- Reversible constitutional switching between macrocycles and polymers induced by shape change in a dynamic covalent system
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We report here the development of morphological switches as a new tool that can be used in constitutional dynamic chemistry (CDC) to control the constitution of the whole dynamic system. Molecules that have well-defined but switchable shapes were designed and synthesized. Their restrained conformational states were characterized both in the solid and in solution. The addition of metal ions induces a shape change through coordination; the shape generated was also fully investigated both in the solid and in solution. Such molecules constitute morphological switches, meaning that they can explore various shape states as a result of controlled well-defined shape changes triggered by an effector. These morphological switches were then integrated into covalent dynamic systems through formation of reversible imine bonds. Thermodynamic and kinetic analyses were performed in order to quantify the covalent equilibrium and to investigate the labile character of the covalent reversible link. It was then demonstrated that the molecular shape state of the morphological switches induces a well-defined constitution through covalent self-assembly, and that the system can be steered, quantitatively and reversibly without significant fatigue, between two different constitutional states, respectively, polymeric and macrocyclic assemblies. The dynamic covalent polymeric assemblies were analysed by DOSY NMR and small angle neutrons scattering (SANS). Their dynamic behaviour as a function of the concentration and the temperature was demonstrated and characterized. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
- Ulrich, Sebastien,Buhler, Eric,Lehn, Jean-Marie
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Read Online
- Side Arm Effects on Cation Binding, Extraction, and Transport Functions of Oligopyridine-Functionalized Aza-Crown Ethers
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A new series of lariat ethers and double-armed crown ethers was prepared in which oligopyridine-functionalized side arms were attached as secondary donor sites.A novel preparative method of oligopyridine derivatives was successfully applied to the synthes
- Tsukube, Hiroshi,Uenishi, Jun'ichi,Higaki, Hiromi,Kikkawa, Ken'ichi,Tanaka, Takakazu,et al.
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Read Online
- Two new ligands for carbonic anhydrase mimicry
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The syntheses of tris(2-nicotinic acid)methanol methyl ether 5 and tris(2-picolinic acid)methanol methyl ether 6, two tridentate ligands designed to also act as scaffolds for constructing chiral environments around their metal binding sites, is described. Improved yields for the essential lithiation-alkylation reactions that generate the trispyridyl core of these types of ligands are reported.
- Li, Xuehe,Gibb, Corinne L.D,Kuebel, Marie E,Gibb, Bruce C
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Read Online
- Photochemical C-H Silylation and Hydroxymethylation of Pyridines and Related Structures: Synthetic Scope and Mechanisms
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Considering the synthetic relevance of heteroarenes in various areas ranging from organic synthesis to medicinal chemistry, developing practically simple methodologies to access functionalized heteroarenes is of a significant value. Described herein is an efficient approach for C-H silylation and hydroxymethylation of pyridines and related heterocycles by the combination of silanes or methanol with readily available N-methoxypyridinium ions with a low catalyst loading (2 mol %) under blue light irradiation. The synthetic importance of the developed reactions is demonstrated by the synthesis of biologically relevant compounds. Electron paramagnetic resonance spectroscopy, quantum yield measurements, and density-functional theory calculations allowed us to understand reaction mechanisms of both photocatalytic reactions.
- Rammal, Fatima,Gao, Di,Boujnah, Sondes,Hussein, Aqeel A.,Lalevée, Jacques,Gaumont, Annie-Claude,Morlet-Savary, Fabrice,Lakhdar, Sami
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p. 13710 - 13717
(2020/11/30)
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- Bimetallic Bis-NHC-Ir(III) Complex Bearing 2-Arylbenzo[d]oxazolyl Ligand: Synthesis, Catalysis, and Bimetallic Effects
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Herein, an unprecedented bimetallic bis-NHC Cp*Ir complex 1 bearing 2-arylbenzo[d]oxazolyl and NHC ligands is reported. A significant increase in activity was observed for N-methylation of amines and reduction of aldehydes with MeOH catalyzed by 1 compared to the monometallic analogues (2-11). Under the optimal conditions, it showed to be highly effective in N-methylation of nitroarenes with MeOH as both C1 and H2 source. Substrates, including aromatic amines, ketones, and nitro compounds with various functional groups, can be well-tolerated. Mechanistic studies and DFT calculation highlight the significance of bimetallic centers cooperativity.
