Discovery of 1-[9-(4-Chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4-ethylaminopiperidine-4-carboxylic Acid Amide Hydrochloride (CP-945,598), a Novel, Potent, and Selective Cannabinoid Type 1 Receptor Antagonist

Discovery of 1-[9-(4-Chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4-ethylaminopiperidine-4-carboxylic Acid Amide Hydrochloride (CP-945,598), a Novel, Potent, and Selective Cannabinoid Type 1 Receptor Antagonist

We report the structure−activity relationships, design, and synthesis of the novel cannabinoid type 1 (CB1) receptor antagonist 3a (CP-945,598). Compound 3a showed subnanomolar potency at human CB1 receptors in binding (K i = 0.7 nM) and functional assays (K i = 0.12 nM). In vivo, compound 3a revers...

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Veröffentlicht in:Journal of medicinal chemistry 2009-01, Vol.52 (2), p.234-237
Hauptverfasser: Griffith, David A, Hadcock, John R, Black, Shawn C, Iredale, Philip A, Carpino, Philip A, DaSilva-Jardine, Paul, Day, Robert, DiBrino, Joseph, Dow, Robert L, Landis, Margaret S, O’Connor, Rebecca E, Scott, Dennis O
Format: Artikel
Sprache:eng
Schlagworte:
Animals
Dogs
Drug Discovery
Energy Metabolism
Fats - metabolism
Oxidation-Reduction
Piperidines - chemistry
Piperidines - pharmacology
Purines - chemistry
Purines - pharmacology
Receptor, Cannabinoid, CB1 - antagonists & inhibitors
Structure-Activity Relationship
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Zusammenfassung:We report the structure−activity relationships, design, and synthesis of the novel cannabinoid type 1 (CB1) receptor antagonist 3a (CP-945,598). Compound 3a showed subnanomolar potency at human CB1 receptors in binding (K i = 0.7 nM) and functional assays (K i = 0.12 nM). In vivo, compound 3a reversed cannabinoid agonist-mediated responses, reduced food intake, and increased energy expenditure and fat oxidation in rodents.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm8012932