- Investigation of the possible pharmacologically active forms of the nicotinic acetylcholine receptor agonist anabaseine
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Three major forms of the nicotinic agonist toxin anabaseine (cyclic iminium, cyclic imine and the monocationic open-chain ammonium-ketone) co-exist in almost equal concentrations at physiological pH.We asked the question: Which of these forms is pharmacologically active? First, we investigated the pH dependence of anabaseine inhibition of [3H]-methylcarbamylcholine binding at rat brain α4β2 nicotinic acetylcholine receptors (nAChRs). These experiments indicated that one or both monocationic forms interact with the orthosteric binding site for ACh. However, since they occur at equal concentrations near physiological pH, we employed another approach, preparing a stable analog of each form and examining its agonist activities and binding affinities at several vertebrate brain and neuromuscular nAChRs. Only 2-(3-pyridyl)-1,4,5,6-tetrahydropyrimidine monohydrogen chloride (PTHP), the cyclic iminium analog, displayed nAChR potencies and binding affinities similar to anabaseine. The cyclic imine analog 2,3'-bipyridyl and the open-chain ammonium-ketone analog 5-methylamino-1-(3-pyridyl)-1-pentanone (MAPP), displayed ≤1% of the activity predicted if the one form was solely active. The lower potency of weakly basic 2,3'-bipyridyl can be explained by the presence of a small concentration of its monocationic form. Since the open chain ammonium-ketone monocationic form of anabaseine has some structural similarity to the neurotransmitter GABA, we also tested the ability of anabaseine and its 1,2-dehydropyrrolidinyl analog myosmine to activate a mammalian GABAA receptor, but no activity was detected. We conclude that the monocationic cyclic iminium is the form which avidly binds and activates vertebrate nAChRs.
- Andrud, Kristin,Xing, Hong,Gabrielsen, Bjarne,Bloom, Linda,Mahnir, Vladimir,Lee, Stephen,Green, Benedict T.,Lindstrom, Jon,Kem, William
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Read Online
- Continuous Flow as Enabling Technology: Synthesis of Heteroaromatic Sulfinates as Bench Stable Cross-Coupling Partners
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An enabling continuous flow setup for handling of unstable organolithium intermediates and synthesis of heteroaryl sulfinates on a multigram scale is described. The developed continuous flow process allows for the synthesis and simple isolation of heteroaryl sulfinates which are otherwise challenging to access in classical batch mode. The lithium sulfinate salts prepared by this method were shown to be efficient reaction partners in palladium catalyzed C(sp2)-C(sp2) cross-coupling to access medicinally relevant bis-heteroaryl motifs.
- Lima, Fabio,André, Jér?me,Marziale, Alexander,Greb, Andreas,Glowienke, Susanne,Meisenbach, Mark,Schenkel, Berthold,Martin, Benjamin,Sedelmeier, Joerg
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Read Online
- Nicotine-related alkaloids and metabolites as inhibitors of human cytochrome P-450 2A6
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S-(-)-Nicotine and 13 of the most prevalent nicotine-related alkaloids and metabolites (i.e., S-(-)-nornicotine, myosmine, β-nicotyrine, S-cotinine, S-norcotinine, S-(-)-nicotine N-1′-oxide, S-(-)-nicotine Δ 1′-5′-iminium ion, S-(-)-anabasine,
- Denton, Travis T.,Zhang, Xiaodong,Cashman, John R.
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Read Online
- Base-Activated Latent Heteroaromatic Sulfinates as Nucleophilic Coupling Partners in Palladium-Catalyzed Cross-Coupling Reactions
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Heteroaromatic sulfinates are effective nucleophilic reagents in Pd0-catalyzed cross-coupling reactions with aryl halides. However, metal sulfinate salts can be challenging to purify, solubilize in reaction media, and are not tolerant to multi-step transformations. Here we introduce base-activated, latent sulfinate reagents: β-nitrile and β-ester sulfones. We show that under the cross-coupling conditions, these species generate the sulfinate salt in situ, which then undergo efficient palladium-catalyzed desulfinative cross-coupling with (hetero)aryl bromides to deliver a broad range of biaryls. These latent sulfinate reagents have proven to be stable through multi-step substrate elaboration, and amenable to scale-up.
- Blakemore, David C.,Cook, Xinlan A. F.,Moses, Ian B.,Pantaine, Lo?c R. E.,Sach, Neal W.,Shavnya, Andre,Willis, Michael C.
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p. 22461 - 22468
(2021/09/09)
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- Ligand-to-metal charge transfer of a pyridine surface complex on TiO2for selective dehydrogenative cross-coupling with benzene
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Dehydrogenative cross-coupling (DCC) between pyridine and benzene proceeded selectively using a TiO2 photocatalyst under visible light irradiation at optimized concentrations of the substrates. Visible light induces ligand-to-metal charge transfer (LMCT) between pyridine and a TiO2 surface to give a pyridine radical cation, which produces a pyridyl radical by its deprotonation or oxidation of another pyridine molecule. The pyridyl radical attacks a benzene ring to form an sp2C-sp2C bond and a hydrogen atom is subsequently removed to complete DCC. Selective excitation of the pyridine LMCT complex in the presence of an excess amount of benzene would be the key for higher selectivity. This journal is
- Hishitani, Shinichiro,Naniwa, Shimpei,Yamamoto, Akira,Yoshida, Hisao
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p. 11366 - 11373
(2021/05/31)
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- Synthesis of Bis-heteroaryls Using Grignard Reagents and Pyridylsulfonium Salts
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Herein are reported ligand-coupling reactions of Grignard reagents with pyridylsulfonium salts. The method has wide functional group tolerance and enables the formation of bis-heterocycle linkages, including 2,4′-, 2,3′-, and 2,2′-bipyridines, as well as pyridines linked to pyrimidines, pyrazines, isoxazoles, and benzothiophenes. The methodology was successfully applied to the synthesis of the natural products caerulomycin A and E.