- Huang, Shuang,Hong, Xi,Cui, He-Zhen,Zhan, Bing,Li, Zhi-Ming,Hou, Xiu-Feng
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p. 3514 - 3523
(2020/10/09)
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- Homogeneous Hydrogenation with a Cobalt/Tetraphosphine Catalyst: A Superior Hydride Donor for Polar Double Bonds and N-Heteroarenes
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The development of catalysts based on earth abundant metals in place of noble metals is becoming a central topic of catalysis. We herein report a cobalt/tetraphosphine complex-catalyzed homogeneous hydrogenation of polar unsaturated compounds using an air- and moisture-stable and scalable precatalyst. By activation with potassium hydroxide, this cobalt system shows both high efficiency (up to 24 000 TON and 12 000 h-1 TOF) and excellent chemoselectivities with various aldehydes, ketones, imines, and even N-heteroarenes. The preference for 1,2-reduction over 1,4-reduction makes this method an efficient way to prepare allylic alcohols and amines. Meanwhile, efficient hydrogenation of the challenging N-heteroarenes is also furnished with excellent functional group tolerance. Mechanistic studies and control experiments demonstrated that a CoIH complex functions as a strong hydride donor in the catalytic cycle. Each cobalt intermediate on the catalytic cycle was characterized, and a plausible outer-sphere mechanism was proposed. Noteworthy, external inorganic base plays multiple roles in this reaction and functions in almost every step of the catalytic cycle.
- Duan, Ya-Nan,Du, Xiaoyong,Cui, Zhikai,Zeng, Yiqun,Liu, Yufeng,Yang, Tilong,Wen, Jialin,Zhang, Xumu
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supporting information
p. 20424 - 20433
(2019/12/27)
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- Hemilabile Benzyl Ether Enables Γ-C(sp3)-H Carbonylation and Olefination of Alcohols
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Pd-catalyzed C(sp3)-H activation of alcohol typically shows β-selectivity due to the required distance between the chelating atom in the attached directing group and the targeted C-H bonds. Herein we report the design of a hemilabile directing group which exploits the chelation of a readily removable benzyl ether moiety to direct Γ- or δ-C-H carbonylation and olefination of alcohols. The utility of this approach is also demonstrated in the late-stage C-H functionalization of β-estradiol to rapidly prepare desired analogues that required multi-step syntheses with classical methods.
- Tanaka, Keita,Ewing, William R.,Yu, Jin-Quan
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supporting information
p. 15494 - 15497
(2019/10/16)
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- Hemilabile Benzyl Ether Enables γ-C(sp3)-H Carbonylation and Olefination of Alcohols
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Pd-catalyzed C(sp3)-H activation of alcohol typically shows β-selectivity due to the required distance between the chelating atom in the attached directing group and the targeted C-H bonds. Herein we report the design of a hemilabile directing group which exploits the chelation of a readily removable benzyl ether moiety to direct γ- or δ-C-H carbonylation and olefination of alcohols. The utility of this approach is also demonstrated in the late-stage C-H functionalization of β-estradiol to rapidly prepare desired analogues that required multi-step syntheses with classical methods.
- Tanaka, Keita,Ewing, William R.,Yu, Jin-Quan
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supporting information
(2019/10/22)
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- Methanol as hydrogen source: Transfer hydrogenation of aromatic aldehydes with a rhodacycle
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A cyclometalated rhodium complex has been shown to perform highly selective and efficient reduction of aldehydes, deriving the hydrogen from methanol. With methanol as both the solvent and hydrogen donor under mild conditions and an open atmosphere, a wide range of aromatic aldehydes were reduced to the corresponding alcohols, without affecting other functional groups.
- Aboo, Ahmed H.,Bennett, Elliot L.,Deeprose, Mark,Robertson, Craig M.,Iggo, Jonathan A.,Xiao, Jianliang
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supporting information
p. 11805 - 11808
(2018/11/10)
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- BIARYL DERIVATIVE AS GPR120 AGONIST
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The present invention relates to a biaryl derivative expressed by the chemical formula 1, a method for producing the biaryl derivative, a pharmaceutical composition comprising same, and use of same, the biaryl derivative expressed by the chemical formula 1, as a GPR120 agonist, promoting GLP-1 generation in the gastro-intestinal tract, reducing insulin resistance in the liver, muscles and the like from anti-inflammatory activity in the macrophage, pancreatic cells and the like, and allowing effective use in prevention or treatment of inflammation or metabolic diseases such as diabetes, complications from diabetes, obesity, non-alcoholic fatty liver disease, fatty liver disease, and osteoporosis.
