Inflazome Limited

Otsuka Pharmaceutical Company, Limited

Cellcentric Limited

Jonathan Shannon

David Miller

Matthew Cooper

Angus Macleod

Stephen St-Gallay

Stephen Thom

Jimmy Van Wiltenburg

Stuart Thomas Onions

Christopher William Murray

Valerio Berdini

Steven Howard

Ildiko Maria Buck

Alison Jo-Anne Woolford

Charlotte Mary Griffiths-Jones

Thomas Daniel Heightman

David Norton

James Edward Harvey Day

David Michel Adrien Taddei

David Cousin

John Paul Watts

Gareth Harbottle

Silvia Paoletta

Michael Liam Cooke

Neil Anthony Pegg

Marc O'Reilly

Ian Strutt

Jokin Carrillo Arregui

Richard James Brown

Jochem Theodoor Van Herpt

Thomas Alanine

Don Smyth

Johannes Wilhem Georg Meissner

Zhou Min Lion

Ting Qin

Paul Leeson

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 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 invention provides a compound of formula (0): The compounds are inhibitors of ERK1/2 kinases and will be useful in the treatment of ERK1/2-mediated conditions. The compounds are therefore useful in therapy, in particular in the treatment of cancer.

Benzolactam compounds as protein kinase inhibitors

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 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.

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.

Growing community of inventors

Nottingham, United Kingdom

Jonathan Shannon