Chemical and Pharmaceutical Bulletin p. 755 - 771 (1999)
Update date:2022-07-29
Topics:
Takeda, Yasuyuki
Kawagoe, Keiichi
Yokomizo, Aki
Yokomizo, Yoshihiro
Hosokami, Toru
Shimoto, Yoshimasa
Tabuchi, Yoshiaki
Ogihara, Yoshiyasu
Honda, Yuko
Kawarabayashi, Keiko
Iseri, Miki
Yokohama, Shuichi
In order to improve the biological characteristics of DA-3934 (5), a novel gastrin/cholecystokinin (CCK)-B receptor antagonist, phenoxyacetic acid derivatives replacing the N-methyl-N-phenylcarbamoylmethyl moiety of 5 with various alkyl chains have been synthesized and their biological activity evaluated. The relationship between the structure of these compounds and their human gastrin receptor binding affinity showed that there should be the optimal size among the various N-alkyl chains. Also a significant increase in the receptor binding affinity was achieved by several compounds. Among those compounds, 2-[3-[3-[N-cyclohexylmethyl-N-[2-(N-methyl-N- phenylcarbamoylmethoxy)phenyl]carbamoylmethyl]ureido]phenyl]acetic acid (22c) and (±)-2-[3-[3[N-[2-(N-methyl-N-phenylcarbamoylmethoxy)phenyl]-N-(3- methylpentyl)carbamoylmethyl]ureido]phenyl]acetic acid (22h) exhibited high affinity for human gastrin receptors and were also more potent inhibitors in a pentagastrin-induced gastric acid secretion model than the parent compound, 5. The ED(50) values of these compounds when administered intraduodenally to rats were 0.12 and 0.63 mg/kg, respectively.
View MoreContact:+86-512-69561895
Address:No.111, Building A4, 218 Xinghu Street, Suzhou Industrial Park, P. R. China
Suzhou Kangrun Pharmaceutical, Inc
Contact:86-512-63912376，63913329
Address:Building 2, No. 2358 ,Chang'an Rd, Wujiang Economic Development Zone Pioneering park, china
Zhejiang Kangfeng Chemical Co.,LTD.
Contact:+86-579-86709687
Address:Xueshizhai Industrial Zone, Weishan Town,Dongyang City, Zhejiang Province ,China
Daqing New Century Fine Chemical Co., Ltd.(expird)
Contact:010-57126694
Address:No.39, jinxing cun, honggang district
Contact:+86-511-88790000
Address:338 North Yushan Rd, Zhenjiang, Jiangsu 212016
Doi:10.1070/MC2005v015n01ABEH001946
(2005)Doi:10.1002/ejoc.201000425
(2010)Doi:10.1016/j.mencom.2010.06.019
(2010)Doi:10.1021/jo00291a024
(1990)Doi:10.1039/b927442a
(2010)Doi:10.1002/adsc.201000180
(2010)
