- Solid-phase cross-coupling reaction of aryl(fluoro)silanes with 4- iodobenzoic acid
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Aryl(alkyl)(difluoro)silanes undergo a facile and efficient palladium- catalyzed cross-coupling reaction with iodobenzoic acid tethered to the Wang resin. Acid cleavage releases unsymmetrical biaryl carboxylic acids with high conversions, purities, and yields. (C) 2000 Elsevier Science Ltd.
- Homsi, Fadi,Nozaki, Kyoko,Hiyama, Tamejiro
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Read Online
- Nickel and palladium nanocomposite carbon aerogels as recyclable catalysts for Suzuki-Miyaura reaction under aerobic and phosphine-free conditions in water
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Recyclable and readily prepared Ni and Pd nanocomposite carbon aerogels have been successfully used in the Suzuki-Miyaura reaction in water medium and aerobic conditions. In these ligand-free and environmentally-friendly conditions the Ni-carbon aerogel shows better recyclability than the corresponding palladium material. No appreciable leaching of Nickel could be detected after six reaction cycles. Interestingly enough, we have demonstrated for the first time that metal embedded carbon aerogels can be also used in water medium.
- Martín, Laura,Molins, Elies,Vallribera, Adelina
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Read Online
- Improving the metabolic stability of antifungal compounds based on a scaffold hopping strategy: Design, synthesis, and structure-activity relationship studies of dihydrooxazole derivatives
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L-amino alcohol derivatives exhibited high antifungal activity, but the metabolic stability of human liver microsomes in vitro was poor, and the half-life of optimal compound 5 was less than 5 min. To improve the metabolic properties of the compounds, the scaffold hopping strategy was adopted and a series of antifungal compounds with a dihydrooxazole scaffold was designed and synthesized. Compounds A33-A38 substituted with 4-phenyl group on dihydrooxazole ring exhibited excellent antifungal activities against C. albicans, C. tropicalis and C. krusei, with MIC values in the range of 0.03–0.25 μg/mL. In addition, the metabolic stability of compounds A33 and A34 in human liver microsomes in vitro was improved significantly, with the half-life greater than 145 min and the half-life of 59.1 min, respectively. Moreover, pharmacokinetic studies in SD rats showed that A33 exhibited favourable pharmacokinetic properties, with a bioavailability of 77.69%, and half-life (intravenous administration) of 9.35 h, indicating that A33 is worthy of further study.
- Cheng, Maosheng,Su, Xin,Sun, Nannan,Sun, Yin,Tian, Linfeng,Yin, Wenbo,Zhang, Chu,Zhao, Dongmei,Zhao, Liyu,Zhao, Shizhen,Zheng, Yang
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- Mimics of Pincer Ligands: An Accessible Phosphine-Free N-(Pyrimidin-2-yl)-1,2-azole-3-carboxamide Framework for Binuclear Pd(II) Complexes and High-Turnover Catalysis in Water
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We report for the first time cyclic phosphine-free "head to tail"N,N,N pincer-like (pincer complexes mimicking) N-(pyrimidin-2-yl)-1,2-azole-3-carboxamide Pd(II) complexes with deprotonated amide groups as high-turnover catalysts (TON up to 106, TOF up to 1.2 × 107 h-1) for cross-coupling reactions on the background of up to quantitative yields under Green Chemistry conditions. The potency of the described catalyst family representatives was demonstrated in Suzuki-Miyaura, Mizoroki-Heck, and Sonogashira reactions on industrially practical examples. Corresponding ligands could be synthesized based on readily available reagents through simple chemical transformations. Within the complex structures, a highly unusual 1,3,5,7-tetraza-2,6-dipalladocane frame could be observed.
- Bumagin, Nikolay A.,Dikusar, Evgenij A.,Ivashkevich, Ludmila S.,Kletskov, Alexey V.,Kolesnik, Iryna A.,Lyakhov, Alexander S.,Petkevich, Sergey K.,Potkin, Vladimir I.
