Method of treating atherosclerosis in high triglyceride subjects

Patent metadata

Field	Value
Publication number	US-9867811-B2
Application number	US-201214128877-A
Country	US
Kind code	B2
Filing date	Jul 6, 2012
Priority date	Jul 8, 2011
Publication date	Jan 16, 2018
Grant date	Jan 16, 2018

Abstract

The present invention provides a compound of Formula I:

for use in the treatment, amelioration and/or prevention of diseases and conditions associated with CETP activity, such as atherosclerosis and dyslipidemia, in a subject with high triglyceride level; wherein R 1 , X 1 , R 7 , R 5 , C, L and p are defined herein. The present invention further provides a combination of pharmacologically active agents for use in the treatment, amelioration and/or prevention of diseases and conditions associated with CETP activity, such as atherosclerosis and dyslipidemia, in a subject with high triglyceride levels.

First claim

What is claimed is:

1. A method of treating or ameliorating atherosclerosis by raising HDL-C and/or lowering LDL-C, in a subject comprising, administering to the subject a therapeutically effective amount of the following compound:

or a pharmaceutically acceptable salt thereof, wherein the subject's triglyceride level is a fasting triglyceride level greater than 500 mg/dL.

2. A method of treating atherosclerosis by raising HDL-C and/or lowering LDL-C comprising:
a. selecting a subject with a fasting triglyceride level greater than 500 mg/dL; and
b. administering to said subject a therapeutically effective amount of a compound of the formula:

or a pharmaceutically acceptable salt thereof.

3. The method according to claim 1 or claim 2 further comprising administering at least one other therapeutic agent selected from: statin, cholesterol absorption inhibitor, apoA-I up-regulator/inducer, pre-beta HDL mimetic, ABCA1 stabilizer or inducer, LXR agonist, FXR agonist, phospholipid transfer protein (PLTP) inhibitor, aldosterone synthase inhibitor (ASI), fibric acid derivative, fish oil, DGAT1 inhibitor and endothelial lipase inhibitor, or a pharmaceutically acceptable salt thereof.

4. The method according to claim 1 wherein the compound maintains greater than or equal to 50% inhibition of CETP inhibitory activity in subjects with high plasma triglycerides when compared to subject with normal plasma triglycerides.

5. The method according to claim 2 wherein the compound maintains greater than or equal to 50% inhibition of CETP inhibitory activity in subjects with high plasma triglycerides when compared to subject with normal plasma triglycerides.

6. The method of claim 3 , wherein the at least one other therapeutic agent is a statin or a pharmaceutically acceptable salt thereof.

7. The method of claim 3 , wherein the at least one other therapeutic agent is a cholesterol absorption inhibitor or a pharmaceutically acceptable salt thereof.

8. The method of claim 3 , wherein the at least one other therapeutic agent is a apoA-I up-regulator/inducer or a pharmaceutically acceptable salt thereof.

9. The method of claim 3 , wherein the at least one other therapeutic agent is a pre-beta HDL mimetic or a pharmaceutically acceptable salt thereof.

10. The method of claim 3 , wherein the at least one other therapeutic agent is a ABCA1 stabilizer or inducer or a pharmaceutically acceptable salt thereof.

11. The method of claim 3 , wherein the at least one other therapeutic agent is a LXR agonist or a pharmaceutically acceptable salt thereof.

12. The method of claim 3 , wherein the at least one other therapeutic agent is a FXR agonist or a pharmaceutically acceptable salt thereof.

Assignees

• Arai Yoshie
• Brousseau Margaret Elizabeth
• Gu Jessie
• Hayashi Tomoko
• Mitani Hironobu
• Mogi Muneto
• Nonomura Kazuhiko
• Yamada Ken
• Novartis Ag

Inventors

• Arai Yoshie
• Brousseau Margaret Elizabeth
• Gu Jessie
• Hayashi Tomoko
• Mitani Hironobu
• Mogi Muneto
• Nonomura Kazuhiko
• Yamada Ken

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P43/00

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

• A61P3/06

  Antihyperlipidemics · CPC title

• A61K31/506 Primary

  not condensed and containing further heterocyclic rings · CPC title

• A61K31/41

  having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole · CPC title