65295-62-7Relevant 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
supporting information, 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.
POLYCYCLIC LYSOPHOSPHATIDYLSERINE DERIVATIVE
-
Paragraph 0165-0167, (2017/05/12)
PROBLEM TO BE SOLVED: To provide a polycyclic lysophosphatidylserine derivative having lysophosphatidylserine receptor agonist activity or salt thereof, a fatty acid surrogate which can be used as a synthetic intermediate for these compounds, and a pharmaceutical composition or lysophosphatidylserine receptor function regulator comprising the lysophosphatidylserine derivative and salt thereof. SOLUTION: The present invention provides a polycyclic lysophosphatidylserine derivative represented by formula (I), or salt thereof. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
The SAR of brain penetration for a series of heteroaryl urea FAAH inhibitors
Keith, John M.,Tichenor, Mark S.,Apodaca, Richard L.,Xiao, Wei,Jones, William M.,Seierstad, Mark,Pierce, Joan M.,Palmer, James A.,Webb, Michael,Karbarz, Mark J.,Scott, Brian P.,Wilson, Sandy J.,Wennerholm, Michelle L.,Rizzolio, Michele,Rynberg, Raymond,Chaplan, Sandra R.,Breitenbucher, J. Guy
supporting information, p. 3109 - 3114 (2016/06/13)
The SAR of brain penetration for a series of heteroaryl piperazinyl- and piperadinyl-urea fatty acid amide hydrolase (FAAH) inhibitors is described. Brain/plasma (B/P) ratios ranging from >4:1 to as low as 0.02:1 were obtained through relatively simple st
Insecticidal ethers
-
, (2008/06/13)
This invention relates to novel fluorinated ethers, useful as insecticides and acaricides, to processes and intermediates for their preparation, to insecticidal and acaricidal compositions thereof and to methods of combating and controlling insect and acarine pests therewith.
