Structurally Rigid Dopamine D3 Receptor Selective Ligands as Cocaine and Methamphetamine Abuse Therapeutics
Description of Invention:
The dopamine D3 receptor subtype has been implicated in a number of central nervous system (CNS) disorders including but not limited to drug abuse, schizophrenia and Parkinson's disease. Since D3 receptor ligands show efficacy in animal models of cocaine self-administration and Parkinson's disease, there has been a significant effort to design and develop novel dopamine D3 ligands. However most currently known compounds are highly lipophilic, leading to poor bioavailablility and toxicity, or are not highly D3 selective.
The present invention provides a family of structurally rigid, potent and selective D3 receptor antagonists and partial agonists with lowered lipophilicity. Bioavailable compounds that bind with high affinity and selectivity to D3 receptors can not only provide important tools with which to study the structure and function of this receptor subtype, but may also have therapeutic uses in psychiatric, behavioral and neurologic disorders.
DHHS Reference No. E-251-2002/1 --
International Application No. PCT/US03/28895 filed 15 Sep 2003, which published as WO 2004/024878 on 25 Mar 2004
U.S. Patent Application No. 10/527,594 filed 14 Mar 2005
Relevant Publication: AH Newman et al. N-(4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl, butenyl and butynyl)arylcarboxamides as novel dopamine D(3) receptor antagonists. Bioorg Med Chem Lett. 2003 Jul 7;13(13):2179-2183. [PubMed abs]
Portfolios: Research Materials Central Nervous System
Central Nervous System -Therapeutics-Neurological Therapeutics-Antiparkinsonian Central Nervous System -Therapeutics-Neurological Therapeutics-Alzheimer Central Nervous System -Therapeutics-Psychotherapeutics-Drug Dependence Central Nervous System -Therapeutics
For Additional Information Please Contact: Tara L. Kirby Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4426
Email: tarak@mail.nih.gov
Fax: (301)402-0220
