- Pd(ii) complexes of N,S-heterocyclic carbenes with pendant and coordinated allyl function and their Suzuki coupling activities
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3-(2-Propenyl)benzothiazolium bromide (A) provides a direct and simple entry to Pd(ii) complexes with N,S-heterocyclic carbene (NSHC) ligands functionalized with an allyl pendant with hemilabile potential. Addition of salt A to Pd(OAc)2 eliminates HOAc and affords the bis(carbene) complexes cis-[PdBr2(NHSC)2] (cis-1, NSHC = 3-(2-propenyl) benzothiazolin-2-ylidene) and trans-[PdBr2(NHSC)2] (trans-1) along with the monocarbene complexes [PdBr2(NSHC)] (2) and trans-[PdBr2(benzothiazole-κN)(NSHC)] (3) as minor side products. Salt-metathesis of cis-1 with AgO2CCF3 yields the mixed dicarboxylato-bis(carbene) complex cis-[Pd(O2CCF 3)2(NSHC)2] (4). Complexes cis-1, trans-1 and 4 were characterized by multinuclear NMR spectroscopies, ESI mass spectrometry and elemental analysis. The molecular structures of complexes cis-1, 2 and 3 have been determined by X-ray single crystal diffraction. Complexes cis-1 and 4 as well as an in situ mixture of Pd(OAc)2 and salt A are active toward Suzuki-Miyaura coupling of aryl bromides and activated aryl chlorides giving good conversions. The Royal Society of Chemistry.
- Yen, Swee Kuan,Koh, Lip Lin,Huynh, Han Vinh,Hor, T. S. Andy
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Read Online
- Gold catalysed Suzuki-Miyaura coupling of arenediazonium o-benzenedisulfonimides
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Arenediazonium o-benzenedisulfonimides have been used as efficient electrophilic partners in Au(I) catalysed Suzuki coupling reactions. The synthetic protocol is general, easy and produced either biaryls or heteroaryl arenes in good yields (51 positive examples, average yield 80%). o-Benzenedisulfonimide was recovered at the end of the reactions and was reused to prepare the starting salts for further reactions. Mechanistic insights suggest that the o-benzenedisulfonimide anion act as an electron transfer agent and promotes a catalytic cycle which does not require the presence of photocatalysts or external oxidants.
- Barbero, Margherita,Dughera, Stefano
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Read Online
- Generation of 3-Pyridyl Biaryl Systems Via Palladium-Catalyzed Suzuki Cross-Couplings of Aryl Halides with 3-Pyridylboroxin
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The synthesis of 3-pyridyl biaryl systems can be readily achieved by means of palladium-catalyzed Suzuki cross-coupling reactions between aryl halides and 3-pyridyl-boroxin. A series of cross-couplings were conducted in order to investigate the scope and limitations of this protocol.
- Cioffi, Christopher L.,Spencer, William T.,Richards, Justin J.,Herr, R. Jason
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Read Online
- Antitubercular and Antiparasitic 2-Nitroimidazopyrazinones with Improved Potency and Solubility
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Following the approval of delamanid and pretomanid as new drugs to treat drug-resistant tuberculosis, there is now a renewed interest in bicyclic nitroimidazole scaffolds as a source of therapeutics against infectious diseases. We recently described a nitroimidazopyrazinone bicyclic subclass with promising antitubercular and antiparasitic activity, prompting additional efforts to generate analogs with improved solubility and enhanced potency. The key pendant aryl substituent was modified by (i) introducing polar functionality to the methylene linker, (ii) replacing the terminal phenyl group with less lipophilic heterocycles, or (iii) generating extended biaryl side chains. Improved antitubercular and antitrypanosomal activity was observed with the biaryl side chains, with most analogs achieved 2- to 175-fold higher activity than the monoaryl parent compounds, with encouraging improvements in solubility when pyridyl groups were incorporated. This study has contributed to understanding the existing structure-activity relationship (SAR) of the nitroimidazopyrazinone scaffold against a panel of disease-causing organisms to support future lead optimization.
- Ang, Chee Wei,Tan, Lendl,Sykes, Melissa L.,Abugharbiyeh, Neda,Debnath, Anjan,Reid, Janet C.,West, Nicholas P.,Avery, Vicky M.,Cooper, Matthew A.,Blaskovich, Mark A. T.
