- Preparation and characterization of oligo-(2,2′-bipyridyl)pyrazines
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An improved preparation of 2,2′-bipyridine-6-carboxaldehyde 1 provides this compound in good yield for the further syntheses of oligo-(2,2′-bipyridyl)pyrazines 6-8, new ligands for supramolecular metallorganic complexes. According to 1H-NMR spectroscopic and X-ray crystallographic studies, the bis(2,2′-bipyridyl) compound 6 exists in a helical conformation in solution and in the solid state. The structure of the tetrakis(2,2′-bipyridyl) compound 8 is also confirmed through its crystal structure. VCH Verlagsgesellschaft mbH, 1997.
- Heirtzler, Fenton R.,Neuburger, Markus,Zehnder, Margareta,Constable, Edwin C.
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- Use of Stille-type cross-coupling as a route to oligopyridylimines
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The new tin reagents, 2-(n-Bu3Sn)-6-{C(R)OCH2CH 2O}-C5H3N, (R=H a, Me b), have been employed in Stille-type cross-coupling reactions with a range of oligopyridylbromides generating, following a facile deprotection step, a series of formyl- and acetyl-functionalised oligopyridines. Condensation reactions with 2,6-diisopropylaniline has allowed access to families of novel sterically bulky multidentate N,N,N,N (tetradentate), N,N,N,N,N (pentadentate), N,N,N,N,N,N (sexidentate) and N,N,N,N,N,N,N (heptadentate) nitrogen donor ligands. This work represents a straightforward and rapid synthetic route for the preparation of oligopyridylimines, which are expected to act as useful components for the self-assembly of polymetallic complexes.
- Champouret, Yohan D.M.,Chaggar, Rajinder K.,Dadhiwala, Ishaq,Fawcett, John,Solan, Gregory A.
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- Investigation of ‘head-to-tail’-connected oligoaryl n,o-ligands as recognition motifs for cancer-relevant G-quadruplexes
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Oligomeric compounds, constituted of consecutive N,O-heteroaromatic rings, introduce useful and tunable properties as alternative ligands for biomolecular recognition. In this study, we have explored a synthetic scheme relying on Van Leusen oxazole formation, in conjunction with C–H activation of the formed oxazoles and their subsequent C–C cross-coupling to 2-bromopyridines in order to assemble a library of variable-length, ‘head-to-tail’-connected, pyridyl-oxazole ligands. Through investigation of the interaction of the three longer ligands (5-mer, 6-mer, 7-mer) with cancer-relevant G-quadruplex structures (human telomeric/22AG and c-Myc oncogene promoter/Myc2345-Pu22), the asymmetric pyridyl-oxazole motif has been demonstrated to be a prominent recognition element for G-quadruplexes. Fluorescence titrations reveal excellent binding affinities of the 7-mer and 6-mer for a Na+-induced antiparallel 22AG G-quadruplex (KD = 0.6 × 10?7 M?1 and 0.8 × 10?7 M?1, respectively), and satisfactory (albeit lower) affinities for the 22AG/K+ and Myc2345-Pu22/K+ G-quadruplexes. All ligands tested exhibit substantial selectivity for G-quadruplex versus duplex (ds26) DNA, as evidenced by competitive F rster resonance energy transfer (FRET) melting assays. Additionally, the 7-mer and 6-mer are capable of promoting a sharp morphology transition of 22AG/K+ G-quadruplex.
