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EP-4739667-A2 - INDOLE DERIVATIVES WITH FACTOR B INHIBITORY ACTIVITY

EP4739667A2EP 4739667 A2EP4739667 A2EP 4739667A2EP-4739667-A2

Abstract

The present invention relates to active esters of Factor B inhibitors, and to associated salts, solvates, prodrugs and pharmaceutical compositions. The present invention further relates to methods of synthesising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by Factor B inhibition.

Inventors

  • CHRISTOPHER, JOHN ANDREW
  • WYATT, PAUL GRAHAM
  • HORNSBY, Thomas William
  • COOPER, MARTIN EDWARD
  • Mills, Mark

Assignees

  • Sitala Bio Ltd

Dates

Publication Date
20260513
Application Date
20240705

Claims (20)

  1. Claims 1. A compound of Formula (I): o u a ( ) or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof; wherein: R 1 is hydrogen; R 2 is selected from hydrogen or a halo group; R 3 is selected from hydrogen or a halo, -SO2NH2, or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight- chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety; R 4 is selected from hydrogen or a halo, -OH, -NH2, -SO2NH2, or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety; R 5 is selected from hydrogen or a halo group; R 6 is selected from hydrogen or a halo, -R 60 or -OR 60 group, wherein R 60 is selected from a C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C 1 -C 4 fluoroalkyl or C 3 -C 4 fluorocycloalkyl group; R 7 and R 8 are each independently selected from hydrogen or a fluoro or a C1-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 7 or R 8 that is directly attached to the reminder of the molecule is a carbon atom; or R 7 and R 8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R 7 and R 8 are attached is a ring carbon atom, wherein the cyclic group may optionally by substituted with one or more substituents each independently selected from a halo, oxo (=O), -OH, -NH 2 or a C 1 -C 4 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton; ring A is a phenyl or a 5- or 6-membered heteroaryl ring; R 9 is an aryl or a heteroaryl group, wherein the aryl or the heteroaryl group is a monocylic group or a fused bicyclic or fused tricyclic group, and wherein the aryl or the heteroaryl group may optionally be substituted with one or more substituents each independently selected from a halo, -OH, -NH2, -NO2, -SH, -SO2H, -SO3H, -SO2NH2, -R 90 or -SO 2 R 90 group, wherein each R 90 is independently selected from a C 1 -C 4 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton; p is 0, 1, 2, 3 or 4; each R 10 is independently selected from a halo, -OH, -NH2 or a C1-C4 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight- chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton; or any two adjacent R 10 may together form a C1-C6 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight-chained or branched, or be or include a cyclic group, wherein the hydrocarbylene group may optionally be substituted with one or more groups R 101 , wherein each R 101 is independently selected from a halo group, and wherein the hydrocarbylene group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton; X 12 is NR 121 or C(R 122 )(R 123 ); m is 0, 1 or 2, and n is 0, 1 or 2, provided that (i) m + n < 4, and (ii) when X 12 is NR 121 , m is 1 or 2 and n is 1 or 2; q is 0, 1, 2, 3, 4, 5, 6, 7 or 8; R 11 is selected from hydrogen or a fluoro or a C 1 -C 8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 11 that is directly attached to the reminder of the molecule is a carbon atom; R 121 is selected from hydrogen or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 121 that is directly attached to the reminder of the molecule is a carbon atom; R 122 is selected from hydrogen or a fluoro, -OH, -NH2, -SH, -SO2H, -SO3H, -SO 2 NH 2 , or a C 1 -C 8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; R 123 is selected from hydrogen or a fluoro or a C 1 -C 8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 123 that is directly attached to the reminder of the molecule is a carbon atom; each R 13 is independently selected from selected from a fluoro, -OH, -NH2, -SH, -SO 2 H, -SO 3 H, -SO 2 NH 2 , or a C 1 -C 8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that when R 13 is directly attached to a carbon atom which in turn is directly attached to an oxygen, nitrogen or sulphur atom, the atom of R 13 that is directly attached to the remainder of the molecule is a fluorine or carbon atom; or R 11 and R 121 , or R 11 and R 122 , or R 11 and R 123 , or R 11 and any R 13 , or R 121 and any R 13 , or R 122 and R 123 , or R 122 and any R 13 , or R 123 and any R 13 , or any two R 13 may together form a C 1 -C 8 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbylene group may optionally be substituted with one or more halo groups, wherein the hydrocarbylene group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; or R 3 and R 7 , or R 4 and R 7 , or R 4 and any R 10 , or R 4 and any R 101 , or R 4 and R 11 , or R 4 and R 121 , or R 4 and R 122 , or R 4 and R 123 , or R 4 and any R 13 , or R 7 and any R 10 , or R 7 and any R 101 , or R 7 and R 11 , or R 7 and R 121 , or R 7 and R 122 , or R 7 and R 123 , or R 7 and any R 13 , or any R 10 and R 11 , or any R 10 and R 121 , or any R 10 and R 122 , or any R 10 and R 123 , or any R 10 and any R 13 , or any R 101 and R 11 , or any R 101 and R 121 , or any R 101 and R 122 , or any R 101 and R 123 , or any R 101 and any R 13 , may together form a C1-C12 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight- chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbylene group may optionally be substituted with one or more halo groups, wherein the hydrocarbylene group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety.
