Phosphonate derivatives and methods of use thereof in the treatment of Alzheimer's disease

Patent metadata

Field	Value
Publication number	US-9738668-B2
Application number	US-201615163275-A
Country	US
Kind code	B2
Filing date	May 24, 2016
Priority date	May 14, 2012
Publication date	Aug 22, 2017
Grant date	Aug 22, 2017

Abstract

Benzothiazole phosphonate analogs and methods of using the same to inhibit the activity of Amyloid Binding Alcohol Dehydrogenase and in the amelioration or treatment of Alzheimer's disease are provided.

First claim

What is claimed is:

1. A compound of Formula II, or an analog, stereoisomer, tautomer, pharmaceutically acceptable salt, or prodrug thereof,

wherein
X is S or O;
one of R 1 or R 2 is a halo, alkoxyl, hydroxyl or methylcarboxylate group and the other of R 1 or R 2 a hydrogen, hydroxyl, halo, alkoxy, or methylcarboxylate group;
R 4 is a phosphonate group; and
R 5 is a substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl group, wherein said substituted aryl or substituted heteroaryl comprises one or two substituents selected from the group of —NO 2 , —CN, —NH 2 , —COOH, —OH, —OCH 3 , —OCF 3 , —CONH 2 , -alkyl, -alkoxy or a methylcarboxylate group.

2. The compound of claim 1 , wherein X is S; R 1 is H; R 2 is alkoxy; R 4 is a phosphonate group having the structure —PO(OR 7 ) 2 , wherein each R 7 is a methyl group; and R 5 is an aryl substituted with an —OH, methylcarboxylate group or a combination thereof.

3. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

4. A method for inhibiting the activity of Amyloid Binding Alcohol Dehydrogenase (ABAD) comprising contacting ABAD with a compound of claim 1 thereby inhibiting the activity of ABAD.

5. A method for ameliorating or treating Alzheimer's Disease comprising administering to a subject in need thereof the pharmaceutical composition of claim 3 thereby ameliorating or treating the subject's Alzheimer's Disease.

Assignees

• Univ Kansas

Inventors

• Yan Shidu
• Valasani Koteswara Rao

Classifications

• C07F9/65586

  at least one of the hetero rings does not contain nitrogen as ring hetero atom · CPC title

• C07F9/6541 Primary

  condensed with carbocyclic rings or {carbocyclic} ring systems · CPC title

• C07F9/4056

  Esters of arylalkanephosphonic acids (C07F9/4025 takes precedence) · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title

• C07F9/65583

  each of the hetero rings containing nitrogen as ring hetero atom · CPC title