Therapeutic uses of PPAR mediators

• US 20030220373A1
• Filed: 09/09/2002
• Published: 11/27/2003
• Est. Priority Date: 03/09/2000
• Status: Abandoned Application

• Current Assignee: Aventis Pharmaceuticals Incorporated (Sanofi )
• Original Assignee: Aventis Pharmaceuticals Incorporated (Sanofi )
• Inventors: Searfoss, George, Minnich, Anne, Duverger, Nicolas, Jaye, Michael
• Application Number:
  US10/237,578
• Publication Number:
  US 20030220373A1
• Time in Patent Office: Days
• US Class Current: 514/342
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/12 Ketones
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/201 having one or two double bonds, e.g. oleic, linoleic acids
• CPC Class Codes: A61K 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/41 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• 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 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/50 : for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Use of PPAR mediators, and their pharmaceutical compositions, as ATP binding cassette transporter 1 (ABC-1) expression modulators, wherein the PPAR ligand receptor agonists of this invention are useful as inducers of ABC-1 expression.

Claims

1. A method for modulating ABC-1 gene expression comprising contacting a PPAR receptor with a PPAR mediator.

2. A method according to claim 1 wherein the PPAR receptor is a PPAR-γ

receptor.

3. A method according to claim 1 wherein the PPAR receptor is a PPAR-α

receptor.

4. A method according to claim 1 wherein the PPAR receptor is a PPAR-δ

receptor.

5. A method according to claim 1 wherein the PPAR mediator is a PPAR agonist.

6. A method according to claim 1 wherein the PPAR mediator is a PPAR antagonist.

7. A method according to claim 1 wherein ABC-1 gene expression is induced by a PPAR agonists.

8. A method according to claim 1 wherein ABC-1 gene expression is repressed by a PPAR antagonist.

15. A method according to claim 1 or 9 wherein the PPAR mediator is selected from the group consisting of Nafenopn, UF-5, ETYA, GW2331, 15-deoxy-Δ

^12,14-prostaglandin J₂, clofibric, linoleic acid, BRL-49653, fenofibrate, WR-1339, Pioglitazone, Ciglitazone, Englitazone, Troglitazone, LY-171883, AD 5075, 5-[[4-[2-(methyl-2-pyridinylamino)ethoxy]phenyl]methyl]-2,4-thiazolidinedione, WAY-120,744, and Darglitazone and their pharmaceutically acceptable salts.

16. A method according to claim 1 or 9 wherein the PPAR mediator is a compound of formula (I)

17. A method according to claim 1 or 9 wherein the PPAR mediator is selected from the group consisting of

18. A method according to claim 1 or 9 wherein the PPAR mediator is selected from the group consisting of

19. A method according to claim 1 or 9 wherein the PPAR mediator is

9. 9. A method of treating a physiological condition in a patient associated with ABC-1 gene expression comprising administering to a patient in need of such treatment, a pharmaceutically effective amount of a PPAR mediator.

10. A method according to claim 9 wherein the physiological condition is associated with ABC-1 deficiency.

11. A method according to claim 10 wherein the physiological condition is low levels of HDL.

12. A method according to claim 10 wherein the physiological condition is atherosclerosis, fish-eye disease, familial HDL deficiencies (FHD), Tangier disease, LCAT deficiency, cholesterol efflux, malaria or diabetes.

13. A method according to claim 9 wherein the physiological condition is associated with elevated levels of ABC-1.

14. A method according to claim 12 wherein the physiological condition is inflammation.