- "Super hybrid tridentate ligands": 4-substituted-2-(1-butyl-1H-1, 2,3-triazol-4-yl)-6-(1H-pyrazol-1-yl)pyridine ligands coordinated to Fe(ii) ions display above room temperature spin transitions
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A series of novel "super hybrid tridentate ligands" based on (2-(1-butyl-1H-1,2,3-triazol-4-yl)-6-(1H-pyrazol-1-yl)pyridine (tpp) derivatives were synthesized. Their Fe(ii) complexes display around (T = 287 K) and above room temperature (T ? 375 K) spin transition temperatures.
- Chandrasekhar, Naisa,Chandrasekar, Rajadurai
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Read Online
- Protein-Induced Change in Ligand Protonation during Trypsin and Thrombin Binding: Hint on Differences in Selectivity Determinants of Both Proteins?
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Trypsin and thrombin, structurally similar serine proteases, recognize different substrates; thrombin cleaves after Arg, whereas trypsin cleaves after Lys/Arg. Both recognize basic substrate headgroups via Asp189 at the bottom of the S1 pocket. By crystal
- Ngo, Khang,Collins-Kautz, Chelsey,Gerstenecker, Stefan,Wagner, Bj?rn,Heine, Andreas,Klebe, Gerhard
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Read Online
- 6,6′-dibromo-4,4′-di(hexoxymethyl)-2,2′-bipyridine: A new solubilizing building block for macromolecular and supramolecular applications
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Although brominated bipyridines and terpyridines are highly desirable synthetic building blocks for both ligand design and macro- or supramolecular applications, few such synthetic precursors have been reported that include much-needed solubilizing groups. Reported here is an inexpensive route to 2,6-dibromo-4-(hexoxymethyl)pyridine from citrazinic acid with an overall yield of 44% and its efficient conversion (60%) to 6,6′-dibromo-4,4′- di(hexoxymethyl)-2,2′-bipyridine via oxidative coupling.
- Amb, Chad M.,Rasmussen, Seth C.
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Read Online
- Azacrown-attached meta-ethynylpyridine polymer: Saccharide recognition regulated by supramolecular device
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Polymeric synthetic host 2, azacrown-attached 2,6-pyridylene ethynylene polymer, was investigated for its saccharide recognition and the additive effect of triethylene tetramine-trifluoroacetic acid; heteroallosteric effects were observed on the basis of CD and UV/Vis analyses, which indicated saccharide-dependent stabilization and destabilization of helical complexes by the formation of pseudopolyrotaxanes.
- Abe, Hajime,Takashima, Shunsuke,Yamamoto, Tsuyoshi,Inouye, Masahiko
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Read Online
- Highly active electrocatalytic CO2 reduction with manganese N-heterocyclic carbene pincer by para electronic tuning
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Electronic tuning by para substitutions was explored to achieve a highly active manganese N-heterocyclic carbene pincer complex for the selective electrocatalytic reduction of CO2 to CO. [MnCNCOMe]BF4 (L2-Mn) bearing an electron-donating group (–OMe) showed high activity with 63 × catalytic current enhancement, average Faradaic efficiency of 104%, and a TOFmax value of 26,127 s?1, which is 127 times higher than that of unsubstituted [MnCNCH]Br (L1-Mn) reported previously. In contrast, the electron-withdrawing group (–COOMe) in [MnCNCCOOMe]PF6 (L3-Mn) inhibited the electrocatalytic activity. Ambient Br?nstic acid, however, suppressed the activity of L2-Mn probably due to the protonation of the –OMe group. These findings indicate a potential electronic tuning strategy to improved manganese N-heterocyclic carbene catalysts for CO2 reduction.
- Huang, Can,Liu, Jiahao,Huang, Hai-Hua,Xu, Xianfang,Ke, Zhuofeng
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supporting information
p. 262 - 265
(2021/07/14)
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- RSV INHIBITING 3-SUBSTITUTED QUINOLINE AND CINNOLINE DERIVATIVES
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The invention concerns compounds of formula (I) having antiviral activity, in particular, having an inhibitory activity on the replication of the respiratory syncytial virus (RSV). The invention further concerns pharmaceutical compositions comprising these compounds and the compounds for use in the treatment of respiratory syncytial virus infection.