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p. 15726 - 15751
(2020/12/02)
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- One-Pot Palladium-Catalyzed Cross-Coupling Treble of Borylation, the Suzuki Reaction and Amination
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A methodology for a sequential palladium-catalyzed cross-coupling procedure consisting of borylation, the Suzuki reaction and amination has been developed for the assembly of molecules with multi-aryl backbones. The linchpin of this development is the meta-terarylphosphine ligand, Cy*Phine, which has been employed as an air- and moisture-stable precatalyst, Pd(Cy*Phine)2Cl2, to improve the efficiency of one-pot borylation–Suzuki reactions. Additionally, the reactivity of the Pd-Cy*Phine system could be tuned to furnish a one-pot, borylation–Suzuki reaction–amination (BSA) cross-coupling treble. The methodology successfully integrated complementary conditions for three distinctly different and modular reactions. Average yields of 74–94% could be achieved for each segment that cumulatively afforded 50–84% yield over the entire three-step sequence in a single pot. (Figure presented.).
- Jong, Howard,Eey, Stanley T.-C.,Lim, Yee Hwee,Pandey, Sangeeta,Iqbal, Nurul Azmah Bte,Yong, Fui Fong,Robins, Edward G.,Johannes, Charles W.
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supporting information
p. 616 - 622
(2017/02/23)
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- Carboxyamido/carbene ligated palladium (II) complex: A versatile catalyst for the synthesis of aryl-substituted heteroarenes
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Carboxy amido/carbene ligated Pd-complex catalyzed Suzuki-Miyaura cross-coupling of aryl-boronic acids with heteroaryl bromides is described. The protocol has a broad substrate scope that includes electron-rich, electron-deficient and sterically hindered arylboronic acids and heteroaryl bromides. The catalytic activity of the catalyst has been further investigated in the coupling of 2,6-dibromopyridine with arylboronic acids.
- Vishnuvardhan Reddy, Police,Parsharamulu, Thupakula,Annapurna, Manne,Likhar, Pravin R.,Kantam, Mannepalli Lakshmi,Bhargava, Suresh
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supporting information
p. 150 - 153
(2016/12/06)
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- VP1 crystal structure-guided exploration and optimization of 4,5-dimethoxybenzene-based inhibitors of rhinovirus 14 infection
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Human rhinoviruses (HRV) are the predominant cause of common colds and flu-like illnesses, but are also responsible for virus-induced exacerbations of asthma and chronic obstructive pulmonary disease. However, to date, no drug has been approved yet for clinical use. In this study, we present the results of the structure-based lead optimization of a class of new small-molecule inhibitors that we previously reported to bind into the pocket beneath the canyon of the VP1 protein. A small series of analogues that we designed based on the available structure and interaction data were synthesized and evaluated for their potency to inhibit the replication of HRV serotype 14. 2-(4,5-Dimethoxy-2-nitrophenyl)-1-(4-(pyridin-4-yl)phenyl)ethanol (3v) was found to be a potent inhibitor exhibiting micromolar activity (EC50 Combining double low line 3.4 ± 1.0 μM) with a toxicity for HeLa cells that was significantly lower than that of our previous hit (LPCRW-0005, CC50 Combining double low line 104.0 ± 22.2 μM; 3v, CC50 > 263 μM).
- Da Costa, Laurène,Roche, Manon,Scheers, Els,Coluccia, Antonio,Neyts, Johan,Terme, Thierry,Leyssen, Pieter,Silvestri, Romano,Vanelle, Patrice
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p. 453 - 462
(2016/04/19)
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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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- Cyclometalated Pd(ii) and Ir(iii) 2-(4-bromophenyl)pyridine complexes with N-heterocyclic carbenes (NHCs) and acetylacetonate (acac): Synthesis, structures, luminescent properties and application in one-pot oxidation/Suzuki coupling of aryl chlorides containing hydroxymethyl
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A series of cyclopalladated 2-(4-bromophenyl)pyridine (bpp) complexes [Pd(bpp)(NHC)Cl] 1-3, [Pd(bpp)(acac)] 4, cyclometalated iridium(iii) complexes [Ir(bpp)2Cl]25 and [Ir(bpp)2(acac)] 6 have been synthesized and characterized. Their detailed structures have been determined by X-ray diffraction and many intermolecular C-H...X (Cl, Br, π) and π...π interactions were found in their crystals. Cyclometalated complexes 1-4 and 6 exhibit luminescence with emission peaks of 390-543 nm in dichloromethane solution under UV irradiation. Their application to coupling reactions of aryl chlorides containing hydroxymethyl was also investigated. An efficient 3/Cu cocatalyzed oxidation/Suzuki reaction for the synthesis of biarylaldehydes from chloro-phenylmethanol and arylboronic acids in air has been developed. In addition, a 6/3-cocatalyzed one-pot reaction of acetylferrocene, (2-amino-5-chlorophenyl)methanol, and arylboronic acids provided 6-aryl-2-ferrocenylquinolines in moderate to good yields.
