79559-59-4Relevant articles and documents
GPR52 Antagonist Reduces Huntingtin Levels and Ameliorates Huntington's Disease-Related Phenotypes
Wang, Congcong,Zhang, Yu-Fang,Guo, Shimeng,Zhao, Quan,Zeng, Yanping,Xie, Zhicheng,Xie, Xin,Lu, Boxun,Hu, Youhong
, p. 941 - 957 (2020/11/30)
GPR52 is an orphan G protein-coupled receptor (GPCR) that has been recently implicated as a potential drug target of Huntington's disease (HD), an incurable monogenic neurodegenerative disorder. In this research, we found that striatal knockdown of GPR52 reduces mHTT levels in adult HdhQ140 mice, validating GPR52 as an HD target. In addition, we discovered a highly potent and specific GPR52 antagonist Comp-43 with an IC50 value of 0.63 μM by a structure-activity relationship (SAR) study. Further studies showed that Comp-43 reduces mHTT levels by targeting GPR52 and promotes survival of mouse primary striatal neurons. Moreover, in vivo study showed that Comp-43 not only reduces mHTT levels but also rescues HD-related phenotypes in HdhQ140 mice. Taken together, our study confirms that inhibition of GPR52 is a promising strategy for HD therapy, and the GPR52 antagonist Comp-43 might serve as a lead compound for further investigation.
A General Stereocontrolled Synthesis of Opines through Asymmetric Pd-Catalyzed N-Allylation of Amino Acid Esters
Albat, Dominik,Neud?rfl, J?rg-Martin,Schmalz, Hans-Günther
supporting information, p. 2099 - 2102 (2021/07/22)
A stereo-divergent synthesis of natural and unnatural opines in stereochemically pure form is based on the direct palladium-catalyzed N-allylation of α-amino acid esters (up to 97 % ee or 99 : 1 d.r.) using methyl (E)-2-penten-4-yl carbonate in the presence of only 1 mol% of a catalyst, prepared in-situ from the C2-symmetric diphosphine iPr-MediPhos and [Pd(allyl)Cl]2. Selected target compounds (incl. a derivative of the drug enalapril) were efficiently obtained from the N-allylated intermediates by oxidative cleavage (ozonolysis) of the allylic C=C bond under temporary N-Boc-protection.
Chromium carbides and cyclopropenylidenes
Irifune, Keiichi,Kurogi, Takashi,Takai, Kazuhiko
, p. 14281 - 14287 (2021/11/12)
Carbon tetrabromide can be reduced with CrBr2in THF to form a dinuclear carbido complex, [CrBr2(thf)2)][CrBr2(thf)3](μ-C), along with formation of [CrBr3(thf)3]. An X-ray diffraction (XRD) study of the pyridine adduct displayed a dinuclear structure bridged by a carbido ligand between 5- and 6-coordinate chromium centers. The carbido complex reacted with two equivalents of aldehydes to form α,β-unsaturated ketones. Treatment of the carbido complex with alkenes resulted in a formal double-cyclopropanation of alkenes by the carbido moiety to afford spiropentanes. Isotope labeling studies using a13C-enriched carbido complex, [CrBr2(thf)2)][CrBr2(thf)3](μ-13C), identified that the quaternary carbon in the spiropentane framework was delivered by carbide transfer from the carbido complex. Terminal and internal alkynes also reacted with the carbido complex to form cyclopropenylidene complexes. A solid-state structure of the diethylcyclopropenylidene complex, prepared from 3-hexyne, showed a mononuclear cyclopropenylidene chromium(iii) structure.
Unsaturated ketone compound as well as preparation method and application thereof
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, (2020/10/30)
The present invention relates to a novel GPR52 antagonist. Specifically, the invention relates to an unsaturated ketone compound, a pharmaceutically acceptable salt, a stereoisomer or a prodrug molecule thereof, and a method for preparing a pharmaceutical composition thereof. The invention further relates to the use of the GPR52 antagonist as an orphan G protein coupled receptor GPR52 antagonist,and further relates to the use of the GPR52 antagonist in the preparation of drugs for preventing and treating Huntington's disease.
Asymmetric synthesis of allylic secondary alcohols: Anewgeneral approach for the preparation of α-amino acids
Drummond, Lorna J.,Sutherland, Andrew
experimental part, p. 5349 - 5356 (2010/08/06)
A new general approach for the synthesis of optically active a-amino acids has been developed.The key steps involve a ruthenium catalysed cross-coupling reaction to give a range of α,β-unsaturated ketones, which were then reduced to allylic secondary alcohols in the presence of a chiral CBS oxazaborolidine.A thermal Overman rearrangement was used to prepare a series of allylic trichloroacetimidates and these were converted under standard conditions to the target α-amino acids in good overall yields.
Compounds with pharmaceutical properties
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, (2008/06/13)
A pharmaceutical compound of the formula in which R1 is C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-10 alkyl, C3-10 cycloalkyl-C2-10 alkenyl, C3-10 cycloalky-C2-10 alkynyl, optionally substituted phenyl-C1-10 alkyl, optionally substituted phenyl-C2-10 alkenyl, optionally substituted phenyl-C2-10 alkynyl, optionally substituted naphthyl, optionally substituted naphthyl-C1-10 alkyl, C1-10 alkoxy-C1-10 alkyl, C3-10 cycloalkoxy-C1-10 alkyl, optionally substituted heterocyclyl, optionally substituted heterocyclyl-C1-10 alkyl, optionally substituted phenyl fused to C5-10 cycloalkyl, optionally substituted tricyclic, optionally substituted tricyclic-C1-10 alkyl, or [optionally substituted phenyl(CH2)n]2-C1-10 alkyl, where n is 0 or 1 to 4, and R2 is hydrogen or one of the values for R1; or a salt or ester thereof.
2, 3'-disubstituted-2-(2'-carboxycyclopropyl)glycines as potent and selective antagonists of metabotropic glutamate receptors
Collado, Ivan,Ezquerra, Jesus,Mazon, Angel,Pedregal, Concepcion,Yruretagoyena, Belen,Kingston, Anne E.,Tomlinson, Rosemary,Wright, Rebecca A.,Johnson, Bryan G.,Schoepp, Darryle D.
, p. 2849 - 2854 (2007/10/03)
2-(9-Xanthylmethyl)-2-(2'-carboxycyclopropyl) glycine 6e is a novel metabotropic glutamate receptor antagonist. A series of alpha, C-3' disubstituted (carboxycyclopropyl)glycines 6f-n were prepared. Antagonist activity was observed for all these compounds at group 2 and group 3 mGluRs. Although they were slightly less active on group 2 mGluRs than non C-3, substituted 6e, the compounds 6f-n were more selective with lesser or no activity on group 1 mGluR subtypes (IC50 values greater than 100μm).
NEW METHODS AND REAGENTS IN ORGANIC SYNTHESIS. 47. A GENERAL, EFFICIENT, AND CONVENIENT SYNTHESIS OF DIARYLHEPTANOIDS
Kato, Nobuharu,Hamada, Yasumasa,Shioiri, Takayuki
, p. 3323 - 3326 (2007/10/02)
An efficient synthesis of physiologically interesting diarylheptanoids has been carried out through direct C-acylation using diethyl phosphorocyanidate (DEPC) followed by Grignard reactions with aldehydes.Keywords - diarylheptanoid; C-acylation; diethyl p
