1,5-Benzodioxepin derivatives as a novel class of muscarinic M3 receptor antagonists.
The structure-activity relationships of novel 1,5-benzodioxepin derivatives as muscarinic M(1)-M(3) receptor antagonists are reported. Some of these compounds were found to possess high binding affinity for the muscarinic M(3) receptor and potent effect on rhythmic increase in bladder pressure in unanesthetized rats following oral administration. These compounds displayed selectivity for the bladder over the salivary gland.
Sonda
Shuji
S
Process Chemistry Laboratories, Pharmaceutical Technology Center, Mitsubishi Pharma Corporation, 14, Sunayama, Kamisu, Ibaraki 314-0255, Japan. Sonda.Shuuji@ma.m-pharma.co.jp
Katayama
Kenichi
K
Fujio
Masakazu
M
Sakashita
Hiroshi
H
Inaba
Kenichi
K
Asano
Kiyoshi
K
Akira
Toshiaki
T
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007202:Indicators and Reagents; D007313:Insecta; D008333:Mandelic Acids / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D010082:Oxepins / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors*; D012469:Salivary Glands / Q000187:drug effects; D012601:Scopolamine / Q000378:metabolism; D013329:Structure-Activity Relationship; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy
D007202:Indicators and Reagents; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D010082:Oxepins; D043587:Receptor, Muscarinic M3; D012601:Scopolamine; C005419:oxybutynin