N-(pyridin-2-yl)-sulfonamide derivatives

• US 20070072914A1
• Filed: 06/15/2006
• Published: 03/29/2007
• Est. Priority Date: 06/16/2005
• Status: Active Grant

• Current Assignee: Agouron Pharmaceuticals Incorporated (Pfizer Inc.), Pfizer Inc.
• Original Assignee: Agouron Pharmaceuticals Incorporated (Pfizer Inc.), Pfizer Inc.
• Inventors: Siu, Michael, Taylor, Wendy, Nair, Sajiv Krishnan
• Granted Patent: US 7,462,634 B2
• Time in Patent Office: Days
• US Class Current: 514/342
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/24 Antidepressants
• 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 27/06 Antiglaucoma agents or miotics
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• 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: 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 213/75 Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention relates to novel compounds, to pharmaceutical compositions comprising the compounds described herein, their pharmaceutically acceptable salts, hydrates and solvates, as well as to the use of the compounds in medicine and for the preparation of a medicament which acts on the human 11-β-hydroxysteroid dehydrogenase type 1 enzyme (11βHSD1).

Claims

1. A compound of formula (I):

2. The compound or pharmaceutically acceptable salt thereof according to claim 1, wherein R¹ is H.

3. The compound or pharmaceutically acceptable salt thereof according to claim 1, wherein R³ is H or CH₃.

4. The compound or pharmaceutically acceptable salt thereof according to claim 1, wherein R² is —

CH₂CH₃.

5. The compound or pharmaceutically acceptable salt thereof according to claim 1, which is chiral.

6. The compound or pharmaceutically acceptable salt thereof according to claim 5, which is a (+) enantiomer.

10. A pharmaceutical composition comprising an effective amount of a compound or a pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable carrier.

12. A method for treating a disease;

condition or disorder which would benefit by treatment with a 11β

HSD1 inhibitor comprising administering to a mammal an effective amount of a compound, pharmaceutically acceptable salt thereof according to claim 1.

14. The method according to claim 12 wherein the disease, condition or disorder is type 2 diabetes.

16. The method according to claim 12 wherein the disease, condition or disorder is selected from metabolic syndrome, insulin resistance syndrome, obesity, glaucoma, hyperlipidemia, hyperglycemia, hyperinsulinemia, osteoporosis, atherosclerosis, dementia, depression, or diseases in which the liver is a target organ.

17. The method according to claim 12 wherein the disease, condition or disorder is glaucoma.

18. The method according to claim 17 wherein said effective amount of a compound or a pharmaceutically acceptable salt thereof is administered to said mammal in combination with a prostanoid receptor agonist.

19. The method according to claim 18, wherein the prostanoid receptor agonist is latanoprost, bimatoprost, travaprost, or unoprost.

7. A compound selected from the group consisting of:

8. The compound of formula (Ib), (Ic), (Id), or pharmaceutically acceptable salt thereof according to claim 7, which is a (+) enantiomer.

9. A compound having the formula (II):

11. A pharmaceutical composition comprising an effective amount of a compound or a pharmaceutically acceptable salt thereof according to claim 9, and a pharmaceutically acceptable carrier.

13. A method for treating a disease, condition or disorder which would benefit by treatment with a 11β

HSD1 inhibitor comprising administering to a mammal an effective amount of a compound, pharmaceutically acceptable salt thereof according to claim 9.

15. The method according to claim 13 wherein the disease, condition or disorder is type 2 diabetes.

20. The method according to claim 13 wherein the disease, condition or disorder is glaucoma.

21. The method according to claim 20 wherein said effective amount of a compound or a pharmaceutically acceptable salt thereof is administered to said mammal in combination with a prostanoid receptor agonist.

22. The method according to claim 21, wherein the prostanoid receptor agonist is latanoprost, bimatoprost, travaprost, or unoprost.