- Horan, Alexandra M.,Duong, Vincent K.,McGarrigle, Eoghan M.
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supporting information
p. 9089 - 9093
(2021/11/30)
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- Synthesis of Pyridylsulfonium Salts and Their Application in the Formation of Functionalized Bipyridines
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An S-selective arylation of pyridylsulfides with good functional group tolerance was developed. To demonstrate synthetic utility, the resulting pyridylsulfonium salts were used in a scalable transition-metal-free coupling protocol, yielding functionalized bipyridines with extensive functional group tolerance. This modular methodology permits selective introduction of functional groups from commercially available pyridyl halides, furnishing symmetrical and unsymmetrical 2,2′- A nd 2,3′-bipyridines. Iterative application of the methodology enabled the synthesis of a functionalized terpyridine with three different pyridine components.
- Duong, Vincent K.,Horan, Alexandra M.,McGarrigle, Eoghan M.
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p. 8451 - 8457
(2020/11/12)
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- Sulfur(IV)-Mediated Unsymmetrical Heterocycle Cross-Couplings
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Despite the tremendous utilities of metal-mediated cross-couplings in modern organic chemistry, coupling reactions involving nitrogenous heteroarenes remain a challenging undertaking – coordination of Lewis basic atoms into metal centers often necessitate elevated temperature, high catalyst loading, etc. Herein, we report a sulfur (IV) mediated cross-coupling amendable for the efficient synthesis of heteroaromatic substrates. Addition of heteroaryl nucleophiles to a simple, readily-accessible alkyl sulfinyl (IV) chloride allows formation of a trigonal bipyramidal sulfurane intermediate. Reductive elimination therefrom provides bis-heteroaryl products in a practical and efficient fashion.
- Zhou, Min,Tsien, Jet,Qin, Tian
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p. 7372 - 7376
(2020/04/09)
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- Visible-light photoexcitation of pyridine surface complex, leading to selective dehydrogenative cross-coupling with cyclohexane
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Upon photoirradiation with visible light, a pyridine molecule adsorbed on a TiO2 surface can be photoexcited to give a pyridine radical cation via ligand-to-metal charge transfer (LMCT) between pyridine and titanium. This leads to dehydrogenative cross-coupling (DCC) between pyridine and cyclohexane with concomitant hydrogen evolution. Since the radical cation can selectively oxidize cyclohexane to a cyclohexyl radical, the cross-coupling between pyridine and cyclohexane proceeds with higher selectivity compared with that in photocatalysis by TiO2 under UV irradiation.
- Naniwa, Shimpei,Tyagi, Akanksha,Yamamoto, Akira,Yoshida, Hisao
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p. 28375 - 28381
(2018/11/30)
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- Pyridine sulfinates as general nucleophilic coupling partners in palladium-catalyzed cross-coupling reactions with aryl halides
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Pyridine rings are ubiquitous in drug molecules; however, the pre-eminent reaction used to form carbon-carbon bonds in the pharmaceutical industry, the Suzuki-Miyaura cross-coupling reaction, often fails when applied to these structures. This phenomenon is most pronounced in 2-substituted pyridines, and results from the difficulty in preparing, the poor stability of, and low efficiency in reactions of pyridine-2-boronates. We demonstrate that by replacing these boronates with pyridine-2-sulfinates, a cross-coupling process of unrivalled scope and utility is realized. The corresponding 3-And 4-substituted pyridine variants are also efficient coupling partners. In addition, we apply these sulfinates in a library format to the preparation of medicinally relevant derivatives of the drugs varenicline (Chantix) and mepyramine (Anthisan).
- Markovic, Tim,Rocke, Benjamin N.,Blakemore, David C.,Mascitti, Vincent,Willis, Michael C.
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p. 4437 - 4442
(2017/07/11)
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- Au-complex containing phosphino and imidazolyl moieties as a bi-functional catalyst for one-pot synthesis of pyridine derivatives
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The complex of Au-L1 containing imidazolyl ring and the phosphine-ligated-Au moiety was synthesized and applied as the efficient bi-functional catalyst for the one-pot sequential condensation/annulation reaction for the synthesis of pyridine derivatives. It was found that, as for Au-L1, the involved imidazolyl group acted as a Lewis base to catalyze the condensation of carbonyl compounds with propargylamine to form the imino intermediate, and the involved Au+-complex species with alkynophilicity corresponded to the subsequent activation of imino-tailed alkynyl to afford dehydropyridine intermediate. The latter proceeded auto-oxidation reaction to afford the pyridine derivatives. The observed sequential catalysis over Au-L1 proved more efficient than that over the mechanical mixtures of the Au-complex (Au-L2) and N-methylimidazole, because the free N-methylimidazole as an N-containing donor competed with the alkyne substrate to coordinate to Au-center. Moreover, Au-L1 exhibited good generality to a wide range of the substrates for the synthesis of 2,3-fused pyridine derivatives and 2-aryl(heteroaryl)-substituted pyridines.
