Discovery of novel diarylamides as orally active diuretics targeting urea transporters.
- Author:
Shun ZHANG
1
;
Yan ZHAO
2
;
Shuyuan WANG
2
;
Min LI
2
;
Yue XU
2
;
Jianhua RAN
3
;
Xiaoqiang GENG
2
;
Jinzhao HE
2
;
Jia MENG
2
;
Guangying SHAO
2
;
Hong ZHOU
2
;
Zemei GE
2
;
Guangping CHEN
4
;
Runtao LI
2
;
Baoxue YANG
1
Author Information
- Publication Type:Journal Article
- Keywords: AQP1, aquaporin 1; BCRP, breast cancer resistance protein; CCK-8, cell counting kit-8; CMC-Na, carboxymethylcellulose sodium; DMF, N,N-dimethylformamide; Diuretic; Fa, fraction absorbance; GFR, glomerular filtration rate; HDL-C and LDL-C, high- and low-density lipoprotein; IC50, half maximal inhibitory concentration; IMCD, inner medulla collecting duct; Oral administration; P-gp, P-glycoprotein; PBS, phosphate buffered saline; Papp, apparent permeability; Structure optimization; THF, tetrahydrofuran; UT, urea transporter; Urea transporter inhibitor; r.t., room temperature
- From: Acta Pharmaceutica Sinica B 2021;11(1):181-202
- CountryChina
- Language:English
- Abstract: Urea transporters (UT) play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics. Thus, UT inhibitors are promising for development as novel diuretics. In the present study, a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening. Optimization of the inhibitor led to the identification of a promising preclinical candidate,
