Perforin inhibiting benzenesulfonamide compounds, preparation and uses thereof

• Main Authors: Huttunen Kristiina, Denny William Alexander, Spicer Julie Ann, Miller Christian Karl, Trapani Joseph A, Alexander Kylie, Hill Geoff, O'connor Patrick David
• Format: Patent
• Language: English
• Published: 23.02.2018
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The present invention relates to compounds capable of modulating perforin activity, to their preparation, and to their use as tools for biological studies or as agents or drugs for immunosuppressive therapies. More specifically, the present invention relates to benzenesulfonamides and related compounds of formula (Ia) wherein Ring A is selected from optionally substituted phenylene, pyridinylene or thiophenylene; Ring B is selected from optionally substituted phenylene or pyridinylene; Ring C is selected from thiophenylene, pyridinylene or thiazolylene; Ring D is a benzofused 9 11 membered heterocyclyl or benzofused 9 11 membered heteroaryl; L is a linker selected from branched and unbranched C1-C4 alkylene, -S(O)2-NH-, C(O) NH-, -NH-C(O)-NH-, -S(O)2-NH-C(O)-NH-, -S(O)2-NH-C(O)- and -CH=CH-; wherein Rings B and C, and Rings C and D, are connected to each other via a C-C bond at any of the available C atoms on each respective ring and pharmaceutically acceptable salts, solvates, and hydrates thereof.