- Rizeq, Natalia,Georgiades, Savvas N
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- An acyclic oligoheteroaryle that discriminates strongly between diverse G-Quadruplex topologies
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Feeling groovy: A family of nonmacrocyclic G-quadruplex binders with alternate oxazole and pyridine motifs was prepared. The shown heptacyclic derivative exhibits an unprecedented binding preference for certain quadruplex topologies: it recognizes exclusively the human telomeric quadruplex in Na + buffer but not in K+ buffer. This unique quadruplex binding profile is strongly dependent on the size of the ligand and may result from groove interactions. Copyright
- Hamon, Florian,Largy, Eric,Guedin-Beaurepaire, Aurore,Rouchon-Dagois, Myriam,Sidibe, Assitan,Monchaud, David,Mergny, Jean-Louis,Riou, Jean-Francois,Nguyen, Chi-Hung,Teulade-Fichou, Marie-Paule
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- CBP/CATENIN SIGNALING PATHWAY INHIBITORS AND USES THEREOF
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Provided are compounds of formula (Ia), (Ib) and (IIa), and pharmaceutically acceptable salts thereof. Additionally provided are compositions and pharmaceutical compositions comprising the compounds, therapeutic methods using same for modulating (e.g., inhibiting) CREB binding protein (CBP)/β-catenin mediated signaling in treating a condition, disease or disorder (e.g., fibrosis, cancer, neurological conditions, metabolic disorders (e.g., diabetes, etc.), and skin conditions (dermatitis, psoriasis, scarring, alopecia, etc.) mediated by aberrant CBP/β -catenin signaling, and cosmetic methods for treating skin conditions (e.g., aging, etc.). Additionally provided are methods for enhancing vaccine efficacy using the compounds and compositions. Further provided are methods for efficiently synthesizing a clinical grade drug, comprising use, in a penultimate, or last reaction step under GMP conditions, of an intermediate 2-propynyl-compound to form a clinical grade isoxazole derivative (e.g., via 3+2 cycloaddition).
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Page/Page column 53-54
(2021/09/17)
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- Such pyridine skeleton of a chiral shan lin ligand CF - Phos and its preparation method and application (by machine translation)
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The invention discloses a pyridine skeleton of chiral shan lin ligand CF - Phos and its preparation method and application, the [...] ligand is compound 1 or compound 1 of the enantiomer, racemate and diastereoisomer; the ligand to the preparation method of the compound is and As the raw material, the condensation reaction, the substitution reaction, hydrolysis reaction, addition reaction for preparing the states shan lin ligand; or in order to compound and As the raw material, a condensation reaction, and or The addition reaction for preparing the states shan lin ligand. The present invention through the use of two configurations of the compound And different types of metal reagent addition reaction, can be obtained by states chiral shan lin ligand i.e. compound 1 (S, Rs ), 1 (R, Rs ), 1 (S, Ss ) And 1 (R, Ss ) Of four full-configuration of optically pure. The invention also discloses the ligands copper catalytic unsaturated carboxylic acid in the application of the asymmetric lactonization reaction, has wide application value. (by machine translation)
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Paragraph 0108-0110
(2019/05/02)
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- Palladium pyridine imine complex for preparing synthetic lubricating oil for preparation of alpha-olefins as well as preparation method and application of palladium pyridine imine complex
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The invention discloses a palladium pyridine imine complex for preparing synthetic lubricating oil for preparation of alpha-olefins as well as a preparation method and application of the palladium pyridine imine complex. The complex (I) is prepared by the following steps: synthesizing a compound (II), a compound (III), a compound (IV) and a compound (V) in sequence, and finally synthesizing the complex (I) from the compound (V). The complex serves as a catalyst for preparing lower poly-alpha-olefins. The complex catalyst prepared with the method disclosed by the invention is applied to preparation of the lower poly-alpha-olefins and can replace a metallocene (MAO) catalytic system, so that MAO and other catalysts are avoided in the oligomerization process of the alpha-olefins, the processcost is reduced, reaction conditions are mild because the MAO is not needed to be added, the reaction does not need to be carried out under harsh water-free and oxygen-free conditions, and the processdifficulty is reduced. Moreover, after the prepared lower poly-alpha-olefins are subjected to hydrogenated saturation, base oil of PAO lubricating oil can be obtained.
