Bioorganic and Medicinal Chemistry Letters p. 2627 - 2633 (2002)
Update date:2022-07-29
Topics: Synthesis Biological Evaluation Design
Roumelioti, Panagiota
Polevaya, Ludmila
Zoumpoulakis, Panagiotis
Giatas, Nektarios
Mutule, Ilze
Keivish, Tatjana
Zoga, Anastasia
Vlahakos, Demetrios
Iliodromitis
Kremastinos, Demetrios
Grdadolnik, Simona Golic
Mavromoustakos, Thomas
Matsoukas, John
The novel amide linked Angiotensin II (ANG II) cyclic analogues: γ,ε-cyclo(3, 5)-[Sar1-Glu3-Lys5-Ile8] ANG II (I) and γ, ε-cyclo(3, 5)-[Sar1-Glu3-Lys5-Phe8] ANG II (II) have been designed, synthesized and bioassayed in anesthetized rabbits in order to unravel structural ring cluster characteristics important for receptor activation. Analogue I with Ile at position 8 was an inhibitor of Angiotensin II while analogue II with Phe at position 8 was found to be an agonist. Similar results were reported for cyclic compounds that have reversed the linking between positions 3 and 5. The overall results show that positions 3 and 5 do not govern the biological activity of the synthetic analogues. It also appears that the aromatic ring cluster (Tyr-His-Phe) in agonist peptides is an essential stereo-electronic feature for Angiotensin II to exert its biological activity. A non-peptide mimetic of ANG II, 1-[2′-[(N-benzyl)tetrazol-5-yl]biphenyl-4-yl]methyl]-2- hydroxymethylbenzimidazole (BZI8) has been designed and synthesized. This molecule is more rigid and much less active than AT1 non-peptide mimetic losartan probably because it lacks to mimic the orientation of tetrazole and the pharmacophore segments of butyl chain and imidazole ring.
View MoreHangzhou jls Flame Retardants Chemical Co.,Ltd
Contact:+86-571-87250387/87250386
Address:MOGANSHAN RODA 1418# SHANGCHENG INDUSTRIAL PARK
Contact:+86-21-56338808
Address:799 Dunhuang Road, Putuo
Wuhan Sunrise Pharmaceutical Technology Co., Ltd
Contact:+86-27-83314682
Address:Room 340, New material Industrial base No.17, Gu Tian Five Lu , Qiaokou District, Wuhan , China
Chongqing maohuan Chemicals Co., Ltd
website:http://www.bschem.com
Contact:+86 13996103726
Address:Chongqing Nan'an District Tu Town
shanghai Tauto Biotech Co., Ltd
website:http://www.tautobiotech.com/en/index.htm
Contact:+86-21-51320588 ext. 8025
Address:No. 326, Aidisheng Rd , Zhangjiang Hi-tech Park, Shanghai , P.R.CHINA
Doi:10.1021/jo00975a009
(1972)Doi:10.1016/j.jorganchem.2004.12.012
(2005)Doi:10.1021/jo015786d
(2001)Doi:10.1016/j.bioorg.2020.104088
(2020)Doi:10.1021/ic50018a013
(1964)Doi:10.1039/c5ra10887j
(2015)