- Synthesis, structure-activity relationships, and antitumor studies of 2-benzoxazolyl hydrazones derived from alpha-(N)-acyl heteroaromatics
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Recently we have described the antitumor activities of 2- benzoxazolylhydrazones derived from 2-formyl and 2-acetylpyridines. In search of a more efficacious analogue, compounds in which the 2-acetylpyridine moiety has been replaced by 2-acylpyridine and α-(N)-acetyldiazine/quinoline groups have been synthesized. The 2-acylpyridyl hydrazones inhibited in vitro cell proliferation in the nM range, whereas the hydrazones derived from the α-(N)-acetyldiazines/quinolines inhibited cell growth in the μM range. Compounds tested in the NCI-60 cell assay were effective inhibitors of leukemia, colon, and ovarian cancer cells. E-13k [N-benzoxazol-2-yl-N′-(1- isoquinolin-3-yl-ethylidene)-hydrazine] inhibited the proliferation of MCF-7 breast carcinoma cells more efficiently than nontransformed MCF-10A cells. It is not transported by P-glycoprotein and a weak MRP substrate. Increased concentrations of serum or α1-acid glycoprotein did not reduce the antiproliferative activity of the compound. In the in vivo hollow fiber assay, E-13k achieved a score of 24, with a net cell kill of OVCAR-3 (ovarian) and SF2-95 (CNS) tumor cells.
- Easmon, Johnny,Pürstinger, Gerhard,Thies, Katrin-Sofia,Heinisch, Gottfried,Hofmann, Johann
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- Site-Selective Pd-Catalyzed C(sp3)?H Arylation of Heteroaromatic Ketones
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A ligand-controlled site-selective C(sp3)?H arylation of heteroaromatic ketones has been developed using Pd catalysis. The reaction occurred selectively at the α- or β-position of the ketone side-chain. The switch from α- to β-arylation was realized by addition of a pyridone ligand. The α-arylation process showed broad scope and high site- and chemoselectivity, whereas the β-arylation was more limited. Mechanistic investigations suggested that α-arylation occurs through C?H activation/oxidative addition/reductive elimination whereas β-arylation involves desaturation and aryl insertion.
- Kudashev, Anton,Baudoin, Olivier
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supporting information
p. 17688 - 17694
(2021/11/16)
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- Catalytic α-Deracemization of Ketones Enabled by Photoredox Deprotonation and Enantioselective Protonation
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This study reports the catalytic deracemization of ketones bearing stereocenters in the α-position in a single reaction via deprotonation, followed by enantioselective protonation. The principle of microscopic reversibility, which has previously rendered this strategy elusive, is overcome by a photoredox deprotonation through single electron transfer and subsequent hydrogen atom transfer (HAT). Specifically, the irradiation of racemic pyridylketones in the presence of a single photocatalyst and a tertiary amine provides nonracemic carbonyl compounds with up to 97% enantiomeric excess. The photocatalyst harvests the visible light, induces the redox process, and is responsible for the asymmetric induction, while the amine serves as a single electron donor, HAT reagent, and proton source. This conceptually simple light-driven strategy of coupling a photoredox deprotonation with a stereocontrolled protonation, in conjunction with an enrichment process, serves as a blueprint for other deracemizations of ubiquitous carbonyl compounds.
- Zhang, Chenhao,Gao, Anthony Z.,Nie, Xin,Ye, Chen-Xi,Ivlev, Sergei I.,Chen, Shuming,Meggers, Eric
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supporting information
p. 13393 - 13400
(2021/09/03)
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- Pd-Catalyzed Alkylation of (Iso)quinolines and Arenes: 2-Acylpyridine Compounds as Alkylation Reagents
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The first Pd-catalyzed alkylation of (iso)quinolines and arenes is reported. The readily available and bench-stable 2-acylpyridine compounds were used as an alkylation reagent to form the structurally versatile alkylated (iso)quinolines and arenes. The method affords a convenient pathway for the introduction of alkyl groups into organic molecules.