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Paragraph 0505
(2017/11/17)
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- COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR
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Disclosed are compounds of Formula I: or a pharmaceutically acceptable salt, a solvate, a tautomer, an isomer or a deuterated analog thereof, wherein Z2, Z3, and Z5 are as described herein, compositions thereof, and uses t
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Paragraph 0546; 0547
(2017/07/01)
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- New hybrid bromopyridine-chalcones as in vivo phase II enzyme inducers: potential chemopreventive agents
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Cancer prevention can be achieved by the administration of cancer chemopreventive agents (CCAs) that prevent, delay or reverse the carcinogenic process. CCAs that are able to induce detoxification enzymes, especially monofunctional phase II enzymes, have become an excellent therapeutic strategy. Herein, we report the synthesis of eighteen new potential CCAs, structurally designed to combine (naphtho)chalcone and (bromo)pyridine skeletons. After a selection process involving in vitro phase II induction studies, cytotoxicity against tumoral cells, mutagenicity (the Ames test), and capability for DNA strand breakage (the alkaline comet assay), compound 22, (E)-3-(2-bromopyridin-3-yl)-1-(2-hydroxyphenyl)-2-propen-1-one, was selected for animal studies. The in vivo proof of concept study for derivative 22 demonstrated that it was able to significantly increase the QR and GST activities in the liver, colon and mammary gland without significant induction of the phase I enzyme, CYP. Additionally, we found that for 22 and another in vitro QR activity inducer, (E)-1-(2-hydroxyphenyl)-3-(naphthalen-1-yl)-2-propen-1-one (compound 8), Nrf2 nuclear translocation is operative allowing the exertion of protective effects via the expression of downstream phase II enzymes.
- Cabrera, Mauricio,Cerecetto, Hugo,González, Mercedes
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p. 2395 - 2409
(2016/12/18)
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- N-SUBSTITUTED PYRAZOLE DERIVATIVE
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PROBLEM TO BE SOLVED: To provide a novel compound having antagonism to a group II metabolism type glutamic acid (mGlu) receptor or salt which is permitted in medical field, in addition, to provide an agent for preventing or treating novel mood disorders (
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Paragraph 0079
(2016/10/08)
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- HETEROARYL COMPOUNDS USEFUL AS INHIBITORS OF SUMO ACTIVATING ENZYME
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Disclosed are compounds of formula (I): or a pharmaceutically acceptable salt thereof; wherein Y, Ra, Ra', Rc, Rf, X2, Rd, Rd', Re, Re', m, and G have the values described herein and stereochemical configurations depicted at asterisked positions indicate absolute stereochemistry, useful as inhibitors of Sumo Activating Enzyme (SAE). Further provided are pharmaceutical compositions comprising a compound of the disclosure and methods of using the compositions in the treatment of proliferative, inflammatory, cardiovascular and neurodegenerative diseases or disorders.
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Paragraph 00167
(2015/01/16)
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- Strain-Induced Reactivity in the Dynamic Covalent Chemistry of Macrocyclic Imines
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The displacement of molecular structures from their thermodynamically most stable state by imposition of various types of electronic and conformational constraints generates highly strained entities that tend to release the accumulated strain energy by undergoing either structural changes or chemical reactions. The latter case amounts to strain-induced reactivity (SIR) that may enforce specific chemical transformations. A particular case concerns dynamic covalent chemistry which may present SIR, whereby reversible reactions are activated by coupling to a high-energy state. We herewith describe such a dynamic covalent chemical (DCC) system involving the reversible imine formation reaction. It is based on the formation of strained macrocyclic bis-imine metal complexes in which the macrocyclic ligand is in a high energy form enforced by the coordination of the metal cation. Subsequent demetallation generates a highly strained free macrocycle that releases its accumulated strain energy by hydrolysis and reassembly into a resting state. Specifically, the metal-templated condensation of a dialdehyde with a linear diamine leads to a bis-imine [1+1]-macrocyclic complex in which the macrocyclic ligand is in a coordination-enforced strained conformation. Removal of the metal cation by a competing ligand yields a highly reactive [1+1]-macrocycle, which then undergoes hydrolysis to transient non-cyclic aminoaldehyde species, which then recondense to a strain-free [2+2]-macrocyclic resting state. The process can be monitored by 1H NMR spectroscopy. Energy differences between different conformational states have been evaluated by Hartree-Fock (HF) computations. One may note that the stabilisation of high-energy molecular forms by metal ion coordination followed by removal of the latter, offers a general procedure for producing out-of-equilibrium molecular states, the fate of which may then be examined, in particular when coupled to dynamic covalent chemical processes.
