Ohmomo Y, Murakami K, Hirata M, Sugimoto A, Magata Y, Miyahara N, Tanaka C, Yokoyama A
Osaka University of Pharmaceutical Sciences, Japan.
Chem Pharm Bull (Tokyo). 1992 Jul;40(7):1789-92. doi: 10.1248/cpb.40.1789.
A new series of iodinated analogues of N-(2-aminoethyl)benzamide was synthesized and evaluated for inhibitory potency and specificity toward monoamine oxidase type-B (MAO-B). Among them, N-(2-aminoethyl)-2-chloro-4-iodobenzamide hydrochloride (2d) showed high inhibitory potency and selectivity against MAO-B. The type of MAO-B inhibition by 2d was non-competitive and the inhibition constant (Ki) was 0.80 microM. Strong and selective in vivo MAO-B inhibition by 2d was also confirmed. The brain MAO-B inhibition by 2d was reversible and the enzyme activity completely returned to the control value 24 h after administration. Compound 2d was, therefore, considered to be a candidate for advanced development as a radioiodinated ligand that may be useful for functional MAO-B studies in the living brain using single photon emission computer tomography.
合成了一系列新型的N-(2-氨基乙基)苯甲酰胺的碘化类似物，并对其对B型单胺氧化酶(MAO-B)的抑制效力和特异性进行了评估。其中，N-(2-氨基乙基)-2-氯-4-碘苯甲酰胺盐酸盐(2d)对MAO-B表现出高抑制效力和选择性。2d对MAO-B的抑制类型为非竞争性，抑制常数(Ki)为0.80微摩尔。还证实了2d在体内对MAO-B有强烈且选择性的抑制作用。2d对脑MAO-B的抑制是可逆的，给药后24小时酶活性完全恢复到对照值。因此，化合物2d被认为是一种放射性碘化配体进一步开发的候选物，该配体可能有助于使用单光子发射计算机断层扫描对活体大脑中的MAO-B进行功能研究。