- Wu, Qingsong,Han, Shuaijun,Ren, Xiaoxiao,Lu, Hongtao,Li, Jingya,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
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supporting information
p. 6345 - 6348
(2018/10/20)
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- Engineering an iridium-containing metal-organic molecular capsule for induced-fit geometrical conversion and dual catalysis
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By introducing photoactive fac-tris(2-phenylpyridine)iridium moieties as a ligand backbone to constrain the coordination geometry of cobalt ions, a multifunctional Ir2Co3-type capsule was achieved and showed induced-fit capsule-capsule conversion by cooperative binding one carbonate anion with the equatorial Co(ii) centers. The capsule combined photocatalysis and transition metal activation synergistically and exhibited efficient catalytic ability on visible light-activated α-trichloromethylation.
- Li, Xuezhao,Wu, Jinguo,Chen, Liyong,Zhong, Xiaoming,He, Cheng,Zhang, Rong,Duan, Chunying
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supporting information
p. 9628 - 9631
(2016/08/04)
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- SUBSTITUTED AMINOTHIAZOLES AS INHIBITORS OF CANCERS, INCLUDING HEPATOCELLULAR CARCINOMA, AND AS INHIBITORS OF HEPATITIS VIRUS REPLICATION
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Pharmaceutical compositions of the invention are presented which comprise substiuted aminothiazoles derivatives. The substiuted aminothiazoles derivatives have a disease-modifying action in the treatment of diseases associated with unregulated cell growth. Such diseases include cancers such as hepatocellular carcinoma, and viral infections from a hepatitis virus.
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Paragraph 0140; 0141; 0150; 0151
(2013/04/24)
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- Solubility and transfer processes of some hydrazones in biologically relevant solvents
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Solubility values of 20 hydrazones in water, 1-octanol and hexane were determined by the isothermal saturation method. Thermophysical characteristics of fusion processes (melting points and fusion enthalpies) of the selected substances were measured by DS
- Perlovich, German L.,Kazachenko, Vladimir P.,Strakhova, Nadezda N.,Schaper, Klaus-J.,Raevsky, Oleg A.
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p. 2659 - 2667
(2013/09/24)
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- THIAZOLYL COMPOUNDS USEFUL AS KINASE INHIBITORS
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The invention provides compounds of formula I [INSERT CHEMICAL STRUCTURE HERE] (I) and pharmaceutically acceptable salts thereof. The formula I thiazolyl compounds inhibit tyrosine kinase activity thereby making them useful as anticancer agents and for the treatment of Alzheimer's Disease.
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Page/Page column 23
(2010/03/31)
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- A new and highly efficient water-soluble copper complex for the oxidation of secondary 1-heteroaryl alcohols by tert-butyl hydroperoxide
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The water-soluble copper complex generated in situ from CuCl2 and 2,2′-biquinoline-4,4′-dicarboxylic acid dipotassium salt (BQC), has been revealed as a highly efficient and selective catalyst for the oxidation of secondary 1-heteroaryl alcohols to the corresponding heteroaromatic ketones with aqueous tert-butyl hydroperoxide, under mild conditions. The catalytic system is compatible with different heterocycles such as pyridines, pyrroles, indoles, thiophens, furans, thiazoles, and imidazoles.
- Boudreau, Josée,Doucette, Mike,Ajjou, Abdelaziz Nait
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p. 1695 - 1698
(2007/10/03)
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- Mesoions and ketene valence isomers. Pyrrolo[1,2-a]pyridinylium olates and (2-pyridyl)carbonylketenes
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The synthesis and isolation of the pyrrolopyridinium olate system was discussed. The zwitterionic compounds were obtained by flash vacuum thermolysis (FVT) of picolinoylacetates. Nucleophilic addition reactions of zwitterionic compounds occurred by C-N bond cleavage to afford pyridine derivatives. The kinetic monitoring of such reactions revealed that they have extremely low activation enthalpies and very large negative activation entropies.
