Journal of Medicinal Chemistry p. 2877 - 2882 (1991)
Update date:2022-08-05
Topics: Potent Selective Antagonists N^6,9-Disubstituted Adenines A1 Adenosine Receptor
Thompson, Robert D.
Secunda, Sherrie
Daly, John W.
Olsson, Ray A.
N6-Substituted 9-methyladenines are potent antagonists of the activation of A1 adenosine receptors.The present study assessed the effect of N6 and N-9-substituents on the binding of adenines to the A1 and A2 receptors, respectively, of rat brain cortex and striatum and also on the antagonism of the A2 receptor mediated stimulation of the adenylate cyclase of PC12 cells by N-ethyladenosine-5'-uronamide.The potency ranking of 9-substituted adenines varied directly with the hydrophobicity of the substituent: cyclopentyl > phenyl > tetrahydrofuryl > ethyl > methyl > 2-hydroxyethyl.The 9-substituted adenines showed little selectivity for either receptor and the R enantiomer of N6-(1-phenyl-2-propyl)-9-methyladenine was only 4-fold more potent than the S enantiomer at the A1 receptor.An N6-cyclopentyl substituent increased potency at the A1 receptor and decreased potency at the A2 receptor, resulting in selectivity for the A1 receptor of up to 39-fold.The N6-cyclopentyl group completely overshadowed the effect of the hydrophobicity of the 9-substituent.A 2-chloro substituent did not alter the potency of an N6-substituted 9-methyladenine.
View MoreTAIZHOU XINGCHENG CHEMPHARM CO.,LTD.
Contact:0086-0576-88551200,88886292 ,88880039
Address:B Area. 10 Floor.Yaodadasha. 289#.Shifu Road.Taizhou.Zhejiang.China
Jiangsu Zhenfang Chemical CO.,LTD.(Suzhou Zhenfang Chemical Factory)
Contact:+86-512-69598882
Address:Room1201, Jiayuan Road No.1018, Xiangcheng District, Suzhou, China
Zhejiang Kaili Industrial Co., Ltd
Contact:+86-571-85241926
Address:lantian business center,No.18 Moganshan Road
Tianjin Puck Rice Chemicals Co., Ltd.
Contact:022-58054572
Address:Weidi Road
Xi'an Galaxy Chemicals CO., Ltd
Contact:86-29-89380370
Address:No.8, Gaoxin three road, Xi'an city.
Doi:10.1021/op500116w
(2014)Doi:10.1246/cl.1987.121
(1987)Doi:10.1016/j.tet.2008.09.081
(2008)Doi:10.1021/ja01597a063
(1956)Doi:10.1021/acs.organomet.5b00464
(2015)Doi:10.1021/jm8016317
(2009)