Synthesis and analgesic activity of N-aryl/arylalkyl 3-(1-pyrrolidinyl/piperidinyl)butyramides.
Conjugate addition of pyrrolidine or piperidine to methyl crotonate, and hydrolysis of the resulting methyl butyrates gave the (+/-)-3-pyrrolidino or piperidinobutyric acids 17 and 18, respectively. Coupling of these racemic acids to arylalkylamines, L-phenylalaninamide or L-phenylalanine methyl ester gave the N-substituted butyramides 3-14 which were tested as analgesics using the hot-plate method. (+/-)-N-(2-Phenethyl)-3-(1-pyrrolidinyl)butyramide (6) showed naloxone-attenuated analgesia but was considerably less potent than morphine and of shorter duration of action. Diastereomeric butyramides containing Phe residue (11-14) were less active than 6, but unlike N-arylalkylsubstituted derivatives, showed no toxic effects on locomotor activity at the high doses (30-60 mg/kg) used for testing. In all cases, analgesia was accompanied by an inhibition of spontaneous motor activity and sedation.
Essawi
M Y
MY
Department of Organic Chemistry, Faculty of Pharmacy, Cairo University, Egypt.
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D013237:Stereoisomerism
D000577:Amides; D018712:Analgesics, Non-Narcotic