Novel N-[1-(1-substituted 4-piperidinylmethyl)-4-piperidinyl]benzamides as potent colonic prokinetic agents.
A series of novel N-[1-(1-substituted 4-piperidinylmethyl)-4-piperidinyl]benzamides was prepared and its compounds were evaluated for their binding to 5-HT(4) receptors and effects on gastrointestinal motility in conscious dogs. 4-Amino-N-[1-[1-(4-aminobutyl)-4-piperidinylmethyl]-4-piperidinyl]-5-chloro-2-methoxybenzamide (15) was found to have a potent binding affinity for 5-HT(4) receptors (IC(50): 6.47nM) and showed excellent colonic prokinetic activity.
Harada
Hiroshi
H
Medicinal Chemistry Group, Chemistry Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Enoki 33-94, Osaka 564-0053, Suita, Japan.
Yamazaki
Hiroshi
H
Toyotomi
Yoshihito
Y
Tateishi
Hirotaka
H
Mine
Yukiko
Y
Yoshida
Naoyuki
N
Kato
Shiro
S
D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D004064:Digestive System / Q000187:drug effects; D004285:Dogs; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001549:Benzamides; D005765:Gastrointestinal Agents; D017366:Serotonin Receptor Agonists; D012701:Serotonin