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AssigneeThirtyFiveBio Limited
InventorsChristopher Andrew LUCKHURST, Roger John BUTLIN, Monica Jade CLEMENTS, Timothy HUXFORD, Ageo MICCOLI, Gianna TOSCHI
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One aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, X is NH and Y is CO ring C is a 6-membered heteroaryl or aryl group, or a partially or fully unsaturated 6-membered heterocyclic group containing at least one N, and optionally comprising at least one CO group, and wherein said aryl, heteroaryl or heterocyclic group is optionally further substituted by one or more substituents selected from alkyl, haloalkyl, alkoxy, haloalkoxy, halo, cyano, NR9SO2R11, NR9COR12, NR13R14, OH, CO2R15, SO2NR16R17, CONR18R19, cycloalkyl and (CH2)q-heterocycloalkyl; ring A is a group: wherein A is phenyl group or a 6-membered heteroaryl group; or ring A is a group: wherein A is a 5-membered heteroaryl group; wherein in each case the wavy lines indicate the point of attachment to Y and ring C respectively; ring B is a phenyl group or a 6-membered heteroaryl group; R2 is (CR33R34)mCOOH; each R6 is independently selected from alkyl, halo, haloalkyl, alkoxy, haloalkoxy, cyano, NR10COR20, NR10SO2R21, (CH2)qSR22, (CH2)qSOR23, (CH2)qSO2R24, SO2NR25R26, (CH2)qOH, (CH2)qOR27, NR28R29, CONR30R31, cycloalkyl and (CH2)q-heterocycloalkyl; each R8 is independently selected from alkyl, halo, haloalkyl, alkoxy, haloalkoxy, cyano, NR10COR20, NR10SO2R21, (CH2)qSR22, (CH2)qSOR23, (CH2)qSO2R24, SO2NR25R26, (CH2)qOH, (CH2)qOR27, NR28R29, CONR30R31, cycloalkyl and (CH2)q-heterocycloalkyl; R7 is selected from H and alkyl; each R9 is independently selected from H and alkyl; each R10 is independently selected from H and alkyl; R11-R31 are each independently selected from H, alkyl, haloalkyl, aralkyl, alkoxy, alkoxyalkyl, hydroxyalkyl and cycloalkyl; m, n and p are each independently an integer from 0 to 4; each q is independently an integer from 0 to 4; L is a direct bond or is a group selected from, —SO2—, —O—SO2—, —SO2—O—, —O—, —NR32—SO2—, —NR32—SO2-alkylene, —SO2—NR32—, —SO2—NR32-alkylene, alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, alkylene-cycloalkylene, alkylene-SO2—, —SO2-alkylene, alkylene-SO—, —SO-alkylene, alkylene-SO2-alkylene, alkylene-SO-alkylene, cycloalkylene-alkylene, alkylene-heterocycloalkylene, heterocycloalkylene-alkylene, heteroalkylene-heterocycloalkylene, heterocycloalkylene-heteroalkylene, heteroalkylene-cycloalkylene, cycloalkylene-heteroalkylene, wherein the alkylene moiety in the above groups is optionally substituted by one or more substituents selected from halo, alkyl, haloalkyl and cycloalkyl; R32, R33 and R34 are each independently selected from H and alkyl; and Z is a group selected from alkyl, cycloalkyl, aryl, heteroaryl and heterocycloalkyl, each of which is optionally further substituted by one or more groups selected from CN, halo, alkyl, haloalkyl, alkenyl, alkynyl, alkoxy and haloalkoxy. Further aspects of the invention relate to pharmaceutical compositions comprising compounds of formula (I), and the use of said compounds in the treatment of various GPR35-related disorders.
A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof,
A compound according to any preceding claim wherein n is 0.
A compound according to any preceding claim wherein R2 is COOH.
A compound according to any preceding claim wherein B is a phenyl group, optionally substituted by one or two halo groups.
A compound according to any preceding claim wherein Z is a group selected from C1-6-alkyl, phenyl, C3-6-cycloalkyl and a 5- or 6-membered heterocycloalkyl group, each of which is optionally further substituted by one or more groups selected from alkyl, halo, haloalkyl, CN, alkenyl, alkynyl and alkoxy.
A compound according to any preceding claim wherein Z is a group selected from phenyl, pyridinyl, piperidinyl, cyclopropyl and tetrahydropyranyl, more preferably phenyl, each of which is optionally further substituted by one or more groups selected from alkyl, halo, haloalkyl, CN, alkenyl, alkynyl and alkoxy.
A compound according to any preceding claim L is selected from —O—, —NH—SO2—, —NH—SO2—(CR′R″)a—, —(CR′R″)a—SO2—NH—, —SO2—NH—, —SO2—NH—(CR′R″)a—, —(CR′R″)a—NH—SO2—, —O—SO2—, —SO2—O—, —(CR′R″)a—, —(CR′R″)a—O—, O—(CR′R″)a—, —(CR′R″)a—O—(CR′R″)b—, —(CR′R″)a—S—(CR′R″)b—, —(CR′R″)a—SO—(CR′R″)b—, —(CR′R″)a—SO2—, —SO2—(CR′R″)a—, —(CR′R″)a—SO—, —SO—(CR′R″)a—, —(CR′R″)a—SO2—(CR′R″)b—, —(CR′R″)a—S—(CR′R″)b—O—, —O—(CR′R″)a—S—(CR′R″)b—, —(CR′R″)a—O—(CR′R″)b—S—, —S—(CR′R″)a—O—(CR′R″)b—, heterocycloalkylene-(CR′R″)a—O—, —O—(CR′R″)a-heterocycloalkylene-, —(CR′R″)a—O-heterocycloalkylene, heterocycloalkylene-O—(CR′R″)a—, —O-heterocycloalkylene-(CR′R″)a— and —(CR′R″)a-heterocycloalkylene-O—, wherein a and b are each independently an integer from 1 to 6, and each R′ and each R″ is independently selected from H and alkyl, more preferably where R′ and R″ are both H.
A compound according to any preceding claim wherein L is selected from —CH2—, —CH2CH2CH2—, —CH2CH2—, —CH2O—, —OCH2—, —CH(Me)OCH2, —CH2OCH(Me)-, —CH(CF3)OCH2, —CH2OCH(CF3)—, —CH2CH2O—, —OCH2CH2—, —CH2CH2CH2O—, —OCH2CH2CH2—, —CH2SO2CH2—, —CH2SOCH2—, —CH2SCH2—, —NH—SO2—, —NH—SO2—CH2—, —CH2—SO2—NH—, —SO2—NH—, —SO2—NH—CH2—, —CH2—NH—SO2—, —CH2CH2CH2CH2O—, —OCH2CH2CH2CH2—, —CH2SO2—, —SO2CH2—, —CH2SO—, —SOCH2—, —CH2OCH2, —CH(Me)O—, —OCH(Me)-, —CH(CF3)O—, —OCH(CF3)—, —CH2SCH2O— and —OCH2SCH2—.
A compound according to any preceding claim wherein L-Z is —OCH2CH2Ph, —OCH2Ph, —OCH2CH2CH(Me)2, —OCH2CH(Me)2, —OSO2-(4-methylphenyl), —CH2SO2CH2-Ph, —CH2SO2-Ph, —OCH2-cyclopropyl, —OCH2CH2CH2CH3, —OCH2CH2CH2CH2Ph, —CH2OCH2Ph, —OCH2SCH2Ph, —CH2OCH2Ph, —CH2CH2Ph, —CH2SO2-(4-methylphenyl), —CH2SO2-(4-methoxyphenyl), —CH2SO2-(4-chlorophenyl), —CH2SO2-(3-chlorophenyl), —CH2SO2-(2-chlorophenyl), —CH2OCH(Me)-Ph, —CH2OCH(CF3)-Ph, —CH2OCH2-cyclopropyl, —CH2O-cyclopropyl, —OCH(Me)-cyclopropyl, —CH(Me)O-cyclopropyl, —OCH(CF3)-cyclopropyl, —CH(CF3)O-cyclopropyl, CH2OCH2-(pyridin-2-yl), —CH2OCH2(4-methoxyphenyl), CH2OCH2(3-methoxyphenyl), —CH2SO2-(4-methylpyridin-3-yl)-chlorophenyl),
A compound according to any preceding claim wherein L-Z is —OCH2CH2Ph, —OCH2CH2CH2CH2Ph or —CH2OCH2Ph, more preferably —OCH2CH2Ph.
A compound which is selected from the following:
Dependencies are inferred from the claim text.