Chiral 3-(4,5-dihydrooxazol-2-yl)phenyl alkylcarbamates as novel FAAH inhibitors: Insight into FAAH enantioselectivity by molecular docking and interaction fields
dc.contributor | Aalto-yliopisto | fi |
dc.contributor | Aalto University | en |
dc.contributor.author | Myllymaki, Mikko J. | en_US |
dc.contributor.author | Kasnanen, Heikki | en_US |
dc.contributor.author | Kataja, Antti O. | en_US |
dc.contributor.author | Lahtela-Kakkonen, Maija | en_US |
dc.contributor.author | Saario, Susanna M. | en_US |
dc.contributor.author | Poso, Antti | en_US |
dc.contributor.author | Koskinen, Ari M.P. | en_US |
dc.contributor.department | Department of Chemistry | en |
dc.date.accessioned | 2016-09-23T09:25:40Z | |
dc.date.issued | 2009 | en_US |
dc.description.abstract | 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. | en |
dc.description.version | Peer reviewed | en |
dc.format.extent | 4179-4191 | |
dc.format.mimetype | application/pdf | en_US |
dc.identifier.citation | 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 | en |
dc.identifier.doi | 10.1016/j.ejmech.2009.05.012 | en_US |
dc.identifier.issn | 0223-5234 | |
dc.identifier.other | PURE UUID: 8e2297c5-d6f6-4931-a126-dd166aeb3d7d | en_US |
dc.identifier.other | PURE ITEMURL: https://research.aalto.fi/en/publications/8e2297c5-d6f6-4931-a126-dd166aeb3d7d | en_US |
dc.identifier.other | PURE FILEURL: https://research.aalto.fi/files/7159863/ms142.pdf | en_US |
dc.identifier.uri | https://aaltodoc.aalto.fi/handle/123456789/22444 | |
dc.identifier.urn | URN:NBN:fi:aalto-201609234447 | |
dc.language.iso | en | en |
dc.relation.ispartofseries | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | en |
dc.relation.ispartofseries | Volume 44, issue 10 | en |
dc.rights | openAccess | en |
dc.subject.keyword | FAAH inhibitor | en_US |
dc.subject.keyword | fatty acid amide hydrolase (FAAH) | en_US |
dc.subject.keyword | carbamate | en_US |
dc.subject.keyword | enantiomeric pair | en_US |
dc.title | Chiral 3-(4,5-dihydrooxazol-2-yl)phenyl alkylcarbamates as novel FAAH inhibitors: Insight into FAAH enantioselectivity by molecular docking and interaction fields | en |
dc.type | A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä | fi |
dc.type.version | acceptedVersion |