Inflazome Limited

Shire LLC

Angus Macleod

David Miller

Jonathan Shannon

Stephen Thom

Stephen St-Gallay

Ian Strutt

Stuart Thomas Onions

Bernard Thomas Golding

Matthew Cooper

Jimmy Van Wiltenburg

Jokin Carrillo Arregui

Thomas Alanine

Susana Del Rio Gancedo

Samuel Stratford

Richard Franklin

Jochem Theodoor Van Herpt

Peter Cicala

The present invention relates to sulfonylureas and sulfonylthioureas comprising a 5-membered heteroaryl group substituted with a monovalent heteroaryl-containing group. 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 inhibition of NLRP.

Sulfonamide carboxamide compounds

The present invention relates to compounds of formula (I): wherein Q is selected from O or S; Rand Rare each independently hydrogen or an optionally substituted hydrocarbyl group, or Rand Rtogether with the nitrogen atom to which they are attached may form a 3- to 12-membered optionally substituted cyclic group; and Ris a cyclic group substituted at the position, wherein Rmay 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 inhibition of NLRP3.

Sulfonamideurea compounds

The present invention relates to sulfonylureas and sulfonylthioureas comprising as-membered nitrogen-containing heteroaryl ring attached to the sulfonyl group, wherein the heteroaryl ring is substituted with at least one group containing an oxygen atom, and wherein said oxygen atom is attached to the heteroaryl ring via at least two other atoms. 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 inhibition of NLRP3.

The present invention relates to compounds of formula (I) wherein Q is selected from O or S; Ris a non-aromatic heterocyclic group comprising at least one ring nitrogen atom, wherein Ris attached to the sulfur atom of the sulfonylurea group by a ring carbon atom, and wherein Rmay optionally be substituted; and Ris a cyclic group substituted at the α-position, wherein Rmay 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 inhibition of NLRP.

The present invention relates to sulfonylureas and sulfonylthioureas comprising a monocyclic imidazolyl group of formula (I):

Sulfonylureas and sulfonylthioureas as NLRP3 inhibitors

The present invention relates to sulfonylureas and sulfonylthioureas of formula (I) comprising a 5-membered heteroaryl ring attached to the sulfonyl group, wherein the heteroaryl ring is di-substituted at the 3- and 4-positions relative to the point of attachment of the sulfonyl group, and wherein the group attached to the terminal nitrogen atom of the urea group is either a 1,2,3,5,6,7-hexahydro-s-indacen-4-yl group substituted at the 8-position, or a heteroaryl group substituted at the alpha and alpha′ positions. 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 NLRP3 inhibition.

Compounds

The present invention relates to compounds of formula (I): Formula (I) wherein Q is selected from O or S; L is a saturated or unsaturated, optionally substituted C-Chydrocarbylene group optionally including one or more heteroatoms N, O or S; Ris &#x2014;NRR, &#x2014;OR, &#x2014;(C&#x2550;NR)R, &#x2014;(CO)R, &#x2014;CN, &#x2014;N, a quaternary ammonium group or an optionally substituted heterocycle; R, R, R, R, Rand Rare each independently hydrogen or a saturated or unsaturated, optionally substituted C-Chydrocarbyl group optionally including one or more heteroatoms N, O or S; wherein optionally L and R, or L and R, or Rand R, or L and R, or L and R, or L and R, or Rand R, or L and Rtogether with the atom(s) to which they are attached may form a 3- to 12-membered, saturated or unsaturated, optionally substituted cyclic group; and Ris a cyclic group substituted at the a-position, wherein Rmay optionally be further substituted; provided that the atom of L which is attached to the sulfur atom of the sulfonylurea group is a carbon atom and is not a ring atom of a heterocyclic or aromatic group. 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 inhibition of NLRP.

The present invention relates to sulfonylureas and sulfonylthioureas comprising a 5-membered nitrogen-containing heteroaryl ring attached to the sulfonyl group, wherein the heteroaryl ring is substituted with a nitrogen-containing group R' wherein Rcontains from 1 to 7 atoms other than hydrogen or halogen. 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 inhibition of NLRP.

Sulfonylureas and sulfonylthioureas as NLRPinhibitors

The present invention relates to sulfonylureas and sulfonylthioureas comprising a 5-membered heteroaryl ring attached to the sulfonyl group, wherein the heteroaryl ring is di-substituted at the 3- and 4-positions relative to the point of attachment of the sulfonyl group, wherein at least one of the di-substituents contains a nitrogen atom. 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 inhibition of NLRP.

The present invention relates to compounds of formula (I): wherein Q is selected from O or S; Ris a saturated or unsaturated, optionally substituted C-Chydrocarbyl group, wherein the atom of Rwhich is attached to the sulfur atom of the sulfonylurea group is not a ring atom of a cyclic group; and Ris a cyclic group substituted at the &#x3b1;-position, wherein Rmay 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 inhibition of NLRP. 

The present invention relates to compounds of formula (I): wherein Q is selected from O or S; Ris a non-aromatic heterocyclic group comprising at least one ring nitrogen atom, wherein Ris attached to the sulfur atom of the sulfonylurea group by a ring carbon atom, and wherein Rmay optionally be substituted; and Ris a cyclic group substituted at the &#x3b1;-position, wherein Rmay 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 inhibition of NLRP3.

The present invention relates to compounds of formula (I): wherein Q is O or S, Ris a 6-membered heteroaryl group containing at least one nitrogen atom in the 6-membered ring structure, wherein Rmay optionally be substituted, and Ris a cyclic group substituted at the &#x3b1;-position, wherein Rmay 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 inhibition of NLRP3.

The present invention relates to a sodium salt of N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide and to hydrates, solvates and polymorphic forms thereof. The present invention further relates to pharmaceutical compositions comprising this compound and the use of this compound in the treatment and prevention of medical disorders and diseases, most especially by NLRP3 inhibition.

Growing community of inventors

Cambridge, United Kingdom

Angus Macleod