1. Design, synthesis, and structure-activity relationship study of bicyclic piperazine analogs of indole-3-carboxamides as novel cannabinoid CB1 receptor agonists.
- Author
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Moir EM, Yoshiizumi K, Cairns J, Cowley P, Ferguson M, Jeremiah F, Kiyoi T, Morphy R, Tierney J, Wishart G, York M, Baker J, Cottney JE, Houghton AK, McPhail P, Osprey A, Walker G, and Adam JM
- Subjects
- Animals, Azabicyclo Compounds chemistry, Azabicyclo Compounds pharmacology, Drug Design, Humans, Indoles chemistry, Indoles pharmacology, Mice, Microsomes, Liver metabolism, Piperazines chemical synthesis, Piperazines pharmacology, Receptor, Cannabinoid, CB1 metabolism, Structure-Activity Relationship, Amides chemistry, Azabicyclo Compounds chemical synthesis, Bridged Bicyclo Compounds chemistry, Indoles chemical synthesis, Piperazines chemistry, Receptor, Cannabinoid, CB1 agonists
- Abstract
Bicyclic piperazine derivatives were synthesized as conformationally constrained analogs of N-alkyl piperazines and were found to be potent CB1 receptor agonists. The CB1 receptor agonist activity was dependent upon the absolute configuration of the chiral center of the bicyclic ring system. Although the conformational constraint did not protect the compounds from metabolism by N-dealkylation, several bicyclic analogs were found to be more potent than the unconstrained lead compound. Compound 8b demonstrated potent antinociceptive activity in vivo., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
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