2-Acylaminopropoanol-Type Glucosylceramide Synthase Inhibitors

• US 20110184021A1
• Filed: 10/02/2009
• Published: 07/28/2011
• Est. Priority Date: 10/03/2008
• Status: Active Grant

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: Lee, Edward, Xiang, Yibin, Kane, John, Levine, Mikaela, Dios, Angeles, Bastos, Cecilia M., Jozafiak, Thomas H., Cuff, Lisa M., Liao, Junkai, Vinick, Frederic, Siegel, Craig, Harris, David J., Silva, Richard, Celatka, Cassandra A.
• Granted Patent: US 8,309,593 B2
• Time in Patent Office: Days
• US Class Current: 514/321
• 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

1-77. -77. (canceled)

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

79. The method of claim 78, wherein the compound is represented by the following structural formula:

80. The method of claim 79, wherein R³⁰ is independently 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.

81. The method of claim 80, wherein R³⁰ is independently 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.

82. The method of claim 79, wherein the compound is represented by the following structural formula:

83. The method of claim 79, wherein the compound is represented by the following structural formula:

84. The method of claim 79, wherein the compound is represented by the following structural formula:

85. The method of claim 79, wherein the compound is represented by the following structural formula:

86. The method of claim 78, wherein the compound is represented by the following structural formula:

87. The method of claim 86, wherein R³⁰ is independently 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.

88. The method of claim 87, wherein R³⁰ is independently 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.

89. The compound of claim 86, wherein the compound is represented by the following structural formula:

90. The method of claim 86, wherein the compound is represented by the following structural formula:

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