STRUCTURAL, CONFORMATIONAL, BIOCHEMICAL, AND PHARMACOLOGICAL STUDY OFSOME AMIDES DERIVED FROM 3,7-DIMETHYL-3,7-DIAZABICYCLO[3.3.1]NONAN-9-AMINE AS POTENTIAL 5-HT3 RECEPTOR ANTAGONISTS

A series of amides derived from 3,7-dimethyl-3,7-diazabicyclo [3,3.1] nonan-9-amine have been synthesized and examined by H-1 and C-13 NMR s pectroscopy and the crystal structure of 9-(2,4,6-trichlorobenzamido)- 3,7-dimethy 3,7-diazabicyclo[3.3.1] nonane hydrochloride (4a . HCl) ha s been determined by X-ray diffraction. These compounds adopt an almos t perfect chair-chair conformation with the N-CH3 groups in equatorial position. This conformation is nearly the same as that observed for c ompound 4a in the solid state. From binding studies of compounds 4a-c, compound 4b demonstrated the ability to efficiently displace [H-3]GR6 5630 bound to bovine brain area postrema membranes to an extent compar able to MDL 72222, In the von Bezold-Jarish reflex, compound 4b showed significant results at a dose of 25 mg Kg(-1). It is shown for the fi rst time that a series of compounds with a bispidine skeleton linked t hrough an amide moiety to several aromatic rings, shows 5-HT3 antagoni stic profiles.