Pyrazole-based HMG CoA reductase inhibitors

• US 7,446,121 B2
• Filed: 11/18/2005
• Issued: 11/04/2008
• Est. Priority Date: 11/23/2004
• Status: Expired due to Fees

• Current Assignee: Warner-Lambert Company LLC (Pfizer Inc.)
• Original Assignee: Pfizer Inc.
• Inventors: Pfefferkorn, Jeffrey A.
• Primary Examiner(s): Shameem; Golam M
• Application Number:
  US11/283,264
• Publication Number:
  US 20060111422A1
• Time in Patent Office: 1,082 Days
• Field of Search: 548/356.1, 548/373.1, 548/374.1, 514/403, 514/406
• US Class Current: 514/406
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 19/10 for osteoporosis
• 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 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 231/14 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms

Abstract

Novel compounds and pharmaceutical compositions useful as hypocholesterolemic and hypolipidemic agents are described. More specifically, potent inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (“HMG CoA reductase”) are described. Methods of using such compounds and compositions to treat subjects, including humans, suffering from hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, Alzheimer'"'"'s Disease, benign prostatic hypertrophy (BPH), diabetes and osteoporosis are also described.

Claims

1. A compound which is (3R, 5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic acid of the formula

2. A sodium salt of the compound of claim 1.

3. A pharmaceutical composition comprising a salt according to claim 2 and a pharmaceutically acceptable carrier, diluent, solvent or vehicle.

4. A pharmaceutical composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, solvent or vehicle.

5. A method of treating a subject suffering from hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, Alzheimer'"'"'s Disease, benign prostatic hypertrophy (BPH), diabetes, and osteoporosis comprising administering a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, to a subject in need thereof.

6. A method of treating a subject suffering from hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, Alzheimer'"'"'s Disease, benign prostatic hypertrophy (BPH), diabetes, and osteoporosis comprising administering a therapeutically effective amount of the salt of claim 2 to a subject in need thereof.

7. A method according to claim 5 wherein said subject is suffering from hyperlipidemia.

8. A method according to claim 5 wherein said subject is suffering from hypercholesterolemia.

9. A method according to claim 5 wherein said patient is suffering from atherosclerosis.

10. A method according to claim 2 wherein said subject is suffering from hyperlipidemia.

11. A method according to claim 2 wherein said subject is suffering from hypercholesterolemia.

12. A method according to claim 2 wherein said patient is suffering from atherosclerosis.