Anti-viral compounds [0001] This invention relates to compounds that can be used to treat viral infections. The novel compounds of the present invention are enzyme inhibitors and more particularly are papain-like protease (PLpro) inhibitors. [0002] Viral infections have the ability to spread through populations so rapidly that they give rise to epidemics or pandemics. Such occurrences are becoming increasingly common. The most recent example of this was the coronavirus disease 2019 (COVID- 19) pandemic caused by the SARS-CoV-2 virus, that caused death or severe illness in millions of people worldwide and significantly impacted global economies. [0003] Papain-like protease (PLpro) is one of two cysteine proteases that reside within viral polyprotein and is responsible for processing the polyprotein into its functional units. These functional units in turn assemble into complexes to execute viral RNA synthesis. PLpro is therefore essential for viral replication (Nature, 2020, 587, 657-662). [0004] PLpro is conserved across many coronaviruses, including SARS-CoV-1, MERS-CoV and SARS-CoV-2, with high homology seen between species/strains (ACS Infect. Dis., 2020, 6, 8, 2099-2109). If PLpro can be selectively inhibited, it could prevent viral replication and be used in the treatment of viral infections arising from these species and strains. [0005] WO2010/022355A1 discloses compounds and compositions for treating respiratory disease and illness, such as SARS. The compounds disclosed therein show inhibition of SARS-Cov-1 PLpro. [0006] Recent research has shown that the PLpro binding sites for SARS-CoV-1 and SARS-CoV-2 are highly homogenous (ACS Infect. Dis., 2020, 6, 8, 2099-2109). [0007] Shen et al. (J. Med. Chem., 2022, 65, 2940–2955) discloses potent non- covalent inhibitors of SARS-CoV-2 PLpro which are shown to block viral replication in monkey and human cell cultures. [0008] It is an aim of the present invention to provide new compounds which show anti-viral activity, and in particular which inhibit the activity of PLpro. BRIEF SUMMARY OF THE DISCLOSURE [0009] In a first aspect of the invention, there is provided a compound of formula (I) or pharmaceutically acceptable salt thereof: wherein Y is -C(O)-, -C(S)-, -C(=NR ⁶ )-; -L ¹ - is absent or a linker selected from C ₁ alkylene, C ₂ -alkenylene, or C ₂ -alkynylene; -L ² - is selected from -C _1-3 -alkylene-, -C _0-3 -alkylene-C(O)-C _0-3 -alkylene-, -C _1-3 -alkylene- NR ⁶ -C _0-3 -alkylene-, -C _1-3 -alkylene-NR ⁶ -C(O)-C _0-3 -alkylene-, -C _1-3 -alkylene-NR ⁶ -C(O)-L ^2a - C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)NR ⁶ -C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C _0-3 -alkylene-, - C _0-3 -alkylene- L ^2a -C(O)-C _0-3 -alkylene-, and -C _0-3 -alkylene-L ^2a -C(O)NR ⁶ - C _0-3 -alkylene-; - C _0-3 -alkylene-C(O)-L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-; -L ^2a - is selected from phenyl, 5- or 6- membered heteroaryl, 4-, 5- or 6- membered heterocycloalkyl, or C ₅ or C ₆ cycloalkyl; -L ³ - is absent or is selected from -NR ⁶ -NR ⁶ -C(O)-C _0-3 -alkylene, -NR ⁶ -C(O)-C _0-3 -alkylene, -C(O)-C _0-3 -alkylene, -C(O)NR ⁶ -C _0-3 -alkylene, and -NR ⁶ -C _0-3 -alkylene; X ¹ , X ² , X ³ and X ⁴ are each independently selected from carbon and nitrogen wherein no more than two of X ¹ , X ² , X ³ and X ⁴ may be nitrogen, R ¹ is selected from the group comprising:C ₁ or C ₂ alkyl, C ₁ or C ₂ haloalkyl, and C ₁ or C ₂ alkylene-R ^1a ; wherein R ^1a is selected from OR ⁶ , SR ⁶ , NR ⁶ R ⁷ , CO ₂ R ⁶ and CONR ⁶ R ⁶ ; R ² is selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl, and said