Synthesis and resolution of the novel appetite suppressant 2-benzylmorpholine, a nonstimulant isomer of phenmetrazine.
The synthesis of 2-benzylmorpholine from allylbenzene together with its resolution into its (+)- and (-)-enantiomers is reported. Oral dosing of the racemate to dogs caused appetite suppression with an ED50 of 3 and 5.5 mg kg-1 at 1 and 2 h, respectively, after access to a meat meal. No stimulant activity was observed in dogs given oral doses of 200 mg kg-1 but the appetite suppressant effect in dogs declined during 20 days of chronic oral dosing at 10 mg kg-1. Appetite suppression activity was shown to reside in the (+)-enantiomer.
Brown
G R
GR
ICI Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, UK.
Forster
G
G
Foubister
A J
AJ
Stribling
D
D
D000284:Administration, Oral; D000818:Animals; D001066:Appetite / Q000187:drug effects; D001067:Appetite Depressants / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D009025:Morpholines / Q000138:chemical synthesis* / Q000494:pharmacology; D010633:Phenmetrazine / Q000031:analogs & derivatives*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001067:Appetite Depressants; D009025:Morpholines; C068455:2-benzylmorpholine; D010633:Phenmetrazine