Novel acetylcholinesterase inhibitor as increasing agent on rhythmic bladder contractions:: SAR of 8-{3-[1-(3-fluorobenzyl)piperidin-4-yl]propanoyl}-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one (TAK-802) and related compounds

被引：16

作者：

Ishichi, Y

Sasaki, M

Setoh, M

Tsukamoto, T

Miwatashi, S

Nagabukuro, H

Okanishi, S

Imai, S

Saikawa, R

Doi, T

Ishihara, Y

机构：

[1] Takeda Pharmaceut Co Ltd, Div Pharmaceut Res, Med Chem Res Labs, Yodogawa Ku, Osaka 5328686, Japan

[2] Takeda Pharmaceut Co Ltd, Div Pharmaceut Res, Pharmaceut Res Labs 1, Yodogawa Ku, Osaka 5328686, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 06期

关键词：

acetylcholinesterase inhibitor; pyrrolos[3,2,1-ij]quinolin-4-one; rhythmic bladder contraction; TAK-802;

D O I：

10.1016/j.bmc.2005.01.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

As part of an on-going investigation to develop an increasing agent on rhythmic bladder contractions, 1-aryl-3-(1-benzylpiperidin-4-yl)propanones were synthesized and examined as noncarbamate acetylcholinesterase (AChE) inhibitors. Among compounds with various aryl groups, 1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij]quinolin-4-one derivative 9c was found to possess a potent AChE inhibition activity with an IC50 value of 1.3 nM. The compound 9c increased rhythmic bladder contractions in Guinea pigs and rats without affecting the basal intravesical pressure, which suggests that 9c may be useful for the treatment of voiding dysfunction caused by detrusor underactivity. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：1901 / 1911

页数：11

共 23 条

[21] Symptomatic and urodynamic improvement by oral distigmine bromide in poor voiders after transurethral resection of the prostate [J].