Novel Compounds and Methods for Treating Alzheimer’s and Related Diseases
Description of Invention:
The brain cholinergic system is thought to play an important role in learning and memory. The loss of cholinergic neurons early in the course of Alzheimer's Disease may thus be an etiological factor in the cognitive decline that is the hallmark of that disease. Therefore, potentiating cholinergic transmission has been the main pharmacological approach for the treatment of AD patients. Inhibition of acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) enhances cholinergic transmission by reducing enzymatic degradation of acetylcholine.
AChE inhibitors are now used clinically to help restore cognitive function in AD patients. However the therapeutic index for inhibition of AChE is quite low. Drugs with this mechanism of action have to have the proper pharmacodynamic properties to achieve even a marginally useful clinical effect without unacceptable side effects. The presence of BChE in brain tissue makes this enzyme another possible target for increasing the activity of the cholinergic system.
The present invention provides a series of novel and potent tricyclic compounds that have a range of selectivity for inhibiting AchE, as compared to BchE, and possess neuroprotective activity in cell culture models. Also provided are methods of using these compounds to treat a number of different medical conditions such as Alzheimer's Disease, mild cognitive impairment, and other dementia-related disorders.
Inventors:
Nigel H. Greig et al. (NIA)
Patent Status:
DHHS Reference No. E-172-2004/0 --
U.S. Provisional Application No. 60/621,287 filed 22 Oct 2004
PCT Application No. PCT/US2005/038400 filed 24 Oct 2005, which published as WO 2006/060082 on 08 Jun 2006
Licensing Status: In addition to licensing, the technology is available for further development through collaborative research with the inventors via a Cooperative Research and Development Agreement (CRADA).
Portfolios: Internal Medicine Central Nervous System
Central Nervous System -Therapeutics-Neurological Therapeutics-Alzheimer Central Nervous System -Therapeutics Internal Medicine-Therapeutics
For Additional Information Please Contact: Norbert J. Pontzer PhD JD
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-5502
Email: pontzern@mail.nih.gov
Fax: (301) 402-0220