- Yang, Da,Liu, Huan,Wang, Dong-Liang,Lu, Yong,Zhao, Xiao-Li,Liu, Ye
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p. 323 - 330
(2016/09/23)
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- Pd(II)-Catalyzed C3-Selective Arylation of Pyridine with (Hetero)arenes
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Palladium catalyzed, nondirected C3-selective arylation of pyridines with arenes and heteroarenes in the presence of 1,10-phenanthroline as the ligand has been developed. The optimized conditions allow for a highly C3-selective arylation of pyridines, affording various 3,3′-bipyridines and 3-arylpyridines. (Chemical Equation Presented).
- Gao, Guo-Lin,Xia, Wujiong,Jain, Pankaj,Yu, Jin-Quan
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supporting information
p. 744 - 747
(2016/03/01)
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- Metal-free oxidative cyclization of acetophenones with diamines: A facile access to phenylpyridines
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An efficient metal-free access to 2- and 3-phenylpyridines via oxidative coupling of acetophenones or phenylacetones with 1,3-diaminopropane has been described. The reaction involves shorter reaction time, excellent yields and a broad substrate scope. The reaction proceeds via the formation of imine, which further undergoes oxidative C-N bond cleavage, C-C bond formation and oxidation to give a pyridine skeleton. The quantum chemical calculations identified the transition state for the reaction and helped in tracing the reaction mechanism.
- Sharma, Rohit,Patel, Neha,Vishwakarma, Ram A.,Bharatam, Prasad V.,Bharate, Sandip B.
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supporting information
p. 1009 - 1012
(2016/01/16)
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- Palladium-catalyzed decarboxylative cross-coupling of 3-pyridyl and 4-pyridyl carboxylates with aryl bromides
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Decarboxylative cross-coupling of 3-pyridyl and 4-pyridyl carboxylates with aryl bromides is reported. Using a bimetallic system of Cu2O and Pd(PPh3)4, the scope of the reaction is demonstrated by the synthesis of 27 pyridine-containing biaryls in moderate to good yields.
- Chennamaneni, Lohitha Rao,William, Anthony D.,Johannes, Charles W.
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p. 1293 - 1296
(2015/03/04)
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- Aerobic C-N bond activation: A simple strategy to construct pyridines and quinolines
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Inspired by the autoxidation processes, a dioxygen induced C-N bond activation of primary alkyl amines was demonstrated toward the synthesis of pyridines and quinolines. The transition-metal free conditions with O2 as the sole oxidant make this transformation very attractive. Notably, the substrate applicability of different kinds of ketones is greatly broadened for this transformation.
- Wu, Kun,Huang, Zhiliang,Liu, Chao,Zhang, Heng,Lei, Aiwen
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supporting information
p. 2286 - 2289
(2015/02/05)
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- ORGANIC ELECTROLUMINESCENT MATERIALS AND DEVICES
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Disclosed are a compound including a ligand L_A of chemical formula I, and a preparation and a device containing the compound of the chemical formula I. In the compound having a ligand L_A of chemical formula I, R^1 is monosubstitution, bisubstitution, or non-substitution, R^2 is monosubstitution, bisubstitution, trisubstituion, tetrasubstitution, or non-substitution, R is selected from hydrogen, deuterium, alkyl, cycloalkyl, and combination of the same, and R^1 and R^2 are dependently selected from hydrogen, deuterium, alkyl, cycloalkyl, aryl, and combination of the same, a random adjacent substituent of R^2 is randomly connected to form a condensed ring, the ligand L_A is coordinately bonded to metal M, and the ligand L_A is randomly connected to another ligand, and includes a tridentate, tetradentate, pentadentate, and hexadentate.COPYRIGHT KIPO 2015
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Paragraph 0231; 0232
(2016/11/17)
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- General suzuki coupling of heteroaryl bromides by using tri-tert-butylphosphine as a supporting ligand
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A general procedure for the fast Suzuki coupling of major families of heteroaryl bromides was realized by using Pd(OAc)2/PtBu3 as the catalyst. Many couplings were finished within minutes at room temperature in n-butanol. Different from previous studies, three typical heteroaryl bromides were systematically examined in couplings of various heteroaryl and aryl boronic acids. A fast, general coupling of heteroaryl bromides is realized by using a single palladium catalyst supported by tri-tert-butylphosphine.
- Zou, Yinjun,Yue, Guizhou,Xu, Jianwei,Zhou, Jianrong
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supporting information
p. 5901 - 5905
(2015/03/30)
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- Palladacycle-catalyzed Suzuki-Miyaura reaction of aryl/heteroaryl halides with MIDA boronates in EtOH/H2O or H2O
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With good to excellent yields, a series of mono- or diheteroaryl compounds were synthesized via the palladacycle-catalyzed Suzuki-Miyaura reaction of various N-methyliminodiacetic acid (MIDA) boronates with aryl/heteroaryl halides in EtOH/H2O or H2O. This journal is the Partner Organisations 2014.