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supporting information
(2020/08/12)
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- Discovery of biphenyl imidazole derivatives as potent antifungal agents: Design, synthesis, and structure-activity relationship studies
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Fungal infections have became a serious medical problem due to their high incidence and mortality. We describe the discovery and structure-activity relationships studies (SARs) of a series of novel biphenyl imidazole derivatives with excellent antifungal
- Zhao, Dongmei,Zhao, Shizhen,Zhao, Liyu,Zhang, Xiangqian,Wei, Peng,Liu, Chunchi,Hao, Chenzhou,Sun, Bin,Su, Xin,Cheng, Maosheng
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p. 750 - 758
(2016/12/28)
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- Room-temperature cobalt-catalyzed arylation of aromatic acids: overriding the ortho-selectivity via the oxidative assembly of carboxylate and aryl titanate reagents using oxygen
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A room temperature phosphine or NHC ligand-free cobalt-catalyzed arylation of (hetero)aromatic acids has been developed. It involves an oxidative cross-coupling between carboxylate and aryl titanate reagents using oxygen as an oxidant, and the arylation at the position ortho, meta and para to the carboxylic acid group could all be achieved. As application, various (hetero)aromatic acids including xenalipin, tafamidis and the key intermediate for a cardioprotective compound have been efficiently synthesized.
- Liu, Kun-Ming,Zhang, Rui,Duan, Xin-Fang
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supporting information
p. 1593 - 1598
(2016/02/09)
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- Palladium-catalyzed cross-coupling reactions of arylsiloxanes with aryl halides: Application to solid-supported organic synthesis
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The solid-phase version of the Pd-catalyzed Hiyama reaction between a variety of aryltriethoxysilanes and immobilized aryl halides was developed. Smooth cross-coupling was achieved to afford the corresponding biaryl products in moderate to excellent yields. The described protocol would be particularly useful for the construction of 4′-substituted 1,1′-biphenyl derivatives.
- Traficante, Carla I.,Delpiccolo, Carina M. L.,Mata, Ernesto G.
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supporting information
p. 211 - 214
(2014/06/09)
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- Perfluoro-tagged, phosphine-free palladium nanoparticles supported on silica gel: Application to alkynylation of aryl halides, Suzuki-Miyaura cross-coupling, and Heck reactions under aerobic conditions
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The utilization of perfluoro-tagged palladium nanoparticles immobilized on fluorous silica gel through fluorous-fluorous interactions (Pd np-A/FSG) or through covalent bonding to silica gel (Pd np-B) in the alkynylation of aryl halides, in the Suzuki-Miyaura cross-coupling, as well as in the Heck reaction between methyl acrylate and aryl iodides is described. The reactions are carried out under aerobic and phosphine-free conditions with excellent to quantitative product yields in each case. The catalysts are easily recovered and reused several times without significant loss of activity. The alkynylation of aryl halides (under copper-free conditions) and the Suzuki-Miyaura cross-coupling are carried out in water. The Heck reaction of methyl acrylate with aryl iodides is best performed in MeCN. The utilization of Pdnp-B in the synthesis of 2,3-disubstituted indoles from 2-(alkynyl)trifluoroacetanilides and aryl halides is also reported.
- Bernini, Roberta,Cacchi, Sandro,Fabrizi, Giancarlo,Forte, Giovanni,Petrucci, Francesco,Prastaro, Alessandro,Niembro, Sandra,Shafir, Alexandr,Vallribera, Adelina
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supporting information; experimental part
p. 150 - 158
(2010/05/18)
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- Accurate oxidation potentials of benzene and biphenyl derivatives via electron-transfer equilibria and transient kinetics
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(Graph Presented) Nanosecond transient absorption methods were used to determine accurate oxidation potentials (Eox) in acetonitrile for benzene and a number of its alkyl-substituted derivatives. Eox values were obtained from a combination of equilibrium electron-transfer measurements and electron-transfer kinetics of radical cations produced from pairs of benzene and biphenyl derivatives, with one member of the pair acting as a reference. Using a redox-ladder approach, thermodynamic oxidation potentials were determined for 21 benzene and biphenyl derivatives. Of particular interest, Eox values of 2.48 ± 0.03 and 2.26 ± 0.02 V vs SCE were obtained for benzene and toluene, respectively. Because of a significant increase in solvent stabilization of the radical cations with decreasing alkyl substitution, the difference between ionization and oxidation potentials of benzene is ~0.5 eV larger than that of hexamethylbenzene. Oxidation potentials of the biphenyl derivatives show an excellent correlation with substituent σ+ values, which allows Eox predictions for other biphenyl derivatives. Significant dimer radical cation formation was observed in several cases and equilibrium constants for dimerization were determined. Methodologies are described for determining accurate electrontransfer equilibrium constants even when dimer radical cations are formed. Additional equilibrium measurements in trifluoroacetic acid, methylene chloride, and ethyl acetate demonstrated that solvation differences can substantially alter and even reverse relative Eox values.