- Ratjen, Lars,Vantomme, Ghislaine,Lehn, Jean-Marie
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supporting information
p. 10070 - 10081
(2015/07/07)
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- Inhibition of 1-deoxy-d-xylulose-5-phosphate reductoisomerase by lipophilic phosphonates: SAR, QSAR, and crystallographic studies
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1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) is a novel target for developing new antibacterial (including antituberculosis) and antimalaria drugs. Forty-one lipophilic phosphonates, representing a new class of DXR inhibitors, were synthesized, among which 5-phenylpyridin-2-ylmethylphosphonic acid possesses the most activity against E. coli DXR (EcDXR) with a K i of 420 nM. Structure-activity relationships (SAR) are discussed, which can be rationalized using our EcDXR:inhibitor structures, and a predictive quantitative SAR (QSAR) model is also developed. Since inhibition studies of DXR from Mycobacterium tuberculosis (MtDXR) have not been performed well, 48 EcDXR inhibitors with a broad chemical diversity were found, however, to generally exhibit considerably reduced activity against MtDXR. The crystal structure of a MtDXR:inhibitor complex reveals the flexible loop containing the residues 198-208 has no strong interactions with the 3,4-dichlorophenyl group of the inhibitor, representing a structural basis for the reduced activity. Overall, these results provide implications in the future design and development of potent DXR inhibitors.
- Deng, Lisheng,Diao, Jiasheng,Chen, Pinhong,Pujari, Venugopal,Yao, Yuan,Cheng, Gang,Crick, Dean C.,Prasad, B. V. Venkataram,Song, Yongcheng
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experimental part
p. 4721 - 4734
(2011/09/19)
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- Synthesis and luminescence properties of new red-shifted absorption lanthanide(iii) chelates suitable for peptide and protein labelling
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The synthesis and photo-physical properties of an original bis-pyridinylpyrazine chromophore efficiently sensitising europium(iii) and samarium(iii) are described. The corresponding lanthanide(iii) complexes display in aqueous solutions a maximum excitation wavelength which is significantly red-shifted compared to the usual terpyridine-based chelates, and a valuable luminescence brightness above 2 000 dm3 mol-1 cm -1 at 345 nm was obtained with a europium(iii) derivative. Further functionalisation with three different bioconjugatable handles was also investigated and their ability to efficiently label a model hexapeptide was evaluated and compared. Finally, the best bioconjugatable europium(iii) chelate was used in representative labelling experiments involving monoclonal antibodies and the luminescence features of the corresponding bioconjugates remained satisfactory.
