2-acylaminopropoanol-type glucosylceramide synthase inhibitors

• US 8,309,593 B2
• Filed: 10/02/2009
• Issued: 11/13/2012
• Est. Priority Date: 10/03/2008
• Status: Expired due to Fees

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: Siegel, Craig, Bastos, Cecilia M., Harris, David J., Dios, Angeles, Lee, Edward, Silva, Richard, Cuff, Lisa M., Levine, Mikaela, Celatka, Cassandra A., Jozafiak, Thomas H., Xiang, Yibin, Kane, John, Liao, Junkai, Vinick, Frederic
• Primary Examiner(s): McKane, Joseph K.
• Assistant Examiner(s): SHTERENGARTS, SAMANTHA L
• Application Number:
  US13/122,135
• Publication Number:
  US 20110184021A1
• Time in Patent Office: 1,138 Days
• Field of Search: 514/408, 514/422
• US Class Current: 514/408
• CPC Class Codes: A61K 31/4025 not condensed and containing further heterocyclic rings, e.g. cromakalim
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 271/12 to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
• CPC Class Codes: C07D 207/12 Oxygen or sulfur atoms
• CPC Class Codes: C07D 317/60 Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 319/18 Ethylenedioxybenzenes, not substituted on the hetero ring
• CPC Class Codes: C07D 319/20 with substituents attached to the hetero ring
• CPC Class Codes: C07D 333/16 by oxygen atoms
• CPC Class Codes: C07D 407/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 407/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

A compound for use in treating polycystic kidney disease 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 polycystic kidney disease in 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. Methods of treating in polycystic kidney disease 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.

Claims

1. A method of treating polycystic kidney disease in a subject, the method comprising administering to the subject having polycystic kidney disease an effective amount of a compound represented by the following structural formula:

2. The method of claim 1, wherein the compound is represented by the following structural formula:

3. The method of claim 2, wherein R³⁰ is hydrogen;

or a C1-C10 alkyl group optionally substituted with one or more substituents selected from the group consisting of halogen, amino, C1-C6 alkylamino, C1-C6 dialkylamino, C1-C6 alkoxy, nitro, cyano, hydroxy, C1-C6 haloalkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylcarbonyl and C1-C6 haloalkyl.

4. The method of claim 3, wherein R³⁰ is hydrogen, or a C1-C10 alkyl group optionally substituted with one or more substituents selected from the group consisting of halogen, C1-C6 alkoxy, C1-C6 haloalkoxy and hydroxy.

5. The method of claim 2, wherein the compound is represented by the following structural formula:

6. The method of claim 2, wherein the compound is represented by the following structural formula:

7. The method of claim 2, wherein the compound is represented by the following structural formula:

8. The method of claim 2, wherein the compound is represented by the following structural formula:

9. The method of claim 1, wherein the compound is represented by the following structural formula:

10. The method of claim 9, wherein R³⁰ is hydrogen;

or a C1-C10 alkyl group optionally substituted with one or more substituents selected from the group consisting of halogen, amino, C1-C6 alkylamino, C1-C6 dialkylamino, C1-C6 alkoxy, nitro, cyano, hydroxy, C1-C6 haloalkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylcarbonyl and C1-C6 haloalkyl.

11. The method of claim 10, wherein R³⁰ is hydrogen, or a C1-C10 alkyl group optionally substituted with one or more substituents selected from the group consisting of halogen, C1-C6 alkoxy, C1-C6 haloalkoxy and hydroxy.

12. The method of claim 9, wherein the compound is represented by the following structural formula:

13. The method of claim 9, wherein the compound is represented by the following structural formula:

15. The method of claim 1, wherein the compound is represented by the following structural formula:

14. A method of treating polycystic kidney disease in a subject, the method comprising administering to the subject having polycystic kidney disease an effective amount of a compound is represented by the following structural formula: