US 2022/0033412 A1 · 6-HYDROXY-8-OXATRICYCLO[3.2.1.02,4]OCTANE-2-CARBOXAMIDE DERIVATIVES FOR INDUCING CHONDROGENESIS FOR TREATING JOINT DAMAGE

Abstract

The present invention provides 6-hydroxy-8-oxatricyclo[3.2.1.02,4]octane-2-carboxamide derivatives of Formula (1) wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds. The compounds are used for inducing chondrogenesis, in methods of treating or preventing joint damage, resulting from joint injury or arthritis, and for inducing hyaline cartilage production. The present description discloses the preparation of exemplary compounds as well as pharmacological data thereof (examples 1 to 82; tables 1 and 2). An exemplary compound is e.g. rac-(1R,2R,4S,5R,6S)-4-(2-fluoropyridin-4-yl)-6-hydroxy-N-(4-(trifluoromethyl)pyridin-2-yl)-8-oxatricyclo[3.2.1.02,4]octane-2-carboxamide (example 1).

Claims24

Dependent claims

A compound of Formula (1):

or an enantiomer, an enantiomeric mixture thereof or a pharmaceutically acceptable salt thereof;
wherein
W is phenyl or pyridyl;
R1 is hydrogen or C1-8alkyl;
R2 is phenyl or a 5-6 membered heteroaryl having 1-2 heteroatoms selected from N, O and S;
wherein R2 is unsubstituted or substituted by 1-2 substituents independently selected from halo, C1-6 alkyl, C1-8 haloalkyl or C1-6 alkoxy;
R3 is independently selected from halo, cyano, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6 cycloalkyl and 5-6 membered heterocyclyl;
or R3 is hydrogen when n is 0;
and
n is 0-2.

7 more elements

Dependencies are inferred from the claim text.

Facts

Application

17/299,236Filed 4 Dec 2019

Priority

6 Dec 2018

Published

3 Feb 2022

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

A61P 19/02
Drugs for skeletal disorders: for joint disorders, e.g. arthritis, arthrosis
C07D 493/08
In which the condensed system contains two hetero rings: bridged systems
A61K 31/4155
1,2-Diazoles: non condensed and containing further heterocyclic rings
A61K 31/443
Containing further heterocyclic ring systems: containing a five-membered ring with oxygen as a ring hetero atom

6-hydroxy-8-oxatricyclo[3.2.1.02,4]octane-2-carboxamide derivatives for inducing chondrogenesis for treating joint damage

Life of this patent

6-hydroxy-8-oxatricyclo[3.2.1.02,4]octane-2-carboxamide derivatives for inducing chondrogenesis for treating joint damage

Life of this patent

Abstract

Claims24