- Ye, Xuan,Andraos, John,Bibas, Herve,Wong, Ming Wah,Wentrup, Curt
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p. 401 - 406
(2007/10/03)
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- Triplet states mediating hydrogen abstraction in 4-acylpyrimidines, 2-acylpyridines, 2-acylpyrazines, and 3-acylpyridazines
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Irradiation of 9 leads to hydrogen abstraction by N(1) and fragmentation to 8 from a triplet with ET ~78 kcal/mol. Irradiation of 2-acylpyridines (10) leads to abstraction by both nitrogen and oxygen (cf. eq 4), with the same Stern-Volmer kqτ for the two processes. Irradiation of 2-acylpyrazines (11) can lead to abstraction by either nitrogen (φ27 0.77 from 11b) or oxygen (φ11a 0.95 from 11f)- 3-Acylpyridazine 12d is unreactive on direct irradiation or triplet sensitization with sensitizer ET ~70 kcal/mol; it furnishes a small amount of 12a on sensitization by acetone. Ketone 18 is recovered unchanged from irradiation under all conditions used with 12d. These observations suggest a correlation between the photochemistry of each of these compounds and the energy of the nπ* triplet of the heteroaromatic ring. The nature of the excited state(s) responsible for hydrogen abstraction by nitrogen and oxygen in these ketones is discussed.
- Prathapan, Sreedharan,Robinson, Kevin E.,Agosta, William C.
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p. 1838 - 1843
(2007/10/02)
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- Etude de l'action des organomagnesiens sur les derives carboxyliques de la pyridine
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Reactions of Grignard reagents with pyridinecarboxylic esters 1, 2, pyridine-2-carboxylic acid (3), and 2,3-pyridinecarboxylic acid anhydride (5) show regioselectivity at the carbonyl in position 2.This is exemplified by an efficient synthesis of 7,7-dial
- Canonne, P.,Belley, M.
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p. 1885 - 1890
(2007/10/02)
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- NADH MODELS-19 CYCLOPROPANE RING AS A CHEMICAL PROBE IN THE STUDY OF THE MECHANISM OF HYDROGEN TRANSFER BY 1,4-DIHYDROPYRIDINE DERIVATIVES
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N-(Cyclopropylmethylene)phenylamines (1a-c), cyclopropyl 2-pyridyl ketones (5a-c) and ethyl cyclopropylmethylenepyruvate (14) have been subjected to reduction by 1,4-dihydropyridines in the presence of magnesium ions, and by tin hydrides.The reactions with 1,4-dihydropyridines do not involve cleavage of the three-membered ring in the reduction step.The observed acyclic product from 2-pyridyl 2,2-dimethylcyclopropyl ketone (5b) is a consequence of ring cleavage prior to reduction of the carbonyl function.In contrast, reduction of 1a-c and 5a-c by tin hydrides leads to products in which the cyclopropane moiety has undergone ring-opening.These findings support a hydride transfer mechanism for reductions with NADH models.
- Meijer, Louis H. P.,van Niel, Johannes C. G.,Pandit, Upendra K.
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p. 5185 - 5196
(2007/10/02)
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- 2-Acetylpyridine thiosemicarbazones. VI. 2-acetylpyridine and 2-butyrylpyridine thiosemicarbazones as antileukemic agents
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N4-Monosubstituted and N4,N4-disubstituted thiosemicarbazones derived from 2-acetylpyridine, 2-acetyl-6-methylpyridine and 2-butylrylpyridine, and N4,N4-disubstituted selenosemicarbazones derived from 2-acetylpyridine were evaluated against leukemia P388 in the mouse. Significant antitumor activity (T/C > 125%) was observed for members of each class. Enhancement of antitumor activity resulted from increasing the size of the N4-substituent of the thiosemicarbazone moiety. Selenosemicarbazones were less active than the corresponding thiosemicarbazones.
- Klayman,Scovill,Mason,Bartosevich,Bruce,Lin
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p. 909 - 912
(2007/10/02)
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