Synthesis of 1-Azabicyclo[3.3.0]octane Derivatives and Their Effects as Piracetam-like Nootropics.

• DOI: 10.1248/cpb.48.1121
• Publication Date: 2011-12-08T04:48:54Z
• Authors: Mitsuru OKA; Yukiharu MATSUMOTO; Kiyotaka HIROOKA; Tomoo SUZUKI
• Keywords: Mice, Inbred ICR; Molecular Structure; Spectrum Analysis; Brain; Bridged Bicyclo Compounds, Heterocyclic; Piracetam; 01 natural sciences; Rats; 0104 chemical sciences; 3. Good health; Mice; Structure-Activity Relationship; Rats, Inbred SHR; Avoidance Learning; Animals; Nootropic Agents

A useful pharmaceutical intermediate, 5-nitromethyl-1-azabicyclo[3.3.0]octane (1), was prepared in one step from 1,7-dichloro-4-heptanone (4) under mild conditions. Catalytic hydrogenation of 1 over Raney Ni in the presence of sodium hydroxide afforded 5-aminomethyl-1-azabicyclo[3.3.0]octane (2) in high yield. Piracetam analogues 20-23, which were pyrrolidine derivatives involving a 1-azabicyclo[3.3.0]octane ring, were synthesized. Pharmacological tests showed that N-[(1-azabicyclo[3.3.0]octan-5-yl)methyl]-2-oxo-1-pyrrolidineacetamid e (20) improves cerebral function.