Imaging methods using 2-hetaryl imidazol[1,2-a]pyridine derivatives

Patent metadata

Field	Value
Publication number	US-10975073-B2
Application number	US-201816161306-A
Country	US
Kind code	B2
Filing date	Oct 16, 2018
Priority date	Apr 29, 2013
Publication date	Apr 13, 2021
Grant date	Apr 13, 2021

Abstract

The invention relates to small molecule imaging tools.

First claim

The invention claimed is:

1. A method of in vivo imaging a human brain having one or more of tau-aggregate deposits, beta-amyloid aggregates or alpha-synuclein aggregates, the method comprising:
administering a detectable quantity of a compound of formula II to a patient,

wherein:
R 4 is hydrogen or lower alkyl;
R 5 is lower alkyl, cycloalkyl, lower alkyl substituted by hydroxy or lower alkyl substituted by halogen, or
R 4 and R 5 , together with the nitrogen atom to which they are attached, form a ring containing —CH 2 CH 2 CHRCH 2 CH 2 —, —CH 2 CHRCH 2 CH 2 —, —CH 2 CH 2 OCH 2 CH 2 —, —CH 2 CH 2 NR′CH 2 CH 2 —, CH 2 CHR— or —CH 2 CH 2 CH 2 —,
wherein:
R is hydrogen, halogen, lower alkyl, lower alkoxy or lower alkyl substituted by halogen; and
R′ is lower alkyl substituted by halogen;

HetAr is selected from the group consisting of: thiophenyl, furanyl, thiazolyl, benzofuranyl, pyrazolyl, benzoimidazolyl and pyridinyl;
R 6 is hydrogen, halogen or lower alkyl;
n is 1 or 2; and
at least one hydrogen atom is replaced by 3 H;
or a pharmaceutically acceptable acid addition salt, a racemic mixture or its corresponding enantiomer and/or an optical isomer thereof;
allowing sufficient time for the compound of formula II to bind to the tau-aggregate deposits, beta-amyloid aggregates or alpha-synuclein aggregates, and
imaging the brain of the patient in a manner that detects locations where the compound of formula II is bound to one or more of the tau-aggregate deposits, beta-amyloid aggregates or alpha-synuclein aggregates.

2. The method of claim 1 , wherein the imaging is further defined as diagnostic imaging of tau-aggregate deposits in the brain of the patient.

3. The method of claim 2 , wherein the brain of the patient is of a patient having Alzheimer's disease.

4. The method of claim 1 , wherein the compound of formula II is administered in a composition that further comprises a pharmaceutically acceptable carrier.

Assignees

• Hoffmann La Roche

Inventors

• Borroni Edilio
• Gobbi Luca
• Honer Michael
• Knust Henner
• Koerner Matthias
• Muri Dieter

Classifications

• A61K49/00

  Preparations for testing in vivo · CPC title

• A61K49/0002

  General or multifunctional contrast agents, e.g. chelated agents · CPC title

• A61K31/437

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title