Journal of Medicinal Chemistry p. 3821 - 3828 (1993)
Update date:2022-08-04
Topics:
MacPherson
Bayburt
Capparelli
Bohacek
Clarke
Ghai
Sakane
Berry
Peppard
Trapani
A potent macrocyclic inhibitor of neutral endopeptidase (NEP) 24.11 was designed using a computer model of the active site of thermolysin. This 10- membered ring lactam represents a general mimic for any hydrophobic dipeptide in which the two amino acid side chains bind to an enzyme in a contiguous orientation. The parent 10-membered ring lactam was synthesized and exhibited excellent potency as an NEP 24.11 inhibitor (IC50 = 3 nM). In order to improve oral bioavailability, various functionality was attached to the macrocycle. These modifications lead to CGS 25155, an orally active NEP 24.11 inhibitor that slows down the degradation of the cardiac hormone atrial natriuretic factor, producing a lowering of blood pressure in the DOCA-salt rat model of hypertension.
View Morewebsite:http://www.guarson.com
Contact:+86-523-88059600,+86-13805268803
Address:Room B1006,Yafang Building,Jiangyan Avenue,Jiangyan District, Taizhou City,Jiangsu,China
SHANGHAI GILEADER ADVANCE MATERIAL TECHNOLOGY CO.,LTD
Contact:+86-021-58692556
Address:No.6 Building,No. 668 Hengan RD Pudong,Shanghai
Dalian Join King Biochemical Tech. Co., Ltd.
Contact:0411 39216206
Address:814 First State Blvd
Zhejiang Linhai Xinhua Chemicals Factory
Contact:0086-13661858911
Address:Xunqiao Development Zone, Linhai, Zhejiang, China
Beyond Pharmaceutical Co., Ltd
Contact:+86-571-8195-3185
Address:No. 13-1, Liansheng Road, Yuhang District
Doi:10.1016/S0040-4039(00)93411-7
(1993)Doi:10.1002/ardp.19673000111
()Doi:10.1016/0022-1902(60)80220-5
(1960)Doi:10.1021/ol503616y
(2015)Doi:10.1021/jo00070a032
(1993)Doi:10.1002/ardp.19532860406
(1953)