Design and Synthesis of PET Radioligands for alpha 4 beta 2 Nicotinic Acetylcholine Receptors
Contemplated compounds may be particularly useful as ligands for the alpha 4 beta 2 nAChR, and most preferably as an antagonist for the alpha 4 beta 2 nAChR. Numerous diagnostic, therapeutic, and academic uses are contemplated due to the specific binding of the compounds presented herein (Km to alpha 4 beta 2 nAChR is typically at least 10-100 times less than compared to other receptors or biological structures).Where contemplated compounds are radiolabeled, such compounds may be useful for location and/or quantification of alph 4 beta2 nAChR in a biological tissue. Suitable diagnostic methods will generally depend on the particular label. The compound can be detected in vivo via PET or SPECT analysis or in vitro via autoradiography or scintigraphy. Location and quantification of the alpha 4 beta 2 receptor in vivo may be particularly useful in diagnostic use, while quantification of the receptor and/or binding of contemplated labeled compounds in vitro may be especially useful in characterization of a mutant form of a receptor, or in competitive analysis with a second ligand. Therefore, labeled compounds may also be particularly useful in the development and/or characterization of new ligands. In other examples of contemplated uses, and particularly where compounds presented herein are not radioisotope-containing compounds, it should be recognized that the binding of the compounds to the alpha 4 beta 2 nAChR as antagonist (or in some cases as agonist) may be used in a therapeutic manner for treatment of diseases or conditions that are associated with the alpha 4 beta 2 nAChR. For example, diseases and conditions to be treated with contemplated compounds include cognitive dysfunctions and/or attentional disorders (e.g., anxiety disorders, lack of mental focus, ADHD), neurodegenerative diseases (e.g., Alzheimer's and Parkinson's), schizophrenia, pain, depression, epilepsy, Tourette's syndrome, small-cell lung carcinoma, and tobacco dependence.
The present invention is directed to compositions and methods for targeting the alpha 4 beta 2 receptor, wherein compounds in such compositions will selectively bind to the alpha 4 beta 2 receptor. Where the compounds are labeled, it is contemplated that binding and/or location of the alpha 4 beta 2 receptor may be analyzed in vitro and in vivo using PET and SPECT analysis. Alternatively, and/or additionally contemplated compounds can be used as antagonists, partial agonists or agonists in the treatment of diseases or conditions associated with alpha 4 beta 2 dysfunction.
Patent Number: US8378109B2
Application Number: US2007721145A
Inventor: Mukherjee, Jogeshwar | Pichika, Ramaiah | Potkin, Steven | Leslie, Frances | Chattopadhyay, Sankha
Priority Date: 7 Dec 2004
Priority Number: US8378109B2
Application Date: 21 Jul 2009
Publication Date: 19 Feb 2013
IPC Current: C07D040112
US Class: 5462764 | 5462791
Assignee Applicant: The Regents of the University of California
Title: Labeled ALPHA4BETA2 ligands and methods therefor
Usefulness: Labeled ALPHA4BETA2 ligands and methods therefor
Summary: For diagnosing a mammal having a disease associated with α-4-β-2 receptor dysfunction; and in pharmaceutical composition for treating a disease associated with α-4-β-2 receptor dysfunction such as cognitive dysfunction, anxiety disorder, neurodegenerative disease, schizophrenia, pain, depression, epilepsy, Tourette's syndrome, small-cell lung carcinoma, tobacco dependence (all claimed), Alzheimer's disease and Parkinson's disease.
Novelty: New substituted cyclic amines useful for treating diseases associated with α-4-β-2 receptor dysfunction e.g. cognitive dysfunction, anxiety disorder, neurodegenerative disease, pain, depression, epilepsy, Tourette's syndrome
Chemical/Material
Chemical/Material Application
8378109
Tech ID/UC Case 18860/2003-432-0 Related Cases 2003-432-0
USA