  2. 2. A compound as claimed in claim 1, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein the compound has the Formula (Ia): wherein: X A1 is N, C-H or C-R 10 ; X A2 is N, C-H or C-R 10 ; X A3 is N, C-H or C-R 10 ; and X A1 is N, C-H or C-R 10 ; provided that no more than three of X A1 , X A2 , X A3 and X A4 are N; and R 1 to R 11 , X 12 , R 13 , m, n and q are as defined in accordance with claim 1.
  3. 3. A compound as claimed in claim 1 or claim 2, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein R 2 is selected from hydrogen or a fluoro, chloro or bromo group.
  4. 4. A compound as claimed in any one of claims 1 to 3, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein R 3 is selected from hydrogen or a fluoro, chloro, bromo, -R 30 , -CN, -CHO, -COR 30 , -CO2H or -CO2R 30 group, wherein R 30 is selected from a C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, C 2 -C 6 alkenyl, C 2 -C 6 fluoroalkenyl or -R 31 group, wherein R 31 is a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups R 32 , wherein each R 32 is independently selected from a methyl or a fluoromethyl group, provided that the group R 3 , including any optional substituents, contains no more than 8 carbon atoms.
  5. 5. A compound of Formula (II): Formula (II) or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof; wherein: R 1 is hydrogen; R 4 is selected from hydrogen or a halo, -OH, -NH2, -SO2NH2, or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; R 5 is selected from hydrogen or a halo group; R 6 is selected from hydrogen or a halo, -R 60 or -OR 60 group, wherein R 60 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; R 7 and R 8 are each independently selected from hydrogen or a fluoro or a C 1 -C 12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 7 or R 8 that is directly attached to the reminder of the molecule is a carbon atom; or R 7 and R 8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R 7 and R 8 are attached is a ring carbon atom, wherein the cyclic group may optionally by substituted with one or more substituents each independently selected from a halo, oxo (=O), -OH, -NH2 or a C1-C4 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton; ring A is a phenyl or a 5- or 6-membered heteroaryl ring; R 9 is an aryl or a heteroaryl group, wherein the aryl or the heteroaryl group is a monocylic group or a fused bicyclic or fused tricyclic group, and wherein the aryl or the heteroaryl group may optionally be substituted with one or more substituents each independently selected from a halo, -OH, -NH2, -NO2 -SH, -SO2H, -SO3H, -SO2NH2, -R 90 or -SO2R 90 group, wherein each R 90 is independently selected from a C1-C4 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton; p is 0, 1, 2, 3 or 4; each R 10 is independently selected from a halo, -OH, -NH2 or a C1-C4 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight- chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton; or any two adjacent R 10 may together form a C 1 -C 6 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight-chained or branched, or be or include a cyclic group, wherein the hydrocarbylene group may optionally be substituted with one or more groups R 101 , wherein each R 101 is independently selected from a halo group, and wherein the hydrocarbylene group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton; X 12 is NR 121 or C(R 122 )(R 123 ); m is 0, 1 or 2, and n is 0, 1 or 2, provided that (i) m + n < 4, and (ii) when X 12 is NR 121 , m is 1 or 2 and n is 1 or 2; q is 0, 1, 2, 3, 4, 5, 6, 7 or 8; R 11 is selected from hydrogen or a fluoro or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 11 that is directly attached to the reminder of the molecule is a carbon atom; R 121 is selected from hydrogen or a C 1 -C 8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 121 that is directly attached to the reminder of the molecule is a carbon atom; R 122 is selected from hydrogen or a fluoro, -OH, -NH2, -SH, -SO2H, -SO3H, -SO2NH2, or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety; R 123 is selected from hydrogen or a fluoro or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 123 that is directly attached to the reminder of the molecule is a carbon atom; each R 13 is independently selected from selected from a fluoro, -OH, -NH 2 , -SH, -SO2H, -SO3H, -SO2NH2, or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, and wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety, provided that when R 13 is directly attached to a carbon atom which in turn is directly attached to an oxygen, nitrogen or sulphur atom, the atom of R 13 that is directly attached to the remainder of the molecule is a fluorine or carbon atom; or R 11 and R 121 , or R 11 and R 122 , or R 11 and R 123 , or R 11 and any R 13 , or R 121 and any R 13 , or R 122 and R 123 , or R 122 and any R 13 , or R 123 and any R 13 , or any two R 13 may together form a C1-C8 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbylene group may optionally be substituted with one or more halo groups, wherein the hydrocarbylene group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety; each R 14 and R 15 is independently selected from hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C 1 -C 4 fluoroalkyl or C 3 -C 4 fluorocycloalkyl group, or R 14 and R 15 together with the carbon atom to which they are attached form a 3- to 6-membered cyclic group, wherein the cyclic group may optionally by substituted with one or more substituents each independently selected from a fluoro, -OH, oxo (=O), methyl or ethyl group, wherein any methyl or ethyl group may optionally be fluoro substituted; R 16 is selected from hydrogen or a fluoro, -SO 2 NH 2 , or a C 1 -C 8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight- chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; R 17 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; or R 16 and R 17 together with the carbon atom to which they are attached form a 3- to 6-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a fluoro, -OH, oxo (=O), methyl or ethyl group, wherein any methyl or ethyl group may optionally be fluoro substituted; or R 17 and R 7 , or R 4 and R 7 , or R 4 and any R 10 , or R 4 and any R 101 , or R 4 and R 11 , or R 4 and R 121 , or R 4 and R 122 , or R 4 and R 123 , or R 4 and any R 13 , or R 7 and any R 10 , or R 7 and any R 101 , or R 7 and R 11 , or R 7 and R 121 , or R 7 and R 122 , or R 7 and R 123 , or R 7 and any R 13 , or any R 10 and R 11 , or any R 10 and R 121 , or any R 10 and R 122 , or any R 10 and R 123 , or any R 10 and any R 13 , or any R 101 and R 11 , or any R 101 and R 121 , or any R 101 and R 122 , or any R 101 and R 123 , or any R 101 and any R 13 , may together form a C1-C12 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight- chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbylene group may optionally be substituted with one or more halo groups, wherein the hydrocarbylene group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety.
  6. 6. A compound as claimed in claim 5, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein the compound has the Formula (IIa): wherein: X A1 is N, C-H or C-R 10 ; X A2 is N, C-H or C-R 10 ; X A3 is N, C-H or C-R 10 ; and X A4 is N, C-H or C-R 10 ; provided that no more than three of X A1 , X A2 , X A3 and X A4 are N; and R 1 , R 4 to R 11 , X 12 , R 13 to R 17 , m, n and q are as defined in accordance with claim 5.
  7. 7. A compound as claimed in claim 5 or claim 6, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein each R 14 and R 15 is independently selected from hydrogen or a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group, or R 14 and R 15 together with the carbon atom to which they are attached form a cyclopropyl or a cyclobutyl group, wherein the cyclopropyl or cyclobutyl group may optionally be substituted with one or more fluoro groups.
