang, Zhaoda,Zhu, Aijun,Choi, Ji-Kyung,Jokivarsi, Kimmo,Brownell, Anna-Liisa
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p. 9130 - 9138
(2015/03/14)
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- A hetero Diels-Alder approach to the synthesis of chromans (3,4-dihydrobenzopyrans) using oxonium ion chemistry: The oxa-Povarov reaction
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An oxa analogue of the well-known Povarov reaction has been developed for the synthesis of 3,4-dihydrobenzopyrans (chromans). The reaction involves the formal inverse electron demand [4 + 2] cycloaddition reaction of in situ-generated cationic aryl 2-oxadiene oxocarbenium ions with alkenes. The oxonium ion intermediates are generated through Lewis acid (SnCl 4)-promoted reactions of phenol-derived Rychnovsky-type mixed acetals. The yield and diastereoselectivity of the chroman products are found to depend upon the substitution pattern of the precursor alkene (i.e., monosubstituted, trans- or cis-disubstituted and cyclic alkenes). Generally, the reactions afford the endo-diastereomers as the major products, except for the reactions of trans-β-methylstyrene, which afford exo-chromans. A comparison of the product distributions from the reactions of trans- and cis-β-methylstyrene reveal that the reaction proceeds, at least in part, by a nonconcerted ionic pathway. Just as for the aza-Povarov reaction, there are two potential mechanisms for the reaction. The first mechanism involves a direct asynchronous [4 + 2] cycloaddition pathway, while the second occurs through the stepwise Prins addition of the alkene to the aryl 2-oxadiene oxonium ion, followed by an intramolecular aromatic substitution reaction of the resultant cation (i.e., a domino Prins/intramolecular Friedel-Crafts reaction).
- Taylor, Rivka R. R.,Batey, Robert A.
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p. 1404 - 1420
(2013/03/28)
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- Spirocyclic dihydropyridines by electrophile-induced dearomatizing cyclization of N-alkenyl pyridinecarboxamides
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On treatment with acylating or sulfonylating agents, N-alkenyl pyridine carboxamides (N-pyridinecarbonyl enamines) undergo a dearomatizing cyclization initiated by pyridine acylation and followed by intramolecular trapping of the resulting pyridinium cation. The products are spirocyclic dihydropyridines which may be further elaborated to spirocyclic heterocycles with drug-like features.
- Senczyszyn, Jemma,Brice, Heloise,Clayden, Jonathan
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supporting information
p. 1922 - 1925
(2013/06/04)
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- Synthesis and evaluation of gold(III) complexes as efficient DNA binders and cytotoxic agents
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In recent years, great interest has been focused on gold(III) complexes as cytotoxic and antitumor drugs. Recent studies demonstrated that simple bidentate or polydentate ligands containing nitrogen donor atoms may offer sufficient redox stabilization to produce viable Au(III) anticancer drug targets under physiologic conditions. So, we have synthesized square planer Au(III) complexes of type [Au(An)Clx]Cly and characterized them using UV-Vis absorption, C, H, N elemental analysis, FT-IR, LC-MS, 1H and 13C NMR spectroscopy. These compounds manifested significant cytotoxic properties in vitro for brine shrimp lethality bioassay. The metal complexes were screened for series of DNA binding activity using UV-Vis absorption titration, hydrodynamic measurement and thermal DNA denaturation study. The nucleolytic activity was performed on plasmid pUC19 DNA. The Michaelis-Menten kinetic studies were performed to evaluate rate of enhancement in metal complexes mediated DNA cleavage over the non-catalyzed DNA cleavage.
- Patel, Mohan N.,Bhatt, Bhupesh S.,Dosi, Promise A.
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- A scalable synthesis of the (S)-4-(tert-butyl)-2-(pyridin-2-yl)-4,5- dihydrooxazole ((S)-t-BuPyOx) ligand
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An efficient method for the synthesis of the (S)-4-(tert-butyl)-2-(pyridin- 2-yl)-4,5-dihydrooxazole ((S)-t-BuPyOx) ligand has been developed. Inconsistent yields and tedious purification in known routes to (S)-t-BuPyOx suggested the need for an efficient, dependable, and scalable synthetic route. Furthermore, a route suitable for the synthesis of PyOx derivatives is desirable. Herein, we describe the development of a three-step route from inexpensive and commercially available picolinic acid. This short procedure is amenable to multi-gram scale synthesis and provides the target ligand in 64% overall yield.
