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N-芳基2-芳氧基乙酰胺作为一类新型脂肪酸酰胺水解酶（FAAH）抑制剂。

N-aryl 2-aryloxyacetamides as a new class of fatty acid amide hydrolase (FAAH) inhibitors.

作者信息

Sunduru Naresh, Svensson Mona, Cipriano Mariateresa, Marwaha Sania, Andersson C David, Svensson Richard, Fowler Christopher J, Elofsson Mikael

机构信息

a Department of Chemistry , Umeå University , Umeå , Sweden.

b Department of Pharmacology and Clinical Neuroscience , Umeå University , Umeå , Sweden.

出版信息

J Enzyme Inhib Med Chem. 2017 Dec;32(1):513-521. doi: 10.1080/14756366.2016.1265520.

DOI:10.1080/14756366.2016.1265520
PMID:28114819
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6009913/
Abstract

Fatty acid amide hydrolase (FAAH) is a promising target for the development of drugs to treat neurological diseases. In search of new FAAH inhibitors, we identified 2-(4-cyclohexylphenoxy)-N-(3-(oxazolo[4,5-b]pyridin-2-yl)phenyl)acetamide, 4g, with an IC of 2.6 µM as a chemical starting point for the development of potent FAAH inhibitors. Preliminary hit-to-lead optimisation resulted in 2-(4-phenylphenoxy)-N-(3-(oxazolo[4,5-b]pyridin-2-yl)phenyl)acetamide, 4i, with an IC of 0.35 µM.

摘要

脂肪酸酰胺水解酶（FAAH）是开发治疗神经疾病药物的一个有前景的靶点。为了寻找新的FAAH抑制剂，我们确定了2-(4-环己基苯氧基)-N-(3-(恶唑并[4,5-b]吡啶-2-基)苯基)乙酰胺（4g），其IC50为2.6 μM，作为开发强效FAAH抑制剂的化学起始点。初步的从苗头化合物到先导化合物的优化产生了2-(4-苯基苯氧基)-N-(3-(恶唑并[4,5-b]吡啶-2-基)苯基)乙酰胺（4i），其IC50为0.35 μM。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7714/6009913/3dc698f83a08/IENZ_A_1265520_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7714/6009913/ccb78687ce6a/IENZ_A_1265520_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7714/6009913/fef861d2ef11/IENZ_A_1265520_SCH0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7714/6009913/e8fbbc30aba6/IENZ_A_1265520_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7714/6009913/3dc698f83a08/IENZ_A_1265520_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7714/6009913/ccb78687ce6a/IENZ_A_1265520_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7714/6009913/fef861d2ef11/IENZ_A_1265520_SCH0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7714/6009913/e8fbbc30aba6/IENZ_A_1265520_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7714/6009913/3dc698f83a08/IENZ_A_1265520_F0003_C.jpg

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Radiosynthesis and evaluation of [¹¹C-carbonyl]-labeled carbamates as fatty acid amide hydrolase radiotracers for positron emission tomography.[¹¹C-羰基]-标记的氨基甲酸酯类化合物的放射合成与评价作为正电子发射断层扫描的脂肪酸酰胺水解酶放射性示踪剂。
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