(R)-1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines: novel optically active compounds with strong 5-HT1A receptor binding ability exhibiting anticonflict activity and lessening of memory impairment.
(R)-1,2,3,4-Tetrahydro[1]benzothieno[2,3-c]pyridine derivatives (60-114) were synthesized. The (R)-isomers have affinity for the 5-HT1A receptor while the (S)-isomers have no such ability. The affinity of the (R)-isomers was discussed on the basis of structure-activity relationships between the affinity and hydrophobicity of the (R)-isomers. Compounds 71 and 107, which are representative derivative compounds, have anticonflict activity and lessening of memory impairment. In particular, compound 107 cannot bind to receptors other than the 5-HT1A receptor, demonstrating that it is a unique compound with a different mechanism of action from that of conventional anxiolytics.
Kawakubo
H
H
Synthetic Section, Asahi Chemical Industry Company, Ltd., Miyazaki, Japan.
Takagi
S
S
Yamaura
Y
Y
Katoh
S
S
Ishimoto
Y
Y
Nagatani
T
T
Mochizuki
D
D
Kamata
T
T
Sasaki
Y
Y
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001362:Avoidance Learning; D003220:Conflict, Psychological; D008297:Male; D051379:Mice; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D012601:Scopolamine; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D058924:Thienopyridines; D013876:Thiophenes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D011725:Pyridines; D011985:Receptors, Serotonin; D058924:Thienopyridines; D013876:Thiophenes; C084466:3-((2-hydroxycyclohex-1-yl)aminocarbonyl)-1,2,3,4-tetrahydro(1)benzothieno(2,3-c)pyridine; C084467:3-((benzodioxol-5-yl)methylaminocarbonyl)-1,2,3,4-tetrahydro(1)benzothieno(2.3-c)pyridine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012601:Scopolamine