- Merkel, Paul B.,Luo, Pu,Dinnocenzo, Joseph P.,Farid, Samir
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experimental part
p. 5163 - 5173
(2009/12/06)
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- Pharmaceutical compositions, methods of preparation thereof, and methods of treatment
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The present invention provides compositions, useful as pharmaceuticals, comprising 3-biphenyl-4-yl-(2S)-[(4′-trifluoromethyl-biphenyl-4-carbonyl)-amino]-propionic acid. Also disclosed are methods for preparing the compositions and methods for using the compositions.
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Page/Page column 6
(2008/06/13)
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- Novel ATP-competitive kinesin spindle protein inhibitors
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Kinesin spindle protein (KSP), an ATPase responsible for spindle pole separation during mitosis that is present only in proliferating cells, has become a novel and attractive anticancer target with potential for reduced side effects compared to currently available therapies. We report herein the discovery of the first known ATP-competitive inhibitors of KSP, which display a unique activity profile as compared to the known loop 5 (L5) allosteric KSP inhibitors that are currently under clinical evaluation. Optimization of this series led to the identification of biphenyl sulfamide 20, a potent KSP inhibitor with in vitro antiproliferative activity against human cells with either wild-type KSP (HCT116) or mutant KSP (HCT116 D 130V). In a murine xenograft model with HCT116 D130V tumors, 20 showed significant antitumor activity following intraperitoneal dosing, providing in vivo proof-of-principle of the efficacy of an ATP-competitive KSP inhibitor versus tumors that are resistant to the other known KSP inhibitors.
- Parrish, Cynthia A.,Adams, Nicholas D.,Auger, Kurt R.,Burgess, Joelle L.,Carson, Jeffrey D.,Chaudhari, Amita M.,Copeland, Robert A.,Diamond, Melody A.,Donatelli, Carla A.,Duffy, Kevin J.,Faucette, Leo F.,Finer, Jeffrey T.,Huffman, William F.,Hugger, Erin D.,Jackson, Jeffrey R.,Knight, Steven D.,Luo, Lusong,Moore, Michael L.,Newlander, Ken A.,Ridgers, Lance H.,Sakowicz, Roman,Shaw, Antony N.,Sung, Chiu-Mei M.,Sutton, David,Wood, Kenneth W.,Zhang, Shu-Yun,Zimmerman, Michael N.,Dhanak, Dashyant
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p. 4939 - 4952
(2008/03/11)
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- IMIDAZOPYRIDINE DERIVATIVES
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The invention provides imidazopyridine derivatives represented by the general formula [I] [in which R1 and R2 may be the same or different and stand for C1-6 alkyl or the like, R3 and R4 stand for hydrogen atom, methyl group or the like, W stands for mono- or bi-cyclic 3- to 8-membered aromatic or aliphatic heterocycle or the like, and Ar stands for optionally substituted aromatic heterocycle or the like]. These compounds act as melanin-concentrating hormone receptor antagonist and are useful as medicines for central nervous system disorders, cardiovascular system disorders and metabolic disorders.
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Page/Page column 28-29
(2008/06/13)
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- Amide bridged piphenyl or biazaphenyl derivatives
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This invention is concerned with compounds of the formula wherein one of R5, R6 and R7 is and R1 to R13, X1, X2, m and n are defined in the description, and all pharmaceutically
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Page/Page column 25; 30-33
(2008/06/13)
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- Pd-EDTA as an efficient catalyst for Suzuki-Miyaura reactions in water
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PdCl2-EDTA complex 1 is an efficient catalyst for the Suzuki-Miyaura reactions of aryl and heteroaryl halides with aryl(heteroaryl)boronic acids in water at 20-100°C. Aryl iodides and bromides undergo the cross-coupling with turnover numbers (T
- Korolev, Dmitrii N.,Bumagin, Nikolay A.
