Synthesis and human beta-adrenoceptor activity of 1-(3,5-diiodo-4- methoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-6-ol derivatives in vitro.
Synthesis and human beta-adrenoceptor activity of 1-(3,5-diiodo-4- methoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-6-ol derivatives in vitro.
复制标题
1-(3,5-二碘-4-甲氧基苄基)-1,2,3,4-四氢异喹啉-6-醇衍生物的体外合成和人β-肾上腺素受体活性。
DOI：
10.1021/jm990463j
复制
发表时间：
2000
影响因子：
7.3
通讯作者：
Miller,DD
中科院分区：
文献类型：
--
作者：
He,Y;Nikulin,VI;Vansal,SS;Feller,DR;Miller,DD
Trimetoquinol (1, TMQ) is a potent nonselective β-adrenergic receptor (AR) agonist and a thromboxane A2/prostaglandin endoperoxide (TP) receptor antagonist, while 3‘,5‘-diiodo-TMQ (2) exhibits β3-AR selectivity. In search of selective β3-AR agonists as potential drugs for the treatment of human obesity and type II diabetes mellitus, a series of 1-(3,5-diiodo-4-methoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-6-ols has been prepared and evaluated for their biological activities at human β1-, β2-, and β3-ARs expressed in Chinese hamster ovary (CHO) cells. The compounds have been synthesized by the Bischler−Napieralski cyclization of corresponding amides followed by NaBH4reduction, and the halogens in the aromatic ring A were introduced by direct halogenation of protected compound11. Whereas halogen substitution in ring A reduced either potency or intrinsic activity on β3-AR, the non-halogen-substituted compounds8and10were potent, selective, nearly full agonists for β3-AR.
