Synthesis and central nervous system properties of 2-[(alkoxycarbonyl)amino]-4(5)-phenyl-2-imidazolines.
A series of 2-[( alkoxycarbonyl )amino]-4(5)-phenyl-2-imidazolines was prepared and evaluated for central nervous system (CNS) effects (antidepressant, anticonvulsant, muscle relaxant, and depressant) in animal models. Some separation of those CNS activities was achieved through substitutions on the phenyl and imidazoline moieties. Halo-substituted phenyl compounds were among the most potent antidepressants in this series, while imidazole N-alkylation produced compounds with increased depressant effects (loss of righting reflex, mouse behavior). Comparison of in vitro and in vivo data for pairs of 2-[(methoxycarbonyl)amino]-4(5)-phenyl-2-imidazolines and their parent, 2-amino-4(5)-phenyl-2-imidazolines, suggests that the title compounds were prodrugs for the 2-amino-4(5)-phenyl-2-imidazolines in inhibition of norepinephrine reuptake.
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D002491:Central Nervous System Agents / Q000138:chemical synthesis*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000138:chemical synthesis; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011187:Posture; D012110:Reserpine / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D000928:Antidepressive Agents; D002491:Central Nervous System Agents; D007093:Imidazoles; D007202:Indicators and Reagents; D009125:Muscle Relaxants, Central; D012110:Reserpine; D009638:Norepinephrine