- Li, Yabo,Wang, Jingran,Wang, Zhiwei,Huang, Mengmeng,Yan, Beiqi,Cui, Xiuling,Wu, Yusheng,Wu, Yangjie
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p. 36262 - 36266
(2014/11/08)
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- Palladium(II) complexes with salicylideneimine based tridentate ligand and triphenylphosphine: Synthesis, structure and catalytic activity in Suzuki-Miyaura cross coupling reactions
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Square planar palladium(II) complexes of the type [Pd(L)(PPh3)] (1-6) (where L is the dianion of N-(2-mercaptophenyl)salicylideneimine or 5-substituted-N-(2-mercaptophenyl)salicylideneimine or N-(2-mercaptophenyl) naphthylideneimine) have been synthesised from the reactions between [Pd(PPh3)4] and H2L in dichloromethane-ethanol mixture. The new complexes have been characterized by analytical and spectral (electronic, IR, 1H, 13C{1H} and 31P{1H} NMR spectroscopy) techniques. The structures of three complexes (1, 2 and 6) have been solved by single-crystal X-ray diffraction experiments which indicate square planar coordination geometries around palladium(II) by O, N, S and P donor atoms. The palladium(II) complexes (1-6) exhibited good catalytic activity in Suzuki-Miyaura cross-coupling reaction between phenylboronic acid and 4-bromotoluene in N,N-dimethylacetamide at 100 °C. Complex 3 (1 mol%) was found to be the most active and hence was used for probing the scope of possible substrates. Heterocyclic boronic acid and heterocyclic aryl bromides have also been used as substrates to provide heterocyclic biaryls.
- Muthu Tamizh, Manoharan,Cooper, Benjamin F.T.,MacDonald, Charles L.B.,Karvembu, Ramasamy
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p. 391 - 400
(2013/03/13)
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- Tetraphosphine/palladium-catalyzed Suzuki-Miyaura coupling of heteroaryl halides with 3-pyridine- and 3-thiopheneboronic acid: An efficient catalyst for the formation of biheteroaryls
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An easily prepared tetraphosphine N,N,N′,N′- tetra(diphenylphosphinomethyl)-1,2-ethylenediamine (L1) associated with [Pd(η3-C3H5)Cl]2 affords an efficient catalyst for Suzuki-Miyaura coupling of 3-pyridineboronic acid with heteroaryl bromides. Reaction could be performed with as little as 0.02 mol% catalyst and a high turnover number of 2500 is obtained. A wide range of substrates is investigated with satisfactory yields, and good compatibility with aminogroup-substituted pyridines and unprotected indole is exhibited. This protocol can also be applied successfully to the reaction of heteroaryl bromides with 3-thiopheneboronic acid. This Pd-tetraphosphine catalyst efficiently restrains the poisoning effect from heteroaryls, and shows good stability and longevity. Copyright 2013 John Wiley & Sons, Ltd. An easily prepared tetraphosphine L1 was successfully used in Pd catalyzed Suzuki reaction of heteroaryl bromides with 3-pyridineboronic acid. A high turnover number of 2 500 was achieved and a wide range of heteroaryl halides including aminopyridines and indole was tolerated. With this protocol the coupling of 3-thiopheneboronic acid with heteroaryl bromides could also proceed in good yields. This catalyst system efficiently restrained poisoning effect from heteroaryls, and exhibited good stability and longevity. Copyright
- Wang, Kun,Fu, Qi,Zhou, Rong,Zheng, Xueli,Fu, Haiyan,Chen, Hua,Li, Ruixiang
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p. 232 - 238
(2013/05/08)
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- Arylation of 2-substituted pyridines via Pd-catalyzed decarboxylative cross-coupling reactions of 2-picolinic acid
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The novel palladium-catalyzed decarboxylative cross-coupling reactions of 2-picolinic acid with aryl and heteroaryl bromides including benzenes, naphthalenes, pyridines and quinolines for C-C bond formation have been successfully achieved. This journal is
- Li, Xinjian,Zou, Dapeng,Leng, Faqiang,Sun, Chunxia,Li, Jingya,Wu, Yangjie,Wu, Yusheng
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supporting information
p. 312 - 314
(2013/02/22)
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- Remarkable catalytic activity of [PdCl2(CH3CN) 2] in Suzuki-Miyaura cross-coupling reaction in aqueous media under mild conditions
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[PdCl2(CH3CN)2] (2 mol%) was found to be an efficient catalyst for the Suzuki-Miyaura cross coupling reaction between aryl bromide and aryl boronic acid in water solvent at 45 °C. The scope of the protocol was extended to various aryl bromides and aryl boronic acids. In general, an effective method has been developed for the Suzuki-Miyaura cross coupling reaction by using a phosphine-free Pd catalyst.
- Ganesamoorthy,Shanmugasundaram,Karvembu
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p. 118 - 124
(2013/04/23)
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- Synthesis of biaryls through a one-pot tandem borylation/Suzuki-Miyaura cross-coupling reaction catalyzed by a palladacycle
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The tricyclohexylphosphane adduct of cyclopalladated ferrocenylimine I exhibited high catalytic activity in the one-pot borylation/Suzuki-Miyaura coupling (BSC) reaction with low catalyst loading (2 mol-%). Various biaryls were obtained in good to excellent yields for 37 examples. This process was applied to aryl and heteroaryl halides (Br and Cl) containing a variety of functional groups and did not require an excess amount of phosphane ligand and the addition of the palladium catalyst in the second step. Cyclopalladated ferrocenylimine I exhibited high catalytic activity in the borylation/Suzuki- Miyaura coupling (BSC) reaction with low catalyst loading. Various unsymmetrical biaryls were obtained ingood to excellent yields in one pot. This protocol was applied to aryl and heteroaryl halides (Br and Cl) containing a variety of functional groups without adding catalyst in the second step. Copyright
- Wang, Lianhui,Cui, Xiuling,Li, Jingya,Wu, Yusheng,Zhu, Zhiwu,Wu, Yangjie
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p. 595 - 603
(2012/03/09)
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- Synthesis, crystal structures, and catalytic activities of palladium imidazole complexes formed by 2-hydroxyethyl group cleavage
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N-4,6-dimethyl-2-pyrimidinylimidazole 1 and its hydroxyethyl derivative 1-(2-hydroxyethyl)-3-(4,6-dimethyl-2-pyrimidinyl)imidazolium chloride 2 have been synthesized and characterized. The attempted synthesis of bis(N-heterocyclic carbene)palladium complexes via the direct reaction of 2 with Pd(OAc)2 results in the unexpected formation of a bis(N-arylimidazole) palladium complex 3. Additionally, the analogous bis(N-methylimidazole) palladium complex 4 has also been synthesized by the above method. Compounds 1-4 were characterized by elemental analysis, IR, and 1H NMR. Additionally, their crystal structures have been determined by X-ray diffraction. Complexes 3 and 4 were found to be efficient catalysts for the Suzuki reaction.