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Page/Page column 124-125
(2021/10/30)
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- METHOD FOR SYNTHESIZING ENANIOMERICALLY PURE N-(PYRIDIN-4-YL)-2-HYDROXY-ALKYLAMIDE DERIVATIVES
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The present invention relates to a novel process for preparing enantiomerically pure compounds of N-(pyrid-4-yl)-2-hydroxyalkylamide type corresponding to the general formula (C) below: and also to processes for preparing the reaction intermediates used i
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Paragraph 0212-0215
(2019/01/25)
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- Process Development and Crystallization in Oiling-Out System of a Novel Topical Antiandrogen
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An efficient route to (S)-N-(2-bromo-6-methoxypyridin-4-yl)-2-hydroxy-2,4-dimethylpentanamide 1, a new topical antiandrogen, is described. The target compound has been manufactured on kilogram scale with an overall yield of 25% (HPLC purity 98.8% and >99% ee) from citrazinic acid. The key amide coupling between aminopyridine 4 and α-hydroxy-acid 6 was performed using a temporary protecting group to facilitate the acyl chloride formation. Aminopyridine 4 was manufactured from commercially available citrazinic acid via dibromide formation using phosphorus(V) oxybromide followed by mono SNAr reaction with sodium methoxide and a final Hofmann rearrangement. Enantiopure α-hydroxy-acid 6 was obtained using an enantioselective cyanosilylation followed by salt resolution with (S)-α-methyl benzylamine. The absolute configuration of compound 1 was determined with anomalous scattering and the final crystallization of API was performed after seeding a liquid-liquid mixture below the monotectic temperature and afforded a crystalline powder presenting a "desert rose" shape clusters.
- Daver, Sébastien,Rodeville, Nicolas,Pineau, Francois,Arlabosse, Jean-Marie,Moureou, Christine,Muller, Franck,Pierre, Romain,Bouquet, Karinne,Dumais, Laurence,Boiteau, Jean-Guy,Cardinaud, Isabelle
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p. 231 - 240
(2017/02/26)
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- First Structure-Activity Relationship of 17β-Hydroxysteroid Dehydrogenase Type 14 Nonsteroidal Inhibitors and Crystal Structures in Complex with the Enzyme
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17β-HSD14 belongs to the SDR family and oxidizes the hydroxyl group at position 17 of estradiol and 5-androstenediol using NAD+ as cofactor. The goal of this study was to identify and optimize 17β-HSD14 nonsteroidal inhibitors as well as to disclose their structure-activity relationship. In a first screen, a library of 17β-HSD1 and 17β-HSD2 inhibitors, selected with respect to scaffold diversity, was tested for 17β-HSD14 inhibition. The most interesting hit was taken as starting point for chemical modification applying a ligand-based approach. The designed compounds were synthesized and tested for 17β-HSD14 inhibitory activity. The two best inhibitors identified in this study have a very high affinity to the enzyme with a Ki equal to 7 nM. The strong affinity of these inhibitors to the enzyme active site could be explained by crystallographic structure analysis, which highlighted the role of an extended H-bonding network in the stabilization process. The selectivity of the most potent compounds with respect to 17β-HSD1 and 17β-HSD2 is also addressed.
- Braun, Florian,Bertoletti, Nicole,M?ller, Gabriele,Adamski, Jerzy,Steinmetzer, Torsten,Salah, Mohamed,Abdelsamie, Ahmed S.,Van Koppen, Chris J.,Heine, Andreas,Klebe, Gerhard,Marchais-Oberwinkler, Sandrine
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p. 10719 - 10737
(2016/12/16)
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- Inhibition of cancer-associated mutant isocitrate dehydrogenases: Synthesis, structure-activity relationship, and selective antitumor activity
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Mutations of isocitrate dehydrogenase 1 (IDH1) are frequently found in certain cancers such as glioma. Different from the wild-type (WT) IDH1, the mutant enzymes catalyze the reduction of α-ketoglutaric acid to d-2-hydroxyglutaric acid (D2HG), leading to cancer initiation. Several 1-hydroxypyridin-2-one compounds were identified to be inhibitors of IDH1(R132H). A total of 61 derivatives were synthesized, and their structure-activity relationships were investigated. Potent IDH1(R132H) inhibitors were identified with Ki values as low as 140 nM, while they possess weak or no activity against WT IDH1. Activities of selected compounds against IDH1(R132C) were found to be correlated with their inhibitory activities against IDH1(R132H), as well as cellular production of D2HG, with R2 of 0.83 and 0.73, respectively. Several inhibitors were found to be permeable through the blood-brain barrier in a cell-based model assay and exhibit potent and selective activity (EC50 = 0.26-1.8 μM) against glioma cells with the IDH1 R132H mutation.