- Xu, Chen,Li, Hong-Mei,Xiao, Zhi-Qiang,Wang, Zhi-Qiang,Tang, Si-Fu,Ji, Bao-Ming,Hao, Xin-Qi,Song, Mao-Ping
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p. 10235 - 10247
(2014/06/24)
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- METHOD OF SYNTHESIS MOLECULES USING CATALYST AND COMPOSITES THEREOF
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A method to synthesis molecules is provided. The method employs a catalyst for a cross- coupling react ion to obtain the molecule. The method comprises coupling boronic acid and halide in presence of the catalyst having graphite oxide supported palladium nanoparticles, a solvent and a base by heating. The heating is performed at a temperature lower than the temperature at which the graphite oxide deforms. The molecule is a biaryl. The method further provides obtaining complexs such as boscalid, telmisartan, valsartan, and SPPARMγ.
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Sheet 9/14; 10/14
(2014/11/13)
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- Facile synthesis of 3-arylpyridine derivatives by palladacycle-catalyzed Stille cross-coupling reaction
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The Stille cross-coupling reaction of a variety of aryl halides (X=Cl, Br, I) with 3-alkylstannylpyridines highly catalyzed by cyclopalladated ferrocenylimine has been developed. This reaction allows formation of arylpyridine derivatives in moderate to excellent yields. Functional groups on aryl halides, such as amino, hydroxyl, keto, and aldehyde are tolerated and the reactions with arylbenzoxale substrates also proceed well.
- Ma, Gaizhi,Leng, Yuting,Wu, Yusheng,Wu, Yangjie
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p. 902 - 909
(2013/07/25)
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- Palladium nanoparticles on graphite oxide: A recyclable catalyst for the synthesis of biaryl cores
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The synthesis of life saving drug molecules in a cost-effective and environmentally benign pathway is of paramount significance. We present an environment friendly protocol to prepare core moieties of top selling drug molecules such as boscalid and telmisartan using Suzuki-Miyaura coupling conditions. In contrast to the traditional synthesis of these pharmaceutically important molecules, we have accomplished a graphite oxide (GO) supported palladium nanoparticles (PdNPs) based catalyst which quantitatively produced these core biaryl moieties of top selling drug molecules in a recyclable way. The catalytic activity remained unchanged even after 16 successive catalytic cycles without incorporating any palladium metal impurity in the pharmaceutically significant organic products. A detailed study including IR spectroscopy, solid state NMR spectroscopy, X-ray photoelectron spectroscopy, and DFT calculation was employed to understand the role of solid support on the nondecaying recycling ability of the catalyst during the Suzuki-Miyaura coupling reaction. The study indicates a strong chemical interaction of the different functionalities present in the GO, with the palladium centers which is primarily responsible for such sustained catalytic activity during the consecutive Suzuki-Miyaura coupling cycles.
- Santra, Subhankar,Hota, Pradip Kumar,Bhattacharyya, Rangeet,Bera, Parthasarathi,Ghosh, Prasenjit,Mandal, Swadhin K.
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p. 2776 - 2789
(2014/01/06)
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- Design of substituted imidazolidinylpiperidinylbenzoic acids as chemokine receptor 5 antagonists: Potent inhibitors of R5 HIV-1 replication
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The redesign of the previously reported thiophene-3-yl-methyl urea series, as a result of potential cardiotoxicity, was successfully accomplished, resulting in the identification of a novel potent series of CCR5 antagonists containing the imidazolidinylpiperidinyl scaffold. The main redesign criteria were to reduce the number of rotatable bonds and to maintain an acceptable lipophilicity to mitigate hERG inhibition. The structure-activity relationship (SAR) that was developed was used to identify compounds with the best pharmacological profile to inhibit HIV-1. As a result, five advanced compounds, 6d, 6e, 6i, 6h, and 6k, were further evaluated for receptor selectivity, antiviral activity against CCR5 using (R5) HIV-1 clinical isolates, and in vitro and in vivo safety. On the basis of these results, 6d and 6h were selected for further development.
