Studies on cerebral protective agents. X. Synthesis and evaluation of anticonvulsant activities for novel 4,5,6,7-tetrahydrothieno[3,3-c]pyridines and related compounds.
Novel 4,5,6,7-tetrahydrothieno[3,2-c]pyridines, 1-thienyl-1,2,3,4-tetrahydroisoquinolines and related compounds, in which the benzene rings of (+)-1 (FR115427) were replaced with heteroaromatic rings such as thiophene, furan, benzothiophene and indole, were synthesized and evaluated for anticonvulsant activity against i.c.v. N-methyl-D-aspartate (NMDA)-induced seizures in mice. Among these compounds, (+)-4-methyl-4-phenyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride ((+)-2a), (+)-4-methyl-4-(2-thienyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride ((+)-2g), and (-)1-methyl-2-(2-thienyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride ((-)-3a) showed significant anticonvulsant activity. The structure-activity relationships with regard to the anticonvulsant activity of this series of compounds are discussed.
Ohkubo
M
M
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Kuno
A
A
Katsuta
K
K
Ueda
Y
Y
Shirakawa
K
K
Nakanishi
H
H
Kinoshita
T
T
Takasugi
H
H
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology; D003292:Convulsants / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology; D014961:X-Ray Diffraction
D000927:Anticonvulsants; D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D011725:Pyridines; D013876:Thiophenes; D016202:N-Methylaspartate