公开(公告)号：KR101861869B1

公开(公告)日：2018-05-28

申请号：KR1020130108748

申请日：2013-09-10

Applicant: 경희대학교 산학협력단 ,  전남대학교산학협력단

Inventor： 김성수 ,  조원제 ,  조티,케이.알.

IPC: C07C233/05 ,  A61K31/16 ,  A61P31/12

CPC classification number: A61K31/404 ,  A23L33/175 ,  A61K31/167 ,  A61K31/357 ,  A61K31/44 ,  A61K31/7056 ,  A61K38/07 ,  A61K38/212 ,  C07C231/06 ,  C07C237/22 ,  C07C2601/14 ,  C07D209/18 ,  C07D209/42 ,  C07D213/82 ,  C07D317/60 ,  C07D405/12

Abstract: 본발명은신규한비스-아미드유도체화합물, 또는이의약학적으로허용가능한염, 이의제조방법, 및상기비스-아미드유도체화합물또는이의약학적으로허용가능한염을유효성분으로포함하는, C형간염바이러스감염에의해유발되는질환의예방또는치료용약학적조성물및 C형간염바이러스감염에의해유발되는질환의예방또는개선용건강기능식품에관한것이다. 본발명의신규한비스-아미드유도체화합물특히, WJCPA-126은 CypA의촉매자리에특이적으로결합하여이소머라제활성을효과적으로억제하며, 낮은해리속도(K)을나타내는높은결합력으로 CypA에결합하므로상기억제효과지속시간을연장시킬수 있다. 이에따라 WJCPA-126은비독성및 비-면역억제특성을가지며시험관내(in vitro) 및생체내(in vivo) 모델시스템에서 HCV 복제를효과적으로억제할수 있다. 나아가, WJCPA-126은 IFN 자극유전자(ISGs)의발현증가및 인터루킨-8(IL-8) 분비억제를통하여숙주인터페론반응을재활성화한다. 따라서, 상기 WJCPA-126을포함한일련의비스-아미드유도체들은항바이러스효능을나타내는새로운종류의 CypA 억제제로서유용하게사용될수 있다.

公开(公告)号：KR1020150029482A

公开(公告)日：2015-03-18

申请号：KR1020130108748

申请日：2013-09-10

Applicant: 경희대학교 산학협력단 ,  전남대학교산학협력단

Inventor： 김성수 ,  조원제 ,  조티,케이.알.

IPC: C07C233/05 ,  A61K31/16 ,  A61P31/12

CPC classification number: A61K31/404 ,  A23L33/175 ,  A61K31/167 ,  A61K31/357 ,  A61K31/44 ,  A61K31/7056 ,  A61K38/07 ,  C07C231/06 ,  C07C237/22 ,  C07C2601/14 ,  C07D209/18 ,  C07D209/42 ,  C07D213/82 ,  C07D317/60 ,  C07D405/12 ,  C07C233/05 ,  A61K31/16

Abstract: The present invention relates to a novel bis-amide derivative compound or a pharmaceutically acceptable salt thereof, a manufacturing method thereof, a pharmacological composition for the prevention or treatment of diseases induced by hepatitis C virus infection which includes the bis-amide derivative compound or pharmaceutically acceptable salt thereof as an effective ingredient and a health functional food for the prevention or treatment of diseases induced by hepatitis C virus infection. The novel bis-amide derivative compound of the present invention and, especially, WJCPA-126 are specifically combined to a catalyst position of CypA, effectively inhibits the activity of an isomerase and are able to extend inhibition effect duration by being combined to CypA with high combining force exhibiting low dissociation rate (K_off). Accordingly, WJCPA-126 has non-toxic and non-immunosuppressive properties and effectively inhibit HCV replication in vivo and in vitro model systems. The WJCPA-126 reactivates host interferon reactions through inhibiting interlukin-8 (IL-8) and increasing expression of an IFN stimulating gens (ISGs). Accordingly, the bis-amide derivatives including WJCPA-126 are able to be usefully used as novel CypA inhibitors exhibiting antivirus activity.

Abstract translation: 本发明涉及一种新颖的双酰胺衍生物化合物或其药学上可接受的盐，其制备方法，用于预防或治疗丙型肝炎病毒感染引起的疾病的药物组合物，其包括双酰胺衍生物化合物或药学上可接受的盐 可接受的盐作为有效成分，以及用于预防或治疗由丙型肝炎病毒感染引起的疾病的健康功能食品。 本发明的新颖的双酰胺衍生物化合物，特别是WJCPA-126特异性地结合到CypA的催化剂位置，有效抑制异构酶的活性，能够通过与CypA高度结合来延长抑制作用的持续时间 显示低解离速率（K_off）的组合力。 因此，WJCPA-126具有无毒和非免疫抑制特性，并有效抑制体内和体外模型系统中的HCV复制。 WJCPA-126通过抑制白介素-8（IL-8）和增加IFN刺激性​​发生（ISG）的表达来重新激活宿主干扰素反应。 因此，包括WJCPA-126的双酰胺衍生物能够有效地用作显示抗病毒活性的新型CypA抑制剂。