- Skerlj, Renato,Bridger, Gary,Zhou, Yuanxi,Bourque, Elyse,McEachern, Ernest,Metz, Markus,Harwig, Curtis,Li, Tong-Shuang,Yang, Wen,Bogucki, David,Zhu, Yongbao,Langille, Jonathan,Veale, Duane,Ba, Tuya,Bey, Michael,Baird, Ian,Kaller, Alan,Krumpak, Maria,Leitch, David,Satori, Michael,Vocadlo, Krystyna,Guay, Danielle,Nan, Susan,Yee, Helen,Crawford, Jason,Chen, Gang,Wilson, Trevor,Carpenter, Bryon,Gauthier, David,MacFarland, Ron,Mosi, Renee,Bodart, Veronique,Wong, Rebecca,Fricker, Simon,Schols, Dominique
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supporting information
p. 8049 - 8065
(2013/11/06)
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- Room-temperature Suzuki-Miyaura coupling of heteroaryl chlorides and tosylates
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Suzuki-Miyaura coupling of heteroaryls is an important method for the preparation of compound libraries for medicinal chemistry and materials research. Although many catalysts have been developed, none of them have been generally applicable to the coupling reactions of heteroaryl chlorides and tosylates at room temperature. We discovered that a catalyst combination of Pd(OAc)2 and XPhos (2-dicyclohexylphosphanyl-2',4',6'- triisopropylbiphenyl) could efficiently catalyze these couplings. Besides the choice of catalyst, the use of hydroxide bases in an aqueous alcoholic solvent was essential for fast couplings. These conditions promoted fast release of active catalyst (XPhos)Pd0, and accelerated the transmetalation in the catalytic cycle. Most of the major families of heteroaryl chlorides (31 examples) and tosylates (17 examples) reached full conversion within minutes to hours at room temperature. The method could be easily scaled up for gram-scale synthesis. Furthermore, we examined the relative reactivity of coupling partners in whole reactions. Electron-rich heteroaryl chlorides and tosylates reacted more slowly than electron-deficient ones, in the order of indole, pyrrole furan, thiophene > pyridine. Similarly, electron-deficient arylboronic acids were less reactive than electron-neutral and electron-rich ones. The reactivity trends from this study can help to choose appropriate coupling partners for Suzuki reactions.
- Yang, Junfeng,Liu, Sijia,Zheng, Jian-Feng,Zhou, Jianrong
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supporting information
p. 6248 - 6259,12
(2020/09/16)
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- Palladium nanoparticles on amphiphilic carbon spheres: A green catalyst for Suzuki-Miyaura reaction
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We report the use of palladium nanoparticles stabilized on amphiphilic glucose-derived carbon spheres as heterogeneous catalysts for Suzuki-Miyaura reactions. Reactions of aryl halides with various boronic acids in the presence of different bases and solvents including organic polar, non-polar and water as sole solvent without the aid of phase-transfer catalysts, under phosphine-free and aerobic conditions have been studied. Especially, deactivated aryl bromides and activated aryl chlorides afforded good isolated yields in pure water. The catalyst was reused for up to four cycles without any marked loss in the activity. Copyright
- Putta, Chandra Babu,Ghosh, Sutapa
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experimental part
p. 1889 - 1896
(2011/10/08)
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- Efficient diphosphane-based catalyst for the palladium-catalyzed suzuki cross-coupling reaction of 3-pyridylboronic acids
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A highly active catalyst system derived from PdCl2 and 2,2',6,6'- tetramethoxy-4,4'-bis(diphenylphosphanyl)-3,3'-bi- pyridine (P-Phos) has been developed for the Suzuki cross- coupling reaction of pyridylboronic acid with a variety of aryl halides in good to excellent yields, even in the presence of hindered and functional groups. In addition, P-Phos also exhibited high activity in the palladium-catalyzed Suzuki reaction of 2,6-dimethoxypyridylboronic acid in excellent yields with a fast rate. The steric and electronic effects of the P- Phos-palladium complex to this cross-coupling reaction were also discussed.
