[Studies of synthesis and structure-activity relationships of analogs of the muscle relaxant--baclofen].
In an effort to study the structure-activity relationship of analogs of baclofen and to search for more potent and less toxic muscle relaxants and analgesics, fifteen 3-substituted pheny-4-aminobutyric acids and their derivatives were synthesized. Preliminary pharmacological tests in albino mice showed that some of the target compounds exhibited muscle relaxant and analgesic effects. Compounds Ib, IIb, IIIa, IIIc and compounds Ib, IIb, IIIa, IIIb were, respectively, more potent in hot plate tests and morphine-induced straub tail reaction tests than other analogs, but they were still less potent than baclofen. The structure-activity relationship showed that the effects of baclofen were strongly structure specific, and the results also suggested that at least three groups in baclofen-phenyl, amino and carboxy--take important parts in the combination of baclofen with GABAB receptor.
Guo
Z W
ZW
Department of Pharmacy, Second Military Medical College, Shanghai.
Tu
S Z
SZ
Li
W H
WH
Chen
J
J
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects; D010146:Pain / Q000503:physiopathology; D011963:Receptors, GABA-A / Q000187:drug effects; D012684:Sensory Thresholds / Q000187:drug effects; D013329:Structure-Activity Relationship
D011963:Receptors, GABA-A; D001418:Baclofen