Synthesis and antinociceptive activity of 4-(cyclopropylmethyl)-3,4,5,6-tetrahydro-2H-1,5-methano-1,4- benzodiazocin-9-amine and congeners

Article abstract of DOI:10.1021/jm00383a007

The synthesis of 1,4-benzodiazocines has been extended to include the 9-amines. The title compound, 6, was prepared from the known nor-base by N-acylation with cyclopropanecarboxylic acid anhydride, followed by nitration of the aromatic ring and sequential reduction of the resulting nitroamide. Standard in vivo bioassays for antinociceptive and opiate antagonist activities indicated that 6 is an analgesic agonist mixed narcotic antagonist whose oral to parenteral activity ratio approaches unity. Resolution of 6 established that the activity of the racemate resides in the dextrorotatory antipode. Several congeners were also prepared and tested. Their synthesis and structure-activity relationship are given in this paper.