Grunewald G L, Monn J A, Rafferty M F, Borchardt R T, Krass P
J Med Chem. 1982 Oct;25(10):1248-50. doi: 10.1021/jm00352a031.
A series of omega-substituted analogues of amphetamine and alpha-methylbenzylamine were prepared and evaluated as inhibitors of norepinephrine N-methyltransferase (NMT). These included several alkyl side chain extended analogues (1-5), as well as the terminally hydroxylated derivatives phenylalanol (6a) and phenylglycinol (7a). None of the alkyl-substituted derivatives displayed appreciable activity as inhibitors; however, the hydroxylated analogues were up to twofold more potent than the parent compounds. The positive contribution of the side-chain hydroxy suggests that the terminal methyl group of the lead compounds is situated close to a hydrophilic area or hydrogen bonding functional group within the active site.
制备了一系列安非他明和α-甲基苄胺的ω-取代类似物，并将其作为去甲肾上腺素N-甲基转移酶（NMT）的抑制剂进行评估。这些类似物包括几种烷基侧链延长的类似物（1-5），以及末端羟基化的衍生物苯丙醇（6a）和苯甘醇（7a）。没有一种烷基取代的衍生物表现出可观的抑制活性；然而，羟基化类似物的效力比母体化合物高两倍。侧链羟基的积极作用表明，先导化合物的末端甲基位于活性位点内的亲水区域或氢键官能团附近。