- Liu, Zhen,Yao, Yuan,Kogiso, Mari,Zheng, Baisong,Deng, Lisheng,Qiu, Jihui J.,Dong, Shuo,Lv, Hua,Gallo, James M.,Li, Xiao-Nan,Song, Yongcheng
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p. 8307 - 8318
(2014/12/11)
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- Crystallographic investigation and selective inhibition of mutant isocitrate dehydrogenase
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Mutations in isocitrate dehydrogenase (IDH), a key enzyme in the tricarboxylic acid cycle, have recently been found in ～75% glioma and ～20% acute myeloid leukemia. Different from the wild-type enzyme, mutant IDH1 catalyzes the reduction of α-ketoglutaric
- Zheng, Baisong,Yao, Yuan,Liu, Zhen,Deng, Lisheng,Anglin, Justin L.,Jiang, Hong,Prasad, B.V. Venkataram,Song, Yongcheng
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supporting information
p. 542 - 546
(2013/07/26)
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- Thiol-ene reaction: A versatile tool in site-specific labelling of proteins with chemically inert tags for paramagnetic NMR
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Site-specific tagging of proteins with paramagnetic lanthanides generates valuable long-range structure restraints for structural biology by NMR spectroscopy. We show that the thiol-ene addition reaction offers a powerful tool for tagging proteins in a chemically stable manner with very small lanthanide tags. The Royal Society of Chemistry 2012.
- Li, Qing-Feng,Yang, Yin,Maleckis, Ansis,Otting, Gottfried,Su, Xun-Cheng
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supporting information; scheme or table
p. 2704 - 2706
(2012/03/27)
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- CO-CRYSTALS AND SALTS OF CCR3-INHIBITORS
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This invention relates to co-crystals and salts of CCR3 inhibitors of formula (1), pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases related with the CCR3-receptor.
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Page/Page column 25
(2012/04/23)
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- CO-CRYSTALS AND SALTS OF CCR3-INHIBITORS
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This invention relates to co-crystals and salts of CCR3 inhibitors of formula 1, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases related with the CCR3-receptor.
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Page/Page column 9
(2012/10/23)
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- Carbazole-based hole transport and/or electron blocking materials and/or host polymer materials
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This invention relates generally to norbornene-monomer, poly(norbornene)homopolymer, and poly(norbornene)copolymer compounds containing a functionalized carbazole side chain, having desirable solution processability and host characteristics. It also relates to hole transport and/or electron blocking materials, and to organic host materials for an organic luminescence layer, an OLED device, and compositions of matter which include these compounds.
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- Identification of potent and selective amidobipyridyl inhibitors of protein kinase D
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The synthesis and biological evaluation of potent and selective PKD inhibitors are described herein. The compounds described in the present study selectively inhibit PKD among other putative HDAC kinases. The PKD inhibitors of the present study blunt phosphorylation and subsequent nuclear export of HDAC4/5 in response to diverse agonists. These compounds further establish the central role of PKD as an HDAC4/5 kinase and enhance the current understanding of cardiac myocyte signal transduction. The in vivo efficacy of a representative example compound on heart morphology is reported herein.
- Meredith, Erik L.,Beattie, Kimberly,Burgis, Robin,Capparelli, Michael,Chapo, Joseph,Dipietro, Lucian,Gamber, Gabriel,Enyedy, Istvan,Hood, David B.,Hosagrahara, Vinayak,Jewell, Charles,Koch, Keith A.,Lee, Wendy,Lemon, Douglas D.,Mckinsey, Timothy A.,Miranda, Karl,Pagratis, Nikos,Phan, Dillon,Plato, Craig,Rao, Chang,Rozhitskaya, Olga,Soldermann, Nicolas,Springer, Clayton,Van Eis, Maurice,Vega, Richard B.,Yan, Wanlin,Zhu, Qingming,Monovich, Lauren G.
