Abstract: A method of, or the use of compounds of the invention for, treating the cognitive impairments associated with Down syndrome, the method or use comprising treating or administering to a person with an effective amount of phenserine and isomers thereof or a pharmaceutically acceptable salt and derivatives thereof.
Abstract: Phenserine compounds and pharmaceutically acceptable salts thereof are found to be useful in the management or treatment of diabetes and/or complications, such as vascular dementia, and insulin resistance, associated with diabetes. The phenserine compounds of the invention are carbamates that inhibit the activity of acetylcholinesterase.
Abstract: The present invention provides compounds and methods of administering compounds to a subject that can reduce ?APP production and that is not toxic in a wide range of dosages. The present invention also provides non-carbamate compounds and methods of administering such compounds to a subject that can reduce ?APP production and that is not tocix in a wide range of dosages. It has been discovered that either the racemic or enantiomerically pure non-carbamate compounds can be used to decrease ?APP production.
Type:
Grant
Filed:
November 2, 2001
Date of Patent:
December 26, 2006
Assignees:
The United States of America as represented by the Department of Health and Human Services, The National Institutes of Health and Axonyx, Inc.
Inventors:
Nigel H. Greig, Karen T. Y. Shaw, Qiang-Sheng Yu, Harold W. Holloway, Timothy T. Sencrant, Tada Utsuki, Donald Ingram, Arnold Brossi, Anthony Giordano, Gordon Powers, Diane Davidson, Michael Sturgess
Abstract: Described is the efficient synthesis of an easy to manipulate and utilize, soluble tartrate salt of a potent, reversible butyrylcholinesterase inhibitor, (?)-(3aS)-3a-methyl-1,2,3,3a,8,8a-hexahydropyrrolo-[2,3-b]indol-5-yl N—4?-isopropylphenylcarbamate (“MHI tartrate”), for use in altering the enzymatic activity of butyrylcholinesterase and/or acetylcholinesterase in a subject exhibiting or predicted to exhibit cognitive disorders associated with diabetes. Subjects may be suffering from or predicted to suffer from abnormal acetylcholinesterase and/or butyrylcholinesterase activity levels or from an inability to metabolize or catabolize blood sugar normally. The method comprises administering to the subject an effective amount of MHI tartrate dispensable in discrete pharmaceutically useful dosages. MHI tartrate effectively inhibits both acetylcholinesterase and butyrylcholinesterases and additionally is highly selective for butyrylcholinesterase over acetylcholinesterase.
Abstract: The present invention provides peptide analogs and peptide mimetics that inhibit pleated sheet formation in amyloid ?-peptide, pharmaceutical compositions thereof and their therapeutic use. The inhibitory peptides possess activity as inhibitors in the formation of amyloid-like deposits and are useful in the treatment of Alzheimer's Disease.
Abstract: The present invention relates to compositions and methods of treating a cognitive disorder in a subject by administering an effective amount of a phenserine compound or a pharmaceutically acceptable salt or ester thereof and an effective amount of a HMG CoA reductase inhibitor or a pharmaceutically acceptable salt thereof to a subject, thereby treating a cognitive disorder in the subject.
Abstract: An improved transdermal delivery composition is provided containing a low molecular weight fatty acid, and a long chain fatty acid or a long chain fatty acid lower alkyl ester, wherein the long chain is between about 1 to about 21 carbons long and preferably, contains at least one cis-olefinic bond. Preferred long chain components are oleic acid and ethyl oleate while the preferred low molecular weight fatty acid is propionic acid. The product may be used for treating a cognitive disorder by administering phenserine through a subject's skin.
Abstract: The present invention provides peptide analogs and peptide mimetics that inhibit pleated sheet formation in amyloid &bgr;-peptide, pharmaceutical compositions thereof and their therapeutic use. The inhibitory peptides possess activity as inhibitors in the formation of amyloid-like deposits and are useful in the treatment of Alzheimer's Disease.
Abstract: A method for treating cognitive impairments associated with aging or Alzheimer's disease which comprises treating a patient at risk for having the cognitive impairment with an effective amount of a highly selective butyrylcholinesterase inhibitor which is N8-benzylnorcymserine, N1-phenethylnorcymserine, N1, N8-bisnorcymserine, N1-N8-bisbenzylnorphysostigmine, N1, N8-bisbenzylnorphenserine, N1, N8-bisbenzylnorcymserine, or pharmaceutical acceptable salts thereof.
Type:
Grant
Filed:
February 7, 2002
Date of Patent:
January 27, 2004
Assignee:
Axonyx, Inc.
Inventors:
Nigel H. Greig, Qian-Sheng Yu, Arnold Brossi, Timothy T. Soncrant, Marvin Hausman
Abstract: A process for preparing phenserine compounds which are known acetylcholinesterase inhibitors from physostigmine compounds by hydrolysis to form an eseroline compound which is then condensed with an isocyanate.