Journal of Medicinal Chemistry p. 1600 - 1606 (1989)
Update date:2022-08-03
Topics:
Smith, Elizabeth M.
Swiss, Gerald F.
Neustadt, Bernard R.
McNamara, Paul
Gold, Elijah H.
et al.
The synthesis of spirapril (5), spiraprilat (25), their RSS stereoisomers, and their glycyl (18b) and lysyl (36, 37) analogues is described.These compounds were evaluated in vivo for inhibition of angiotensin converting enzyme (ACE), and selected compounds were evaluated for in vitro ACE inhibition (spirapril ID50 16 μg/kg; spiraprilat IC50 0.8 nM, ID50 8 μg/kg).In anesthetized rats, iv, esters 5 and 36 are more potent than enalapril, and diacids 25 and 37 are more potent than enalaprilat in vitro.In the conscious rats, orally, 5 and enalapril (2) showed potent and sustained activity at doses of 0.03-1 and 0.1-1 mg/kg, respectively.From this work, spirapril was selected for clinical evaluation as an antihypertensive agent.
View MoreHangzhou J&H Chemical Co., Ltd.
website:http://www.jhechem.com/
Contact:+86-571-87396432
Address:No.200 Zhenhua Rd.Xihu Industrial Park, Hangzhou 310030, China
Beijing Mashi Fine Chemical Co.,Ltd.
Contact:+86-10-61271592
Address:Room 506, Section B, Kaichi Mansion, Industrial Development
JIANGXI ZHANGFENG CHEMICAL CO., LTD.
Contact:+86-0799-3413066
Address:Xiyuan village, Xiabu Town, Xiangdong District
Taizhou YOJOY Chemical Co., Ltd.
Contact:13857143241
Address:Yangfu Industrial Park, Xianju, Zhejiang, P. R. China
website:http://www.joyochem.com
Contact:0531-82687998
Address:Factory Building 11, Jinan Comprehensive free trade zone, Shandong, China
Doi:10.1055/s-0039-1690103
(2019)Doi:10.1016/0040-4020(80)80085-8
(1980)Doi:10.1016/j.tet.2004.06.022
(2004)Doi:10.1016/j.steroids.2018.09.010
(2018)Doi:10.1246/bcsj.53.2091
(1980)Doi:10.1039/P19850001725
(1985)