- Fu, Xing-Li,Wu, Lei-Lei,Fu, Hai-Yan,Chen, Hua,Li, Rui-Xiang
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experimental part
p. 2051 - 2054
(2009/09/06)
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- Air-stable and highly active dendritic phosphine oxide-stabilized palladium nanoparticles: Preparation, characterization and applications in the carbon-carbon bond formation and hydrogenation reactions
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Dendrimer-stabilized palladium nanoparticles were formed in the reduction of palldium bis-(acetylacetonate) [Pd(acac)2] in the presence of phosphine dendrimer ligands using hydrogen in tetrahydrofuran. The resulting Pd nanoparticles were characterized by TEM, 31P NMR and 31P MAS NMR. The results indicated that the dendritic phosphine ligandswere oxidized to phosphine oxides. These dendrimer-stabilized Pd nanoparticles were demonstrated to be efficient catalysts for Suzuki and Stille coupling reactionsand hydrogenations. The dendritic wedges served as a stabilizer for keeping the nanoparticlesfrom aggregating, and asa vehicle for facilitating the separation and/or the recycling of the Pd catalyst. In the case of the Suzuki coupling reaction, these Pd nanoparticles exhibited high catalytic efficiency (TON up to 65,000) and air stability as compared with the commonly used homogeneous catalyst tetrakis(triphenylphosphine)palladium [Pd-(PPh 3)4]. In addition, the results obtained from the bulky dendritic substrate suggest that the Pd nanoparticles might act asres ervoir of catalytically active species, and that the reaction is actually catalyzed by the soluble Pd(0) and/or Pd(II) species leached from the nanoparticle surface.
- Wu, Lei,Li, Zhi-Wei,Zhang, Feng,He, Yan-Mei,Fan, Qing-Hua
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experimental part
p. 846 - 862
(2009/05/07)
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- Process for the preparation of aryl-piridyl compounds
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A method is described for the preparation of aryl-pyridine compounds of formula (I) by cross-coupling reaction, promoted by catalytic systems based on palladium or nickel between compounds of formula (II) and (III) in which:—Met represents Mg or Zn,—Y represents Cl, Br, I or acetoxy,—Z represents I, Br, Cl, triflate, sulphonate, phosphate,—R1, R2, R3, R4, which are the same as one another or different, represent hydrogen, a linear and/or branched C1-C4 alkyl, and/or an aryl, and/or a heteroaryl, or R1 and R2 and/or R3 and R4, taken together, form a C3-C8 ring, an aryl and/or a heteroaryl,—A represents —COR5 where R5 represents hydrogen, a linear and/or branched C1-C4 alkyl, and/or an aryl, and/or a heteroaryl, or—A represents —CRs5(OR6)(OR7) where R5 has the meaning described above and R6 and R7, which are the same as one another or different, represent a linear and/or branched C1-C4 alkyl, and/or an aryl, and/or a heteroaryl, or R6 and R7, joined together, represent a C1-C8 alkyl or alkenyl.
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Page/Page column 3
(2008/06/13)
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- Biarylcarboxybenzamide derivatives as potent vanilloid receptor (VR1) antagonistic ligands
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Seventeen biarylcarboxybenzamide derivatives were prepared for the study of their agonistic/antagonistic activities to the vanilloid receptor (VR1) in rat DRG neurons. The replacement of the piperazine moiety of the lead compound 1 with phenyl ring showed quite enhanced antagonistic activity. Among the prepared derivatives, N-(4-tert-butylphenyl)-4-pyridine-2-yl-benzamide (2, IC 50 = 31 nM) and N-(4-tert-butylphenyl)-4-(3-methylpyridine-2-yl) benzamide (3g, IC50 = 31 nM), showed 5-fold higher antagonistic activity than 1 in 45Ca2+-influx assay.