- Shimizu, Hideki,Holder, Jeffrey C.,Stoltz, Brian M.
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p. 1637 - 1642
(2013/10/22)
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- Copper(II/I) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline: Synthesis, crystal structure, antitumor activity and DNA interaction
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Three new copper(II) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g] isoquinoline (PYP), i.e. [Cu2(PYP)2Cl4] (1), [Cu4(PYP)4(ClO4)2(H 2O)2](ClO4)
- Huang, Ke-Bin,Chen, Zhen-Feng,Liu, Yan-Cheng,Wang, Meng,Wei, Jian-Hua,Xie, Xiao-Li,Zhang, Jian-Lian,Hu, Kun,Liang, Hong
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p. 640 - 648
(2013/12/04)
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- Multiplexing of combinatorial chemistry in antimycin biosynthesis: Expansion of molecular diversity and utility
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Diversity-oriented biosynthesis of a library of antimycin-like compounds (380 altogether) was accomplished by using multiplex combinatorial biosynthesis. The core strategy depends on the use of combinatorial chemistry at different biosynthetic stages. This approach is applicable for the diversification of polyketides, nonribosomal peptides, and the hybrids that share a similar biosynthetic logic. Copyright
- Yan, Yan,Chen, Jing,Zhang, Lihan,Zheng, Qingfei,Han, Ying,Zhang, Hua,Zhang, Daozhong,Awakawa, Takayoshi,Abe, Ikuro,Liu, Wen
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supporting information
p. 12308 - 12312
(2013/12/04)
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- Direct bis-arylation of cyclobutanecarboxamide via double C-H activation: An auxiliary-aided diastereoselective Pd-catalyzed access to trisubstituted cyclobutane scaffolds having three contiguous stereocenters and an all-cis stereochemistry
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An auxiliary-aided Pd-catalyzed highly diastereoselective double C-H activation and direct bis-arylation of methylene C(sp3)-H bonds of cyclobutanecarboxamides and the syntheses of several novel trisubstituted cyclobutanecarboxamide scaffolds h
- Parella, Ramarao,Gopalakrishnan, Bojan,Babu, Srinivasarao Arulananda
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p. 11911 - 11934
(2014/01/06)
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- Design, synthesis, and evaluation of substituted 6-amide-4- anilinoquinazoline derivatives as c-Src inhibitors
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The 4-anilinoquinazoline scaffold has been historically used for designing EGFR/VEGFR/HER2 inhibitors while it has not been reported widely for developing c-Src inhibitors. Thus, a series of novel 4-anilinoquinazoline derivatives grafting different amide moieties at the 6-position were designed and synthesized as potential inhibitors for c-Src. In this manuscript, all of the designed compounds were screened via molecular docking using Discovery Studio 3.5 software. As expected, the results of the docking study revealed that most of these targeted compounds possessed lower binding energy than the positive control Saracatinib. Subsequently, all of the screened compounds were synthesized and evaluated for their c-Src in vitro inhibitory activities and in vitro antiproliferation assays against four human cancer cells (A549, MCF-7, HepG-2, HeLa). Among these compounds, 24 exhibited the most potent inhibitory activity against c-Src kinase as well as at the cellular level, of which the IC50 value reached up to 2.9 nM, comparable to the positive compound Saracatinib. Kinase selectivity profile also demonstrated that compound 24 showed good selectivity over several close kinase targets. These results, along with relative 3D-QSAR study, could provide an important basis for further development of compound 24 as a potent tyrosine kinase inhibitor.
