Novel N-[1-(1-substituted 4-piperidinylmethyl)-4-piperidinyl]benzamides as potent colonic prokinetic agents

Hiroshi Harada; Hiroshi Yamazaki; Yoshihito Toyotomi; Hirotaka Tateishi; Yukiko Mine; Naoyuki Yoshida; Shiro Kato

doi:10.1016/s0960-894x(02)00060-4

Novel N-[1-(1-substituted 4-piperidinylmethyl)-4-piperidinyl]benzamides as potent colonic prokinetic agents

Bioorg Med Chem Lett. 2002 Mar 25;12(6):967-70. doi: 10.1016/s0960-894x(02)00060-4.

Authors

Hiroshi Harada¹, Hiroshi Yamazaki, Yoshihito Toyotomi, Hirotaka Tateishi, Yukiko Mine, Naoyuki Yoshida, Shiro Kato

Affiliation

¹ Medicinal Chemistry Group, Chemistry Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Enoki 33-94, Osaka 564-0053, Suita, Japan.

PMID: 11959005
DOI: 10.1016/s0960-894x(02)00060-4

Abstract

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.

MeSH terms

Animals
Benzamides / administration & dosage
Benzamides / chemical synthesis*
Benzamides / pharmacology
Digestive System / drug effects
Dogs
Gastrointestinal Agents / administration & dosage
Gastrointestinal Agents / chemical synthesis*
Gastrointestinal Agents / pharmacology
Protein Binding
Serotonin / metabolism
Serotonin Receptor Agonists / administration & dosage
Serotonin Receptor Agonists / chemical synthesis
Serotonin Receptor Agonists / pharmacology
Structure-Activity Relationship

Substances

Benzamides
Gastrointestinal Agents
Serotonin Receptor Agonists
Serotonin