  8. 8. A compound as claimed in any one of claims 5 to 7, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: R 16 is selected from hydrogen or a fluoro, -R 160 , -CN, -CHO, -COR 160 , -CO2H or -CO2R 160 group, provided that R 16 , including any optional substituents, contains no more than 8 carbon atoms; R 160 is selected from a C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, C 2 -C 6 alkenyl, C 2 -C 6 fluoroalkenyl or -R 161 group; R 161 is a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups R 162 ; each R 162 is independently selected from a methyl or a fluoromethyl group; and R 17 is selected from hydrogen or a fluoro, C 1 -C 3 alkyl, cyclopropyl, C 1 -C 3 fluoroalkyl or fluorocyclopropyl group; or R 16 and R 17 together with the carbon atom to which they are attached form a 3- to 5-membered saturated monocyclic group, wherein the saturated monocyclic group may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from oxo (=O) or a methyl or fluoromethyl group.
  9. 9. A compound as claimed in any one of claims 1 to 8, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: R 9 is a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more substituents each independently selected from fluoro, chloro and bromo, and/or with one or two substituents each independently selected from a -OH, -NH2, -NO2, -SH, -SO2H, -SO3H, -SO2NH2, -R 90 or -SO2R 90 group; and each R 90 is independently selected from a C 1 -C 3 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and/or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton.
  10. 10. A compound of Formula (III): Formula (III) or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof; wherein: R 1 is hydrogen; R 2 is selected from hydrogen or a halo group; R 3 is selected from hydrogen or a halo, -SO2NH2, or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight- chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; R 4 is selected from hydrogen or a halo, -OH, -NH 2 , -SO 2 NH 2 , or a C 1 -C 8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; R 5 is selected from hydrogen or a halo group; R 6 is selected from hydrogen or a halo, -R 60 or -OR 60 group, wherein R 60 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; R 7 and R 8 are each independently selected from hydrogen or a fluoro or a C1-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 7 or R 8 that is directly attached to the reminder of the molecule is a carbon atom; or R 7 and R 8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R 7 and R 8 are attached is a ring carbon atom, wherein the cyclic group may optionally by substituted with one or more substituents each independently selected from a halo, oxo (=O), -OH, -NH2 or a C1-C4 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton; ring A is a phenyl or a 5- or 6-membered heteroaryl ring; p is 0, 1, 2, 3 or 4; each R 10 is independently selected from a halo, -OH, -NH2 or a C1-C4 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight- chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton; or any two adjacent R 10 may together form a C 1 -C 6 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight-chained or branched, or be or include a cyclic group, wherein the hydrocarbylene group may optionally be substituted with one or more groups R 101 , wherein each R 101 is independently selected from a halo group, and wherein the hydrocarbylene group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton; X 12 is NR 121 or C(R 122 )(R 123 ); m is 0, 1 or 2, and n is 0, 1 or 2, provided that (i) m + n < 4, and (ii) when X 12 is NR 121 , m is 1 or 2 and n is 1 or 2; q is 0, 1, 2, 3, 4, 5, 6, 7 or 8; R 11 is selected from hydrogen or a fluoro or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 11 that is directly attached to the reminder of the molecule is a carbon atom; R 121 is selected from hydrogen or a C 1 -C 8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 121 that is directly attached to the reminder of the molecule is a carbon atom; R 122 is selected from hydrogen or a fluoro, -OH, -NH2, -SH, -SO2H, -SO3H, -SO2NH2, or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety; R 123 is selected from hydrogen or a fluoro or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 123 that is directly attached to the reminder of the molecule is a carbon atom; each R 13 is independently selected from selected from a fluoro, -OH, -NH 2 , -SH, -SO2H, -SO3H, -SO2NH2, or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety, provided that when R 13 is directly attached to a carbon atom which in turn is directly attached to an oxygen, nitrogen or sulphur atom, the atom of R 13 that is directly attached to the remainder of the molecule is a fluorine or carbon atom; or R 11 and R 121 , or R 11 and R 122 , or R 11 and R 123 , or R 11 and any R 13 , or R 121 and any R 13 , or R 122 and R 123 , or R 122 and any R 13 , or R 123 and any R 13 , or any two R 13 may together form a C1-C8 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbylene group may optionally be substituted with one or more halo groups, wherein the hydrocarbylene group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety; or R 3 and R 7 , or R 4 and R 7 , or R 4 and any R 10 , or R 4 and any R 101 , or R 4 and R 11 , or R 4 and R 121 , or R 4 and R 122 , or R 4 and R 123 , or R 4 and any R 13 , or R 7 and any R 10 , or R 7 and any R 101 , or R 7 and R 11 , or R 7 and R 121 , or R 7 and R 122 , or R 7 and R 123 , or R 7 and any R 13 , or any R 10 and R 11 , or any R 10 and R 121 , or any R 10 and R 122 , or any R 10 and R 123 , or any R 10 and any R 13 , or any R 101 and R 11 , or any R 101 and R 121 , or any R 101 and R 122 , or any R 101 and R 123 , or any R 101 and any R 13 , may together form a C 1 -C 12 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight- chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbylene group may optionally be substituted with one or more halo groups, wherein the hydrocarbylene group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; R 18 is selected from hydrogen or a C 1 -C 10 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 18 that is directly attached to the reminder of the molecule is a carbon atom; and R 19 is selected from a C1-C10 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; or R 18 and R 19 may together form a C1-C10 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbylene group may optionally be substituted with one or more halo groups, wherein the hydrocarbylene group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety.
