Method of treating polycystic kidney diseases with ceramide derivatives

• US 10,220,039 B2
• Filed: 01/25/2017
• Issued: 03/05/2019
• 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): Klinkel, Kortney L.
• Assistant Examiner(s): Lee, William Y
• Application Number:
  US15/414,838
• Publication Number:
  US 20170258802A1
• Time in Patent Office: 769 Days
• Field of Search: None
• 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, comprising administering to the subject an effective amount of a compound represented by the following structural formula:

2. The method of claim 1, wherein —

N(R²R³) is an unsubstituted pyrrolidinyl, azetidinyl, piperidinyl, piperazinyl or morpholinyl group.

3. The method of claim 2, wherein —

N(R²R³) is N-pyrrolidinyl or N-morpholinyl.

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

5. The method of claim 4, wherein R⁴ is a C6-C8 alkyl group.

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

7. The method of claim 1, wherein the compound is a (1R, 2R) stereoisomer.

8. The method of claim 1, wherein R¹ is

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

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

OH, —

OCH₃, —

OC₂H₅, C1-C6 alkyl and —

O—

[CH₂]_p—

O—

.