Maeda J

References (3)

Title : Design, Synthesis, and Evaluation of (4 R)-1-{3-[2-((18)F)Fluoro-4-methylpyridin-3-yl]phenyl}-4-[4-(1,3-thiazol-2-ylcarbo nyl)piperazin-1-yl]pyrrolidin-2-one ([(18)F]T-401) as a Novel Positron-Emission Tomography Imaging Agent for Monoacylglycerol Lipase - Hattori_2019_J.Med.Chem_62_2362
Author(s) : Hattori Y , Aoyama K , Maeda J , Arimura N , Takahashi Y , Sasaki M , Fujinaga M , Seki C , Nagai Y , Kawamura K , Yamasaki T , Zhang MR , Higuchi M , Koike T
Ref : Journal of Medicinal Chemistry , 62 :2362 , 2019
Abstract : Monoacylglycerol lipase (MAGL) is a cytosolic serine hydrolase involved in endocannabinoid and inflammatory signaling. Positron-emission tomography (PET) imaging of MAGL serves to validate target engagement of therapeutic MAGL inhibitors as well as to investigate MAGL levels under normal and disease conditions. However, PET radioligands with reversible binding kinetics for MAGL, which allow quantitative assessment of MAGL, are hitherto unavailable. In this study, we designed and synthesized fluoro-containing PET probes starting from a recently identified piperazinyl pyrrolidine-2-one derivative with reversible binding to MAGL. By tailoring the lipophilicity of the molecule to optimize nonspecific binding and blood-brain barrier permeability, we successfully identified two compounds that show high uptake to regions enriched with MAGL. PET imaging of wild-type and MAGL-deficient mice as well as a macaque monkey indicated that [(18)F]5 ((4 R)-1-{3-[2-((18)F)fluoro-4-methylpyridin-3-yl]phenyl}-4-[4-(1,3-thiazol-2-ylcarbo nyl)piperazin-1-yl]pyrrolidin-2-one, [(18)F]T-401) specifically binds to MAGL with adequate reversibility, yielding a high contrast for MAGL within an appropriate imaging time.
ESTHER : Hattori_2019_J.Med.Chem_62_2362
PubMedSearch : Hattori_2019_J.Med.Chem_62_2362
PubMedID: 30753069
Gene_locus related to this paper: human-MGLL

Title : Draft Genome Sequence of Thiostrepton-Producing Streptomyces azureus ATCC 14921 - Sakihara_2015_Genome.Announc_3_e01183
Author(s) : Sakihara K , Maeda J , Tashiro K , Fujino Y , Kuhara S , Ohshima T , Ogata S , Doi K
Ref : Genome Announc , 3 : , 2015
Abstract : Streptomyces azureus ATCC 14921 belongs to the Streptomyces cyaneus cluster and is known to be a thiostrepton producer. Here, we report a draft genome sequence for this strain, consisting of 350 contigs containing a total of 8,790,525 bp, 8,164 predicted coding sequences, and a G+C content of 70.9%.
ESTHER : Sakihara_2015_Genome.Announc_3_e01183
PubMedSearch : Sakihara_2015_Genome.Announc_3_e01183
PubMedID: 26494661
Gene_locus related to this paper: straj-a0a0k8pgz2 , straj-a0a0k8pxt3

Title : N-[18F]fluoroethyl-4-piperidyl acetate ([18F]FEtP4A): A PET tracer for imaging brain acetylcholinesterase in vivo - Zhang_2003_Bioorg.Med.Chem_11_2519
Author(s) : Zhang MR , Furutsuka K , Maeda J , Kikuchi T , Kida T , Okauchi T , Irie T , Suzuki K
Ref : Bioorganic & Medicinal Chemistry , 11 :2519 , 2003
Abstract : N-[(18)F]Fluoroethyl-4-piperidyl acetate ([(18)F]FEtP4A) was synthesized and evaluated as a PET tracer for imaging brain acetylcholinesterase (AchE) in vivo. [(18)F]FEtP4A was previously prepared by reacting 4-piperidyl acetate (P4A) with 2-[(18)F]fluoroethyl bromide ([(18)F]FEtBr) at 130 degrees C for 30 min in 37% radiochemical yield using an automated synthetic system. In this work, [(18)F]FEtP4A was synthesized by reacting P4A with 2-[(18)F]fluoroethyl iodide ([(18)F]FEtI) or 2-[(18)F]fluoroethyl triflate ([(18)F]FEtOTf in improved radiochemical yields, compared with [(18)F]FEtBr under the corresponding condition. Ex vivo autoradiogram of rat brain and PET summation image of monkey brain after iv injection of [(18)F]FEtP4A displayed a high radioactivity in the striatum, a region with the highest AchE activity in the brain. Moreover, the distribution pattern of (18)F radioactivity was consistent with that of AchE in the brain: striatum>frontal cortex>cerebellum. In the rat and monkey plasma, two radioactive metabolites were detected. However, their presence might not preclude the imaging studies for AchE in the brain, because they were too hydrophilic to pass the blood-brain barrier and to enter the brain. In the rat brain, only [(18)F]fluoroethyl-4-piperidinol ([(18)F]FEtP4OH) was detected at 30 min postinjection. The hydrolytic [(18)F]FEtP4OH displayed a slow washout and a long retention in the monkey brain until the PET experiment (120 min). Although [(18)F]FEtP4A is a potential PET tracer for imaging AchE in vivo, its lower hydrolytic rate and lower specificity for AchE than those of [(11)C]MP4A may limit its usefulness for the quantitative measurement for AchE in the primate brain.
ESTHER : Zhang_2003_Bioorg.Med.Chem_11_2519
PubMedSearch : Zhang_2003_Bioorg.Med.Chem_11_2519
PubMedID: 12757720