  11. 11. A compound as claimed in claim 10, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein the compound has the Formula (IIIa): Formula (IIIa) wherein: X A1 is N, C-H or C-R 10 ; X A2 is N, C-H or C-R 10 ; X A3 is N, C-H or C-R 10 ; and X A4 is N, C-H or C-R 10 ; provided that no more than three of X A1 , X A2 , X A3 and X A4 are N; and R 1 to R 8 , R 10 , R 11 , X 12 , R 13 , R 18 , R 19 , m, n and q are as defined in accordance with claim 10.
  12. 12. A compound as claimed in claim 10 or claim 11, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein R 2 is selected from hydrogen or a fluoro, chloro or bromo group.
  13. 13. A compound as claimed in any one of claims 10 to 12, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein R 3 is selected from hydrogen or a fluoro, chloro, bromo, -R 30 , -CN, -CHO, -COR 30 , -CO2H or -CO2R 30 group, wherein R 30 is selected from a C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 fluoroalkenyl or -R 31 group, wherein R 31 is a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups R 32 , wherein each R 32 is independently selected from a methyl or a fluoromethyl group, provided that the group R 3 , including any optional substituents, contains no more than 8 carbon atoms.
  14. 14. A compound of Formula (IV): Formula (IV) or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof; wherein: R 1 is hydrogen; R 4 is selected from hydrogen or a halo, -OH, -NH2, -SO2NH2, or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety; R 5 is selected from hydrogen or a halo group; R 6 is selected from hydrogen or a halo, -R 60 or -OR 60 group, wherein R 60 is selected from a C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C 1 -C 4 fluoroalkyl or C 3 -C 4 fluorocycloalkyl group; R 7 and R 8 are each independently selected from hydrogen or a fluoro or a C1-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 7 or R 8 that is directly attached to the reminder of the molecule is a carbon atom; or R 7 and R 8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R 7 and R 8 are attached is a ring carbon atom, wherein the cyclic group may optionally by substituted with one or more substituents each independently selected from a halo, oxo (=O), -OH, -NH2 or a C1-C4 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton; ring A is a phenyl or a 5- or 6-membered heteroaryl ring; p is 0, 1, 2, 3 or 4; each R 10 is independently selected from a halo, -OH, -NH2 or a C1-C4 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight- chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton; or any two adjacent R 10 may together form a C 1 -C 6 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight-chained or branched, or be or include a cyclic group, wherein the hydrocarbylene group may optionally be substituted with one or more groups R 101 , wherein each R 101 is independently selected from a halo group, and wherein the hydrocarbylene group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton; X 12 is NR 121 or C(R 122 )(R 123 ); m is 0, 1 or 2, and n is 0, 1 or 2, provided that (i) m + n < 4, and (ii) when X 12 is NR 121 , m is 1 or 2 and n is 1 or 2; q is 0, 1, 2, 3, 4, 5, 6, 7 or 8; R 11 is selected from hydrogen or a fluoro or a C 1 -C 8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 11 that is directly attached to the reminder of the molecule is a carbon atom; R 121 is selected from hydrogen or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 121 that is directly attached to the reminder of the molecule is a carbon atom; R 122 is selected from hydrogen or a fluoro, -OH, -NH 2 , -SH, -SO 2 H, -SO 3 H, -SO 2 NH 2 , or a C 1 -C 8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; R 123 is selected from hydrogen or a fluoro or a C 1 -C 8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 123 that is directly attached to the reminder of the molecule is a carbon atom; each R 13 is independently selected from selected from a fluoro, -OH, -NH2, -SH, -SO2H, -SO3H, -SO2NH2, or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that when R 13 is directly attached to a carbon atom which in turn is directly attached to an oxygen, nitrogen or sulphur atom, the atom of R 13 that is directly attached to the remainder of the molecule is a fluorine or carbon atom; or R 11 and R 121 , or R 11 and R 122 , or R 11 and R 123 , or R 11 and any R 13 , or R 121 and any R 13 , or R 122 and R 123 , or R 122 and any R 13 , or R 123 and any R 13 , or any two R 13 may together form a C 1 -C 8 