phenyl, heteroaryl or cycloalkyl is optionally fused to or substituted with a group selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cycloalkyl is optionally substituted with at least one R ⁹ group; R ³ , R ⁶ and R ¹¹ are each independently at each occurrence selected from the group comprising: H and C ₁ -C ₆ -alkyl; R ^4a is a group capable of reacting with a cysteine residue to form a C-S bond, wherein the carbon atom of the C-S bond is present in the R ^4a group and the sulfur atom of the C-S bond is from the SH of the cysteine residue R ⁴ is independently at each occurrence selected from the group comprising: halo, C ₁ -C ₆ - alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, phenyl and 5- or 6- membered heteroaryl; R ⁵ is absent or is selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , -C _0-3 - alkylene-NR ⁶ R ¹⁴ , -OR ¹⁰ , phenyl, 5- or 6- membered heteroaryl; 4-, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group; wherein when the X ¹ , X ² , X ³ or X ⁴ onto which R ⁵ is substituted is nitrogen, R ⁵ is selected such that R ⁵ is attached to said nitrogen atom via a carbon atom of R ⁵ ; R ⁷ is independently at each occurrence selected from the group comprising: H, C ₁ -C ₆ - alkyl, C(O)-C ₁ -C ₆ -alkyl and S(O) ₂ -C ₁ -C ₆ -alkyl; R ⁸ is independently at each occurrence selected from the group comprising: halo, C ₁ -C ₆ - alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; wherein where R ⁸ is heterocycloalkyl, phenyl or heteroaryl, R ⁸ is optionally substituted where chemically possible with one or more R ^8c groups; R ^8c is independently selected at each occurrence from: halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , C ₁ -C ₆ -alkylene-NR ⁶ R ¹⁰ , -OR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ ; R ⁹ is independently at each occurrence selected from the group comprising: =O, =S, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -NR ¹¹ R ¹² , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, 4-, 5- or 6- membered heterocycloalkyl, C _2-6 -alkenyl C _2-6 -alkynyl and C ₁ -C ₃ -alkylene-R ^9a ; wherein R ^9a is selected from OR ⁶ , SR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ NR ⁶ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ , CONR ⁶ R ⁶ , 4-, 5- or 6- membered heterocycloalkyl, and cyclopropyl; R ¹⁰ is independently selected at each occurrence from the group comprising: H, C ₁ -C ₆ - alkyl, C ₁ -C ₆ -haloalkyl, C ₀ -C ₆ -alkylene-R ^10a , C _3-8 cycloalkyl, 4-, 5-, 6-, 7- or 8- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; wherein R ^10a is independently selected at each occurrence from C _3-8 cycloalkyl, OR ⁶ , SR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ , CONR ⁶ R ⁶ , phenyl, 5- or 6- membered heteroaryl, and 5- or 6- membered heterocycloalkyl; R ¹² is 6-membered heterocycloalkyl; wherein said heterocycloalkyl is optionally substituted with at least one R ¹³ group; R ¹³ is independently at each occurrence selected from: =O, =S, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - haloalkyl, -OR ⁶ , cyano, nitro, -NR ⁶ R ⁷ , -SR ⁶ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ⁶ , - S(O) ₂ R ⁶ , -S(O) ₂ NR ⁶ R ⁶ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl and C ₁ -C ₃ -alkylene-R ^13a ; wherein R ^13a is selected from OR ⁶ , SR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ and CONR ⁶ R ⁶ ; R ¹⁴ is selected from H and C ₁ -C ₃ -alkylene-R ^14a ; wherein R ^14a is selected from OR ⁶ , SR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ , CONR ⁶ R ⁶ , C _3-8 cycloalkyl, or 4-, 5-, 6-, 7- or 8- membered heterocycloalkyl; and n is an integer selected