Kostić S, Soskić V, Joksimović J
Institute for Chemistry, Technology and Metallurgy, Belgrade, Yugoslavia.
Arzneimittelforschung. 1994 Jun;44(6):697-702.
Two series of non-catechol dopamine (DA) bioisosteres with the hydroxyl groups on the benzene ring replaced by N-H groups were synthesized using phenethylamine as a parent molecule. Compounds from the first series (1-9) contained a primary amine group, while those from the second one (10-19) had a N,N-di-propylamino group introduced into the side chain of the phenethylamine. The affinity and selectivity of these compounds for the D-1 and D-2 subtypes of the DA receptor were determined in competition binding assays using synaptosomal membranes from bovine caudate nuclei and [3H]SCH 23390 (D-1 selective) and [3H]spiperone (D-2 selective) as radioligands. None of the 19 compounds examined expressed significant affinity for D-1 receptors, while compounds 15, 17 and 19, in this order of potency, strongly competed with [3H]spiperone binding to D-2 receptors under conditions that prevented radioligand binding to serotonin 5HT2 receptors. Varying affinities of the compounds examined for the DA receptors can be ascribed to different acidity of the N-H groups introduced at meta- and para-positions of the phenethylamine molecule.
以苯乙胺为母体分子，合成了两系列苯环上羟基被N-H基团取代的非儿茶酚多巴胺（DA）生物电子等排体。第一系列（1-9）的化合物含有伯胺基团，而第二系列（10-19）的化合物在苯乙胺侧链引入了N,N-二丙基氨基。使用来自牛尾状核的突触体膜以及[3H]SCH 23390（D-1选择性）和[3H]螺哌隆（D-2选择性）作为放射性配体，通过竞争结合试验测定了这些化合物对DA受体D-1和D-2亚型的亲和力和选择性。所检测的19种化合物中没有一种对D-1受体表现出显著亲和力，而化合物15、17和19按效力顺序在防止放射性配体与5-羟色胺5HT2受体结合的条件下，与[3H]螺哌隆竞争结合D-2受体的能力很强。所检测化合物对DA受体的不同亲和力可归因于在苯乙胺分子间位和对位引入的N-H基团的不同酸度。
