发现7-羟基阿朴啡作为β-1和β-2肾上腺素能受体的构象受限配体。
Discovery of 7-hydroxyaporphines as conformationally restricted ligands for beta-1 and beta-2 adrenergic receptors.
作者信息
Ku Angela F, Cuny Gregory D
机构信息
Department of Pharmacological and Pharmaceutical Sciences , University of Houston , Science and Research Building 2 , Houston , Texas 77204 , USA . Email:
出版信息
Medchemcomm. 2018 Jan 22;9(2):353-356. doi: 10.1039/c7md00656j. eCollection 2018 Feb 1.
Abstract
A series of (-)-nornuciferidine derivatives was synthesized and the non-natural enantiomer of the aporphine alkaloid was discovered to be a potent β- and β-adrenergic receptor ligand that antagonized isoproterenol and procaterol induced cyclic AMP increases from adenylyl cyclase, respectively. Progressive deconstruction of the tetracyclic scaffold to less complex cyclic and acyclic analogues revealed that the conformationally restricted (6a-,7-)-7-hydroxyaporphine 2 () was necessary for efficient receptor binding and antagonism.
摘要
合成了一系列（-）-去甲荷叶碱衍生物，发现阿朴菲生物碱的非天然对映体是一种有效的β和β-肾上腺素能受体配体，分别拮抗异丙肾上腺素和丙卡特罗诱导的腺苷酸环化酶产生的环磷酸腺苷增加。将四环骨架逐步解构为较简单的环状和非环状类似物，结果表明构象受限的（6a-，7-）-7-羟基阿朴菲2（）对于有效的受体结合和拮抗作用是必需的。
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