公开(公告)号：EP3896069A1

公开(公告)日：2021-10-20

申请号：EP21160074.7

申请日：2010-11-24

申请人： Genzyme Corporation

发明人： LIU, Hanlan ,  WILLIS, Chris ,  BHARDWAJ, Renu ,  COPELAND, Diane P. ,  HARIANAWALA, Abizer ,  SKELL, Jeffrey ,  MARSHALL, John ,  KOCHLING, Jianmei ,  PALACE, Gerard ,  PETERSCHMITT, Judith ,  SIEGEL, Craig ,  CHENG, Seng

IPC分类号： C07D405/06 ,  C07D319/16 ,  A61K31/4025 ,  A61P35/00

摘要： The hemitartrate salt of a compound represented by the following structural formula:

(Formula I Hemitartrate), which may be used in pharmaceutical applications, are disclosed. Particular single crystalline forms of the Formula (I) Hemitartrate are characterized by a variety of properties and physical measurements. As well, methods of producing crystalline Formula (I) Hemitartrate, and using it to inhibit glucosylceramide synthase or lowering glycosphingolipid concentrations in subjects to treat a number of diseases, are also discussed. Pharmaceutical compositions are also described.

公开(公告)号：EP2970251A1

公开(公告)日：2016-01-20

申请号：EP14718835.3

申请日：2014-03-13

申请人： Genzyme Corporation

发明人： SIEGEL, Craig ,  GIMI, Rayomand ,  REARDON, Michael ,  ZHAO, Jin

IPC分类号： C07D453/02 ,  C07D417/06 ,  C07D277/30

CPC分类号： C07D453/02 ,  C07D277/30 ,  C07D417/06 ,  C07D417/12

摘要： The invention relates to a method of preparing inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer.

摘要翻译： 本发明涉及制备可用于单独或与酶替代疗法组合用于治疗代谢疾病（例如溶酶体贮积症）和用于治疗癌症的葡糖基神经酰胺合酶（GCS）抑制剂的方法。

公开(公告)号：EP2970250A1

公开(公告)日：2016-01-20

申请号：EP14718854.4

申请日：2014-03-14

申请人： Genzyme Corporation

发明人： SIEGEL, Craig ,  ZHAO, Jin

IPC分类号： C07D453/00 ,  A61K31/439 ,  A61P35/00 ,  A61P3/00

CPC分类号： C07D453/00 ,  C07C59/245

摘要： The present invention relates to novel salt forms of (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate useful as an inhibitor of glucosylceramide synthase (GCS) and for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer.

摘要翻译： 本发明涉及用作葡萄糖神经酰胺合酶抑制剂的（S） - 奎宁环-3-基（2-（2-（2-（4-氟苯基）噻唑-4-基）丙-2-基）氨基甲酸酯的新型盐形式 GCS）和用于治疗代谢疾病如溶酶体贮积病，单独或与酶替代疗法组合，以及用于治疗癌症。

公开(公告)号：EP3599237A1

公开(公告)日：2020-01-29

申请号：EP19182732.8

申请日：2010-11-24

申请人： Genzyme Corporation

发明人： LIU, Hanlan ,  WILLIS, Chris ,  BHARDWAJ, Renu ,  COPELAND, Diane P. ,  HARIANAWALA, Abizer ,  SKELL, Jeffrey ,  MARSHALL, John ,  KOCHLING, Jianmei ,  PALACE, Gerard ,  PETERSCHMITT, Judith ,  SIEGEL, Craig ,  CHENG, Seng

IPC分类号： C07D405/06 ,  C07D319/16 ,  A61K31/4025 ,  A61P35/00

摘要： The present invention relates to a pharmaceutical composition comprising the hemitartrate salt of Eliglustat (Genz 112638; N-[(1R,2R)-2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-hydroxy-1-(1-pyrrolidinylmethyl)ethyl]-octanamide) represented by the following structural formula:

(Formula I Hemitartrate)
as an inhibitor of the glucosylceramide synthase (GCS) for use in a method of treating Fabry's or Gaucher's disease, the method comprising adjusting the individual therapeutical dose to the P450 metabolism of the patient.
Particular single crystalline forms of Eliglustat Hemitartrate are characterized by a variety of properties and physical measurements as well as methods of producing crystalline Eliglustat Hemitartrate and using it to inhibit glucosylceramide synthase or lowering glycosphingolipid concentrations 10 in subjects to treat Fabry's or Gaucher's disease, are also discussed.