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbylene group may optionally be substituted with one or more halo groups, wherein the hydrocarbylene group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; each R 14 and R 15 is independently selected from hydrogen or a C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group, or R 14 and R 15 together with the carbon atom to which they are attached form a 3- to 6-membered cyclic group, wherein the cyclic group may optionally by substituted with one or more substituents each independently selected from a fluoro, -OH, oxo (=O), methyl or ethyl group, wherein any methyl or ethyl group may optionally be fluoro substituted; R 16 is selected from hydrogen or a fluoro, -SO2NH2, or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight- chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; R 17 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C 3 -C 4 fluorocycloalkyl group; or R 16 and R 17 together with the carbon atom to which they are attached form a 3- to 6-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a fluoro, -OH, oxo (=O), methyl or ethyl group, wherein any methyl or ethyl group may optionally be fluoro substituted; or R 17 and R 7 , or R 4 and R 7 , or R 4 and any R 10 , or R 4 and any R 101 , or R 4 and R 11 , or R 4 and R 121 , or R 4 and R 122 , or R 4 and R 123 , or R 4 and any R 13 , or R 7 and any R 10 , or R 7 and any R 101 , or R 7 and R 11 , or R 7 and R 121 , or R 7 and R 122 , or R 7 and R 123 , or R 7 and any R 13 , or any R 10 and R 11 , or any R 10 and R 121 , or any R 10 and R 122 , or any R 10 and R 123 , or any R 10 and any R 13 , or any R 101 and R 11 , or any R 101 and R 121 , or any R 101 and R 122 , or any R 101 and R 123 , or any R 101 and any R 13 , may together form a C1-C12 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight- chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbylene group may optionally be substituted with one or more halo groups, wherein the hydrocarbylene group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; R 18 is selected from hydrogen or a C 1 -C 10 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO 2 -, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of any hydrocarbyl group of R 18 that is directly attached to the reminder of the molecule is a carbon atom; and R 19 is selected from a C1-C10 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; or R 18 and R 19 may together form a C1-C10 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbylene group may optionally be substituted with one or more halo groups, wherein the hydrocarbylene group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety.
  15. 15. A compound as claimed in claim 14, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein the compound has the Formula (IVa): wherein: X A1 is N, C-H or C-R 10 ; X A2 is N, C-H or C-R 10 ; X A3 is N, C-H or C-R 10 ; and X A4 is N, C-H or C-R 10 ; provided that no more than three of X A1 , X A2 , X A3 and X A4 are N; and R 1 , R 4 to R 8 , R 10 , R 11 , X 12 , R 13 to R 19 , m, n and q are as defined in accordance with claim 14.
  16. 16. A compound as claimed in claim 14 or claim 15, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein each R 14 and R 15 is independently selected from hydrogen or a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group, or R 14 and R 15 together with the carbon atom to which they are attached form a cyclopropyl or a cyclobutyl group, wherein the cyclopropyl or cyclobutyl group may optionally be substituted with one or more fluoro groups.
  17. 17. A compound as claimed in any one of claims 14 to 16, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: R 16 is selected from hydrogen or a fluoro, -R 160 , -CN, -CHO, -COR 160 , -CO2H or -CO2R 160 group, provided that R 16 , including any optional substituents, contains no more than 8 carbon atoms; R 160 is selected from a C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, C 2 -C 6 alkenyl, C 2 -C 6 fluoroalkenyl or -R 161 group; R 161 is a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups R 162 ; each R 162 is independently selected from a methyl or a fluoromethyl group; and R 17 is selected from hydrogen or a fluoro, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; or R 16 and R 17 together with the carbon atom to which they are attached form a 3- to 5-membered saturated monocyclic group, wherein the saturated monocyclic group may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from oxo (=O) or a methyl or fluoromethyl group.