- Maindron, Nicolas,Poupart, Severine,Hamon, Maxime,Langlois, Jean-Baptiste,Ple, Nelly,Jean, Ludovic,Romieu, Anthony,Renard, Pierre-Yves
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experimental part
p. 2357 - 2370
(2011/05/13)
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- Addressing the poly- to oligo-ketone selectivity in styrene carbonylation catalyzed by palladium/bpy complexes. effect of the 6-alkyl substitution
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Two series of organometallic Pd complexes, namely, (i) [Pd(CH 3)(CH3CN)(N-N′)][PF6] and (ii) [Pd(CH3)(N-N′)2][PF6], with a range of 6-alkyl-substituted-2,2′-bipyridine ligands, including the new 6-(1-methoxyethyl)-2,2′-bipyridine, in both racemic and enantiopure form, and 2-(methoxymethyl)-6-(1H-1,2,3-triazol-1-yl)pyridine, have been studied. 6-(1-Methoxyethyl)-2,2′-bipyridine was synthesized both in racemic and in the opposite homochiral enantiomeric forms by two stereocomplementary chemoenzymatic procedures. The characterization of the new complexes, both in solid state and in solution, provides evidence for the formation of a unique isomer featuring the methyl ligand trans to the Pd-N bond of the substituted pyridine ring. For the complex with the bpy ligand having the sec-butyl substituent a cyclometalation reaction with the release of methane occurs, leading the substituted bpy to act as a terdentate N-N′-C ligand. Complexes of series ii feature one chelate N-N′ ligand, while the other one is coordinated to Pd in a monodentate fashion. In solution a fluxional process that makes equivalent the two N-N′ ligands is present, and the static 1H NMR spectra correspond to an averaged structure where palladium is a stereogenic center. All these complexes behave as catalysts for styrene carbonylation, yielding CO/styrene oligoketones, which are optically active when catalysts containing chiral, enantiomerically pure, ligands are applied. For both series of complexes the reactivity with labeled CO has been investigated, leading to the formation of the corresponding Pd-acetyl species, with that for complexes of series ii featuring both N-N′ molecules bonded to the same metal center.
- D'Amora, Angela,Fanfoni, Lidia,Cozzula, Daniela,Guidolin, Nicol,Zangrando, Ennio,Felluga, Fulvia,Gladiali, Serafino,Benedetti, Fabio,Milani, Barbara
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experimental part
p. 4472 - 4485
(2011/01/06)
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- BICYCLIC NITROIMIDAZOLES COVALENTLY LINKED TO SUBSTITUTED PHENYL OXAZOLIDINONES
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The current invention provides a series of bicyclic nitroimidazole- substituted phenyl oxazolidinones in which a bicyclic nitroimidazole pharmacophore is covalently bonded to a phenyl oxazolidinone, their pharmaceutical compositions, and the method of use of the compositions for prevention and treatment of bacterial infections. The bicyclic nitroimidazole-substituted phenyl oxazolidinones possess surprising antibacterial activity against wild- type and resistant strains of pathogens, and are therefore useful for the prevention, control and treatment of a number of human and veterinary bacterial infections caused by these pathogens, such as Mycobacterium tuberculosis.
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Page/Page column 80; 81
(2009/10/22)
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- TRIAZOLO [4, 5-D] PYRAMIDINE DERIVATIVES AND THEIR USE AS PURINE RECEPTOR ANTAGONISTS
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Compounds of formula (I) that are capable of acting as purine receptor antagonists, pharmaceutical compositions including the compounds, and methods of making the compounds, are. disclosed. The compounds and compositions can be used in treating or preventing disorders related to purine receptor hyperfunctioning.
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Page/Page column 59
(2010/01/30)
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- Orally Bioavailable Caffeic Acid Related Anticancer Drugs
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The present invention concerns compounds and their use to treat cell proliferative diseases such as cancer. Compounds of the present invention display significant potency as inhibitors of Jak2/STAT3 pathways and downstream targets and inhibit the growth and survival of cancerous cell lines.
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Page/Page column 18
(2008/06/13)
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- 2,6-Disubstituted N-arylsulfonyl piperidines as γ-secretase inhibitors
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A novel piperidine series of γ-secretase inhibitors, potentially useful for the treatment of Alzheimer's disease, is disclosed. SAR investigation revealed the requirement for cis-stereochemistry of the substituents attached to the core, which resulted in
- Pissarnitski, Dmitri A.,Asberom, Theodros,Bara, Thomas A.,Buevich, Alex V.,Clader, John W.,Greenlee, William J.,Guzik, Henry S.,Josien, Hubert B.,Li, Wei,McEwan, Michael,McKittrick, Brian A.,Nechuta, Terry L.,Parker, Eric M.,Sinning, Lisa,Smith, Elizabeth M.,Song, Lixin,Vaccaro, Henry A.,Voigt, Johannes H.,Zhang, Lili,Zhang, Qi,Zhao, Zhiqiang
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- New pyridine ONN-pincer gold and palladium complexes: Synthesis, characterization and catalysis in hydrogenation, hydrosilylation and C-C cross-coupling reactions
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The ONN-tridentate unsymmetrical pincer 2-[6-(pyrrolidin-1-ylmethyl) pyridin-2-yl]phenol and N-terf-butyl-1-{[6-(2-hydroxyphenyl)pyridin-2-yi] metriyl}pyrrolidine-2-carboxamide ligands were synthesized by an easy method in high purity and good yields. All the organic compounds were characterized by elemental analysis, mass spectrometry, IR and 1H and 13C NMR spectroscopy. Palladium(II) and gold(III) complexes have been prepared as air-stable solids, with the ONN-tridentate ligand after deprotonation of the hydroxy group, the coordination of the metal ion is completely stereospecific and gives rise to only one diastereoisomer. These complexes were shown to be very active catalysts in the hydrogenation (80 % ee was achieved with the chiral gold complex), hydrosilylation and C-C coupling, Suzuki and Heck, reactions, under mild conditions.
