5684-81-1Relevant academic research and scientific papers
NOVEL GLYCINE TRANSPORT INHIBITORS FOR THE TREATMENT OF PAIN
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Page/Page column 54; 55, (2018/08/12)
The present invention relates to novel glycine transport inhibitor compounds and their use for treating pain.
Synthesis and Characterization of Novel Acyl-Glycine Inhibitors of GlyT2
Mostyn, Shannon N.,Carland, Jane E.,Shimmon, Susan,Ryan, Renae M.,Rawling, Tristan,Vandenberg, Robert J.
, p. 1949 - 1959 (2017/09/26)
It has been demonstrated previously that the endogenous compound N-arachidonyl-glycine inhibits the glycine transporter GlyT2, stimulates glycinergic neurotransmission, and provides analgesia in animal models of neuropathic and inflammatory pain. However, it is a relatively weak inhibitor with an IC50 of 9 μM and is subject to oxidation via cyclooxygenase, limiting its therapeutic value. In this paper we describe the synthesis and testing of a novel series of monounsaturated C18 and C16 acyl-glycine molecules as inhibitors of the glycine transporter GlyT2. We demonstrate that they are up to 28 fold more potent that N-arachidonyl-glycine with no activity at the closely related GlyT1 transporter at concentrations up to 30 μM. This novel class of compounds show considerable promise as a first generation of GlyT2 transport inhibitors.
Optimizing reaction conditions for the isomerization of fatty acids and fatty acid methyl esters to their branch chain products
Reaume, Stephen J.,Ellis, Naoko
experimental part, p. 661 - 671 (2012/01/31)
In order to improve the oxidative stability and cold flow properties of oleic acid or methyl oleate, branch chain isomerization was conducted using a beta zeolite catalyst. Reaction conditions of temperature (200-300 °C), pressure (0.1-3.0 MPa), and co-catalyst (0-2 wt%) were optimized based on branch chain conversion and the cloud point of the ester following the isomerization reaction of oleic acid or methyl oleate. Fourier transform infrared spectroscopy (FTIR) and Gas Chromatograph equipped with Mass Spectrometry (GC/MS) analyses were used to analyze and quantify the isomerization product samples, while the cloud point of each sample was tested. The lowest and therefore, best cloud point measured was -15.2 °C at conditions of 200 °C, 3 MPa, and 2% co-catalyst using methyl oleate as a starting material. The highest branch chain conversion achieved was 50% under conditions of 300 °C, 1.5 MPa and 0% co-catalyst using oleic acid as a starting material. The use of oleic acid and methyl oleate is based on whether it is optimal to carry out the skeletal isomerization before or after the esterification reaction. Performing the isomerization reaction on the ester was preferred over the fatty acid based on the trans isomerization and cloud point results. Reducing the unbranched trans isomers was desirable in obtaining a low cloud point. AOCS 2010.
Structure determination of an endogenous sleep-inducing lipid, cis-9-octadecenamide (oleamide): A synthetic approach to the chemical analysis of trace quantities of a natural product
Cravatt, Benjamin F.,Lerner, Richard A.,Boger, Dale L.
, p. 580 - 590 (2007/10/03)
The pursuit of endogenous sleep-inducing substances has been the focus of an extensive, complicated body of research. Several compounds, including Δ-sleep-inducing peptide and prostaglandin D2, have been suggested to play a role in sleep induction, and yet, the molecular mechanisms of this physiological process remain largely unknown. In recent efforts, the cerebrospinal fluid of sleep-deprived cats was analyzed in search of compounds that accumulated during sleep deprivation. An agent with the chemical formula C18H35NO was found to cycle with sleep-wake patterns, increasing in concentration with sleep deprivation and decreasing in amount upon recovery sleep. Since the material was generated in minute quantities and only under the special conditions of sleep deprivation, efforts to isolate sufficient material for adequate characterization, structure identification, and subsequent detailed evaluation of its properties proved unrealistic. With the trace amounts of the impure endogenous compound available, extensive MS studies on the agent were completed, revealing key structural features of the molecule including two degrees of unsaturation, a long alkyl chain, and a nitrogen substituent capable of fragmenting as ammonia. Additionally, HPLC traces suggested a weak UV absorbance for the unknown material. With this data in hand and encouraged by the relatively small size of the molecule, MW = 281, a synthetic approach toward the structural identification of the natural compound was initiated. Herein, we report the full details of the synthesis and comparative characterization of candidate structures for this endogenous agent that led to the unambiguous structural correlation with synthetic cis-9-octadecenamide.