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Paragraph 0043; 0045-0047; 0060; 0062-0064
(2019/10/23)
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- Non-symmetrical, potentially redox non-innocent imino NHC pyridine 'pincers': Via a zinc ion template-assisted synthesis
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New non-symmetrical, redox-active imino NHC pyridine pincer ligands, 2-(R1-imidazol-2-ylidene)-6-(R2NCH)-pyridine (R1 = 2,6-diisopropylphenyl (DiPP), R2 = 2,4,6-trimethylphenyl (Mes), 4B; R1 = R2 = DiPP, 4C), have been accessed by a ZnII-promoted modular synthesis involving the quaternization of R1-imidazole by [Zn(κNimineκNpyridine)(2-(R2NCH)-6-bromo-pyridine)Cl2], followed by ZnII removal and deprotonation of imidazolium pro-ligands. Redox active forms of 4B were implicated in the two complexes obtained by its reaction with FeBr2/KC8; metrical data analysis pointed to the occurrence of radical anionic and dianionic redox states of 4B.
- Simler, Thomas,Danopoulos, Andreas A.,Braunstein, Pierre
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p. 5955 - 5964
(2017/07/10)
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- Linear and Branched Pyridyl-Oxazole Oligomers: Synthesis and Circular Dichroism Detectable Effect on c-Myc G-Quadruplex Helicity
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Five unprecedented pyridyl-oxazole oligomers exhibiting either linear or branched connectivity of their subunits were developed as a family of potential G-quadruplex-interacting ligands. Our synthesis employed variations of a key Pd/Cu-mediated C-C cross-coupling/C-H activation reaction to gain access to the oligomer products from a small set of substituted pyridine building blocks. The effect of the compounds on the conformation of a c-myc oncogene promoter G-quadruplex was investigated by circular dichroism under various conditions. Some or all of the compounds induced detectable helicity enhancement in low-cation and Na+-rich Tris-HCl (pH 7.4) buffers, respectively, in which the helix was only partially prefolded.
- Rizeq, Natalia,Georgiades, Savvas N.
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p. 122 - 131
(2016/01/26)
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- NOVEL CARBENE PRECURSOR COMPOUND, OLEFINIC CATALYST FOR POLYMERIZATION COMPRISING THE SAME, AND METHOD FOR PRODUCING OLEFINIC COPOLYMER
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PROBLEM TO BE SOLVED: To provide a novel carbene precursor compound, an olefinic catalyst for polymerization comprising the same, and a method for producing an olefinic copolymer. SOLUTION: A carbene precursor compound is represented by the formula (5) or (6). SELECTED DRAWING: None COPYRIGHT: (C)2016,JPO&INPIT
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Paragraph 0161; 0162
(2016/11/09)
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- ANTIBACTERIAL BASIC BIAROMATIC DERIVATIVES WITH AMINOALKOXY SUBSTITUTION
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The invention relates to antibacterial compounds of formula I wherein R1a, R2a, R2b, R3a, R3b, R4, R5, U1, U2, U3, U4, V1, V2, V3, V4, X and Q and n are as defined in the specification. It further relates pharmaceutical compositions containing these compounds and the uses of these compounds in the manufacture of medicaments for the treatment of bacterial infections. These compounds are useful antimicrobial agents effective against a variety of human and veterinary pathogens including among others Gram-positive and Gram-negative aerobic and anaerobic bacteria.
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Page/Page column 67
(2016/12/26)
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- CYCLIC AMINES AS BROMODOMAIN INHIBITORS
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The present disclosure relates to compounds, which are useful for inhibition of BET protein function by binding to bromodomains, and their use in therapy.
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Paragraph 0585; 0586
(2014/05/25)
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- DIACYLGLYCEROL ACYLTRANSFERASE 2 INHIBITORS
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Derivatives of purine, 3H-imidazo[4,5-b]pyrimidine and 1H- imidazo[4,5-d]pyrazine of Formula I that inhibit the activity of the diacylglycerol acyltransferase 2 (DGAT2) and their uses in the treatment of diseases linked thereto in animals are described herein.
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Page/Page column 82; 83
(2013/10/22)
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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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- Tri-substituted heteroaryls and methods of making and using the same
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Compounds of formula (I) possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of the general formula (I).