公开(公告)号：EP3133070B1

公开(公告)日：2019-08-14

申请号：EP16175117.7

申请日：2010-11-24

申请人： Genzyme Corporation

发明人： LIU, Hanlan ,  WILLIS, Chris ,  BHARDWAJ, Renu ,  COPELAND, Diane P. ,  HARIANAWALA, Abizer ,  SKELL, Jeffrey ,  MARSHALL, John ,  KOCHLING, Jianmei ,  PALACE, Gerard ,  PETERSCHMITT, Judith ,  SIEGEL, Craig ,  CHENG, Seng

IPC分类号： C07D405/06 ,  A61K45/06 ,  A61K31/4025 ,  A61P35/00

公开(公告)号：EP2504332B1

公开(公告)日：2014-06-04

申请号：EP10785289.9

申请日：2010-11-24

申请人： Genzyme Corporation

发明人： LIU, Hanlan ,  WILLIS, Chris ,  BHARDWAJ, Renu ,  COPELAND, Diane, P. ,  HARIANAWALA, Abizer ,  SKELL, Jeffrey ,  MARSHALL, John ,  KOCHLING, Jianmei ,  PALACE, Gerard ,  PETERSCHMITT, Judith ,  SIEGEL, Craig ,  CHENG, Seng

IPC分类号： C07D405/06 ,  A61K31/4025 ,  A61P35/00

CPC分类号： A61K31/4025 ,  A61K45/06 ,  C07D319/16 ,  C07D405/06

公开(公告)号：EP3133070A1

公开(公告)日：2017-02-22

申请号：EP16175117.7

申请日：2010-11-24

申请人： Genzyme Corporation

发明人： LIU, Hanlan ,  WILLIS, Chris ,  BHARDWAJ, Renu ,  COPELAND, Diane P. ,  HARIANAWALA, Abizer ,  SKELL, Jeffrey ,  MARSHALL, John ,  KOCHLING, Jianmei ,  PALACE, Gerard ,  PETERSCHMITT, Judith ,  SIEGEL, Craig ,  CHENG, Seng

IPC分类号： C07D405/06 ,  A61K45/06 ,  A61K31/4025 ,  A61P35/00

CPC分类号： A61K31/4025 ,  A61K45/06 ,  C07D319/16 ,  C07D405/06

摘要： Eliglustat (Genz 112638; N-[(1R,2R)-2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-hydroxy-1-(1-pyrrolidinylmethyl)ethyl]-octanamide) as an inhibitor of the glucosylceramide synthase (GCS) for use in a method of treating Fabry's or Gaucher's disease, the method comprising adjusting the individual therapeutical dose to the P450 metabolism of the patient.

摘要翻译： Eliglustat（GENZ 112638; N - [（1R，2R）-2-（2,3-二氢-1,4-苯并二恶英-6-基）-2-羟基-1-（1-吡咯烷基甲基）乙基] - 辛酰胺） 作为葡糖合酶（GCS），用于在治疗法布里或Gaucher氏病，所述方法包括调节所述个体治疗剂量给患者的代谢P450的方法的抑制剂。

公开(公告)号：EP2504332A1

公开(公告)日：2012-10-03

申请号：EP10785289.9

申请日：2010-11-24

申请人： Genzyme Corporation

发明人： LIU, Hanlan ,  WILLIS, Chris ,  BHARDWAJ, Renu ,  COPELAND, Diane, P. ,  HARIANAWALA, Abizer ,  SKELL, Jeffrey ,  MARSHALL, John ,  KOCHLING, Jianmei ,  PALACE, Gerard ,  PETERSCHMITT, Judith ,  SIEGEL, Craig ,  CHENG, Seng

