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Substituted 1,2-ethylenediamines, methods for preparing them and uses thereof

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Title: Substituted 1,2-ethylenediamines, methods for preparing them and uses thereof.
Abstract: wherein the groups R1 to R15, A, B, L, i as well as X1-X4 are defined as in the specification and claims and the use thereof for the treatment of Alzheimer's disease (AD) and similar diseases. The present invention relates to substituted 1,2-ethylenediamines of general formula (I) ...


USPTO Applicaton #: #20090325940 - Class: 5142225 (USPTO) - 12/31/09 - Class 514 
Drug, Bio-affecting And Body Treating Compositions > Designated Organic Active Ingredient Containing (doai) >Heterocyclic Carbon Compounds Containing A Hetero Ring Having Chalcogen (i.e., O,s,se Or Te) Or Nitrogen As The Only Ring Hetero Atoms Doai >Hetero Ring Is Six-membered And Includes At Least Nitrogen And Sulfur As Ring Members >Three Or More Ring Hetero Atoms In The Six-membered Hetero Ring

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The Patent Description & Claims data below is from USPTO Patent Application 20090325940, Substituted 1,2-ethylenediamines, methods for preparing them and uses thereof.

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RELATED APPLICATIONS

This application is a divisional of U.S. Ser. No. 11/278,059, filed Mar. 30, 2006. This application claims priority to European Patent Application No. 05 006 939.2, filed Mar. 30, 2005. The contents of each of the above are incorporated herein by reference in their entirety.

FIELD OF THE INVENTION

The present invention relates to substituted 1,2-ethylenediamines of general formula (I)

wherein the groups R1 to R15, A, B, L, i and X1-X4 are defined below, including the tautomers, the stereoisomers, the mixtures thereof and the salts thereof. A further object of this invention relates to pharmaceutical compositions containing a compound of formula (I) according to the invention and the use of a compound according to the invention for preparing a pharmaceutical composition for the treatment and/or prevention of Alzheimer\'s disease (AD) and other diseases associated with abnormal processing of Amyloid Precursor Protein (APP) or aggregation of the Abeta peptide, as well as diseases which can be treated or prevented by the inhibition of β-secretase. Such diseases include MCI (“mild cognitive impairment”), trisomy 21 (Down\'s syndrome), cerebral amyloid angiopathy, degenerative dementias, hereditary cerebral haemorrhage with amyloidosis, Dutch type (HCHWA-D), Alzheimer\'s dementia with Lewy bodies, trauma, stroke, pancreatitis, Inclusion Body Myositis (IBM), and other peripheral amyloidoses, diabetes and arteriosclerosis.

The compounds according to the invention also inhibit the aspartylprotease cathepsin D and are therefore suitable for suppressing the metastasisation of tumour cells.

The invention further relates to processes for preparing a pharmaceutical composition and a compound according to the invention.

BACKGROUND OF THE INVENTION

EP 652 009 A1 describes inhibitors of aspartate protease which inhibit the production of beta-amyloid peptides in cell culture and in vivo.

WO 00/69262 discloses a beta-secretase and the use thereof in assays for finding potential active substances for the treatment of AD.

WO 01/00663 discloses memapsin 2 (human beta-secretase) as well as a recombinant catalytically active enzyme. Methods of identifying inhibitors of memapsin 2 are also described.

WO 01/00665 discloses inhibitors of memapsin 2 for the treatment of AD.

WO 03/057721 discloses substituted aminocarboxamides for the treatment of AD.

At present there are no effective treatment methods capable of preventing, stopping or reversing AD.

The objective of the present invention is therefore to provide new substituted 1,2-ethylenediamines which inhibit the cleaving of APP (Amyloid Precursor Protein) mediated by β-secretase.

A further objective of the present invention is to provide physiologically acceptable salts of the compounds according to the invention with inorganic or organic acids.

Another objective of the present invention is to provide pharmaceutical compositions containing at least one compound according to the invention or a physiologically acceptable salt according to the invention, optionally together with one or more inert carriers and/or diluents.

The present invention further relates to pharmaceutical compositions containing one or more, preferably one active substance, which is selected from the compounds according to the invention and/or the corresponding salts, as well as one or more, preferably one additional active substance optionally together with one or more inert carriers and/or diluents.

This invention further relates to the use of at least one of the compounds according to the invention for inhibiting β-secretase.

The invention also sets out to provide new pharmaceutical compositions which are suitable for the treatment or prevention of diseases or conditions associated with the abnormal processing of Amyloid Precursor Protein (APP) or aggregation of Abeta peptide.

The invention also sets out to provide new pharmaceutical compositions which are suitable for the treatment or prevention of diseases or conditions which can be influenced by inhibiting the β-secretase activity.

The invention also sets out to provide new pharmaceutical compositions which are suitable for the treatment and/or prevention of Alzheimer\'s disease (AD) and other diseases which are associated with the abnormal processing of APP or aggregation of Abeta peptide, as well as diseases which can be treated or prevented by the inhibition of β-secretase, particularly AD.



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stats Patent Info
Application #
US 20090325940 A1
Publish Date
12/31/2009
Document #
12511474
File Date
07/29/2009
USPTO Class
5142225
Other USPTO Classes
5142312, 514616, 544/8, 544173, 564153
International Class
/
Drawings
0


Alzheimer
Alzheimer's Disease
Alzheimer\'s Disease
Amine
Diseases
Ethylene


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