Discovery of novel spirocyclic inhibitors of fatty acid amide hydrolase (FAAH). Part 1: Identification of 7-azaspiro[3.5]nonane and 1-oxa-8-azaspiro[4.5]decane as lead scaffolds

作者：Meyers Marvin J^*; Long Scott A; Pelc Matthew J; Wang Jane L; Bowen Scott J; Walker Mark C; Schweitzer Barbara A; Madsen Heather M; Tenbrink Ruth E; McDonald Joseph; Smith Sarah E; Foltin Susan; Beidler David; Thorarensen Atli

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(21): 6538-6544.

DOI：10.1016/j.bmcl.2011.08.055

• Fatty acid amide hydrolase, FAAH
• Pain
• Endocannabinoid

Herein we report the identification of two new fatty acid amide hydrolase (FAAH) inhibitor lead series with FAAH k(inact)/K(i) potency values greater than 1500 M (1) s (1). The two novel spirocyclic cores, 7-azaspiro[3.5]nonane and 1-oxa-8-azaspiro[4.5]decane, clearly distinguished themselves from the other spirocyclic cores on the basis of their superior potency for FAAH. Lead compounds from these two series have suitable FAAH potency and selectivity for additional medicinal chemistry optimization.

• 出版日期2011-11-1