Bioorganic and Medicinal Chemistry p. 4353 - 4360 (2006)
Update date:2022-07-29
Topics:
Mavromoustakos
Moutevelis-Minakakis
Kokotos
Kontogianni
Politi
Zoumpoulakis
Findlay
Cox
Balmforth
Zoga
Iliodromitis
AT1 antagonists (SARTANs) constitute the last generation of drugs for the treatment of hypertension, designed and synthesized to mimic the C-terminal segment of the vasoconstrictive hormone angiotensin II (AngII). They exert their action by blocking the binding of AngII on the AT1 receptor. Up to date eight AT1 antagonists have been approved for the regulation of high blood pressure. Although these molecules share common structural features and are designed to act under the same mechanism, they have differences in their pharmacological profiles and antihypertensive efficacy. Thus, there is still a need for novel analogues with better pharmacological and financial profiles. An example of a novel synthetic non peptide AT1 antagonist which devoids the classical template of SARTANs is MM1. In vivo studies showed that MMK molecules, which fall in the same class of MM1, had a significant antihypertensive (40-80% compared to the drug losartan) activity. However, in vitro affinity studies showed that losartan has considerably higher affinity. The theoretical docking studies showed that MM1 acts on the same site of the receptor as losartan. They exert hydrophobic interactions with amino acid Val108 of the third helix of the AT1 receptor and other hydrophobic amino acids in spatial vicinity. In addition, losartan favours multiple hydrogen bondings between its tetrazole group with Lys199. These additional interactions may in part explain its higher in vitro binding affinity.
View MoreContact:86-25-58619180
Address:Nanjing High-Tech Zone 10 Xinghuo Road Pukou District Nanjing, Jiangsu 210061 The People's Republic of China
TIANJIN GST CHEMICAL TECHNOLOGY CO., LTD
Contact:+86-22-25210964
Address:Room. 208, No. -12-C, No. 13, Xinbei Road, Tanggu District, New Haixin Area, Tianjin City, China
Shanghai Kefu Chemical Co.,Ltd.
Contact:+86-21-34616196
Address:Room601-602, Xuhui Business Building, No.168, Yude Road, Shanghai
Wuxi Zuping Food Science And Technology Co.,LTD.
Contact:+86-510-87210822
Address:Guanlin town
Xinjiang Fufeng Biotechnologies Co., Ltd.
Contact:+86-539-7287111
Address:GANQUANPU INDUSTRIAL PARK, ECONOMIC AND TECHNOLOGICAL DEVELOPMENT AREA (TOUTUNHE DISTRICT) OF URUMQI
Doi:10.1002/anie.201303662
(2013)Doi:10.1080/15421406.2011.564076
(2011)Doi:10.1002/anie.201604950
(2016)Doi:10.1002/chem.200500478
(2005)Doi:10.1016/0022-328X(83)85038-4
(1983)Doi:10.1080/10426500590905978
(2005)