Inflazome Limited

The University of Queensland

The Provost, Fellows, Foundation Scholars, and the Other Members of Board, of the College of the Holy and Undivided Trinity of Queen Elizabeth Near Dublin

University of California

The University of Texas System

University of Sheffield

Cambridge University Technical Services Limited

Inverness Medical Switzerland Gmbh

Alere Switzerland Gmbh

Adprotech Limited

Matthew Cooper

David Miller

Jonathan Shannon

Angus Macleod

Stephen St-Gallay

Jimmy Van Wiltenburg

Stephen Thom

Luke O'Neill

Kate Schroder

Rebecca Coll

Avril Robertson

Ian Strutt

Jokin Carrillo Arregui

Stuart Thomas Onions

Johannes Zuegg

Robert John Capon

Thomas Alanine

Jochem Theodoor Van Herpt

Jeroen Overman

Sreeman Kumar Mamidyala

Mark Blaskovich

Angela Aguslyarti Salim

Frank Roger Fontaine

Avril Alexis Barbara Robertson

David John Miller

Angus Murray MacLeod

Mathias Francois

Jason Richard Betley

David Klenerman

Victor Petrovich Ostanin

Richard John Hammond

Christodoulos A Floudas

Craig Muldoon

Bernd Becker

Fedor Nikolaievich Dultsev

Trent Martin Woodruff

Karl Hansford

Alexander Sleptsov

Alejandra Gallardo-Godoy

Dimitrios Monikis

Daniel E Croker

Peter N Monk

Johannes Wilhem Georg Meissner

Alysha Elliott

Zhou Min Lion

Disclosed are compounds of a formula provided herein that show efficacy in the inhibition of SOX18 protein activity, and in particular with respect to the ability of SOX18 to bind DNA and/or particular protein partners. Further, methods of treating angiogenesis- and/or lymphangiogenesis-related diseases, disorders or conditions, such as cancer metastasis and vascular cancers, are provided herein.

Compounds and use thereof in methods of treatment

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 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), and pharmaceutically acceptable salts, solvates and prodrugs thereof: wherein Q is selected from O, S and Se; J is S or Se; Wand W, when present, are independently selected from N and C; Rand Rare independently selected from the group consisting of hydrogen, C-Calkyl, C-Calkenyl, C-Calkynyl, aryl, heterocyclyl, heteroaryl, cycloalkyl, cycloalkenyl, amino, amido, alkylthio, acyl, arylalkyl and acylamido, all of which may be optionally substituted; and wherein at least one of Wand Wis present and is a nitrogen atom and when Ror Rare cyclic then the respective Wor Wmay form part of the ring structure. The present invention also relates to pharmaceutical compositions including such compounds, to methods of treatment using such compounds, in particular in relation to NLRP3 inflammasome mediated disorders, and to associated diagnostic uses.

Sulfonylureas and related compounds and use of same

The present invention relates to compounds of formula (I): wherein Q is O or S; Ris a cyclic group substituted with at least one group X, wherein Rmay optionally be further substituted; X is any group comprising a carbonyl 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 dual action of NLRPinhibition and the stimulation of insulin secretion.

Compounds and uses

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 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.

Growing community of inventors

Cambridge, United Kingdom

Matthew Cooper