Synthesis of 1-azabicyclo[3.3.0]octane derivatives and their effects as piracetam-like nootropics.
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.
Oka
M
M
Central Research Laboratory, Sanwa Kagaku Kenkyusho, Co., Ltd., Inabe-gun, Mie, Japan. m_oka@mb6.skk-net.com
Matsumoto
Y
Y
Hirooka
K
K
Suzuki
T
T
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010889:Piracetam / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018697:Nootropic Agents; D010889:Piracetam