- Debono,Iglesias,Sanchez
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p. 2470 - 2476
(2008/09/19)
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- Bis(oxazoline) lewis acid catalyzed aldol reactions of pyridine N-oxide aldehydes-synthesis of optically active 2-(1-hydroxyalkyl)pyridine derivatives: Development, scope, and total synthesis of an indolizine alkaloid
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A new. short, and simplified procedure for the synthesis of optically active pyridine derivatives from prochiral pyridine-N-oxides is presented. The catalytic and asymmetric Mukaiyama aldol reaction between ketene silyl acetals and l-oxypyridine-2-carhaldehyde derivatives catalyzed by chiral copper(ii)-bis(oxazoline) complexes gave optically active 2-(hydroxyalkyl)-and 2-(anti-1.2-dihydroxyalkyl)pyridine derivatives in good yields and diastereoselectivities, and in excellent enantioselectivities - up to 99% enantiomeric excess. As a synthetic application of the developed method, a full account for the asymmetric total synthesis of a nonnatural indolizine alkaloid is provided.
- Landa, Aitor,Minkkilae, Anna,Blay, Gonzalo,Jergensen, Karl Anker
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p. 3472 - 3483
(2008/02/03)
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- POTENTIATORS OF GLUTAMATE RECEPTORS
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The present invention provides compounds of formula (I); pharmaceutical compositions thereof, and methods of using the same, processes or preparing the same, and intermediates thereof.
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Page/Page column 116-117
(2010/11/08)
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- COMPOUNDS USEFUL AS A3 ADENOSINE RECEPTOR AGONISTS
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Compounds useful as A3 Adenosine Receptor Agonists. Adenosine analogue-type A3 receptor agonists having an N6 substituent of the formula CR20R21CYCLE where CYCLE is a specified heterocycle, e.g. a substituted pyridyl group or a substituted oxazolyl-containing bicyclic ring. 10
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Page/Page column 50
(2010/02/10)
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- CYCLIC COMPOUNDS
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There is provided a CRF receptor antagonist comprising a compound of the formula (I): A-W-Ar wherein, A is a group represented by the formula (A1) or (A2) (wherein, ring Aa is a 5-or 6-membered ring which may be further substituted; ring Ab is a 5-or 6-membered ring which may be further substituted; ring Ac is a 5- or 6-membered ring which may be substituted; R1 is optionally substituted alkyl, substituted amino, substituted hydroxy, etc.; X is carbonyl, -O-, -S-, etc.; Y1, Y2 and Q are independently optionally substituted carbon or nitrogen; … is a single or double bond); W is a bond, optionally substituted methylene, optionally substituted imino, -O-, -S-, etc.; Ar is optionally substituted aryl or optionally substituted heteroaryl; or a salt thereof or a prodrug thereof.
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Page/Page column 208-209
(2010/02/14)
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- 2,3-Diarylthiophenes as selective EP1 receptor antagonists
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The synthesis and the EP1 receptor binding affinity of 2,3-diarylthiophene derivatives are described. The evaluation of the structure-activity relationship (SAR) in this series led to the identification of compounds 4, 7, and 12a, which exhibit high affinity for the human EP 1 receptor and a selectivity greater than 100-fold against the EP2, EP3, EP4, DP, FP, and IP receptors and greater than 25-fold versus the TP receptor. These three antagonists present good pharmacokinetics in rats and significant differences in the way they are distributed in the brain.
