公开(公告)号：EP3145935A1

公开(公告)日：2017-03-29

申请号：EP16727341.6

申请日：2016-05-23

申请人： Universiteit Leiden

发明人： VAN DER STELT, Mario ,  JANSSEN, Freek ,  BAGGELAAR, Marc ,  HUMMEL, Jessica

IPC分类号： C07D498/04 ,  C07D263/56 ,  A61K31/423 ,  A61K31/424 ,  A61P25/30 ,  A61P3/04 ,  A61P25/28

CPC分类号： C07D498/04 ,  C07D263/56

摘要： The present invention relates to novel compounds which are selective inhibitors of diacylglycerol lipase alpha and beta. These compounds are suitable for the treatment or prevention of disorders associated with, accompanied by or caused by increased 2-arachidonoylglycerol levels. Diacylglycerol lipase-a (alternative name: Snl-specific diacylglycerol hydrolase a; DAGL-a) and -β are enzymes responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol. Selective and reversible inhibitors are required to study the function of DAGLs in neuronal cells in an acute and temporal fashion. The inventive compounds are in particular suitable for the treatment of neurodegenerative diseases, inflammatory diseases, drug abuse and impaired energy balance, such as obesity, wherein X
1 is -CH-, -CF- or -N-.

公开(公告)号：EP3095787A1

公开(公告)日：2016-11-23

申请号：EP15169052.6

申请日：2015-05-22

申请人： Universiteit Leiden

发明人： VAN DER STELT, Mario ,  JANSSEN, Freek ,  BAGGELAAR, Marc ,  HUMMEL, Jessica

IPC分类号： C07D498/04 ,  C07D263/56 ,  A61K31/423 ,  A61K31/424 ,  A61P25/30 ,  A61P3/04 ,  A61P25/28

CPC分类号： C07D498/04 ,  C07D263/56

摘要： The present invention relates to novel compounds which are highly selective inhibitors of diacylglycerol lipase α and β. These compounds are suitable for the treatment or prevention of disorders associated with, accompanied by or caused by increased 2-arachidonoylglycerol levels. Diacylglycerol lipase-α (alternative name: Sn1-specific diacylglycerol hydrolase a; DAGL-α) and -β are enzymes responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol. Selective and reversible inhibitors are required to study the function of DAGLs in neuronal cells in an acute and temporal fashion. The inventive ompounds are in particular suitable for the treatment of neurodegenerative diseases, inflammatory diseases, drug abuse and impaired energy balance, such as obesity.

摘要翻译： 本发明涉及二酰基甘油脂肪酶±和²的高选择性抑制剂的新型化合物。 这些化合物适用于治疗或预防与2-花生四烯酰甘油水平升高伴随或引起的疾病。 二酰基甘油脂肪酶（替代名称：Sn1特异性二酰基甘油水解酶a; DAGL-±）和--2是负责内源性大麻素2-花生四烯酰甘油的生物合成的酶。 需要选择性和可逆抑制剂以急性和时间方式研究神经元细胞中DAGLs的功能。 本发明的特征特别适用于治疗神经变性疾病，炎性疾病，药物滥用和受损的能量平衡，例如肥胖症。