- VU6010608, a Novel mGlu7 NAM from a Series of N-(2-(1H-1,2,4-Triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamides
-
Herein, we report the structure-activity relationships within a series of mGlu7 NAMs based on an N-(2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamide core with excellent CNS penetration (Kp 1.9-5.8 and Kp,uu 0.4-1.4). Analogues in this series displayed steep SAR. Of these, VU6010608 (11a) emerged with robust efficacy in blocking high frequency stimulated long-term potentiation in electrophysiology studies.
- Reed, Carson W.,McGowan, Kevin M.,Spearing, Paul K.,Stansley, Branden J.,Roenfanz, Hanna F.,Engers, Darren W.,Rodriguez, Alice L.,Engelberg, Eileen M.,Luscombe, Vincent B.,Loch, Matthew T.,Remke, Daniel H.,Rook, Jerri M.,Blobaum, Anna L.,Conn, P. Jeffrey,Niswender, Colleen M.,Lindsley, Craig W.
-
supporting information
p. 1326 - 1330
(2017/12/26)
-
- Rational Design of Rod-Like Liquid Crystals Exhibiting Two Nematic Phases
-
Recently, a polar, rod-like liquid-crystalline material was reported to exhibit two distinct nematic mesophases (termed N and NX) separated by a weakly first-order transition. Herein, we present our initial studies into the structure–property relationships that underpin the occurrence of the lower-temperature nematic phase, and report several new materials that exhibit this same transformation. We have prepared material with significantly enhanced temperature ranges, allowing us to perform a detailed study of both the upper- and lower-temperature nematic phases by using small-angle X-ray scattering. We observed a continuous change in d spacing rather than a sharp change at the phase transition, a result consistent with a transition between two nematic phases, structures of which are presumably degenerate.
- Mandle, Richard J.,Cowling, Stephen J.,Goodby, John W.
-
supporting information
p. 14554 - 14562
(2017/10/23)
-
- SELECTIVE CARBON-CARBON BOND CLEAVAGE BY EARTH ABUNDANT VANADIUM COMPOUNDS UNDER VISIBLE LIGHT PHOTOCATALYSIS
-
Provided herein a vanadium(V) complex of formula I, where R1 to R8 are as defined herein. Also provided herein are reactions making use of the vanadium(V) complex of formula I, such as selective sp3-sp3 carbon-carbon bond cleavage under visible light photocatalysis and photodegradation of lignin.
- -
-
Page/Page column 48
(2016/09/22)
-
- Selective photocatalytic C-C bond cleavage under ambient conditions with earth abundant vanadium complexes
-
Selective C-C bond cleavage under ambient conditions is a challenging chemical transformation that can be a valuable tool for organic syntheses and macromolecular disassembly. Herein, we show that base metal vanadium photocatalysts can harvest visible light to effect the chemoselective C-C bond cleavage of lignin model compounds under ambient conditions. Lignin, a major aromatic constituent of non-food biomass, is an inexpensive, accessible source of fine chemical feedstocks such as phenols and aryl ethers. However, existing lignin degradation technologies are harsh and indiscriminately degrade valuable functional groups to produce intractable mixtures. The selective, photocatalytic depolymerization of lignin remains underexplored. In the course of our studies on lignin model compounds, we have uncovered a new C-C activation reaction that takes place under exceptionally mild conditions with high conversions. We present our fundamental studies on representative lignin model compounds, with the aim of expanding and generalizing the substrate scope in the future. Visible light is employed in the presence of earth-abundant vanadium oxo catalysts under ambient conditions. Selective C-C bond cleavage leads to valuable and functionally rich fine chemicals such as substituted aryl aldehydes and formates. Isotope labeling experiments, product analyses, and intermediate radical trapping, together with density functional theory studies, suggest a unique pathway that involves a photogenerated T1 state during the C-C bond cleavage reactions. Our study demonstrates a sustainable approach to harvest sunlight for an unusual, selective bond activation, which can potentially be applied in organic transformations and biomass valorization.
- Gazi, Sarifuddin,Hung Ng, Wilson Kwok,Ganguly, Rakesh,Putra Moeljadi, Adhitya Mangala,Hirao, Hajime,Soo, Han Sen
-
p. 7130 - 7142
(2015/11/24)
-
- Photoacid generators (PAGs) based on N-acyl-N-phenylhydroxylamines for carboxylic and sulfonic acids
-
Simple and efficient photoacid generators (PAGs) for carboxylic and sulfonic acids based on N-acyl-N-phenylhydroxylamines have been demonstrated. Irradiation of o-carboxylates and thermally rearranged o-arenesulfonates of N-acyl-N-phenylhydroxylamines using UV light (≥254 nm) in aqueous methanolic solution resulted in efficient generation of carboxylic and sulfonic acids, respectively. The carboxylic acid generation ability of N-acyl-N- phenylhydroxylamines was found to be dependent on their N-acyl substituents. Further, polymer bearing o-arenesulfonates of N-acyl-N-phenylhydroxylamine was synthesized and demonstrated as PAG for sulfonic acids.
