Academic Journal
Chiral 3-(4,5-dihydrooxazol-2-yl)phenyl alkylcarbamates as novel FAAH inhibitors: Insight into FAAH enantioselectivity by molecular docking and interaction fields
| العنوان: | Chiral 3-(4,5-dihydrooxazol-2-yl)phenyl alkylcarbamates as novel FAAH inhibitors: Insight into FAAH enantioselectivity by molecular docking and interaction fields |
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| المؤلفون: | Myllymaki, Mikko J., Kasnanen, Heikki, Kataja, Antti O., Lahtela-Kakkonen, Maija, Saario, Susanna M., Poso, Antti, Koskinen, Ari M.P. |
| المساهمون: | Department of Chemistry, Aalto-yliopisto, Aalto University |
| سنة النشر: | 2016 |
| المجموعة: | Aalto University Publication Archive (Aaltodoc) / Aalto-yliopiston julkaisuarkistoa |
| مصطلحات موضوعية: | FAAH inhibitor, fatty acid amide hydrolase (FAAH), carbamate, enantiomeric pair |
| الوصف: | Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) are the main enzymes responsible for the hydrolysis of endogenous cannabinoids N-arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), respectively. Phenyl alkylcarbamates are FAAH inhibitors with anxiolytic and analgesic activities in vivo. Herein we present for the first time the synthesis and biological evaluation of a series of chiral 3-(2-oxazoline)-phenyl N-alkylcarbamates as FAAH inhibitors. Furthermore, the structural background of chirality on the FAAH inhibition is explored by analyzing the protein–ligand interactions. Remarkably, 10-fold difference in potency was observed for (R)- and (S)-derivatives of 3-(5-methyl-4,5-dihydrooxazol-2-yl)phenyl cyclohexylcarbamate (6a vs. 6b). Molecular modelling indicated an important interaction between the oxazoline nitrogen and FAAH active site. ; Peer reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0223-5234 |
| Relation: | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; Volume 44, issue 10; Myllymaki , M J , Kasnanen , H , Kataja , A O , Lahtela-Kakkonen , M , Saario , S M , Poso , A & Koskinen , A M P 2009 , ' Chiral 3-(4,5-dihydrooxazol-2-yl)phenyl alkylcarbamates as novel FAAH inhibitors: Insight into FAAH enantioselectivity by molecular docking and interaction fields ' , EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY , vol. 44 , no. 10 , pp. 4179-4191 . https://doi.org/10.1016/j.ejmech.2009.05.012; PURE UUID: 8e2297c5-d6f6-4931-a126-dd166aeb3d7d; PURE ITEMURL: https://research.aalto.fi/en/publications/8e2297c5-d6f6-4931-a126-dd166aeb3d7d; PURE FILEURL: https://research.aalto.fi/files/7159863/ms142.pdf; https://aaltodoc.aalto.fi/handle/123456789/22444; URN:NBN:fi:aalto-201609234447 |
| DOI: | 10.1016/j.ejmech.2009.05.012 |
| الاتاحة: | https://aaltodoc.aalto.fi/handle/123456789/22444 https://doi.org/10.1016/j.ejmech.2009.05.012 |
| Rights: | openAccess |
| رقم الانضمام: | edsbas.43C14D07 |
| قاعدة البيانات: | BASE |
| تدمد: | 02235234 |
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| DOI: | 10.1016/j.ejmech.2009.05.012 |