Heterocyclic amide derivatives and their use as dopamine D3 receptor ligands

• US 7,550,469 B2
• Filed: 12/21/2006
• Issued: 06/23/2009
• Est. Priority Date: 02/16/2001
• Status: Expired due to Fees

• Current Assignee: Aventis Pharmaceuticals Incorporated (Sanofi-Aventis U.S., LLC)
• Original Assignee: Aventis Pharmaceuticals Incorporated (Sanofi-Aventis U.S., LLC)
• Inventors: Hemmerle, Horst, Mueller, Paul Justin, Gill, Harpal, Hendrix, James A, Jackson, Sharon Anne, Weiberth, Franz J, Urmann, Matthias, Shutske, Gregory, Bordeau, Kenneth, Nieduzak, Thaddeus, Jurcak, John G, Zhao, Xu-Yang, Strupczewski, Joseph T
• Primary Examiner(s): BERNHARDT, EMILY B
• Application Number:
  US11/643,594
• Publication Number:
  US 20070142351A1
• Time in Patent Office: 915 Days
• Field of Search: None
• US Class Current: 514/254.04
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• 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 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 233/56 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 249/08 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• CPC Class Codes: C07D 333/58 Radicals substituted by nitrogen atoms
• CPC Class Codes: C07D 333/66 Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 333/68 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 333/70 attached in position 2
• CPC Class Codes: C07D 409/04 directly linked by a ring-member-to-ring-member bond
• 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 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 451/02 : containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 495/04 : Ortho-condensed systems

Abstract

The invention relates to heterocyclic substituted amide derivatives that display selective binding to dopamine D₃ receptors. In another aspect, the invention relates to a method for treating central nervous system disorders associated with the dopamine D₃ receptor activity in a patient in need of such treatment comprising administering to the subject a therapeutically effective amount of said compounds for alleviation of such disorder. The central nervous system disorders that may be treated with these compounds include Psychotic Disorders, Substance Dependence, Substance Abuse, Dyskinetic Disorders (e.g. Parkinson'"'"'s Disease, Parkinsonism, Neuroleptic-Induced Tardive Dyskinesia, Gilles de la Tourette Syndrome and Huntington'"'"'s Disease), Dementia, Anxiety Disorders, Sleep Disorders, Circadian Rhythm Disorders and Mood Disorders. The subject invention is also directed towards processes for the preparation of the compounds described herein as well as methods for making and using the compounds as imaging agents for dopamine D₃ receptors.

Claims

1. A compound of the formula (I):

2. A pharmaceutical composition comprising an effective amount of a compound of claim 1 with a pharmaceutically-acceptable carrier or diluent.

3. A depot pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1, wherein the compound contains an acylated hydroxy group, or an acylated amino group.

4. A compound according to claim 1 wherein R is group (b).

5. A compound according to claim 1 wherein R is group (d).