  18. 18. A compound as claimed in any one of claims 10 to 17, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: R 18 is selected from hydrogen or a -R 181 or -COR 181 group, provided that where R 18 is -R 181 , the atom of the hydrocarbyl group of R 181 that is directly attached to the reminder of the molecule is a carbon atom; R 181 is a C 1 -C 8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and wherein the hydrocarbyl group may optionally include one, two, three or four heteroatoms each independently selected from N and O in its carbon skeleton; and R 19 is a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and wherein the hydrocarbyl group may optionally include one, two, three or four heteroatoms each independently selected from N and O in its carbon skeleton.
  19. 19. A compound as claimed in any one of claims 10 to 17, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: R 18 and R 19 together form a group -L 189 -, wherein -L 189 - is a C2-C4 straight chained alkylene or alkenylene group, wherein the alkylene or alkenylene group may optionally include a nitrogen atom in its carbon skeleton, wherein the alkylene or alkenylene group has a chain length of 3 or 4 atoms, and wherein the alkylene or alkenylene group may optionally be substituted with one or more groups -R 189 , provided that -L 189 -, including any optional substituents, contains no more than 10 carbon atoms; each R 189 is independently selected from a fluoro, chloro, bromo, -OH, -NH2, -SH, -SO 2 H, -SO 3 H, -SO 2 NH 2 , -R 190 or -SO 2 R 190 group, and/or any two R 189 attached to the same carbon atom may together form an oxo (=O) group, and/or any two R 189 attached to the same or different atoms may together with the atom or atoms to which they are attached form a 3- to 7-membered cyclic group, wherein the 3- to 7-membered cyclic group may optionally be substituted with one or more groups each independently selected from a fluoro, chloro, bromo, -OH, -NH 2 , -SH, -SO 2 H, -SO 3 H, -SO 2 NH 2 , -R 190 or -SO2R 190 group; and each R 190 is independently selected from a C1-C4 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton.
  20. 20. A compound as claimed in any one of claims 1 to 19, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: R 4 is selected from a fluoro, chloro, bromo, -OH, -OR 41 , -N(R 42 )2, -SO2-R 41 , -SO 2 -N(R 42 ) 2 , -L 4 -OH, -L 4 -OR 41 , -L 4 -N(R 42 ) 2 , -L 4 -SO 2 -R 41 , -L 4 -SO 2 -N(R 42 ) 2 , -O-L 4 -OH, -O-L 4 -OR 41 , -O-L 4 -N(R 42 )2, -O-L 4 -SO2-R 41 , -O-L 4 -SO2-N(R 42 )2, -NR 43 -L 4 -OH, -NR 43 -L 4 -OR 41 , -NR 43 -L 4 -N(R 42 )2, -NR 43 -L 4 -SO2-R 41 , -NR 43 -L 4 -SO2-N(R 42 )2, -SO2-L 4 -OH, -SO2-L 4 -OR 41 , -SO2-L 4 -N(R 42 )2, -R 44 , -R 45 or -L 4 -R 45 group, provided that R 4 , including any optional substituents, contains no more than 8 carbon atoms; R 41 is selected from a -R 44 or -R 45 group; each R 42 is independently selected from hydrogen or a -R 44 or -R 45 group, or any two R 42 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; L 4 is a straight-chained alkylene group, wherein the straight-chained alkylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L 4 has a chain length of from 1 to 4 atoms, and wherein L 4 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups R L4 ; each R L4 is independently selected from a fluoro, methyl or fluoromethyl group; or any R L4 and R 41 , or any R L4 and any R 42 , may together with the atoms to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; R 43 is selected from hydrogen or a -R 44 group; each R 44 is independently selected from a C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl group, wherein the C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; and each R 45 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein any methyl group of R 45 may optionally be fluoro substituted.

