US 9,000,185 B2Granted

Cycloalkyl ether compounds and their use as BACE inhibitors

AssigneeAstraZeneca AB

InventorsSofia Karlstrom, Peter Soderman, Britt-Marie Swahn, Laszlo Rakos, Liselotte Ohberg

Life of this patent

Estimating the term…

Loading patent…

Abstract

Cycloalkyl ether compounds, therapeutically acceptable salts thereof, processes for preparation thereof, therapeutic uses of such compounds for treating Aβ-related pathologies such as Down's syndrome, β-amyloid angiopathy, Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration and pharmaceutical compositions containing such compounds.

Claims7

Dependent claims

A compound of Formula 1

wherein
A is —O—, or —CH2—;
n is 0 or 1;
R1 is C1-6alkyl or C1-6haloalkyl;
R2 is C1-6alkyl, or C1-6haloalkyl;
wherein said C1-6alkyl or C1-6haloalkyl is substituted with one to three groups independently selected from C3-6halocycloalkyl;
R5 and R6 is independently hydrogen, heterocyclyl, C3-6cycloalkyl, aryl, heteroaryl or C1-6alkyl, wherein said heterocyclyl, C3-6cycloalkyl, aryl, heteroaryl or C1-6alkyl is optionally substituted with one or two substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, or cyano;
or R5 and R6 together with the carbon to which they are attached, form a ring B, which is a 3-14 membered cycloalkyl or heterocyclyl monocyclic ring, or a 9-14 membered bicyclic cycloalkyl or heterocyclyl ring;
and wherein ring B is optionally substituted by one or two substituents independently selected from oxo, halogen, C1-6alkyl, C1-6haloalkyl, cyano, or OR7;
R7 is independently hydrogen, C1-6alkyl, C1-6haloalkyl, or C0-6alkylC3-6cycloalkyl;
R8 is hydrogen, halogen or methyl;
as a free base or a pharmaceutically acceptable salt thereof.

9 more elements

A compound selected from the group consisting of:

(1r,4r)-4-Methoxy-5″-methyl-6′-[(1-methylcyclopropyl)methoxy]-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;
(1r,4r)-6′-[(3,3-Difluorocyclobutyl)methoxy]-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;
(1r,4r)-6′-(Cyclopropylmethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;
(1r,1′R,4R)-6′-(Cyclopropylmethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;
(1r,1′S,4S)-6′-(Cyclopropylmethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;
(1r,4r)-6′-[(2,2-Difluorocyclopropyl)methoxy]-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;
(1r,1′R,4R)-6′-(Cyclobutylmethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;
(1r,1′S,4S)-6′-(Cyclobutylmethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine, and
(1r,4r)-6′-(2-Cyclopropylethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine,
or a pharmaceutically acceptable salt of any foregoing compound.

7 more elements

A compound selected from the group consisting of:

(1r,4r)-4-Methoxy-5″-methyl-6′-[(1-methylcyclopropyl)methoxy]-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;
(1r,4r)-6′-[(3,3-Difluorocyclobutyl)methoxy]-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;
(1r,4r)-6′-(Cyclopropylmethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;
(1r,1′R,4R)-6′-(Cyclopropylmethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;
(1r, 1′S,4S)-6′-(Cyclopropylmethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;
(1r,4r)-6′-[(2,2-Difluorocyclopropyl)methoxy]-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;
and
(1r,4r)-6′-(2-Cyclopropylethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine,
or a pharmaceutically acceptable salt of any foregoing compound.

6 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/916,740Filed 13 Jun 2013 · us provisional application
Priority: 20 Jun 2012
Published: US 2013/0345272 A126 Dec 2013
Granted: 7 Apr 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 235/02
Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings: condensed with carbocyclic rings or…
A61K 31/428
Thiazoles: condensed with carbocyclic rings
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…
A61P 9/00
Drugs for disorders of the cardiovascular system