SYNTHESIS AND MYELOSTIMULATORY ACTIVITY OF B-CYCLODEXTRIN COMPLEXES OF 3,7-DIAZABICYCLO[3.3.1]NONAN-9-ONE DERIVATIVES

Simultaneous Mannich condensation of 1-(3-methoxypropyl)piperidone-4 with paraformaldehyde and 1-(2-pyridinoethyl)amine yielded 3-(3methoxypropyl)-7-[2-(pyridin-2-yl)ethyl]-3,7-diazabicyclo[3.3.1]nonan-9-one, which was reduced to the corresponding bicyclic nonane under Huang-Minlon reaction conditions. The reaction of 3,7-diazabicyclo[3.3.1]nonan-9-one with hydroxylamine hydrochloride led to the corresponding oxime, subsequent acylation of which synthesized itsO-benzoyloxime. Replacement of the morpholine or piperazine ring in 3-(3-ethoxy- or isopropoxypropyl)-7-[2-(N-morpholino- orN-piperazino) ethyl]-3,7-diazabicyclo[3.3.1]nonane by pyridine led to a loss of activity. However, 3-(3-methoxy- and isopropoxypropyl)-7-[2-(pyridin-2-yl- andN-piperazino)ethyl]-3,7-diazabicyclo[3.3.1]nonan-9-oneO-benzoyloximes were myelostimulators although they differed in that the beta-cyclodextrin complex of 3-(3-methoxypropyl)-7-[2-(pyridin-2-yl)ethyl]-3,7-diazabicyclo[3.3.1]nonan-9-oneO-benzoyloxime stimulated both erythro- and leukopoiesis while itsN-piperazine analog stimulated only leukopoiesis.