Inflazome Limited

Takeda Pharmaceutical Company Limited

Paradigm Therapeutics Ltd

David Miller

Matthew Cooper

Jonathan Shannon

Angus Macleod

Stephen St-Gallay

Stephen Thom

Jimmy Van Wiltenburg

William John Farnaby

Natasha Kinsella

Kevin Merchant

Charlotte Fieldhouse

David Livermore

Katherine Hazel

Catrina Kerr

Ian Strutt

Jokin Carrillo Arregui

Stuart Thomas Onions

Thomas Alanine

Jochem Theodoor Van Herpt

Xiao-Ling Fan Cockcroft

Susana Del Rio Gancedo

Samuel Stratford

Louise Walsh

Parminder Kaur Ruprah

Graham Andrew Showell

Paul Leeson

Johannes Wilhem Georg Meissner

Zhou Min Lion

Xiao-Ling Cockcroft

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 provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein Rand Rare as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

Pyridazinone compounds and their use as DAAO inhibitors

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 compounds of formula (I): (I) wherein Q is selected from O or S; Ris an optionally substituted hydrocarbyl group which may optionally include one or more heteroatoms N, O or S in its carbon skeleton, provided that the hydrocarbyl group includes at least one heteroatom N, O or S in its carbon skeleton or is substituted with a substituent comprising at least one heteroatom N, O or S, and provided that the atom of Rwhich is attached to the sulfur atom of the remainder of the molecule is not a ring atom of a cyclic group; Ris an α,α'-substituted cyclic group which may optionally be further substituted; Rand Rare each independently hydrogen, halogen, —OH, —NH, —CN, —R, —OR, —NHRs or —N(R); or Rand Rtogether with the carbon atom to which they are attached may form a 3- to 7-membered saturated or unsaturated, optionally substituted cyclic group; and Ris independently optionally substituted C-Calkyl. 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 derivates as NLRP3 inhibitors

The present invention relates to compounds of formula (I) wherein Q is selected from O or S; Ris a saturated or unsaturated, optionally substituted hydrocarbyl group optionally including one or more heteroatoms N, O or S; Ris a cyclic group substituted at the a and a' positions, wherein the substituent at the α-position is a monovalent heterocyclic group or a monovalent aromatic group, wherein the heterocyclic or aromatic group may optionally be substituted, and wherein the cyclic group may optionally be further substituted; Rand Rare each independently hydrogen, halogen, —OH, —NH, —CN, —R, —OR, —NHRor —N(R); or Rand Rtogether with the carbon atom to which they are attached may form a 3- to 7-membered saturated or unsaturated, optionally substituted cyclic group; and Ris independently optionally substituted C-Calkyl. 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.

Sulfonyl acetamides as NLRP3 inhibitors

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 (1): wherein Q is selected from O or S; Ris a 5-membered nitrogen-containing heteroaryl group substituted with Rand optionally further substituted; Ris an alpha, alpha′-substituted cyclic group which may optionally be further substituted; Rand Rare each independently hydrogen, halogen, —OH, —NH, —CN, —R, —OR, —NHRor —N(R); or Rand Rtogether with the carbon atom to which they are attached may form a 3 to 7 membered saturated or unsaturated, optionally substituted cyclic group; Ris independently an optionally substituted C-Calkyl group; and Ris any group comprising 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): comprising a 5-membered nitrogen-containing heteroaryl ring A, wherein the heteroaryl ring A is substituted with at least one group containing an oxygen atom, and wherein said oxygen atom is attached to the heteroaryl ring A 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): 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 compounds of formula (I): wherein Q is selected from O or S; Ris a saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include cyclic groups, wherein the hydrocarbyl group may optionally be substituted, and wherein the hydrocarbyl group may optionally include one or more heteroatoms N, O or S in its carbon skeleton; and Ris a cyclic group substituted at the a-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 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.

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Cambridge, United Kingdom

David Miller