Synthetic analogs of sphingolipids

Patent metadata

Field	Value
Publication number	US-9340488-B2
Application number	US-201414540621-A
Country	US
Kind code	B2
Filing date	Nov 13, 2014
Priority date	Nov 8, 2007
Publication date	May 17, 2016
Grant date	May 17, 2016

Abstract

The present invention provides new ceramide analogs indicated as the compounds of formula (II). These novel analogs exhibit a significant anti cancerous effect and are therefore provided as a pharmaceutical composition for treating cell proliferative diseases, neurodegenerative disorders, metabolism-associated conditions, infectious diseases, and immune-related disorders. The invention further provides combined compositions and kits combining the novel ceramide analogs of formula (II) with an additional therapeutic agent.

First claim

The invention claimed is:

1. A method for the treatment of a subject suffering from cancer, the method comprising the step of administering to said subject a therapeutically effective amount of the compound of Formula 11 , or a pharmaceutically acceptable salt thereof or any composition comprising same:

wherein
X represents OH;
Y represents

 wherein R 6 represents a C 2-20 linear or branched alkyl or alkenyl chain which may be optionally substituted with hydroxyl; and
W represents C 1-20 linear or branched alkyl or alkenyl chain substituted with hydroxyl,
wherein said cancer is selected from colon cancer, pancreatic cancer, prostate cancer, leukemia, lung cancer, sarcoma and melanoma.

2. A method for the treatment of cancer, the method comprising administering to a subject a therapeutically effective amount of compound of follnula (I):

wherein
R represents a hydrogen atom, or phenyl optionally substituted by nitro, amino, alkylamino, acylamino, —NHC(S)NH-alkyl, sulfonylamido-alkyl,

 adamantane wherein n is an integer of from 1 to 20, or
—NH-adamantane;
X represents OH;
Y represents

 wherein n is an integer of from 0 to 6, and wherein R 6 represents a C 2 - 20 linear or branched alkyl or alkenyl chain which may be optionally substituted with hydroxyl,

wherein R 1 , R 2 and R 3 , independently represent C 1 -C 6 alkyl or C i -C 6 alkenyl;
Z represents —OH; and
W represents C 1-20 linear or branched alkyl or alkenyl chain substituted with hydroxyl,
with the proviso that if R is hydrogen, Y is not

wherein said cancer is selected from colon cancer, pancreatic cancer, prostate cancer, leukemia, lung cancer, sarcoma and melanoma.

3. The method of claim 1 , wherein the compound of Formula (II) is

2-(octadecylamino)-2-(hydroxymethyl)propane-1,3-diol, also designated herein ADYZ197.

4. The method of claim 1 , wherein the compound of Formula II is

2-(decylamino)-2-(hydroxymethyl)propane-1,3-diol, also designated herein as ADYZ195.

Assignees

• Hadasit Med Res Service
• Yissum Res Dev Co

Inventors

• Dagan Arie
• Slavin Shimon
• Gatt Shimon
• Zahavy Jeremy

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title