New azacannabinoids highly active in the central nervous system

Pursuit of the hypothesis that optimum central nervous system (CNS) activity in 2-azacannabinoids (I and II) requires a moderately basic nitrogen atom (pK = 5-7) has led to several very active alpha -amino amide derivatives, namely 10-hydroxy-N,5,5-trimethyl-8-(1,2-dimethylheptyl)-1,2,3,4-tetrahyd ro-5H-(1)benzopyranol(4,3-c)pyridine-2-acetamide (3a), 8-(5-(4-fluorophenyl)-2-pentyl)-10-hydroxy-N,5,5-trimethyl-1,2,3,4 -tetrahydro-5H-(1)benzopyrano(4,3-c)-pyridine-2-acetamide (3b), and the corresponding acetylurea, 7b. In a battery of seven CNS tests, 7b is one of the most potent cannabinoids so far reported.