- Xu, Chen,Li, Zhen,Duan, Lu-Meng,Wang, Zhi-Qiang,Fu, Wei-Jun,Hao, Xin-Qi,Song, Mao-Ping
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supporting information; experimental part
p. 373 - 378
(2012/07/31)
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- Metal-free arylation of benzene and pyridine promoted by amino-linked nitrogen heterocyclic carbenes
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An amino-linked nitrogen heterocyclic carbene (amino-NHC), 1-tBu, has been shown to mediate carbon-carbon coupling through the direct C-H functionalization of benzene and pyridine in the absence of a metal catalyst. Using EPR, the first spectroscopic evidence corroborating the single electron transfer mechanism for the metal-free carbon-carbon coupling manifold, as reported by others, is introduced.
- Chen, Wen-Ching,Hsu, Yu-Chen,Shih, Wei-Chun,Lee, Ching-Yu,Chuang, Wen-Han,Tsai, Yi-Fang,Chen, Peter Ping-Yu,Ong, Tiow-Gan
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supporting information; experimental part
p. 6702 - 6704
(2012/07/14)
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- PdCl2(dppf)-catalyzed in situ coupling of 2-hydroxypyridines with aryl boronic acids mediated by PyBroP and the one-pot chemo- and regioselective construction of two distinct aryl-aryl bonds
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We present a PdCl2(dppf)-catalyzed synthesis of 2-arylated pyridine derivatives via the in situ coupling of 2-OH pyridines and boronic acids mediated by PyBroP. In addition, the highly chemo- and regioselective construction of two different aryl-aryl bonds via a one-pot operation has also been demonstrated by the orthogonal use of this method with the Ni-catalyzed Suzuki-Miyaura coupling of phenols.
- Li, Shui-Ming,Huang, Jie,Chen, Guo-Jun,Han, Fu-She
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supporting information; experimental part
p. 12840 - 12842
(2012/01/05)
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- 2-Pyridyl and 3-pyridylzinc bromides: direct preparation and coupling reaction
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A facile synthetic approach to the direct preparation of 2-pyridyl and 3-pyridylzinc bromides has been demonstrated using Rieke zinc with 2-bromopyridine and 3-bromopyridine, respectively. A variety of different electrophiles have been coupled with the resulting organozinc reagents to give the corresponding cross-coupling products in moderate to good yields.
- Kim, Seung-Hoi,Rieke, Reuben D.
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scheme or table
p. 3135 - 3146
(2010/06/13)
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- Highly active and recyclable silica gel-supported palladium catalyst for mild cross-coupling reactions of unactivated heteroaryl chlorides
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Silica gel-supported β-ketoiminatophosphane-Pd complex (Pd@SiO 2) was shown to be a highly active and long-lived catalyst for aqueous Suzuki, Stille and Sonogashira coupling reactions of heteroaryl chlorides. A wide range of heteroaryl chlorides could be efficiently coupled with different nucleophilic partners in the presence of only 0.5 mol% catalyst and under mild conditions. This is one of the most powerful heterogeneous catalysts for the couplings of diverse heteroaryl chlorides. Furthermore, the catalyst could be reused with almost consistent activity. The Royal Society of Chemistry 2010.
- Lee, Dong-Hwan,Jung, Ji-Young,Jin, Myung-Jong
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experimental part
p. 2024 - 2029
(2011/02/22)
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- Scope of the suzuki-Miyaura cross-coupling reactions of potassium heteroaryltrifluoroborates
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A wide variety of bench-stable potassium heteroaryltrifluoroborates were prepared, and general reaction conditions were developed for their cross-coupling to aryl and heteroaryl halides. The cross-coupled products were obtained in good to excellent yields. This method represents an efficient and facile installation of heterocyclic building blocks onto preexisting organic substructures.
- Molander, Gary A.,Canturk, Belgin,Kennedy, Lauren E.