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p. 5751 - 5754
(2007/10/03)
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- INDANE DERIVATES AS MUSCARINIC RECEPTOR AGONISTS
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The present invention relates to compounds of Formula I: I which are agonists of the M-1 muscarinic receptor.
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- MELANIN-CONCENTRATING HORMONE RECEPTOR ANTAGONISTS AND COMPOSITIONS AND METHODS RELATED THERETO
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Melanin-concentrating hormone (MCH) receptor antagonists are disclosed having utility for the treatment of MCH receptor-based disorders such as obesity. The compounds of this invention have the following structure: including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein m, n, X, R1, R2, R3, R4, and R5 are as defined herein. Also disclosed are compositions containing a compound of this invention, as well as methods relating to the use thereof.
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Page 135-136
(2010/02/08)
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- ARYL AND HETEROARYL COMPOUNDS AND METHODS TO MODULATE COAGULATION
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This invention provides certain compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention are useful as antagonists, or more preferably, partial antagonist of factor IX and thus, may be used to inhibit the intrinsic pathway of blood coagulation. The compounds are useful in a variety of applications including the management, treatment and/or control of diseases caused in part by the intrinsic clotting pathway utilizing factor IX. Such diseases or disease states include stroke, myocardial infarction, aneurysm surgery, and deep vein thrombosis associated with surgical procedures, long periods of confinement, and acquired or inherited pro-coagulant states.
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Page 179; 181
(2010/11/30)
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- Solid-phase Suzuki cross-coupling reactions using a phosphine ligand based on a phospha-adamantane framework
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The use of a catalyst system based on Pd2dba3· CHCl3 and 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6-phospha- adamantane allows for Suzuki coupling aryl halides with an array of boronic acids on a solid-phase platform. The reactions can be carried out at room temperature with low palladium loadings in high yields.
- Ohnmacht, Stephan A.,Brenstrum, Tim,Bleicher, Konrad H.,McNulty, James,Capretta, Alfredo
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p. 5661 - 5663
(2007/10/03)
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- MUSCARINIC AGONISTS
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The present invention relates to compounds of Formula (I): which are agonists of the M-1 muscarinic receptor.
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- MUSCARINIC AGONISTS
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The present invention relates to compounds of Formula (I): which are agonists of the M-1 muscarinic receptor.
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- Solid phase cross-coupling reaction of aryl(halo)silanes with 4-iodobenzoic acid
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Aryl(alkyl)(halo)silanes undergo facile and efficient palladium catalyzed cross-coupling reaction with iodobenzoic acid tethered to the Wang resin. Acid cleavage releases unsymmetrical biaryl carboxylic acids with high conversions, purities and yields.
- Homsi, Fadi,Hosoi, Kazushi,Nozaki, Kyoko,Hiyama, Tamejiro
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p. 208 - 216
(2007/10/03)
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- NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein
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The E2 protein is required for the replication of human papillomaviruses (HPVs), which are responsible for anogenital warts and cervical carcinomas. Using an NMR-based screen we tested compounds for binding to the DNA-binding domain of the HPV-E2 protein. Three classes of compounds were identified which bound to two distinct sites on the protein. Biphenyl and biphenyl ether compounds containing a carboxylic acid bind to a site near the DNA recognition helix and inhibit the binding of E2 to DNA. Benzophenone- containing compounds which lack a carboxylic acid group bind to the β- barrel formed by the dimer interface and exhibit negligible effects on the binding of E2 to DNA. Structure-activity relationships from the biphenyl and biphenyl ether compounds were combined to produce a compound [5-(3'- (3'',5''-dichlorophenoxy)-phenyl)-2,4-pentadienoic acid] with an IC50 value of approximately 10 μM. This compound represents a useful lead for the development of antiviral agents that interfere with HPV replication and further illustrates the usefulness of the SAR by NMR method in the drug discovery process.
- Hajduk, Philip J.,Dinges, Jürgen,Miknis, Gregory F.,Merlock, Megan,Middleton, Tim,Kempf, Dale J.,Egan, David A.,Walter, Karl A.,Robins, Terry S.,Shuker, Suzy B.,Holzman, Thomas F.,Fesik, Stephen W.
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p. 3144 - 3150
(2007/10/03)
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