- Fang, Fei,Li, Dong-Dong,Li, Jing-Ran,Sun, Jian,Du, Qian-Ru,Gong, Hai-Bin,Zhu, Hai-Liang
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p. 26230 - 26240
(2013/12/04)
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- L-Proline-derived ligands to mimic the '2-His-1-carboxylate' triad of the non-haem iron oxidase active site
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Non-haem iron(II) oxidases (NHIOs) catalyse a variety of oxidative transformations in biology. The iron-binding environment of the NHIO active site typically incorporates a '2-His-1-carboxylate' facial triad of amino acid side-chains, a motif that has emerged as a defining feature of the enzyme family. Towards the goal of biomimetic, iron-mediated C-H activation we have synthesized a series of peptidomimetic ligands from l-proline. By coupling l-proline to 2,6-bis(bromomethyl)pyridine, 2-(bromomethyl)-6-((tert- butyldimethylsilyloxy)methyl)pyridine and picolinic acid, we have generated several new ligand architectures designed to complex with iron(II) and mimic the NHIO active site. The resulting iron complexes promote modest levels of alkene dihydroxylation and allylic oxidation using hydrogen peroxide as oxidant.
- Dungan, Victoria J.,Wong, Shwo Mun,Barry, Sarah M.,Rutledge, Peter J.
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experimental part
p. 3231 - 3236
(2012/06/01)
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- Decarbonylative C-H coupling of azoles and aryl esters: Unprecedented nickel catalysis and application to the synthesis of muscoride A
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A nickel-catalyzed decarbonylative C-H biaryl coupling of azoles and aryl esters is described. The newly developed catalytic system does not require the use of expensive metal catalysts or silver- or copper-based stoichiometric oxidants. We have successfully applied this new C-H arylation reaction to a convergent formal synthesis of muscoride A.
- Amaike, Kazuma,Muto, Kei,Yamaguchi, Junichiro,Itami, Kenichiro
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supporting information; experimental part
p. 13573 - 13576
(2012/10/08)
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- Novel tetrahydropyrido[1,2-a]isoindolone derivatives (valmerins): Potent cyclin-dependent kinase/glycogen synthase kinase 3 inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts
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The development of CDK and GSK3 inhibitors has been regarded as a potential therapeutic approach, and a substantial number of diverse structures have been reported to inhibit CDKs and GSK-3β in recent years. Only a few molecules have gone through or are currently undergoing clinical trials as CDK and GSK inhibitors. In this paper, we prepared valmerins, a new family containing the tetrahydropyrido[1,2-a]isoindone core. The fused heterocycle was prepared with a straightforward synthesis that was functionalized by a (het)arylurea. Twelve valmerins inhibited the CDK5 and GSK3 with an IC50 100 nM. A semiquantitative kinase scoring was realized, and a cellular screening was done. At the end of our study, we investigated the in vivo potency of one valmerin. Mice exhibited good tolerance to our lead, which proved its efficacy and clearly blocked tumor growth. Valmerins appear also as good candidates for further development as anticancer agents.
- Boulahjar, Rajaa,Ouach, Aziz,Matteo, Chiurato,Bourg, Stephane,Ravache, Myriam,Guével, Rémy Le,Marionneau, Séverine,Oullier, Thibauld,Lozach, Olivier,Meijer, Laurent,Guguen-Guillouzo, Christiane,Lazar, Sa?d,Akssira, Mohamed,Troin, Yves,Guillaumet, Gérald,Routier, Sylvain
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p. 9589 - 9606
(2013/01/16)
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- Structure-activity relationships of 1,3-benzoxazole-4-carbonitriles as novel antifungal agents with potent in vivo efficacy
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A series of 1,3-benzoxazole-4-carbonitriles was synthesized and evaluated for its antifungal activity, solubility, and metabolic stability. Among those compounds, 4-cyano-N,N,5-trimethyl-7-[(3S)-3-methyl-3-(methylamino) pyrrolidin-1-yl]-6-phenyl-1,3-benzoxazole-2-carboxamide (16b) exhibited potent in vitro activity against Candida species, higher water solubility, and improved metabolic stability compared to lead compound 1. Compound 16b showed potent in vivo efficacy against mice Candida infection models and good bioavailability in rats.
