PHOSPHOLIPID COMPOUND CONTAINING UNSATURATED FATTY ACID DERIVATIVE HAVING CYCLOPROPANE RING

• US 20150376213A1
• Filed: 02/14/2014
• Published: 12/31/2015
• Est. Priority Date: 02/15/2013
• Status: Active Grant

• Current Assignee: Nishizaki Bioinformation Research Institute
• Original Assignee: Nishizaki Bioinformation Research Institute
• Inventors: NISHIZAKI, Tomoyuki, TANAKA, Akito
• Granted Patent: US 9,512,152 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/661 Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
• CPC Class Codes: A61K 31/683 Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
• CPC Class Codes: A61K 31/685 one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07F 9/062 Organo-phosphoranes without P-C bonds
• CPC Class Codes: C07F 9/106 Adducts, complexes, salts of phosphatides
• CPC Class Codes: C07F 9/117 with cycloaliphatic alcohols

Abstract

The invention provides a phospholipid compound containing unsaturated fatty acid having a cyclopropane ring such as 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) and 8-(2-octylcyclopropyl)octanoic acid (DCP-OA) and the like, particularly 1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidylethanolamine (diDCP-LA-PE), which has a cognitive function improving effect and an anti-diabetes action, and which is useful as a medicine such as a therapeutic drug for dementia, a therapeutic drug for diabetes and the like.

Claims

1. A medicine comprising a phospholipid compound containing an unsaturated fatty acid having a cyclopropane ring as an active ingredient.

2. The medicine according to claim 1, wherein the unsaturated fatty acid having a cyclopropane ring is an unsaturated fatty acid having a double bond converted to a cyclopropane ring.

3. The medicine according to claim 1, wherein the unsaturated fatty acid having a cyclopropane ring is 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) or 8-(2-octylcyclopropyl)octanoic acid (DCP-OA).

4. The medicine according to claim 1, wherein the phospholipid compound is phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine, or phosphatidylinositol.

5. The medicine according to claim 1, wherein the phospholipid compound is

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidylethanolamine (diDCP-LA-PE),

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidyl-L-serine (diDCP-LA-PS),

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-3-glycero-3-phosphatidylcholine (diDCP-LA-PC),

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidyl-D-1-inositol(diDCP-LA-PI), or

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidyl-L-1-inositol(diDCP-LA-PI ent).

6. The medicine according to claim 1, which is a therapeutic drug for diabetes.

7. The medicine according to claim 6, wherein the diabetes is type 1 diabetes or type 2 diabetes.

10. The medicine according to claim 1, which is a therapeutic drug for dementia.

11. The medicine according to claim 10, wherein the dementia is Alzheimer-type dementia.

12. The medicine according to claim 1, which is an anti-aging drug.

8-9. -9. (canceled)

13. A reagent comprising a phospholipid compound containing an unsaturated fatty acid derivative having a cyclopropane ring as an active ingredient.

14. The reagent according to claim 13, wherein the unsaturated fatty acid having a cyclopropane ring is an unsaturated fatty acid converted a double bond to a cyclopropane ring.

15. The reagent according to claim 13, wherein the unsaturated fatty acid having a cyclopropane ring is 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) or 8-(2-octylcyclopropyl)octanoic acid (DCP-OA).

16. The reagent according to claim 13, wherein the phospholipid compound is phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine, or phosphatidylinositol.

17. The reagent according to claim 13, wherein the phospholipid compound is

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidylethanolamine (diDCP-LA-PE),

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidyl-L-serine (diDCP-LA-PS),

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-3-glycero-3-phosphatidylcholine (diDCP-LA-PC),

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidyl-D-1-inositol(diDCP-LA-PI), or

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidyl-L-1-inositol (diDCP-LA-PI ent).

18. The reagent according to claim 13, which is a protein tyrosine phosphatase 1B inhibitor.

19. The reagent according to claim 13, which is an Akt activator.

20. The reagent according to claim 13, which is a protein phosphorylated enzyme C (PKC) activator.

21. The reagent according to claim 20, wherein the PKC is PKCι

and/or PKCζ

.

22. A compound selected from the group consisting of

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidylethanolamine (diDCP-LA-PE),

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidyl-L-serine (diDCP-LA-PS),

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-3-glycero-3-phosphatidylcholine (diDCP-LA-PC),

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidyl-D-1-inositol (diDCP-LA-PI), and

1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidyl-L-1-inositol (diDCP-LA-PI ent).