- Park, Hyeung-Geun,Choi, Ji-Yeon,Kim, Mi-Hyun,Choi, Sea-Hoon,Park, Mi-Kyung,Lee, Jihye,Suh, Young-Ger,Cho, Hawon,Oh, Uhtaek,Kim, Hee-Doo,Joo, Yung Hyup,Shin, Song Seok,Kim, Jin Kwan,Jeong, Yeon Su,Koh, Hyun-Ju,Park, Young-Ho,Jew, Sang-Sup
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p. 631 - 634
(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 108
(2010/02/12)
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- Methods of treatment using an EP2 selective receptor agonist
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The present invention relates to methods of treating pulmonary hypertension, facilitating joint fusion, facilitating tendon and ligament repair, reducing the occurrence of secondary fracture, treating avascular necrosis, facilitating cartilage repair, facilitating bone healing after limb transplantation, facilitating liver regeneration, facilitating wound healing, reducing the occurrence of gastric ulceration, treating hypertension, facilitating the growth of tooth enamel or finger or toe nails, treating glaucoma, treating ocular hypertension, and repairing damage caused by metastatic bone disease using an EP2 selective receptor agonist.
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Page/Page column 48
(2010/02/13)
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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 THE PREPARATION OF ARYL-PIRIDYL COMPOUNDS
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A method is described for the preparation of aryl-pyridine compounds of formula (I) by cross-coupling reaction, promoted by catalytic systems based on palladium or nickel between compounds of formula (II) and (III) in which: - Met represents Mg or Zn, - Y represents C1, Br, I or acetoxy, - Z represents I, Br, Cl, triflate, sulphonate, phosphate, - Rl, R2, R3, R4, which are the same as one another or different, represent hydrogen, a linear and/or branched Cl-C4 alkyl, and/or an aryl, and/or a heteroaryl, or Rl and R2 and/or R3and R4, taken together, form a C3-C8 ring, an aryl and/or a heteroaryl, - A represents -COR5 where R5 represents hydrogen, a linear and/or branched Cl-C4 alkyl, and/or an aryl, and/or a heteroaryl, or - A represents -CRs5(OR6)(OR7) where R5 has the meaning described above and R6 and R7, which are the same as one another or different, represent a linear and/or branched C1-C4 alkyl, and/or an aryl, and/or a heteroaryl, or R6 and R7, joined together, represent a C1-C8 alkyl or alkenyl.
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- Process for the preparation of aryl-pyridinyl compounds
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A process is described for the preparation of arylpyridine compounds by aryl-aryl cross-coupling reactions between a halopyridine and an arylmagnesium halide carried out in the presence of a catalytic amount of a zinc salt and a catalytic amount of palladium. The zinc salt is preferably selected from ZnCl2, ZnBr2 and/or Zn(OAc)2, while the palladium is preferably used in the form of Pd(PPh3)4 or Pd(OAc)2 +4 PPh3. The reaction can also be carried out in the presence of bidentate phosphines, such as, for example, 1,3-bis(diphenylphosphine)propane or 1,4-bis(diphenylphosphine)-butane. It is thus possible to obtain molar yields higher than 97% (calculated relative to the halopyridine) and a catalyticity of more than 2000.
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Page column 14
(2010/02/07)
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- Synthesis of novel palladacycles and their application in heck and Suzuki reactions under aerobic conditions
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(Chemical Equation Presented) Design and synthesis of a novel family of furancarbothioamide-based palladacycles are reported herein. These palladacycles are thermally stable, not sensitive to air or moisture, and are applied effectively in the Heck reaction of aryl halides with terminal olefins and in the Suzuki reaction of aryl halides with arylboronic acids. These reactions were performed under aerobic conditions, leading to turnover numbers (TONs) up to 1 × 105.
- Xiong, Zhengchang,Wang, Nengdong,Dai, Mingji,Li, Ang,Chen, Jiahua,Yang, Zhen
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p. 3337 - 3340
(2007/10/03)
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- 2, 3, 6-TRISUBSTITUTED-4-PYRIMIDONE DERIVATIVES
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A pyrimidone derivative having tau protein kinase 1 inhibitory activity which is represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof; useful for prventive and/or therapeutic treatment of diseass such as neurodegenerative diseases (e.g. Alzheimer disease); wherein Q represents CH or nitrogen atom; R represents a C1-C12 alkyl group; the ring of Formula (I): represents piperazine ring or piperidine ring; each X independently represents a C1-C8 alkyl group, an optionally partially hydrogenated C6-C10 aryl ring, an indan ring or the like; m represents an integer of 1 to 3; each Y independently represents a halogen atom, a hydroxy group, a cyano group, a C1-C6 alkyl group or the like; n represents an integer of 0 to 8; when X and Y or two Y groups are attached on the same carbon atom, they may combine to each other to form a C2-C6 alkylene group.
