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 MoreNanjing Zelang Medical Technology Co. Ltd
Contact:86-25-83063290/13770714480
Address:Ganjiabian 108# 01 Unit,701-702 room,Yao Hua Street,Qixia District,Nanjing,Jiangsu,China
Hefei EnliPharma Tecnology Co.,Ltd
Contact:0086-551-66399836
Address:Qing Cheng ShuiXiang Building 805, Mengcheng North Road , ShuangFeng Economic Development Zone Anhui HeFei
VanderArk International Limited
Contact:86-10-82437576
Address:Qing He
website:http://www.hope-chem.com
Contact:86-21-58090396-805
Address:Floor 4, Building 5, No.588 Tianxiong Road, Zhoupu International Medical Zone, ShangHai, China
Tianjin Tensing Fine Chemical Research Develop Centre
Contact:86-022-23718576,13032267585
Address:2-2-201,13 Guiyuan road,Huayuan Industry district,Tianjin,china
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)