Description

Novel Compounds Field of the Invention The present invention relates to active esters of Factor B inhibitors, and to associated salts, solvates, prodrugs and pharmaceutical compositions. The present invention further relates to methods of synthesising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by Factor B inhibition. Background of the Invention The complement system is a critical part of the innate immune system and serves to help the body fight against infection from pathogens, ultimately leading to inflammation and phagocytic removal of pathogens or foreign particles. The complement system is comprised of multiple proteins, including zymogens which undergo proteolytic cleavage to become activated and facilitate the activation of further zymogens in the cascade. The proteins may be zymogens or proteins without potential for enzymatic activity that change conformation revealing binding sites for other components of the system. These successive enzymatic cleavages lead to a large, amplified response and many regulatory components exist in this system to prevent uncontrolled activation. The complement system can be activated via three pathways: classical, lectin, and alternative. The classical pathway is triggered by antigen:antibody complexes and connects the innate to the adaptive immune system. The lectin pathway is triggered directly by the pathogen when serum protein mannan-binding lectin, collectins or ficolins bind to bacterial or viral mannose-containing carbohydrates. The alternative pathway (also known as the alternate pathway) is initiated by activation of the central complement component, C3, either through spontaneous hydrolysis or enzymatic cleavage. The alternative pathway also serves as a critical amplification loop of all three pathways of complement activation. Ultimately, all of these pathways lead to the generation of C3 convertase which cleaves and activates further C3 molecules to promote: 1) opsonization of pathogens so they can be engulfed by phagocytes that recognise key receptors, 2) the recruitment of inflammatory cells by generating chemoattractants at the site of activation, and 3) formation of the C5 convertase resulting in production of C5a and C5b, the latter of which induces direct killing of pathogens by assembling terminal complement components to create membrane attack complex (MAC) pores in the membrane of bacteria or other target cells (Janeway, C. A. Jr. et al, (2001) The complement system and innate immunity, in Immunobiology: The Immune System in Health and Disease, Garland Science, New York). Factor B, a trypsin-like serine protease, is an element of the alternative pathway of the complement cascade. It exists in circulation in its zymogen form until the pathway becomes activated (Schubart, A. et al, Proc. Natl. Acad. Sci. U.S.A.2019, 116, 7926- 7931). Spontaneous steady-state hydrolysis of C3 leads to the formation of C3(H2O). Factor B can bind to the active forms of C3: C3(H2O) and C3b, generating the proenzyme C3bB (or C3(H2O)B), a target for activation by Factor D. Upon cleavage by Factor D, two fragments are generated: Ba and Bb (Schwaeble, W. J., Ali, Y. M., and Sim, R. B., (2020) Chapter 14 - The Roles and Contributions of the Complement System in the Pathophysiology of Autoimmune Diseases, in The Autoimmune Diseases (Sixth Edition) (Rose, N. R., and Mackay, I. R. eds.), Academic Press). Ba is released and Bb, containing a serine protease domain, remains bound to C3(H2O) and C3b, forming the alternative pathway C3 convertases [C3(H2O)Bb and C3bBb]. These trigger the amplification loop by converting C3 to C3a and more C3b. With the addition of yet another C3b to the C3 convertase, the C5 convertase is generated (C3bBbC3b) (Laskowski, J., Thurman, J. M. (2018) Chapter 14 - Factor B, in The Complement FactsBook (Second Edition) (Barnum, S., and Schein, T. eds.), Academic Press). C5 convertase cleaves C5 to generate the anaphylatoxin C5a, and C5b which serves as a platform for the formation of the membrane attack complex. Dysregulation of the alternative complement pathway due to genetics or the presence of autoantibodies can lead to many different diseases. Inhibition of Factor B is therefore a key therapeutic target for modulation of the alternative pathway and hence the treatment of numerous diseases, disorders and conditions. Iptacopan (LNP023), disclosed in Mainolfi et al., J. Med. Chem., 2020, vol.63, pp. 5697-5722, is a known Factor B inhibitor having the following structure: Iptacopan is highly selective for Factor B, showing no inhibition of Factor D or the classical or lectin complement pathways. Also, no significant effects have been observed in a broad assay panel of receptors, ion channels, kinases, and proteases (Schubart, A. et al, Proc. Natl. Acad. Sci. U.S.A.2019, 116, 7926-7931). The drug has recently undergone successful phase III clinical studies in patien