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supporting information; experimental part
p. 973 - 980
(2009/07/11)
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- Synthesis and spectroscopic comparison of the eight methyl-2,3′-bipyridyls and identification of a hoplonemertine alkaloid as 3-methyl-2,3′-bipyridyl
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The pyridyl ring is frequently found in natural products and drugs. While bipyridyls have served as useful scaffolds for development of industrial and pesticidal chemicals, their biological properties are still not well understood. Only 2,3--bipyridyl, of the six isomeric bipyridyls, has been reported as a natural product in tobacco plants and in a hoplonemertine marine worm, Amphiporus angulatus (Aa), which uses its pyridyl alkaloid-rich venom to paralyze its crustacean prey and chemically defend itself against predators. Here we report for the first time the synthesis and spectroscopic properties of all eight possible methyl 2,3′-bipyridyl isomers and use this data to identify a trace alkaloidal constituent of Aa as 3-methyl-2,3′-bipyridyl. This is only the second reported instance of a methyl-bipyridyl being found as a natural product, the first being the tobacco alkaloid 5-methyl-2,3′-bipyridyl.
- Kem, William R.,Rocca, James,Garraffo, H. Martin,Spande, Thomas F.,Daly, John W.,Soti, Ferenc
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experimental part
p. 1025 - 1041
(2009/12/26)
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- A facile synthetic approach to the preparation of 3-pyridyl derivatives: Preparations and coupling reactions of 3-pyridylzinc and its analogues
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A facile synthetic approach to the direct preparation of 3pyridylzinc bromide has been demonstrated using Rieke zinc with 3-bromopyridine in the presence of a catalytic amount of lithium chloride. A variety of different electrophiles have been coupled to give the corresponding cross-coupling products in moderate to good yields. Also, this methodology has been expanded to the preparation of the corresponding organozinc reagents of 3-bromopyridine analogues. Georg Thieme Verlag Stuttgart.
- Kim, Seung-Hoi,Slocum, Tim B.,Rieke, Reuben D.
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experimental part
p. 3823 - 3827
(2010/03/04)
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- Expanded heterogeneous Suzuki-Miyaura coupling reactions of aryl and heteroaryl chlorides under mild conditions
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A mesoporous LTA zeolite (MP-LTA)-supported palladium catalyst was developed for the highly efficient Suzuki-Miyaura reaction of aryl and heteroaryl chlorides. The couplings of various aryl chlorides with arylboronic acids in aqueous ethanol were efficiently achieved in the presence of 1.0 mol% of the catalyst. Furthermore, the scope of this catalyst was extended to the coupling of heteroaryl chlorides. Regardless of the substituents, all of the coupling reactions were very clean and highly efficient under mild heating. It shows that our catalyst is one of the most powerful heterogeneous catalysts for the coupling of a wide range of aryl and heteroaryl chlorides. The catalyst could be repetitively used at least 10 times without a significant loss of its catalytic activity. Compared to mesoporous SBA-15 and MCM-41 materials, the MP-LTA support proved to be very stable and robust to prevent degradation upon reuse.
- Lee, Dong-Hwan,Choi, Minkee,Yu, Byung-Woo,Ryoo, Ryong,Taher, Abu,Hossain, Shahin,Jin, Myung-Jong
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supporting information; experimental part
p. 2912 - 2920
(2010/04/01)
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- Hydrogen bonding-assisted tautomerization of pyridine moieties in the coordination sphere of an Ir(I) complex
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Ir(I)-induced tautomerization of a pyridine moiety to a carbene in 2,3-bipyridyls has been successfully achieved where an amide group plays a key role as a hydrogen-bonding acceptor and the carbene tautomer is stabilized by both chelation effect and by hydrogen-bonding. The Royal Society of Chemistry.
- Song, Guoyong,Li, Yongxin,Chen, Shanshan,Li, Xingwei
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supporting information; body text
p. 3558 - 3560
(2009/02/05)
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- A general and efficient method for the Suzuki-Miyaura coupling of 2-pyridyl nucleophiles
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(Chemical Equation Presented) One of the most general systems for the cross-coupling of aryl and heteroaryl bromides and chlorides with 2-pyridyl-derived nucleophiles has been developed, for which catalysts comprising [Pd2(dba)3] and either diaryl (1) or dialkyl phosphine oxide (2) supporting ligands were found to be ideal (see scheme).
- Billingsley, Kelvin L.,Buchwald, Stephen L.
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supporting information; experimental part
p. 4695 - 4698
(2009/02/06)
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- Highly efficient suzuki-miyaura coupling of heterocyclic substrates through rational reaction design
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A dicyclohexyl(2-sulfo-9-(3-(4-sulfophenyl)propyl)-9H-fluoren-9-yl) phosphonium salt was synthesized in 64% overall yield in three steps from simple commercially available starting materials. The highly water-soluble catalyst obtained from the corresponding phosphine and [Na2PdCl4] enabled the Suzuki coupling of a broad variety of N- and S-heterocyclic substrates. Chloropyridines (-quinolines) and aryl chlorides were coupled with aryl-, pyridineor indoleboronic acids in quantitative yields in water/n-butanol solvent mixtures in the presence of 0.005-0.05 mol% of Pd catalyst at 100°C, chloropurines were quantitatively Suzuki coupled in the presence of 0.5 mol% of catalyst, and S-heterocyclic aryl chlorides and aryl- or 3-pyridylboronic acids required 0.01-0.05 mol % Pd catalyst for full conversion. The key to the high activity of the Pd-phosphine catalyst is the rational design of the reaction parameters (i.e., the presence of water in the reaction mixture, good solubility of reactants and catalyst in n-butanol/water (3:1), and the electron-rich and sterically demanding nature of the phosphine ligand).
