Oxydecahydronaphthalene modulators of HM74

• US 20050187263A1
• Filed: 02/14/2005
• Published: 08/25/2005
• Est. Priority Date: 02/20/2004
• Status: Active Grant

• Current Assignee: Aventisub LLC (Sanofi )
• Original Assignee: Aventis Pharmaceuticals Incorporated (Sanofi-Aventis U.S., LLC)
• Inventors: Angelastro, Michael, Kuntzweiler, Theresa, Eishingdrelo, Haifeng, Minnich, Anne, Henke, Stephan
• Granted Patent: US 7,264,937 B2
• Time in Patent Office: Days
• US Class Current: 514/356
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 311/02 ortho- or peri-condensed with carbocyclic rings or ring systems

Abstract

Host cells expressing HM74 were used to obtain oxydecalin-like molecules with agonist activity having the following structure:

Claims

1. A therapeutic method for modulating HM74 signaling activity or signal transduction in a patient in need of treatment comprising administering to said patient a molecule having the structure:

2. A method for identifying an agonist of HM74 comprising, contacting a potential agonist with a cell expressing HM74 and determining whether in the presence of said potential agonist the signaling activity of HM74 is increased relative to the activity of HM74 in the absence of said potential agonist, wherein said potential agonist has the structure:

3. A method for identifying an inverse agonist of HM74 comprising, contacting a potential inverse agonist with a cell expressing HM74 and determining whether in the presence of said potential inverse agonist, the activity of HM74 is decreased relative to the activity of HM74 in the absence of said potential inverse agonist, and is decreased in the presence of an agonist, wherein said potential inverse agonist has the structure:

4. A method for identifying an antagonist of HM74 comprising, contacting a potential antagonist with a cell expressing HM74 and determining whether in the presence of said potential antagonist the signaling activity of HM74 is decreased relative to the activity of HM74 in the presence of an agonist, wherein said potential antagonist has the structure:

5. A method of modulating inflammation comprising exposing a patient in need of treatment an inflammation modulating amount of a pharmaceutical composition comprising a compound of the formula:

6. A compound of the formula: