Method of treating polycystic kidney diseases with ceramide derivatives

• US 8,912,177 B2
• Filed: 10/03/2008
• Issued: 12/16/2014
• Est. Priority Date: 10/05/2007
• Status: Active Grant

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: Natoli, Thomas A., Ibraghimov-Beskrovnaya, Oxana, Leonard, John P., Yew, Nelson S., Cheng, Seng H.
• Primary Examiner(s): Lundgren, Jeffrey S.
• Assistant Examiner(s): LEE, WILLIAM Y
• Application Number:
  US12/681,291
• Publication Number:
  US 20100298317A1
• Time in Patent Office: 2,265 Days
• Field of Search: None
• US Class Current: 514/233.8
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/4025 not condensed and containing further heterocyclic rings, e.g. cromakalim
• CPC Class Codes: A61K 31/421 1,3-Oxazoles, e.g. pemoline, trimethadione
• CPC Class Codes: A61K 31/422 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/12 of the kidneys

Abstract

A method of treating polycystic kidney disease in a subject comprises administering to the subject an effective amount of a compound represented by Structural Formula (1): or a pharmaceutically acceptable salt thereof.

Claims

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

2. The method of claim 1, wherein each R³⁰ is independently

i) hydrogen;

or

ii) 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.

3. The method of claim 1, wherein —

N(R²R³) is an unsubstituted pyrrolidinyl group.

4. The method of claim 1, wherein R¹ is 4-hydroxyphenyl or 3,4-ethylenedioxy-1-phenyl.

5. The method of claim 1, wherein the polycystic kidney disease is an autosomal dominant polycystic kidney disease.

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

11. The method of claim 1, wherein R¹ is a phenyl group optionally and independently substituted with one or more substituents selected from the group consisting of —

OH, —

OCH₃, —

OC₂H₅, C1-C6 alkyl and —

O—

[CH₂]_p—

O—

.

12. The method of claim 1, wherein R¹ is

13. The method of claim 1, wherein p is 1 or 2.

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

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

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

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