- Fleckenstein, Christoph A.,Plenio, Herbert
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scheme or table
p. 4267 - 4279
(2009/05/07)
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- New cyclopentadienyl, indenyl or fluorenyl substituted phosphine compounds and their use in catalytic reactions
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The invention is directed to a phosphine compound represented by general formula (1) wherein R' and R" independently are selected from alkyl, cycloalkyl and 2-furyl radicals, or R' and R" are joined together to form with the phosphorous atom a carbon-phosphorous monocycle comprising at least 3 carbon atoms or a carbon-phosphorous bicycle; the alkyl radicals, cycloalkyl radicals, and carbon-phosphorous monocycle being unsubstituted or substituted by at least one radical selected from the group of alkyl, cycloalkyl, aryl, alkoxy, and aryloxy radicals; Cps is a partially substituted or completely substituted cyclopentadien-1-yl group, including substitutions resulting in a fused ring system, and wherein a substitution at the 1-position of the cyclopentadien-1-yl group is mandatory when the cyclopentadien-1-yl group is not part of a fused ring system or is part of an indenyl group. Also claimed is the use of these phosphines as ligands in catalytic reactions and the preparation of these phosphines.
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Page/Page column 53; 58; 59
(2008/06/13)
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- Indium-mediated synthesis of heterobiaryls
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The palladium-mediated coupling reaction between triorganoindium reagents and organic electrophiles is extended to the synthesis of heteroaromatic compounds. Both electron-rich and electron-poor heterocycles can act as the organic electrophile or as the organoindium derivative.
- Font-Sanchis, Enrique,Cespedes-Guirao, F. Javier,Sastre-Santos, Angela,Fernandez-Lazaro, Fernando
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p. 3589 - 3591
(2008/02/04)
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- 9-Fluorenylphosphines for the Pd-catalyzed Sonogashira, Suzuki, and Buchwald-Hartwig coupling reactions in organic solvents and water
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The lithiation/alkylation of fluorene leads to various 9-alkyl-fluorenes (alkyl = Me. Et, /Pr, -Pr. -C18H25) in > 95% yields, for which lithiation and reaction with R2PCl (R = Cy, iPr, tBu) generates 9-alkyl, 9-PR2fluorenes which constitute electron-rich and bulky phosphine ligands. The in-situ-formed palladium-phosphinc complexes ([Na2PdCl4], phosphonium salt, base, substrates) were tested in the Sonogashira. Suzuki, and Buchwald-Hartwig reactions of aryl chlorides and aryl bromides in organic solvents. The Sonogashira coupling of aryl chlorides at 100-120°C leads to >90% yields with 1 mol % of Pd catalyst. The Suzuki coupling of aryl chlorides typically requires 0.05 mol % of Pd catalyst at 100°C in dioxane for quantitative product formation. To carry out "green" cross-coupling reactions in water, 9-ethylfluorenyldicyclohexylphosphine was reacted in sulphuric acid to generate the respective 2-sulfonated phosphonium salt. The Suzuki coupling of activated aryl chlorides by using this water-soluble catalyst requires only 0.01 mol% of Pd catalyst, while a wide range of aryl chlorides can be quantitatively converted into the respective coupling products by using 0.1-0.5 mol % of catalyst in pure water at 100°C. Difficult substrate combinations, such as naphthylboronic acid or 3-pyridylboronic acid and aryl chlorides are coupled at 100°C by using 0.1-0.5 mol % of catalyst in pure water to obtain the respective N-heterocycles in quantitative yields. The copper-free aqueous Sonogashira coupling of aryl bromides generates the respective tolane derivatives in > 95 % yield.
- Fleckenstein, Christoph A.,Plenio, Herbert
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p. 2701 - 2716
(2008/03/14)
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- Microwave-assisted Suzuki coupling reactions with an encapsulated palladium catalyst for batch and continuous-flow transformations
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This article describes the design, optimisation and development of a Suzuki cross-coupling protocol mediated by an efficient palladium-en-capsulated catalyst (Pd EnCat) under microwave irradiation. The methodology has been used in both batch mode for classical library preparation and in continuous-flow applications furnishing multigram quantities of material. Described is a method that uses direct focused microwave heating whilst applying an external cooling source. This enables a lower than normal bulk temperature to be maintained throughout the reaction period leading to significant improvements in the overall yield and purity of the reaction products. Additional aspects of this novel heating protocol are discussed in relation to the prolonged lifetime and enhanced reactivity of the immobilised catalyst system.
- Baxendale, Ian R.,Griffiths-Jones, Charlotte M.,Ley, Steven V.,Tranmer, Geoffrey K.
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p. 4407 - 4416
(2008/02/07)
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- Highly efficient cyclopalladated ferrocenylimine catalyst for Suzuki cross-coupling reaction of 3-pyridylboronic pinacol ester with aryl halides
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The Suzuki cross-coupling reaction of 3-pyridylboronic pinacol ester with aryl iodides, bromides and chlorides was carried out in DMF/H2O (3/1, v/v) at 110 °C in the presence of cyclopalladated ferrocenylimine I and K2CO3 or CsCO3 (1.0 equiv.) without the protection of inert gas. By using this method the synthesis of 3-pyridyl biaryl compounds could be readily achieved.
- Zhang, Jinli,Zhao, Liang,Song, Maoping,Mak, Thomas C.W.,Wu, Yangjie
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p. 1301 - 1306
(2007/10/03)
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- A versatile method for suzuki cross-coupling reactions of nitrogen heterocycles
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(Chemical Equation Presented) A wide-ranging study of Suzuki reactions which use nitrogen-containing heterocycles is described (see scheme; dba = dibenzylideneacetone, Cy = cyclohexyl). This method is highly versatile (a single procedure was used for all substrates, including boronate esters and trifluoroborates), compatible with a variety of unprotected functionalities (e.g., NH2-and OH-substituted substrates), and efficient even with unactivated aryl chlorides.