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experimental part
p. 5422 - 5438
(2010/11/18)
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- Metallo-controlled dynamic molecular tweezers: Design, synthesis, and self-assembly by metal-ion coordination
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The introduction of controllable dynamic features into synthetic receptors represents a step towards "smart" adaptive nanodevices. We report herein our studies on the construction of dynamic molecular tweezers in which the binding of a substrate is allost
- Ulrich, Sebastien,Petitjean, Anne,Lehn, Jean-Marie
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experimental part
p. 1913 - 1928
(2011/01/10)
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- SUBSTITUTED PIPERIDINES AS CCR3 ANTAGONISTS
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Object of the present invention are novel substituted compounds of the formula 1, wherein A, R1, R2, R3 and R4 are defined as in the description. Another object of the present invention is to provide antagonists of CCR3, more particularly to provide pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt thereof.
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(2010/11/03)
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- PH-responsive molecular tweezers
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Molecular tweezers are dynamic devices that are able to switch from one conformation to another upon stimulation by an external trigger. In this work, we report a new water-soluble macromolecular carrier bearing a pH-responsive molecular tweezer, whose affinity for a substrate depends on the external pH. The conformational change of the switching unit was evidenced by 1H NMR spectroscopy, and fluorescence studies conducted in aqueous media demonstrated the ability of the carrier to bind to substrates in a pH-dependent fashion.
- Leblond, Jeanne,Gao, Hui,Petitjean, Anne,Leroux, Jean-Christophe
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supporting information; experimental part
p. 8544 - 8545
(2010/08/06)
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- 2,4'-BIPYRIDINYL COMPOUNDS AS PROTEIN KINASE D INHIBITORS USEFUL FOR THE TREATMENT OF IA HEART FAILURE AND CANCER
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The present invention provides novel organic compounds of Formula I: methods of use, and pharmaceutical compositions thereof.
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Page/Page column 65
(2010/01/07)
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- CARBAZOLE-BASED HOLE TRANSPORT AND /OR ELECTRON BLOCKING MATERIALS AND /OR HOST POLYMER MATERIALS
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This invention relates generally y to norbornene -monomer, poly (norbornene) homopolymer, and poly (norbornene) copolymer compounds containing a functionalized carbazole side chain, having desirable solution processability and host characteristics. It also relates to hole transport and/or electron blocking materials, and to organic host materials for an organic luminescence layer, an OLED device, and compositions of matter which include these compounds.
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(2009/07/25)
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- Buchwald-Hartwig Mono-N-arylation with 2,6-dihaloisonicotinic acid derivatives: A convenient desymmetrization method
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A method for the Buchwald-Hartwig mono-N-arylation of aniline with methyl 2,6-dichloroisonicotinate using Pd(OAc)2, XPhos, and t-BuONa is reported. Use of m-anisidine under the same conditions resulted in the amidation of the methyl ester. Mono-N-arylation of m-anisidine with 2,6-dichloro-N,N- diisopropylisonicotinamide and 2,6-dibromo-N,N-diisopropylisonicotinamide, however, was successfully achieved using Pd(OAc)2/XPhos/t-BuONa or Pd(OAc)2/(±)-BINAP/K2CO3, respectively. The present study demonstrates the sensitivity of this cross-coupling method to both the steric and electronic nature of the coupling partners. Georg Thieme Verlag Stuttgart.
- Lorimer, Anna V.,O'Connor, Patrick D.,Brimble, Margaret A.
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experimental part
p. 2764 - 2770
(2009/04/07)
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- 5,5″-disubstituted 2,2′:6′,2″-terpyridines through and for metal-mediated cross-coupling chemistry
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The 0.3-5 g scale syntheses of the 2,2′:6′,2″-terpyridines 3, 6, 9, and 10 are described. The pyridine units are connected to one another by Pd-catalyzed cross-coupling reactions. This method allows the easy introduction of halogen, stannyl, and boronic ester functionalities at positions C-5 and C-5″; this results in a novel functionality pattern for terpyridines that considerably widens the applicability of this class of tridentate ligands for supra- and macromolecular applications. The feasibility of growth reactions with these novel terpyridines was demonstrated by the synthesis of compounds 12a-c.
- Lehmann, Uwe,Henze, Oliver,Schlueter, A. Dieter
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p. 854 - 859
(2007/10/03)
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