- Kuroyanagi, Jun-Ichi,Kanai, Kazuo,Horiuchi, Takao,Takeshita, Hiroshi,Kobayashi, Shozo,Achiwa, Issei,Yoshida, Kumi,Nakamura, Koichi,Kawakami, Katsuhiro
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experimental part
p. 341 - 352
(2011/05/04)
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- Highly stereoselective double (R)-phenylglycinol-induced cyclocondensation reactions of symmetric aryl bis(oxoacids)
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The double cyclocondensation of symmetric pyridyl bis(oxoacids) 2b and 3b with (R)-phenylglycinol stereoselectively gave access to bis-phenylglycinol- derived oxazolopyrrolidine 9 and oxazolopiperidone 10, respectively. Application of the stereocontrolled
- Amat, Mercedes,Arroniz, Carlos,Molins, Elies,Escolano, Carmen,Bosch, Joan
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scheme or table
p. 2175 - 2184
(2011/05/08)
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- PC-N-Heterocycles: Synthesis of biaryl-type 1,3-benzazaphospholes with ortho-substituted phenyl or 2-heteroaryl groups
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A facile synthesis of functionally substituted 2-(hetero)aryl 1,3-benzazaphospholes via nickel- or palladium-catalyzed phosphonylation of N-acyl-2-bromoanilides 1a-k with triethyl phosphite is presented. Anilidophosphonates 2a-g with naphthoyl-, o-substituted phenyl, furoyl- or thenoyl groups allow direct reductive cyclization with LiAlH4 to benzazaphospholes 3. The reaction of the o-bromoderivative 2d proceeds with concomitant replacement of bromine by hydrogen, whereas the electron-withdrawing pyridyl group of 2h prevents the synthesis of 3h by this short route. An alternative synthesis of 2-pyridylbenzazaphosphole 3hvia anilidophosphonates succeeded starting from Fmoc-anilinophosphonate 2kvia selective cleavage of the N-protecting group, reduction of the resulting phosphonoaniline to phosphinoaniline and cyclization with pyridine-2-carboxaldehyde via a dihydrobenzazaphosphole 8. N-Substituted pyridylmethylbenzazaphosphole 9 was detected as a side product. The structure elucidation of the new compounds is based on multinuclear NMR data and X-ray crystal structure analyses of a phosphonoanilide, underlining the dominance of N-H...OP hydrogen bonds over N-H...OC type hydrogen bonds, of 3h and a supramolecular associate of 3b and its unprecedented air oxidation product 10.
- Aluri, Bhaskar Reddy,Niaz, Basit,Kindermann, Markus K.,Jones, Peter G.,Heinicke, Joachim
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experimental part
p. 211 - 224
(2011/02/16)
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- Design, synthesis and anti-tubercular evaluation of new 2-acylated and 2-alkylated amino-5-(4-(benzyloxy)phenyl)thiophene-3-carboxylic acid derivatives. Part 1
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A series of 2-acylated and 2-alkylated amino-5-(4-(benzyloxy)phenyl) thiophene-3-carboxylic acid derivatives were synthesized and evaluated for anti-tubercular activity. Among these compounds, 10d, 15, 12h and 12k inhibited Mycobacterium tuberculosis (Mtb
- Lu, Xiaoyun,Wan, Baojie,Franzblau, Scott G.,You, Qidong
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experimental part
p. 3551 - 3563
(2011/10/19)
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- Four-component synthesis of functionalized 2,2′-bipyridines based on the Blaise reaction
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In situ C-acylation of the Blaise intermediate - as reported by Lee and coworkers - provides α-acyl-β-enamino esters that are versatile building blocks for the preparation of N-heterocycles. The corresponding N-acylated β-ketoenamides can be employed in the synthesis of 4-hydroxypyridine derivatives. N-Acylation of the α-acyl-β-enamino esters with 2-picolyl chloride furnished β-ketoenamides, and the subsequent TMSOTf/base-promoted intramolecular condensation reaction led to 4-hydroxy-2,2′-bipyridine derivatives. Conversion into 2,2′-bipyrid-4-yl nonaflates allowed further functionalization such as palladium-catalyzed coupling reactions. Georg Thieme Verlag Stuttgart - New York.
