Zhuang Z P, Kung M P, Chumpradit S, Mu M, Kung H F
Department of Radiology, University of Pennsylvania, Philadelphia 19104.
J Med Chem. 1994 Dec 23;37(26):4572-5. doi: 10.1021/jm00052a018.
A series of new p-alkylbenzamido derivatives of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p- iodobenzamido)ethyl]piperazines (p-MPPI) were prepared. In vitro binding studies suggest that p-methyl and p-ethyl substituents on the benzamido group display the same high binding affinity to 5-HT1A receptors (Ki = 2.2 and 9.3 nM, rat hippocampal homogenates). However, when the substitution groups were larger than a C5 pentyl group, the affinity to 5-HT1A receptors dropped below a useful level (Ki > 50 nM). Several irreversible binding agents (CH2Cl, NHCOCH2Cl) and a photoaffinity labeling compound (m-iodo p-azido) which showed good binding affinity to 5-HT1A receptors were successfully prepared.
制备了一系列4-(2'-甲氧基苯基)-1-[2'-(N-2"-吡啶基)-对碘苯甲酰胺基)乙基]哌嗪(p-MPPI)的新型对烷基苯甲酰胺衍生物。体外结合研究表明，苯甲酰胺基团上的对甲基和对乙基取代基对5-HT1A受体表现出相同的高结合亲和力(Ki = 2.2和9.3 nM，大鼠海马匀浆)。然而，当取代基团大于C5戊基时，对5-HT1A受体的亲和力降至有用水平以下(Ki > 50 nM)。成功制备了几种对5-HT1A受体显示出良好结合亲和力的不可逆结合剂(CH2Cl、NHCOCH2Cl)和光亲和标记化合物(间碘对叠氮基)。
