53963-10-3Relevant articles and documents
Synthesis and Preliminary PET Imaging Studies of a FAAH Radiotracer ([11C]MPPO) Based on α-Ketoheterocyclic Scaffold
Wang, Lu,Yui, Joji,Wang, Qifan,Zhang, Yiding,Mori, Wakana,Shimoda, Yoko,Fujinaga, Masayuki,Kumata, Katsushi,Yamasaki, Tomoteru,Hatori, Akiko,Rotstein, Benjamin H.,Collier, Thomas Lee,Ran, Chongzhao,Vasdev, Neil,Zhang, Ming-Rong,Liang, Steven H.
, p. 109 - 118 (2016)
Fatty acid amide hydrolase (FAAH) is one of the principle enzymes for metabolizing endogenous cannabinoid neurotransmitters such as anandamide, and thus regulates endocannabinoid (eCB) signaling. Selective pharmacological blockade of FAAH has emerged as a potential therapy to discern the endogenous functions of anandamide-mediated eCB pathways in anxiety, pain, and addiction. Quantification of FAAH in the living brain by positron emission tomography (PET) would help our understanding of the endocannabinoid system in these conditions. While most FAAH radiotracers operate by an irreversible ("suicide") binding mechanism, a FAAH tracer with reversibility would facilitate quantitative analysis. We have identified and radiolabeled a reversible FAAH inhibitor, 7-(2-[11C]methoxyphenyl)-1-(5-(pyridin-2-yl)oxazol-2-yl)heptan-1-one ([11C]MPPO) in 13% radiochemical yield (nondecay corrected) with >99% radiochemical purity and 2 Ci/μmol (74 GBq/μmol) specific activity. The tracer showed moderate brain uptake (0.8 SUV) with heterogeneous brain distribution. However, blocking studies with a potent FAAH inhibitor URB597 demonstrated a low to modest specificity to the target. Measurement of lipophilicity, metabolite, and efflux pathway analysis were also performed to study the pharmacokinetic profile of [11C]MPPO. In all, we reported an efficient radiolabeling and preliminary evaluation of the first-in-class FAAH inhibitor [11C]MPPO with α-ketoheterocyclic scaffold. (Chemical Equation Presented).
The synthesis of 14-membered macrocyclic ethers
Clyne, Dean S.,Weiler, Larry
, p. 13659 - 13682 (1999)
As part of an ongoing study of the chemistry of macrocyclic compounds, 14-membered macrocyclic ethers with a variety of methyl substitution patterns were synthesized. The preparation of these macrocyclic ethers involved either the Baeyer-Villiger ring expansion of a cyclic ketone, or the macrolactonization of a hydroxy acid to give a lactone. The lactone carbonyl was removed either by conversion to an intermediate thionolactone obtained by reaction with Lawesson's reagent and reduction, or by direct reduction using a boron trifluoride etherate mediated sodium borohydride reaction.
Synthesis and Cytotoxicity of 1,4-Naphthoquinone Oxime Derivatives
Zhang,Dong,Meng,Huang,Li
, p. 2388 - 2393 (2019/01/04)
A series of hydroxylated 1,4-naphthoquinone oximes were designed and synthesized. The in vitro cytotoxicity of these compounds was evaluated against five human cancer cell lines and human skin fibroblast cell line. Among them, compounds (1E,4E)-6-{1-[(5-Hydroxypentyl)oxy]-2,2-dimethylbut-3-en-1-yl}-5,8- dimethoxynaphthalene-1,4-dione dioxime and (1E,4E)-6-{1-[(6-Hydroxyhexyl)oxy]-2,2-dimethylbut-3-en-1-yl}-5,8-dimethoxynaphthalene-1,4-dione dioxime displayed higher cytotoxicity in three cancer cell lines than the positive drug 5-fluorouracil.
Donepezil–melatonin hybrids as butyrylcholinesterase inhibitors: Improving binding affinity through varying mode of linking fragments
?ozińska, Iwona,?wierczyńska, Aleksandra,Mol?da, Zuzanna,Hartman, Alwin M.,Hirsch, Anna K. H.,Czarnocki, Zbigniew
, (2018/10/15)
Hybrid inhibitors of acetyl- and butyrylcholinesterase are compounds that combine structural motifs of two different classical inhibitors, leading to a dual binding ligand. A rapidly growing collection of those compounds involves a wide diversity of structural motifs, but the way of linking two active fragments and its impact on the affinity toward cholinesterases usually remains beyond the extent of investigation. We present hereby a detailed analysis of this aspect using melatonin–donepezil hybrids. A new series of compounds, in which two fragments are connected using a carbamate linker, exhibits excellent activity and selectivity toward butyrylcholinesterase.