- Hommes, Paul,Jungk, Phillip,Reissig, Hans-Ulrich
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experimental part
p. 2311 - 2314
(2011/10/31)
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- Synthesis, biological evaluation and molecular docking studies of 1,3,4-thiadiazole derivatives containing 1,4-benzodioxan as potential antitumor agents
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A series of 1,3,4-thiadiazole derivatives containing 1,4-benzodioxan (2a-2s) have been synthesized to screen for FAK inhibitory activity. Compound 2p showed the most potent biological activity against HEPG2 cancer cell line (EC50 = 10.28 μg/mL
- Sun, Juan,Yang, Yu-Shun,Li, Wei,Zhang, Yan-Bin,Wang, Xiao-Liang,Tang, Jian-Feng,Zhu, Hai-Liang
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scheme or table
p. 6116 - 6121
(2011/10/31)
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- Acid-induced conformational alteration of cis-preferential aromatic amides bearing N-methyl-N-(2-pyridyl) moiety
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A series of cis-preferential aromatic N-methyl amides was designed and synthesized, and acid-induced conformational alteration of these compounds was investigated by means of NMR measurements in solution and X-ray crystal structure analysis. Compounds with a terminal N-methyl-N-(2-pyridyl) amide unit showed acid-induced conformational change from cis to trans, while those with a terminal N-methyl-2-pyridinecarboxamide unit showed a change of the carbonyl orientation from anti to syn with retention of cis conformation.
- Okamoto, Iwao,Terashima, Masayuki,Masu, Hyuma,Nabeta, Mayumi,Ono, Kaori,Morita, Nobuyoshi,Katagiri, Kosuke,Azumaya, Isao,Tamura, Osamu
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experimental part
p. 8536 - 8543
(2011/11/28)
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- Synthesis and docking study of 2-phenylaminopyrimidine Abl tyrosine kinase inhibitors
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Six analogs of imatinib, an Abl kinase inhibitor clinically used as a first-line therapeutic agent for chronic myeloid leukaemia (CML), have been synthesized and characterized. And their potency as Abl kinase inhibitors have been screened by a robust virt
- Lü, Shuang,Luo, Qun,Hao, Xiang,Li, Xianchan,Ji, Liyun,Zheng, Wei,Wang, Fuyi
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experimental part
p. 6964 - 6968
(2012/01/05)
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- NITROGEN CONTAINING HETEROARYL COMPOUNDS
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The invention is concerned with novel nitrogen-containing heteroaryl compounds of formula (I) wherein A1, A2, (a), R1, R2, R3, R4, R5 and R6 are as defined in the desc
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-
Page/Page column 161; 162
(2012/01/04)
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- Diastereoselective assembly of pentanuclear circular helicates
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Reaction of a ligand which contains two N-donor and O-donor tridentate domains separated by a 1,3-phenylene spacer unit with Zn2+ ions results in a pentanuclear circular helicate [Zn5(L)5] 10+ and this structure
- Clegg, Oliver R.,Fennessy, Rebecca V.,Harding, Lindsay P.,Rice, Craig. R.,Riis-Johannessen,Fletcher, Nicholas C.
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experimental part
p. 12381 - 12387
(2012/01/31)
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- Synthesis, crystal structure, and in vitro antitumor activities of copper(II) complexes containing tetradentate pyridine-based ligands
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Several new Cu(II) complexes of Schiff bases obtained by condensation of 2-[N-(α-picolyl)-amino]-benzophenone with different chiral amino acids were synthesized and characterized by physico-chemical and spectroscopic methods. The crystal structure of one
- Yang, Xin-Tao,Wu, Hao,Ma, Shi-Jun,Hu, Juan-Juan,Wang, Yong-Mei
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experimental part
p. 403 - 407
(2012/03/08)
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- Single-pot conversion of an acid to the corresponding 4-chlorobutyl ester
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A single pot conversion of carboxylic acids into the corresponding 4-chlorobutyl esters has been achieved by a novel procedure. The intermediate acid chlorides are not isolated. The double bond and aromatic methoxy group survive the mild reaction conditions. In almost all the examples studied the products are purified by simple flash chromatography.
