el Ahmad Y, Laurent E, Maillet P, Talab A, Teste J F, Dokhan R, Tran G, Ollivier R
Centre de Recherche, Cooperation Pharmaceutique Française, La Rochette, France.
J Med Chem. 1997 Mar 14;40(6):952-60. doi: 10.1021/jm950759z.
A series of 1-(benzocycloalkyl)-4-(benzamidolkyl)piperazine derivatives was prepared in order to obtain compounds with a high affinity and selectivity for 5-HT1A receptors. The modifications of aromatic substituents, the length of the alkyl chain, and the size of the ring were explored. Most of N-(1,2,3,4-tetrahydronaphthyl)-N'-(benzamidoethyl)piperazines (32-37) were bound to 5-HT1A receptors in a nanomolar range and presented a high degree of selectivity. After resolution, levorotatory enantiomers showed affinity and selectivity higher than those of dextrorotory ones for 5-HT1A sites. The agonist type activity of selected derivatives was also confirmed in vitro on the inhibition of the activation of adenylate cyclase induced by forskolin and, in vivo, on the induction of the lower lip retraction in rats.
为了获得对5-HT1A受体具有高亲和力和选择性的化合物，制备了一系列1-(苯并环烷基)-4-(苯甲酰胺基烷基)哌嗪衍生物。研究了芳族取代基的修饰、烷基链的长度和环的大小。大多数N-(1,2,3,4-四氢萘基)-N'-(苯甲酰胺基乙基)哌嗪(32-37)在纳摩尔范围内与5-HT1A受体结合，并表现出高度的选择性。拆分后，左旋对映体对5-HT1A位点的亲和力和选择性高于右旋对映体。所选衍生物的激动剂类型活性在体外也通过抑制福斯高林诱导的腺苷酸环化酶激活得到证实，在体内则通过诱导大鼠下唇回缩得到证实。
