Small molecule inhibitors of rotamase enzyme activity

• US 6,291,510 B1
• Filed: 05/07/1998
• Issued: 09/18/2001
• Est. Priority Date: 06/07/1995
• Status: Expired due to Fees

• Current Assignee: GliaMed, Inc.
• Original Assignee: GPI NIL Holdings Incorporated
• Inventors: Steiner, Joseph P., Hamilton, Gregory S.
• Primary Examiner(s): Gerstl, Robert
• Application Number:
  US09/073,962
• Time in Patent Office: 1,230 Days
• Field of Search: 514/423
• US Class Current: 514/423
• CPC Class Codes: C07D 207/16 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

This invention relates to neurotrophic compounds having an affinity for FKBP-type immunophilins, their preparation and use as inhibitors of the enzyme activity associated with immunophilin proteins, and particularly inhibitors of peptidyl-prolyl isomerase or rotamase enzyme activity.

Claims

1. A method for treating a neurological disorder in an anaimal comprising administering to the animal a therapcutically effective amount of a N-linked 1,2-diketo prolyl ester compound or a N-linked 1,2-diketo prolyl amide compound, wherein said ester compound or said amide compound is non-immunosuppressive.

4. The non-immunosuppressive neurotrophic N-linked 1,2-diketo prolyl ester compound or the non-immunosuppressive neurotrophic N-linked 1,2-diketo prolyl amide compound of claim 1, wherein said ester compound and said amide compound have a molecular weight less than 800 Daltons.

2. A method of promoting neuronal regeneration and growth in animals, comprising administering to a mammal an effective amount of a N-linked 1,2-diketo prolyl ester compound or a N-linked 1,2-diketo prolyl amide compound, wherein said ester compound or said amide compound is non-immunosuppressive.

3. A method of preventing neurodegeneration in an animal comprising administering to an animal an effective amount of a N-linked 1,2-diketo prolyl ester compound, or a N-linked 1,2-diketo prolyl amide compound, wherein said ester compound or said amide compound is non-immunosuppressive.