- Ducharme, Yves,Blouin, Marc,Carriere, Marie-Claude,Chateauneuf, Anne,Cote, Bernard,Denis, Danielle,Frenette, Richard,Greig, Gillian,Kargman, Stacia,Lamontagne, Sonia,Martins, Evelyn,Nantel, Francois,O'Neill, Gary,Sawyer, Nicole,Metters, Kathleen M.,Friesen, Richard W.
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p. 1155 - 1160
(2007/10/03)
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- TETRAHYDROQUINOLINE DERIVATIVES AND A PROCESS FOR PREPARING THE SAME
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A novel compound of the formula (I): wherein R1 is alkoxycarbonyl or the like, R2 is alkyl or the like; R3 is hydrogen or the like; R4 is alkylene or the like; R5 is optionally substituted heterocyclic group; R6, R7, R8 and R9 are independently hydrogen; alkyl, alkoxy, or the like; R10 is optionally substituted aromatic ring, or the like; or a pharmaceutically acceptable salt thereof, which has an inhibitory activity against cholesteryl ester transfer protein (CETP).
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Page/Page column 130
(2010/02/14)
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- PEG-supported pyridylthioesters for racemization-free amide synthesis: A reagent that allows simultaneous product formation and removal from the polymer
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Pyridylthioesters anchored to a modified poly(ethylene glycol) of M w 5000 Da have been prepared in high yields. The thioesters were employed as a convenient starting material for the liquid-phase synthesis of various enantiomerically pure amid
- Benaglia, Maurizio,Guizzetti, Stefania,Rigamonti, Clara,Puglisi, Alessandra
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p. 12100 - 12106
(2007/10/03)
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- Heteroaryl derivatives as superior ligands for nociceptin receptor ORL-1
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Novel compounds of the formula wherein R is optionally substituted heteroaryl or R1 is H or C1—C6 alkyl; and R2 and R3 are —CH3, —OCH3 or halo; or a pharmaceutically acceptable salt or solvate thereof, pharmaceutical compositions therefore, and the use of said compounds in the treatment of pain, anxiety, cough, asthma, depression and alcohol abuse are disclosed.
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- Palladium-catalyzed synthesis of nonsymmetrically functionalized bipyridines, poly(bipyridines) and terpyridines
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Palladium-catalyzed coupling reactions were employed to prepare nonsymmetric, densely functionalized bipyridines and oligo(bipyridines), featuring sensitive functionalities like alcohol, ester and aldehyde groups. Stille coupling between halo (poly)pyridine and the proper (poly)pyridyltin derivative afforded in good yields nonsymmetric, derivatized oligo(bipyridines), amenable to further synthetic modifications. The methodology was used also to synthesize highly functionalized terpyridines. A series of Suzuki and Stille palladium-promoted coupling reactions allowed us to obtain in good yields terpyridines bearing two different and differently functionalizable groups, valuable building blocks for the construction of complex supramolecular frameworks. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Puglisi, Alessandra,Benaglia, Maurizio,Roncan, Giulia
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p. 1552 - 1558
(2007/10/03)
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- Copper(I) ion mediated self-assembly of triple-stranded helicates from oligo(2-ethynylpyridines): Synthesis, structure, and properties
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The reaction of oligo(2-ethynylpyridines) (L1-L8) with copper(I) ions proceeded smoothly to afford tri-, tetra-, and pentanuclear triple-stranded helicates (CL1-CL8) in good yields. If a chiral ligand was used, the stereoselective self-assembly of chiral helicates with one particular chirality was achieved in the solid state. Racemization of copper(I) helicates was also observed in solution.
- Kawano, Tomikazu,Kato, Takahiro,Du, Chong-Xu,Ueda, Ikuo
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p. 709 - 719
(2007/10/03)
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- Synthesis of oligo(2-ethynylpyridines): Novel building blocks for supramolecular systems
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New oligo(2-ethynylpyridines) 1 are synthesized as novel building blocks for the construction of supramolecular systems by the coupling reaction of the novel dibromopyridines 2 with ethynylpyridines 3.
