Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide Hydrolase
Fatty Acid Amide Hydrolase (FAAH) is an intracellular serine enzyme involved in the biological degradation of the fatty acid ethanolamide family of signaling lipids, which exerts neuroprotective, anti-inflammatory, and analgesic properties. In the present study, a conjugated 2,4-dioxo-pyrimidine-1-c...
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| Format: | Article |
| Language: | English |
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MDPI AG
2016-02-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/21/2/229 |
| _version_ | 1818215083863441408 |
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| author | Yan Qiu Yang Zhang Yuhang Li Jie Ren |
| author_facet | Yan Qiu Yang Zhang Yuhang Li Jie Ren |
| author_sort | Yan Qiu |
| collection | DOAJ |
| description | Fatty Acid Amide Hydrolase (FAAH) is an intracellular serine enzyme involved in the biological degradation of the fatty acid ethanolamide family of signaling lipids, which exerts neuroprotective, anti-inflammatory, and analgesic properties. In the present study, a conjugated 2,4-dioxo-pyrimidine-1-carboxamide scaffold was confirmed as a novel template for FAAH inhibitors, based on which, a series of analogues had been prepared for an initial structure-activity relationship (SAR) study. Most of the synthesized compounds displayed moderate to significant FAAH inhibitory potency. Among them, compounds 11 and 14 showed better activity than others, with IC50 values of 21 and 53 nM. SAR analysis indicated that 2,4-dioxopyrimidine-1-carboxamides represented a novel class of potent inhibitors of FAAH, and substitution at the uracil ring or replacement of the N-terminal group might favor the inhibitory potency. Selected compounds of this class may be used as useful parent molecules for further investigation. |
| first_indexed | 2024-12-12T06:30:27Z |
| format | Article |
| id | doaj.art-d880387289a340b994d5435fb4ccc689 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-12T06:30:27Z |
| publishDate | 2016-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-d880387289a340b994d5435fb4ccc6892022-12-22T00:34:37ZengMDPI AGMolecules1420-30492016-02-0121222910.3390/molecules21020229molecules21020229Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide HydrolaseYan Qiu0Yang Zhang1Yuhang Li2Jie Ren3Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen 361102, ChinaDepartment of Basic Medical Sciences, Medical College, Xiamen University, Xiamen 361102, ChinaDepartment of Basic Medical Sciences, Medical College, Xiamen University, Xiamen 361102, ChinaDepartment of Basic Medical Sciences, Medical College, Xiamen University, Xiamen 361102, ChinaFatty Acid Amide Hydrolase (FAAH) is an intracellular serine enzyme involved in the biological degradation of the fatty acid ethanolamide family of signaling lipids, which exerts neuroprotective, anti-inflammatory, and analgesic properties. In the present study, a conjugated 2,4-dioxo-pyrimidine-1-carboxamide scaffold was confirmed as a novel template for FAAH inhibitors, based on which, a series of analogues had been prepared for an initial structure-activity relationship (SAR) study. Most of the synthesized compounds displayed moderate to significant FAAH inhibitory potency. Among them, compounds 11 and 14 showed better activity than others, with IC50 values of 21 and 53 nM. SAR analysis indicated that 2,4-dioxopyrimidine-1-carboxamides represented a novel class of potent inhibitors of FAAH, and substitution at the uracil ring or replacement of the N-terminal group might favor the inhibitory potency. Selected compounds of this class may be used as useful parent molecules for further investigation.http://www.mdpi.com/1420-3049/21/2/229fatty acid amide hydrolase (FAAH)uracil derivativesFAAH inhibitoramidation |
| spellingShingle | Yan Qiu Yang Zhang Yuhang Li Jie Ren Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide Hydrolase Molecules fatty acid amide hydrolase (FAAH) uracil derivatives FAAH inhibitor amidation |
| title | Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide Hydrolase |
| title_full | Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide Hydrolase |
| title_fullStr | Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide Hydrolase |
| title_full_unstemmed | Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide Hydrolase |
| title_short | Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide Hydrolase |
| title_sort | discovery of uracil derivatives as potent inhibitors of fatty acid amide hydrolase |
| topic | fatty acid amide hydrolase (FAAH) uracil derivatives FAAH inhibitor amidation |
| url | http://www.mdpi.com/1420-3049/21/2/229 |
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