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Page/Page column 18
(2008/06/13)
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- Novel fused heteroaromatic compounds as transforming growth factor (TGF) inhibitors
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Novel fused heteroaromatic compounds, including derivatives thereof, to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use are described. The compounds of the present invention are potent inhibitors of transforming growth factor (“TGF”)-β signaling pathway. They are useful in the treatment of various TGF-related disease states including, for example, cancer and fibrotic diseases.
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- Phospho-transfer catalysis on the asymmetric hydrophosphonylation of aldehydes
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We report here a precise, in situ 31P{1H}-NMR method of assaying enantiopurity of α-hydroxyphosphonate esters, the products of the carbonyl hydrophosphonylation (Pudovik) reaction. This method is based upon a diazaphospholidine chiral derivatising agent (CDA) which satisfies all of the criteria for a precise assay; (i) derivatisation of α-hydroxyphosphonate esters is both rapid and clean, (ii) kinetic resolution is absent and (iii) 31P{1H} chemical shift dispersions are excellent (> 5ppm). Calibration of this assay has been achieved by cross-referencing the 31P{1H}-NMR signals obtained for the CDA-derivatised ester of (MeO)2PC=O)CHPh(OH) to optical rotation measurements from scalemic material obtained upon lipase catalysed hydrolysis (F-AP 15, Rhizopus oryzae) of (MeO)2P(=O)CHPh(OAc). Analysis of NMR chemical shift and coupling parameters for a closely related series of derivatised α-hydroxyphosphonate esters support further configuration assignments on the basis of inference. We report also on the configurational stability of α-hydroxyphosphonate esters in the presence of acids, organonitrogen bases and metal salts. 2H-labelling and carbonyl crossover experiments reveal that low levels of epimerisation (α) of α-hydroxyphosphonate esters is possible under certain conditions of catalysis and within certain limits. A design strategy for the construction of catalyst systems in the Pudovik reaction is outlined based upon a combination of Lewis acidic (E) and Lewis basic (N) sites. Four types of catalyst are outlined, members of two distinct Classes I and II according to the nature of the acid and base sites, along with our investigations of representative examples of each Class. A variety of Class I.1 systems based on β-amino alcohols (one hydrogen bonding E site and one organonitrogen N site), have been assayed in the model reaction between (MeO)2P(O)H and PhCHO. Results suggest that catalysis of the Pudovik reaction is clean and efficient in certain cases but that catalytic activity is strongly dependent upon the nature of the basic (N) nitrogen centre. Moreover, only low levels ( 50% more strongly (K11 0.53 mol-1 dm3) than dimethyl-H-phosphonate (K11 0.34 mol-1 dm3, 298 K) and to catalyse the hydrophosphonylation reaction between these two substrates with a second order rate constant comparable to that of triethylamine (both k2 5.9 × 10-2 mol-1 dm3 h-1, 293 K). However, one of the major limitations of this model is that competitive product inhibition dominates after some 15 turnovers (75% completion). Model studies reveal that hydrophosphonylation catalysis via a nitrogen Lewis base is accelerated up to 10-fold upon the introduction of [Zn(OSO2CF3)2] as co-catalyst. Consequently, Class II.1 systems employ metal salts [Zn(OSO2CF3)2] as Lewis acidic E sites and chiral co-catalysts capable of binding to the metal and also acting as Lewis basic N sites. Such systems catalyse the addition of (MeO)2P(O)H to PhCHO cleanly with modest turnover numbers (2P(O)H to PhCHO to afford (MeO)2P(O)CHPh(OH) with an average turnover rate (over a 1 h reaction time at 298 K) of 115 h-1 compared to ca. 1 h-1 for NEt3 under analogous conditions. Chiral variants are proposed.
- Davies, Stephen R.,Mitchell, Michael C.,Cain, Christopher P.,Devitt, Paul G.,Taylor, Roger J.,Kee, Terence P.
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