- Kawano, Tomikazu,Kato, Takahiro,Du, Chong-Xu,Ueda, Ikuo
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p. 6697 - 6700
(2007/10/03)
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- Ligands containing alternating 2,6-linked pyridine and 2,5-linked thiophene units
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A variety of linear assemblies of alternating pyridine (2,6-linked) [P] and thiophene (2,5-linked) [T] units have been generated with up to seven units and their macrocyclisation investigated. The optimal methods involved the palladium(0) catalysed reaction of thienyl Grignard reagents with bromopyridines. In this way were made TPT, TPTPT, TPTPTPT, BrPTPBr and various XCH2PTPTPCH2X derivatives (X = H, Br, OH, OR and SBu-t). Alternative routes whereby pyridine units were 2,6-linked by CH2SCH2 units, with the intention of converting the bridge groups into thiophenes by a Hinsberg reaction, were also studied. The latter products {(HOCH2[P]CH2)2S and (HOCH2[P]-CH2SCH2)2[P]} proved to be highly effective ligands for transition metals, especially divalent ones such as Co2+, Ni2+ and Zn2+. No macrocyclisations were effective.
- Meth-Cohn, Otto,Jiang, Hui
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p. 3737 - 3745
(2007/10/03)
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- Double subroutine self-assembly; spontaneous generation of a nanocyclic dodecanuclear Cu(I) inorganic architecture
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The newly synthesised ligand 2 combines binding components known to undergo specific and distinct self-assembly processes with Cu(I) ions. It complexes Cu(I) to form, in almost quantitative yield, a large inorganic architecture 1 made up from four ligand molecules and twelve metal ions. The structure of 1 was ascertained by X-ray radiocrystallography as well as by NMR spectroscopy and electrospray mass spectrometry. It consists of a macrocycle of nanometric dimension with an external diameter of 28 A; the central cavity has a diameter of 11 A which contains four PF6/- anions as well as solvent molecules. The spontaneous formation of 1 results from a self-assembly process based on a 'program' combining two assembly subroutines, each specific to one of the ligand subunits. Self-assembly through double or, more generally, multipie subroutines can be used to generate a wide variety of highly complex inorganic supramolecular architectures by combination of two or more assembly processes.
- Funeriu, Daniel P.,Lehn, Jean-Marie,Baum, Gerhard,Fenske, Dieter
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- A study of the lithiation of 2,6-dibromopyridine with butyllithium, and its application to synthesis of L-739,010
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Mono-lithiation of 2,6-dibromopyridine by n-BuLi is complicated by deprotonation of the pyridine ring by the resulting mono-lithium species. This problem can be eliminated by a reverse addition, but this causes formation of the undesired dilithio species. However, rapid lithium-halogen exchange between 2,6-dibromopyridine and 2,6-dilithiopyridine produces 2-bromo-6-lithiopyridine cleanly. Thus, using reverse addition, the mono-lithiated pyridine can be generated in 98% yield.
- Cai, Dongwei,Hughes, David L.,Verhoeven, Thomas R.
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p. 2537 - 2540
(2007/10/03)
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- Chiral Pyridyl Alcohol-Promoted Highly Enantioselective and Rapid Addition of Dialkylzinc to Pyridinecarboxaldehydes
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Optically active 1-(2-, 3-, and 4-pyridyl)propanols and 1-(3-pyridyl)ethanol were synthesized in good to high enantiomeric excesses (up to 88percent e.e.) and in a short reaction time by catalyzed asymmetric addition of dialkylzinc to pyridine-2-, 3- and 4-carboxaldehydes and 6-bromopyridine-2-carboxaldehyde in the presence of tridentate chiral 2--1,1-diarylethanols.
- Ishizaki, Miyuki,Hoshino, Osamu
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p. 1337 - 1340
(2007/10/02)
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- Preparation of some Substituted Imidazopyridine Derivatives
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2-Bromopyridine derivatives 2a-2c were prepared. Compounds 2b and 2c and ammonia yielded aminopyridines 3b and 3c which were converted to imidazopyridine derivatives 4b and 4c. Compound 4b was nitrated giving the analogue 5b of metronidazole 1.
- Shawcross, Andrew P.,Stanforth, Stephen P.
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p. 563 - 565
(2007/10/02)
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- Catalyzed Enantioselective Alkylation of Aldehydes
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Enantioselective alkylation of a variety of aldehydes with diethylzinc was achieved by using catalytic amounts of optically active pyridines and C2-symmetric 2,2'-bipyridines.The products were obtained in good yields with high enantioselectivit
- Bolm, Carsten,Schlingloff, Gunther,Harms, Klaus
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p. 1191 - 1204
(2007/10/02)
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