Chiral 3-(4,5-dihydrooxazol-2-yl)phenyl alkylcarbamates as novel FAAH inhibitors: Insight into FAAH enantioselectivity by molecular docking and interaction fields

dc.contributorAalto-yliopistofi
dc.contributorAalto Universityen
dc.contributor.authorMyllymaki, Mikko J.en_US
dc.contributor.authorKasnanen, Heikkien_US
dc.contributor.authorKataja, Antti O.en_US
dc.contributor.authorLahtela-Kakkonen, Maijaen_US
dc.contributor.authorSaario, Susanna M.en_US
dc.contributor.authorPoso, Anttien_US
dc.contributor.authorKoskinen, Ari M.P.en_US
dc.contributor.departmentDepartment of Chemistryen
dc.date.accessioned2016-09-23T09:25:40Z
dc.date.issued2009en_US
dc.description.abstractFatty 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.versionPeer revieweden
dc.format.extent4179-4191
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationMyllymaki, 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.2009.05.012en
dc.identifier.doi10.1016/j.ejmech.2009.05.012en_US
dc.identifier.issn0223-5234
dc.identifier.otherPURE UUID: 8e2297c5-d6f6-4931-a126-dd166aeb3d7den_US
dc.identifier.otherPURE ITEMURL: https://research.aalto.fi/en/publications/8e2297c5-d6f6-4931-a126-dd166aeb3d7den_US
dc.identifier.otherPURE FILEURL: https://research.aalto.fi/files/7159863/ms142.pdfen_US
dc.identifier.urihttps://aaltodoc.aalto.fi/handle/123456789/22444
dc.identifier.urnURN:NBN:fi:aalto-201609234447
dc.language.isoenen
dc.relation.ispartofseriesEUROPEAN JOURNAL OF MEDICINAL CHEMISTRYen
dc.relation.ispartofseriesVolume 44, issue 10en
dc.rightsopenAccessen
dc.subject.keywordFAAH inhibitoren_US
dc.subject.keywordfatty acid amide hydrolase (FAAH)en_US
dc.subject.keywordcarbamateen_US
dc.subject.keywordenantiomeric pairen_US
dc.titleChiral 3-(4,5-dihydrooxazol-2-yl)phenyl alkylcarbamates as novel FAAH inhibitors: Insight into FAAH enantioselectivity by molecular docking and interaction fieldsen
dc.typeA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessäfi
dc.type.versionacceptedVersion

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