- Kudo, Noriaki,Perseghini, Mauro,Fu, Gregory C.
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p. 1282 - 1284
(2007/10/03)
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- Efficient preparation of 2-pyridylpyridines using β-N,N-dialkylated aminoacroleins or their equivalent as vinadinium tetrafluoroborate
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Efficient synthetic procedure for 2-pyridylpyridines using β-N,N-dialkylated aminoacroleins or their equivalent as dipiperidyl vinadinium tetrafluoroborate is described. Copyright
- Kuwabara, Hirokazu,Umihara, Ken,Furugori, Yasushi,Itoh, Isamu
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p. 834 - 835
(2007/10/03)
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- 5-Substituted, 6-substituted, and unsubstituted 3-heteroaromatic pyridine analogues of nicotine as selective inhibitors of cytochrome P-450 2A6
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A series of 5- and 6-substituted and unsubstituted 3-heteroaromatic analogues of nicotine were synthesized in an effort to delineate the structural requirements for selectively inhibiting human cytochrome P-450 (CYP) 2A6, the major nicotine metabolizing enzyme. Thiophene, substituted thiophene, furan, substituted furan, imidazole, substituted imidazole, pyridine, substituted pyridine, thiazole, and quinoline moieties were used to replace the N-methylpyrrolidine ring of nicotine. Bromo and methyl groups were introduced at the 5-position of the pyridine ring and fluoro, chloro, and methoxy groups were placed at the 6-position of the pyridine ring in order to explore the structure-activity relationship (SAR) of inhibition of CYP2A6. The inhibitory activity of the most potent CYP2A6 inhibitors on the functional activity of human cytochrome P450s 3A4, 2E1, 2B6, 2C9, 2C19, and 2D6 was also examined to determine inhibitor selectivity. We identified 36 compounds that were more potent than nicotine at inhibition of coumarin 7-hydroxylase (CYP2A6) activity. We also found a number of compounds to be highly selective for the inhibition of human CYP2A6 versus the other human CYPs examined.
- Denton, Travis T.,Zhang, Xiaodong,Cashman, John R.
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p. 224 - 239
(2007/10/03)
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- PROCESS FOR PRODUCING 2-SUBSTITUTED PYRIDINE DERIVATIVE
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The present invention provides a method of producing a pyridine derivative having a substituent at the 2-position of a heterocyclic structure conveniently and with fine selectivity. The present invention relates to a production method of a pyridine derivative having a substituent at the 2-position of a heterocyclic structure, which is represented by the formula (III), which includes reacting a 2-sulfonylpyridine derivative of the formula (I) with an organometallic compound of the formula (II) and the like, and the like: wherein each symbol is as defined in the Description.
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Page/Page column 12
(2008/06/13)
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- Synthesis of 2-pyridylpyridines via aza-Diels-Alder reactions between 3-pyridyl-1,2,4-triazines and some vinyl alkanoates
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New synthetic procedure for 2,ω-bipyridines involving aza-Diels-Alder reaction between 3-(ω-pyridyl)-1,2,4-triazine and vinyl octanoate or decanoate as a dienophile is described. Copyright
- Shintou, Taichi,Ikeuchi, Fumiaki,Kuwabara, Hirokazu,Umihara, Ken,Itoh, Isamu
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p. 836 - 837
(2007/10/03)
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- SYNTHETIC COMPOUNDS AND DERIVATIVES AS MODULATORS OF SMOKING OR NICOTINE INGESTION AND LUNG CANCER
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Disclosed are nicotine-related compounds that selectively inhibit cytochrome P-450 2A6 (CYP2A6), selectively inhibit cytochrome P-450 2A13 (CYP2A13), and/or selectively modulate a nicotinic acetylcholine receptor (nAChR). Also disclosed are pharmaceutical compositions comprising a compound of the invention, as well as methods of using the pharmaceutical compositions for treating or preventing a disease or disorder associated with nicotine-ingestion, or a disease or disorder amenable to treatment by selective modulation of nAChRs.
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Page/Page column 98
(2010/02/12)
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- Synthesis and electrochemical properties of bis(bipyridine)ruthenium(II) complexes bearing pyridinyl- and pyridinylidene ligands induced by cyclometalation of N′-methylated bipyridinium analogs
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Ruthenium complexes with bipyridine-analogous quaternized (N,C) bidentate ligands [RuL(bpy)2](PF6)2 (bpy = 2,2′-bipyridine, (1), L = L1 = N′-methyl-2,4′- bipyridinium; (2), L = L2 = N′-methyl-2,3′-bipyridinium) were synthesized and characterized. The structure of complex 2 was determined by the X-ray structure analysis. The 13C{1H} NMR spectroscopic and cyclic voltammetric studies indicate that the coordination modes of these ligands are quite different, that is, the C-coordinated rings of (N,C)-ligands in 1 and 2 are linked to ruthenium(II) with a pyridinium manner and a pyridinylidene one, respectively. The ligand-localized redox potentials of 1 and 2 also revealed the substantial difference in the electron donating ability of both ligands.
- Koizumi, Take-Aki,Tomon, Takashi,Tanaka, Koji
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p. 1258 - 1264
(2007/10/03)
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