Compounds and uses

Patent metadata

Field	Value
Publication number	US-11840543-B2
Application number	US-201716614776-A
Country	US
Kind code	B2
Filing date	May 24, 2017
Priority date	May 24, 2017
Publication date	Dec 12, 2023
Grant date	Dec 12, 2023

Abstract

The present invention relates to compounds of formula (I): wherein Q is O or S; R1 is a cyclic group substituted with at least one group X, wherein R1 may optionally be further substituted; X is any group comprising a carbonyl group; and R2 is a cyclic group substituted at the α-position, wherein R2 may optionally be further substituted. The present invention further relates to salts, solvates and prodrugs of such compounds, to pharmaceutical compositions comprising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by the dual action of NLRP3 inhibition and the stimulation of insulin secretion.

First claim

The invention claimed is:

1. A compound of formula (I):

or a pharmaceutically acceptable salt or solvate thereof, wherein:
Q is O or S;
R 1 is a 6-membered cyclic group substituted with at least one group X, wherein R 1 may optionally be further substituted;
X is any group comprising a carbonyl group and containing from 1 to 20 carbon atoms; and
R 2 is a fused aryl or fused heteroaryl group, wherein a cycloalkyl, cycloalkenyl, non-aromatic heterocyclic, aryl or heteroaryl ring is fused to the aryl or heteroaryl group across the α,β positions, wherein the aryl or heteroaryl group is further substituted at the at α′-position, and wherein R 2 may optionally be further substituted.

2. The compound or pharmaceutically acceptable salt or solvate of claim 1 , wherein R 2 is a fused aryl or a fused heteroaryl group, wherein a first cycloalkyl, cycloalkenyl, non-aromatic heterocyclic, aryl or heteroaryl ring is fused to the aryl or heteroaryl group across the α,β positions and a second cycloalkyl, cycloalkenyl, non-aromatic heterocyclic, aryl or heteroaryl ring is fused to the aryl or heteroaryl group across the α′,β′ positions, wherein R 2 may optionally be further substituted.

3. The compound or pharmaceutically acceptable salt or solvate of claim 1 , wherein:
(i) R 1 is a 6-membered cyclic group substituted at the 4-position with at least one group X, wherein X is attached to the 6-membered cyclic group only via the 4-position, and wherein the 6-membered cyclic group may optionally be further substituted; or
(ii) R 1 is a phenyl group or a 6-membered heteroaryl group, wherein the phenyl group or the 6-membered heteroaryl group is substituted at the 4-position with a group X, wherein X is monovalent, and wherein the phenyl group or the 6-membered heteroaryl group may optionally be further substituted.

4. The compound or pharmaceutically acceptable salt or solvate of claim 1 , wherein: R 1 is a 6-membered heterocyclic group substituted with at least one group X, wherein R 1 may optionally be further substituted, and wherein optionally the 6-membered heterocyclic group contains at least one nitrogen atom in the heterocyclic ring.

5. The compound or pharmaceutically acceptable salt or solvate of claim 1 , wherein X— is:

wherein:
L is a bond or an alkylene, alkenylene or alkynylene group, wherein the alkylene, alkenylene or alkynylene group contains from 1 to 6 atoms in its backbone, wherein one or more carbon atoms in the backbone of the alkylene, alkenylene or alkynylene group may optionally be replaced by one or more heteroatoms N, O or S, and wherein the alkylene, alkenylene or alkynylene group may optionally be substituted;
R a and R b together with the atoms to which they are attached may form a cyclic group, or R a and R b are each independently selected from hydrogen or an alkyl, alkenyl, alkynyl, Z—, Z-alkylene-, Z-alkenylene- or Z-alkynylene-group, wherein one or more carbon atoms in the backbone of the alkyl, alkenyl, alkynyl, alkylene, alkenylene or alkynylene group may optionally be replaced by one or more heteroatoms N, O or S, wherein each Z— is a cyclic group; and
wherein any R a and R b may optionally be substituted.

6. The compound or pharmaceutically acceptable salt or solvate of claim 5 , wherein L is an alkylene, alkenylene or alkynylene group, wherein the alkylene, alkenylene or alkynylene group contains from 1 to 6 atoms in its backbone, wherein one or more carbon atoms in the backbone of the alkylene, alkenylene or alkynylene group may optionally be replaced by one or more heteroatoms N, O or S, and wherein the alkylene, alkenylene or alkynylene group may optionally be substituted.

7. The compound or pharmaceutically acceptable salt or solvate of claim 1 , which is (a) a compound selected from the group consisting of:

or (b) a pharmaceutically acceptable salt or solvate thereof.

8. A pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt or solvate of claim 1 , and a pharmaceutically acceptable excipient.

9. A prodrug of the compound as claimed in claim 1 , or a pharmaceutically acceptable salt or solvate thereof.

Assignees

• Univ Queensland
• Provost Fellows Found Scholars & Other Members Board College Holy & Und

Inventors

• O'Neill Luke
• Coll Rebecca
• Cooper Matthew
• Robertson Avril
• Schroder Kate
• Macleod Angus Murray
• Miller David John

Classifications

• C07D495/04 Primary

  Ortho-condensed systems · CPC title

• C07C311/60

  having nitrogen atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings · CPC title

• C07D207/38

  2-Pyrrolones · CPC title

• C07D217/24

  Oxygen atoms · CPC title

• C07D241/24

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title