Compounds and compositions for use in augmentation of glucose

Patent metadata

Field	Value
Publication number	US-9409904-B2
Application number	US-201214236224-A
Country	US
Kind code	B2
Filing date	Aug 1, 2012
Priority date	Aug 1, 2011
Publication date	Aug 9, 2016
Grant date	Aug 9, 2016

Abstract

The present invention is directed to compounds such as: formula wherein linker is independently selected from the group consisting of —S—, —S—S—, —S—(CH2)n-, —NH—, —NH—(CH2)n-, —O—, —SO2-, arylene, heteroarylene; R1 is selected from the group consisting of straight or branched C4-C20 alkyl, straight or branched C4-C20 alkenyl, straight or branched C4-C20 alkynyl, each optionally interrupted with at least one NH, C5-C7 saturated cycloalkyl or heteroalkyl ring, C5-C12 aromatic or heteroaromatic ring, each optionally substituted with at least one group selected from —COOH, —NH2, C1-C8 alkoxy, C1-C5 amidyle, C1-C5 carboxyl, halogen; and R2 is independently selected from the group consisting of H, OH, SH, NH2, NO2, halogen, CN, C1-C8 alkoxy, C1-C5 carboxylic acid, straight or branched C1-C8 alkyl, straight or branched C2-C10 alkenyl, straight or branched C2-C12 alkynyl each optionally substituted by at least one substituent selected from the group consisting of C1-C5 alkoxy, C1-C5 carboxylic acid, OH, SH, NH2, halogen; and compositions for use in the treatment of diabetes and related dis orders.

First claim

The invention claimed is:

1. A compound of formula (II):

wherein
X 1 , X 2 , X 3 and X 4 are each independently selected from the group consisting of S, O, CH 2 , CHR 3 , NH and NR 3 ; provided that at least one of X 1 to X 4 is O or S and at least one of X 1 to X 4 is CHR 3 ;
V 1 , V 2 , V 3 and V 4 are each independently selected from N, C, CH and CR 4 ;
Y and Z are each S;
R 1 and R 2 are each independently selected from straight or branched C 1 -C 20 alkyl, straight or branched C 2 -C 20 alkenyl and straight or branched C 2 -C 20 alkynyl, each optionally interrupted with at least one NH; or wherein R 1 and R 2 together with Y, Z and the carbon atom connecting them form a 5 to 10 membered ring; optionally substituted by at least one group selected from straight or branched C 1 -C 10 alkyl, straight or branched C 2 -C 10 alkenyl and straight or branched C 2 -C 10 alkynyl;
R 4 is selected from the group consisting of halogen, straight or branched C 1 -C 20 alkyl, straight or branched C 2 -C 20 alkenyl and straight or branched C 2 -C 20 alkynyl;
R 3 is selected from the group consisting of straight or branched C 1 -C 12 alkyl, straight or branched C 2 -C 5 alkenyl, straight or branched C 2 -C 5 alkynyl, —COOH, C 1 -C 8 alkoxy, C 1 -C 5 amidyle, C 1 -C 5 carboxyl, C 6 -C 12 aryl, C 4 -C 12 heteroaryl and heterocyclyl, wherein each of aryl, heteroaryl and heterocyclyl is optionally substituted by at least one of alkoxy, alkyl, alkenyl, alkynyl, amino, cyano, halogen, and 1,3-dithian-benzyl.

2. A compound of claim 1 , wherein at least one of X 1 to X 4 is O.

3. A compound of claim 1 , wherein at least two of X 1 to X 4 are O.

4. A compound of claim 1 , wherein R 3 is aryl or heteroaryl.

5. A compound of claim 1 of formula (III):

wherein X 1 to X 4 , V 1 to V 4 , Y, Z and R 1 to R 4 are as defined in claim 1 ; and n is 1 to 5.

6. A medicament comprising the compound of claim 1 and a pharmaceutically acceptable carrier or auxiliary.

7. A method of treating elevated blood glucose levels in a subject in need thereof, said method comprising administering to said subject a compound of claim 1 .

8. A method for the treatment of at least one condition selected from hyperglycemia, diabetes, altered insulin secretion, insulin resistance, obesity and metabolic syndrome X; said method comprising administering to a subject in need thereof an effective amount of a compound according to claim 1 .

9. A method according to claim 8 , wherein said condition is diabetes.

Assignees

• Sasson Shlomo
• Cerasi Erol
• Gruzman Arie Lev
• Meltzer-Mats Ella
• Yissum Res Dev Co
• Diab R&D 1
• Univ Bar Ilan

Inventors

• Sasson Shlomo
• Cerasi Erol
• Gruzman Arie Lev
• Meltzer-Mats Ella

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• C07D277/54

  Nitrogen and either oxygen or sulfur atoms · CPC title

• C07D277/82

  Nitrogen atoms · CPC title

• C07D339/02

  Five-membered rings · CPC title