公开(公告)号：KR100808685B1

公开(公告)日：2008-02-29

申请号：KR1020060101544

申请日：2006-10-18

Applicant: 한국화학연구원

Inventor： 공재양 ,  최일영 ,  임희종 ,  명도 ,  정명희 ,  박우규

IPC: C07D401/08 ,  C07D417/08 ,  C07D413/08

Abstract: A novel piperazine derivative is provided to show excellent antagonism against a dopamine receptor D4, thereby being effective as a therapeutic agent for schizophrenia. A piperazine derivative having a cycloalkyl bicyclic heterocycle group is represented by a formula(1), where R1 is a group represented by the structural formula(1) or (2); X is H, halogen, nitro, cyano, C1-6 alkyl, or C1-6 alkoxy; Y is NH, S or O; R2 is phenyl or pyridine, which may be substituted or unsubstituted by a substituent selected from the group consisting of halogen, C1-6 alkyl, C1-6 alkoxy, and cyano; n is an integer from 1 to 3. A method for preparing a piperazine compound represented by the formula(1b) comprises the steps of: (a) subjecting cyclopentanone carboxylic acid coupled to a Wang resin and represented by the formula(3) with a piperazine to a reducing amination to obtain a compound represented by the formula(3a); and (b) applying microwave to the compound of the formula(3a) with an amine compound represented by the formula(3b) to synthesize the compound of the formula(1b), where R2, X, Y, and n are the same as defined above, and A is Wang resin. A therapeutic agent for schizophrenia comprises the compound of the formula(1) or a pharmaceutically acceptable salt thereof.

Abstract translation: 提供了一种新的哌嗪衍生物，以显示对多巴胺受体D4的极好的拮抗作用，从而作为精神分裂症的治疗剂是有效的。 具有环烷基双环杂环基的哌嗪衍生物由式（1）表示，其中R 1是由结构式（1）或（2）表示的基团。 X是H，卤素，硝基，氰基，C 1-6烷基或C 1-6烷氧基; Y是NH，S或O; R2是苯基或吡啶，其可以被选自卤素，C 1-6烷基，C 1-6烷氧基和氰基的取代基取代或未取代。 n为1〜3的整数。由式（1b）表示的哌嗪化合物的制备方法包括以下步骤：（a）将与式（3）表示的Wang树脂偶联的环戊酮羧酸与 哌嗪还原胺化得到式（3a）表示的化合物; 和（b）用式（3b）表示的胺化合物向式（3a）化合物施加微波以合成式（1b）化合物，其中R 2，X，Y和n与 A为王树脂。 精神分裂症的治疗剂包括式（1）的化合物或其药学上可接受的盐。