IPC分类号： C07D405/06 ,  A61K31/4025 ,  A61P35/00

CPC分类号： A61K31/4025 ,  A61K45/06 ,  C07D319/16 ,  C07D405/06

摘要： The hemitartrate salt of a compound represented by the following structural formula: (Formula I Hemitartrate), which may be used in pharmaceutical applications, are disclosed. Particular single crystalline forms of the Formula (I) Hemitartrate are characterized by a variety of properties and physical measurements. As well, methods of producing crystalline Formula (I) Hemitartrate, and using it to inhibit glucosylceramide synthase or lowering glycosphingolipid concentrations in subjects to treat a number of diseases, are also discussed. Pharmaceutical compositions are also described.

公开(公告)号：EP2167485A2

公开(公告)日：2010-03-31

申请号：EP08768008.8

申请日：2008-05-30

申请人： Genzyme Corporation

发明人： SIEGEL, Craig ,  BASTOS, Cecilia, M. ,  HARRIS, David, J. ,  DIOS, Angeles ,  LEE, Edward ,  SILVA, Richard ,  CUFF, Lisa, M. ,  LEVINE, Mikaela ,  CELATKA, Cassandra ,  VINICK, Frederic ,  JOZEFIAK, Thomas ,  XIANG, Yibin ,  KANE, John ,  LIAO, Junkai

IPC分类号： C07D319/18 ,  C07D405/06 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14 ,  C07D411/12 ,  C07D413/12 ,  C07D413/14 ,  C07D295/125 ,  A61K31/357 ,  A61P3/10

CPC分类号： C07D417/14 ,  C07D295/125 ,  C07D319/18 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14 ,  C07D411/12 ,  C07D413/12 ,  C07D413/14

摘要： A compound is represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. A method of treating a subject in need thereof comprises administering to the subject a therapeutically effective amount of a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. The subject has type 2 diabetes; renal hypertrophy or hyperplasia associated with diabetic nephropathy; Tay-Sachs; Gaucher's or Fabry's disease. Methods of decreasing plasma TNF-±, lowering blood glucose levels, decreasing glycated hemoglobin levels, inhibiting glucosylceramide synthase, and lowering glycosphingolipid concentration in a subject in need thereof respectively comprise administering to the subject a therapeutically effective amount of a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof.

摘要翻译： 化合物由结构式（I）表示：或其药学上可接受的盐。 药物组合物包含由结构式（I）表示的化合物或其药学上可接受的盐。 治疗有此需要的受试者的方法包括向受试者施用治疗有效量的由结构式（I）表示的化合物或其药学上可接受的盐。 受试者患有2型糖尿病; 与糖尿病肾病相关的肾肥大或增生; 戴萨克斯; 高雪; 或法布里病。 在有此需要的受试者中降低血浆TNF-α，降低血糖水平，降低糖化血红蛋白水平，抑制葡萄糖神经酰胺合酶和降低鞘糖脂浓度的方法包括向受试者施用治疗有效量的由结构式 I）或其药学上可接受的盐。

公开(公告)号：EP1409467A1

公开(公告)日：2004-04-21

申请号：EP02750099.0

申请日：2002-07-16

申请人： GENZYME CORPORATION ,  THE REGENTS OF THE UNIVERSITY OF MICHIGAN

发明人： HIRTH, Bradford, H. ,  SIEGEL, Craig ,  SHAYMAN, James A. ,  NELSON, Carol Anne ,  HARRIS, David J. ,  COPELAND, Diane

IPC分类号： C07D295/12 ,  C07C231/18 ,  C07C215/30 ,  C07C237/20 ,  C07D498/04

CPC分类号： C07D405/06 ,  A61K31/4025 ,  C07D295/185 ,  C07D319/18 ,  C07D498/04

摘要： Disclosed is a novel enantiomeric synthesis of ceramide-like inhibitors of UDP-glucose: N-acylsphingosine glucosyltransferase. Also disclosed are novel intermediates formed during the synthesis.