Chemical and Pharmaceutical Bulletin p. 1912 - 1930 (1995)
Update date:2022-08-04
Topics:
Harada
Morie
Hirokawa
Terauchi
Fujiwara
Yoshida
Kato
Our studies on 4-amino-5-chloro-2-ethoxybenzamides led to the discovery that the N-(1,4-dimethylhexahydro-1H-1,4-diazepin-6-yl)benzamide 9 and the 1- benzyl-4-methylhexahydro-1H-1,4-diazepine analogue 10 are potent serotonin-3 (5-HT3) receptor antagonists. Structure-activity relationship (SAR) studies on the influence of the aromatic nucleus of 9 and 10 upon inhibition of the von Bezold-Jarisch reflex in rats are described. Heteroaromatic rings such as pyrrole, thiophene, furan, pyridine, pyridaziae, 1,2-benzisoxazole, indole, quinoline, and isoquinoline rings showed weak 5-HT3 receptor antagonistic activity. Within this series, use of the 1H-indazole ring as an aromatic moiety led to a substantial increase of the activity; the 1H- indazolylcarboxamides 54, 57, 97, and 102 showed potent 5-HT3 receptor antagonistic activity. The optimal compound identified via extensive SAR studies was N-(1-benzyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-1H-indazole- 3-carboxamide (54), whose effect was superior to that of the corresponding benzamide 10 and essentially equipotent to those of ondansetron (1) and granisetron (4).
View MoreGuangzhou Probig Fine Chemical Co., Ltd.
Contact:020-86297874
Address:No.2, 1/F, No.20, Hetai Road,Hebian Village, Baiyun District,Guangzhou,China
Beijing Apis Biotechnology Co., Ltd.
Contact:86-010-67856775-8551
Address:NO.4PUHUANGYU ROAD,FENTAI DISTRICT, BEIJING, CHINA
Luojiang Chenming Biological Products Co
Contact:+86 15000297032
Address:GROUP NO.4, HE SHENG VILLAGE, PANLONG TOWN,
Contact:+86-574-87065746
Address:10th Floor, No.787 Baizhang East Road,
Chuzhou Baiao Biologhy S&T Co., Ltd.
Contact:+86-25-83212599;+86-25-83212699 13705185959
Address:Room 905, Tianzheng International Platza, No.399, Zhongyang Road ,Nanjing, Jiangsu Province, China
Doi:10.1016/S0040-4039(01)00354-9
(2001)Doi:10.1021/jm00108a003
(1991)Doi:10.1021/jm4004895
(2013)Doi:10.1021/ol2016077
(2011)Doi:10.1039/c1cc12827b
(2011)Doi:10.1039/c7cc02430d
(2017)