TRICYCLIC GPR65 MODULATORS

• Main Authors: ESVAN, YANNICK, MOCHEL, TOBIAS, IEVA, MARIA, MILLER, DAVID, MILNE, GAVIN, MCCARTHY, TOM, NAYLOR, ALAN, FEUTRILL, JOHN
• Format: Patent
• Language: English; French
• Published: 27.04.2023
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

One aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, (I) wherein: ring B is: a monocyclic aromatic group; or a monocyclic or bicyclic heteroaromatic group, each of which is optionally substituted by halo, CN, OH, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, hydroxycycloalkyl, O-cycloalkyl, alkoxy, haloalkoxy, heterocycloalkyl, O- heterocycloalkyl, aryl, heteroaryl, O-aryl, NHCO-alkenyl, NHCO-aryl, -(CH2)q-O-heteroaryl, CONH-aryl, aryloxy-alkyl, O-aralkyl, and CO2-alkyl, wherein said aryl, heteroaryl, heterocycloalkyl, O-cycloalkyl, NHCO-aryl, -(CH2)q-O-heteroaryl, CONH-aryl, aryloxy-alkyl, O-aralkyl, and O-aryl groups are each optionally further substituted by one or more groups independently selected from halo, alkyl, haloalkyl, alkoxy, NHCO-alkyl, NR13R13', SO2-alkyl, CN, hydroxyalkyl, CONR14R14', alkyl-NR15R15', heterocycloalkyl, alkyl-heterocycloalkyl, alkyl- cycloalkyl, aryl, (CH2)m-NHSO2-alkyl, CO2R16, alkoxy-alkyl, haloalkoxy, O-heterocycloalkyl, heteroaryl, alkoxy-alkoxy, and O-(CH2)p-cycloalkyl, where in the latter group, said cycloalkyl group is optionally further substituted by one or more halo, haloalkyl, alkyl or alkoxy groups; m is an integer from 0 to 3; p and q are each independently 0 to 3; Z is CR12; Y is CR10 R10', wherein R10 and R10' are each independently selected from H, F, alkyl, and haloalkyl; Ra and Rb are each independently selected from H and alkyl; R6 is selected from H, alkyl, cycloalkyl and hydroxyalkyl; R12 is selected from H, alkyl, haloalkyl, halo, OH and O-alkyl; and R13, R13', R14, R14', R15, R15', and R16 are each independently selected from H, alkyl, and alkoxyalkyl. Further aspects of the invention relate to compounds of formula (I) for use as a medicament, particularly in the field of immuno-oncology, immunology, and related applications. Un aspect de l'invention concerne un composé de formule (I), ou un sel ou un solvant pharmaceutiquement acceptable de celui-ci, (I) : le cycle B représentant un groupe aromatique monocyclique ou un groupe hétéroaromatique monocyclique ou bicyclique, chacun étant éventuellement substitué par des groupes halogéno, CN, hydroxyle, alkyle, haloalkyle, cycloalkyle, halocycloalkyle, hydroxycycloalkyle, O-cycloalkyle, alcoxy, haloalkoxy, hétérocycloalkyle, O-hétérocycloalkyle, aryle, hétéroaryle, O-aryle, NHCO-alkényle, NHCO-aryle, -(CH2)q-O-hétéroaryle, CONH-aryl, aryloxy-alkyle, O-aralkyle et CO2-alkyle, lesdits groupes aryle, hétéroaryle, hétérocycloalkyle, O-cycloalkyle, NHCO-aryl, -(CH2)q-O-hétéroaryle, CONH-aryl, aryloxy-alkyle, O-aralkyle et O-aryle étant chacun éventuellement substitués par un ou plusieurs groupes choisis indépendamment parmi les groupes halothane, alkyle, haloalkyle, alcoxy, NHCO-alkyle, NR13R13?, SO2-alkyle, CN, hydroxyalkyle, CONR14R14?, alkyle-NR15R15?, hétérocycloalkyle, alkyle-hétérocycloalkyle, alkyle-cycloalkyle, aryle, (CH2)m-NHSO2-alkyle, CO2R16, alcoxyalkyle, haloalkoxy, O-hétérocycloalkyle, hétéroaryle, alcoxy et O-(CH2)p-cycloalkyle, ce dernier groupe étant éventuellement substitué par un ou plusieurs groupes halo, haloalkyle, alkyle ou alcoxy ; m représentant un nombre entier compris entre 0 et 3 ; p et q représentant chacun indépendamment compris entre 0 et 3 ; Z représentant CR12 ; Y représentant CR10 R10?, R10 et R10? étant chacun indépendamment choisi parmi les éléments H, F, alkyle et haloalkyle ; Ra et Rb étant chacun indépendamment choisi parmi les éléments H et alkyle ; R6 étant choisi parmi les éléments H, alkyle, cycloalkyle et hydroxyalkyle ; R12 étant choisi parmi les éléments H, alkyle, haloalkyle, halogéno, hydroxyle et O-alkyle ; et R13, R13?, R14, R14?, R15, R15? et R16 étant chacun choisi indépendamment parmi les éléments H, alkyle et alcoxyalkyle. D'autres aspects de l'invention concernent des composés de formule (I) destinés à être utilisés comme médicaments, en particulier dans le domaine de l'immuno-oncologie, de l'immunologie et des applications connexes.