72714-63-7Relevant academic research and scientific papers
Probing the Hydrophobic Binding Pocket of G-Protein-Coupled Lysophosphatidylserine Receptor GPR34/LPS1 by Docking-Aided Structure-Activity Analysis
Sayama, Misa,Inoue, Asuka,Nakamura, Sho,Jung, Sejin,Ikubo, Masaya,Otani, Yuko,Uwamizu, Akiharu,Kishi, Takayuki,Makide, Kumiko,Aoki, Junken,Hirokawa, Takatsugu,Ohwada, Tomohiko
, p. 6384 - 6399 (2017/08/02)
The ligands of certain G-protein-coupled receptors (GPCRs) have been identified as endogenous lipids, such as lysophosphatidylserine (LysoPS). Here, we analyzed the molecular basis of the structure-activity relationship of ligands of GPR34, one of the LysoPS receptor subtypes, focusing on recognition of the long-chain fatty acid moiety by the hydrophobic pocket. By introducing benzene ring(s) into the fatty acid moiety of 2-deoxy-LysoPS, we explored the binding site's preference for the hydrophobic shape. A tribenzene-containing fatty acid surrogate with modifications of the terminal aromatic moiety showed potent agonistic activity toward GPR34. Computational docking of these derivatives with a homology modeling/molecular dynamics-based virtual binding site of GPR34 indicated that a kink in the benzene-based lipid surrogates matches the L-shaped hydrophobic pocket of GPR34. A tetrabenzene-based lipid analogue bearing a bulky tert-butyl group at the 4-position of the terminal benzene ring exhibited potent GPR34 agonistic activity, validating the present hydrophobic binding pocket model.
Conformational Constraint of the Glycerol Moiety of Lysophosphatidylserine Affords Compounds with Receptor Subtype Selectivity
Jung, Sejin,Inoue, Asuka,Nakamura, Sho,Kishi, Takayuki,Uwamizu, Akiharu,Sayama, Misa,Ikubo, Masaya,Otani, Yuko,Kano, Kuniyuki,Makide, Kumiko,Aoki, Junken,Ohwada, Tomohiko
, p. 3750 - 3776 (2016/05/19)
Lysophosphatidylserine (LysoPS) is an endogenous lipid mediator that specifically activates membrane proteins of the P2Y and its related families of G protein-coupled receptors (GPCR), GPR34 (LPS1), P2Y10 (LPS2), and GPR174 (LPS3). Here, in order to increase potency and receptor selectivity, we designed and synthesized LysoPS analogues containing the conformational constraints of the glycerol moiety. These reduced structural flexibility by fixation of the glycerol framework of LysoPS using a 2-hydroxymethyl-3-hydroxytetrahydropyran skeleton, and related structures identified compounds which exhibited high potency and selectivity for activation of GPR34 or P2Y10. Morphing of the structural shape of the 2-hydroxymethyl-3-hydroxytetrahydropyran skeleton into a planar benzene ring enhanced the P2Y10 activation potentcy rather than the GPR34 activation.
Copper-mediated trifluoromethylation of α-diazo esters with TMSCF3: The important role of water as a promoter
Hu, Mingyou,Ni, Chuanfa,Hu, Jinbo
supporting information, p. 15257 - 15260 (2012/10/29)
Copper-mediated trifluoromethylation of α-diazo esters with TMSCF3 reagent has been developed as a new method to prepare α-trifluoromethyl esters. This trifluoromethylation reaction represents the first example of fluoroalkylation of a non-fluorinated carbene precursor. Water plays an important role in promoting the reaction by activating the "CuCF3" species prepared from CuI/TMSCF3/CsF (1.0:1.1:1.1). The scope of this trifluoromethylation reaction is broad, and its efficiency is demonstrated in the synthesis of a variety of aryl-, benzyl-, and alkyl-substituted 3,3,3-trifluoropropanoates.
RECEPTOR FUNCTION REGULATING AGENT
-
Page/Page column 89, (2010/11/23)
An agent for regulating 14273 receptor function, which is useful as a preventing or treating drug for diabetes mellitus, hyperlipidemia or the like, is provided. An agent for regulating 14273 receptor function comprising a compound containing an aromatic ring and a group capable of releasing a cation.