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- A convenient microwave assisted arylzinc generation-Negishi coupling protocol
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Arylzinc reagents were readily prepared from aryl iodides using a Zn-Cu couple in a microwave environment. A sequential arylzinc formation-Negishi cross-coupling protocol suitable for parallel high-throughput synthesis has been developed.
- Mutule, Ilga,Suna, Edgars
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p. 3909 - 3912
(2007/10/03)
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- Tricyclic inhibitors of poly(ADP-ribose) polymerases
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Compounds of the formula shown below are poly(ADP-ribosyl)transferase inhibitors: Such compounds are useful as therapeutics in treating cancers and in ameliorating the effects of stroke, head trauma, and neurodegenerative disease.
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- Method for treating glaucoma
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Methods of using prostaglandin agonists for the reduction of intraocular pressure, and accordingly glaucoma.
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- Prostaglandin agonists and their use to treat bone disorders
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This invention relates to prostaglandin agonists, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits containing such prostaglandin agonists. The prostaglandin agonists are useful for the treatment of bone disorders including osteoporosis.
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- Prevention of loss and restoration of bone mass by certain prostaglandin agonists
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Prostaglandin agonists of formula (I), in which, for example, A is a sulphonyl or acyl group, B is N or CH, M contains a ring and K and Q are linking groups, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits useful for the treatment of bone disorders including osteoporosis. STR1
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- Antagonists of gonadotropin releasing hormone
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There are disclosed compounds of formula (I) and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related and other conditions in both men and women.
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- ANTAGONISTS OF GONADOTROPIN RELEASING HORMONE
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There are disclosed compounds of formula (I) STR1 and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related and other conditions in both men and women.
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- Quinuclidine derivatives as squalene synthase inhibitors
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Compounds of formula (I) and their pharmaceutically acceptable salts in which R1 is hydrogen or hydroxy; R2 is hydrogen; or R1 and R2 are joined together so that CR1 -CR2 is a double bond; X is selected from --CH2 CH2 --, --CH=CH--, --C C--, --CH2 O--, --CH2 NH--, --NHCH2 --, --CH2 CO--, --COCH2 --, --CH2 S-- and --SCH2 --; Ar1 is a phenylene moiety; Ar2 is a heteroaryl moiety; and wherein one or both of Ar1 and Ar2 may optionally bear one or more substituents independently selected from halogeno, hydroxy, amino, nitro, cyano, carboxy, carbamoyl, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, di-alkylamino, N-alkylcarbamoyl, di-N,N-alkylcarbamoyl, alkoxycarbonyl, alkylthio, alkylsulphinyl, alkylsulphonyl, halogeno-alkyl, carboxyalkyl and alkanoylamino; provided that when R1 is hydroxy, X is not selected from --NHCH2 -- and --SCH2 --; are inhibitors of squalene synthase and hence useful in treating medical conditions in which a lowering of cholesterol is beneficial, such as hypercholesterolemia and atherosclerosis. Processes for preparing these derivatives, pharmaceutical compositions containing them are also described together with their use in medicine.
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- ANTIVIRALLY ACTIVE HETEROCYCLIC AZAHEXANE DERIVATIVES
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There are described compounds of formula I*, STR1 wherein R. sub.1 is lower alkoxycarbonyl,R 2 is secondary or tertiary lower alkyl or lower alkylthio-lower alkyl, R. sub.3 is phenyl that is unsubstituted or substituted by one or more lower alkoxy radicals, or C 4-C 8 cycloalkyl,R. sub.4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atom, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl (--SO--) and sulfonyl (--SO 2--) and is unsubstituted or substituted by lower alkyl or by phenyl-lower alkyl,R 5, independently of R 2, has one of the meanings mentioned for R 2, andR 6, independently of R. sub.1, is lower alkoxycarbonyl,or salts thereof, provided that at least one salt-forming group is present. The compounds are inhibitors of retroviral aspartate protease and can be used, for example, in the treatment of AIDS. They exhibit outstanding pharmacodynamic properties.
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