- Pal, Sutanuka,Pal, Sudhir Chandra
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experimental part
p. 596 - 599
(2012/04/18)
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- An NBD-based sensitive and selective fluorescent sensor for copper(II) ion
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A new 7-nitrobenz-2-oxa-1,3-diazole (NBD) derived fluorescent probe (1) exhibiting high selectivity for Cu2+ detection, produced significant fluorescence quenching in the presence of Cu2+ ion, while the metal ions Ca2+, Cd2+, Co2+, Fe2+, Hg 2+, Mg2+, Mn2+, Ni2+ and Zn 2+ produced only minor changes in fluorescence. The apparent association constant (Ka) for Cu2+ binding in chemosensor 1 was found to be 1.22 × 103 M-1. The maximum fluorescence quenching activity caused by Cu2+ binding to 1 was observed over the pH range 6-10. Springer Science+Business Media, LLC 2009.
- Liu, Shi-Rong,Wu, Shu-Pao
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experimental part
p. 1599 - 1605
(2012/06/29)
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- METHODS FOR PREPARING AMIDE DERIVATIVES
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The present invention provides a novel method for preparing an amide derivative. The method of the present invention enables to economically prepare various amide derivatives containing pranlukart by reacting a carboxylic acid derivative 5 and an amine derivative through a brief procedure compared with a conventional technology, and permits to obtain a final product at a high yield rate because it is feasible to eliminate by-products after termination of reactions. Accordingly, the present method is to be quite suitable for massive production.
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Page/Page column 23
(2010/04/03)
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- Design and synthesis of 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles and pyrazolo[3,4-b]pyridines for Aurora-A kinase inhibitors
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Two series of 3-aminopyrazole compounds including 24 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles and 16 pyrazolo[3,4-b]pyridines were synthesized and evaluated against HCT116, A549, and A2780 tumor cell lines. Among them, three compounds were found to have the ideal anti-proliferative activities in vitro. Docking experiments showed that the novel pyrazolo[3,4-b]pyridines share the similar interaction mode with Aurora-A kinase as PHA739358.
- Shi, Jianyou,Xu, Guobin,Zhu, Wei,Ye, Haoyu,Yang, Shengyong,Luo, Youfu,Han, Jing,Yang, Jincheng,Li, Rui,Wei, Yuquan,Chen, Lijuan
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supporting information; experimental part
p. 4273 - 4278
(2010/09/04)
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- N -((1-benzyl-1 H -1,2,3-triazol-4-yl)methyl)arylamide as a new scaffold that provides rapid access to antimicrotubule agents: Synthesis and evaluation of antiproliferative activity against select cancer cell lines
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A series of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamides was synthesized by copper-catalyzed azide-alkyne cycloaddition (CuAAC) and afforded inhibitors of cancer cell growth. For example, compound 13e had an IC 50 of 46 nM against MCF-7 human breast tumor cells. Structure-activity relationship (SAR) studies demonstrated that (i) meta-phenoxy substitution of the N-1-benzyl group is important for antiproliferative activity and (ii) a variety of heterocyclic substitutions for the aryl group of the arylamide are tolerated. In silico COMPARE analysis of antiproliferative activity against the NCI-60 human tumor cell line panel revealed a correlation to clinically useful antimicrotubule agents such as paclitaxel and vincristine. This in silico correlation was supported by (i) in vitro inhibition of tubulin polymerization, (ii) G2/M-phase arrest in HeLa cells as assessed by flow cytometry, and (iii) perturbation of normal microtubule activity in HeLa cells as observed by confocal microscopy. The results demonstrate that N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamide is a readily accessible small molecule scaffold for compounds that inhibit tubulin polymerization and tumor cell growth.
- Stefely, Jonathan A.,Palchaudhuri, Rahul,Miller, Patricia A.,Peterson, Rebecca J.,Moraski, Garrett C.,Hergenrother, Paul J.,Miller, Marvin J.
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supporting information; experimental part
p. 3389 - 3395
(2010/09/04)
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