公开(公告)号：WO1994006758A1

公开(公告)日：1994-03-31

申请号：PCT/CA1993000386

申请日：1993-09-21

Applicant: UNIVERSITY OF SASKATCHEWAN

Inventor： UNIVERSITY OF SASKATCHEWAN ,  DIMMOCK, Jonathan, R.

IPC: C07C281/10

CPC classification number: C07C281/14 ,  A61K31/175 ,  C07C281/10

Abstract: A number of aryl semicarbazones were prepared as candidate anticonvulsants. When administered orally to rats, significant activity was noted in the maximal electroshock (MES) screen and since neurotoxicity was either absent or reduced (as compared to intraperitoneal injection in mice), high protection indices were found in the majority of the compounds. The semicarbazones displayed little or no activity in the subcutaneous pentylenetetrazol screen. These observations support the theory that one large hydrophobic group (in this case the aryl ring) are requirements for protection in the MES screen. In general, the semicarbazones had rapid onsets of action and the most common mechanism of action was interaction with chloride channels. Empirical and semi-empirical conformational calculations indicated that certain molecular fragments and hydrophobicity of these molecules affect bioactivity.

Abstract translation: 制备了许多芳基缩氨基脲作为候选抗惊厥药。 当大鼠口服给药时，在最大电击（MES）屏幕中观察到显着的活性，并且由于神经毒性不存在或减少（与小鼠腹膜内注射相比），在大多数化合物中发现高保护指数。 氨基脲在皮下戊四氮屏幕中显示很少或没有活性。 这些观察结果支持一个大的疏水基团（在这种情况下是芳环）是MES屏幕中的保护要求的理论。 一般来说，缩氨基脲具有快速的作用机制，最常见的作用机制是与氯离子通道相互作用。 经验和半经验构象计算表明某些分子片段和这些分子的疏水性影响生物活性。