- Ikbal, Mohammed,Jana, Avijit,Singh, N.D. Pradeep,Banerjee, Rakesh,Dhara, Dibakar
-
experimental part
p. 3733 - 3742
(2011/06/21)
-
- S1P RECEPTORS MODULATORS
-
The invention relates to novel compounds that have S1P receptor modulating activity and, preferably, apoptotic activity and/or anti proliferative activity against cancer cells and other cell types. Further, the invention relates to a pharmaceutical comprising at least one compound of the invention for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression, for example, cancer. A further aspect of the invention relates to the use of a pharmaceutical comprising at least one compound of the invention for the manufacture of a medicament for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression such as cancer.
- -
-
Page/Page column 125
(2010/04/30)
-
- NOVEL HETEROCYCLIC DERIVATIVES
-
The object of the present invention is to provide soluble β-amyloid precursor protein secretory stimulators, which are effective in treating neurodegenerative diseases as well as cerebrovascular disorder-induced neuronopathy. More specifically, the present invention provides a novel compound of the following Formula (I) or a salt or prodrug thereof: [wherein R1 and R2 each represent a hydrogen atom or a lower alkyl group, etc., Ar1 and the ring B each represent an optionally substituted aromatic group, the ring A represents an optionally substituted benzene ring, the ring C represents an optionally substituted 4- to 8-membered ring which may further be condensed with an optionally substituted ring, X represents CH or N, and Y represents CH or N].
- -
-
-
- Anthranilic acid derivatives as inhibitors of the cGMP-phosphodiesterase
-
Compounds of formula (I) STR1where R 1 is hydrogen; R 2 is nitro, cyano or halo(lower)alkyl; R 3 is phenyl substituted with one or more substituents selected from halogen, cyano and lower alkoxy; A is a lower alkylene group; R 4 is a group CR 6 R 7 R 8 wherein R 6 and R 7 form, together with the carbon atom to which they are attached a cycloalkyl group optionally substituted with hydroxy, lower alkoxy or a lower alkanoylamino; and R 8 is hydrogen; its prodrug and a salt thereof.
- -
-
-
- Studies on chromium trioxide-based oxidative coupling reagents and synthesis of lignan-cagayanone
-
Oxidation of 1-arylprop-1-enes by using the reagent system CrO3-HClO4- CH3CN at 0-5°C gave seven products from methyl isoeugenol, five from ethyl isoeugenol, four from benzyl isoeugenol, and five from isosafrole. Cagayanone was obtained from isosafrole in one step. The structures of the products were elucidated and the mechanism of their formation is discussed.
- Kuo,Lin
-
p. 1507 - 1512
(2007/10/02)
-
- Synthesis and thermal properties of cholesteryl 4-n-alkoxy-3-methoxybenzoates
-
A homologous series of new liquid crystalline compounds, cholesteryl 4-n-alkoxy-3-methoxybenzoate were synthesized from vanillin and their mesomorphic properties were studied by differential scanning calorimetry, polarizing microscopy and x-ray diffractometry.Each of the homologues from cholesteryl 3,4-dimethoxybenzoate (n=1) to cholesteryl 4-n-hexyloxy-3-methoxybenzoate (n=6) showed a cholesteric-nematic phase (NCh).The other higher homologues (from n=7 to n=18) indicated smectic A (SA) and NCh phases.The temperature region of smectic phases increased with the increase of the chain length of the n-alkoxy group.Transition temperatures in each of the homologues were lower than those in a corresponding non-3-methoxy substituted benzoate ester, due to the destabilizing effect of the lateral methoxy group.The effect was more significant on the homologues having a shorter n-alkoxy chain.It was also found that these esters formed a glassy state by quenching from mesophases and/or the isotropic liquid phase.The change of the glass transition temperature on each homologue (from n=1 to n=6) suggested the effect of the chain length of the n-alkoxyl group on the formation of the glassy state.Keywords: liquid crystals, thermal properties, differential scanning calorimetry, cholesteric phas, smectic A phase, glassy phase.
- Kasuga, Kazuyuki,Hatakeyama, Hyoe,Hatakeyama, Tatsuko
-
-
- Metabolism of a Non-phenolic β-O-4 Lignin Substructure Model Compound by Coriolus versicolor
-
A non-phenolic β-O-4 lignin substructure model, 4-ethoxy-3-methoxyphenylglycerol-β-syringaldehyde ether (I), was metabolized by a ligninolytic culture of Coriolus versicolor.Based on the identification of the metbaolic products (II-X1), the following reactions were found to occur in the culture; a) oxidation (III) and reduction (II) at the benzyl (Cα') position of the substrate (I), b) β-ether cleavage to give arylglycerols (IV, V), and c) Cα-Cβ cleavage of the arylglycerols and/or arylglycerol moiety of the substrate (I).In addition, β-deoxy diol (VI) and γ-formylglycerol (VII) were obtained as degradation products from substrate (I).
- Kawai, Shingo,Umezawa, Toshiaki,Higuchi, Takayoshi
-
p. 2325 - 2330
(2007/10/02)
-