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- Title
Synthesis and structure-activity relationships of ionizable 1,3,4-oxadiazol-2(3 H)-ones as peripherally selective FAAH inhibitors with improved aqueous solubility.
- Authors
Beliaev, Alexandre; Ferreira, Humberto S.; Learmonth, David A.; Bonifácio, Maria João; Torrão, Leonel; Pires, Nuno M.; Soares-da-Silva, Patrício; Kiss, László E.
- Abstract
Novel 5-(2,4-difluorophenoxy)-3-aryl-1,3,4-oxadiazol-2(3 H)-ones were prepared and in vivo SAR are discussed. Ionisable substituents on the N-phenyl ring provided compounds with significantly improved aqueous solubility. In addition, these analogues retained equivalent or improved potency against FAAH enzyme compared to the parent phenols 2-3. FAAH inhibition by the 2-(piperazin-1-yl)ethyl and 3-(piperazin-1-yl)propyl derivatives 24 and 30 was confined to the periphery in mice (30 mg/kg), whereas hepatic FAAH activity was inhibited by over 90%.
- Subjects
OXADIAZOLES; SOLUBILITY; HYDROLASES; ENZYME inhibitors; LABORATORY mice
- Publication
Pure & Applied Chemistry, 2016, Vol 88, Issue 4, p341
- ISSN
0033-4545
- Publication type
Article
- DOI
10.1515/pac-2016-0104