from 0, 1, 2 and 3; wherein any aforementioned alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, heterocycloalkyl, phenyl, heteroaryl, alkylene, alkenylene, alkynylene, C(O)-alkyl and S(O) ₂ -alkyl is optionally substituted, where chemically possible, by 1 to 4 substituents which are each independently selected at each occurrence from the group consisting of: =O; =NR ^a , =NOR ^a , C ₁ -C ₄ -alkyl, halo, nitro, cyano, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ - alkynyl, NR ^a R ^b , S(O) ₂ R ^a , S(O)R ^a , S(O)(NR ^a )R ^a , S(O) ₂ NR ^a R ^a , CO ₂ R ^a , C(O)R ^a , CONR ^a R ^a , OR ^a and SR ^a ; wherein R ^a is independently selected from H and C ₁ -C ₄ -alkyl; and R ^b is independently selected from H, C ₁ -C ₄ -alkyl, C(O)-C ₁ -C ₄ -alkyl and S(O) ₂ -C ₁ -C ₄ -alkyl. [0010] In an embodiment of the first aspect, there is provided a compound of formula (Ia) or pharmaceutically acceptable salt thereof: wherein Y is -C(O)-, -C(S)-, -C(=NR ⁶ )-; -L ¹ - is absent or a linker selected from C ₁ alkylene, C ₂ -alkenylene, or C ₂ -alkynylene; -L ² - is selected from -C _1-3 -alkylene-, -C _0-3 -alkylene-C(O)-C _0-3 -alkylene-, -C _1-3 -alkylene- NR ⁶ -C _0-3 -alkylene-, -C _1-3 -alkylene-NR ⁶ -C(O)-C _0-3 -alkylene-, -C _1-3 -alkylene-NR ⁶ -C(O)-L ^2a - C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)NR ⁶ -C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C _0-3 -alkylene-, - C _0-3 -alkylene- L ^2a -C(O)-C _0-3 -alkylene-, and -C _0-3 -alkylene-L ^2a -C(O)NR ⁶ - C _0-3 -alkylene-; - C _0-3 -alkylene-C(O)-L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-; -L ^2a - is selected from phenyl, 5- or 6- membered heteroaryl, 4-, 5- or 6- membered heterocycloalkyl, or C ₅ or C ₆ cycloalkyl; -L ³ - is absent or is selected from -NR ⁶ -NR ⁶ -C(O)-C _0-3 -alkylene, -NR ⁶ -C(O)-C _0-3 -alkylene, -C(O)-C _0-3 -alkylene, -C(O)NR ⁶ -C _0-3 -alkylene, and -NR ⁶ -C _0-3 -alkylene; X ¹ , X ² , X ³ and X ⁴ are each independently selected from carbon and nitrogen wherein no more than two of X ¹ , X ² , X ³ and X ⁴ may be nitrogen, R ¹ is selected from the group comprising: C ₁ or C ₂ alkyl, C ₁ or C ₂ haloalkyl, and C ₁ or C ₂ alkylene-R ^1a ; wherein R ^1a is selected from OR ⁶ , SR ⁶ , NR ⁶ R ⁷ , CO ₂ R ⁶ and CONR ⁶ R ⁶ ; R ² is selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl, and said phenyl, heteroaryl or cycloalkyl is optionally fused to or substituted with a group selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cycloalkyl is optionally substituted with at least one R ⁹ group; R ³ , R ⁶ and R ¹¹ are each independently at each occurrence selected from the group comprising: H and C ₁ -C ₆ -alkyl; R ^4a is a group capable of reacting with a cysteine residue to form a C-S bond, wherein the carbon atom of the C-S bond is present in the R ^4a group and the sulfur atom of the C-S bond is from the SH of the cysteine residue R ⁴ is independently at each occurrence selected from the group comprising: halo, C ₁ -C ₆ - alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, phenyl and 5- or 6- membered heteroaryl; R ⁵ is absent or is selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , -C _0-3 - alkylene-NR ⁶ R ¹⁴ , -OR ¹⁰ , phenyl, 5- or 6- membered heteroaryl; 4-, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group; wherein when the X ¹ , X ² , X ³ or X ⁴ onto which R ⁵ is substituted is nitrogen, R ⁵ is selected such that R ⁵ is attached to said nitrogen atom via a carbon atom of R ⁵ ; R ⁷ is independently at each occurrence selected from the group comprising: H, C ₁ -C ₆ - alkyl, C(O)-C ₁ -C ₆ -alkyl and S(O) ₂ -C ₁ -C ₆ -alkyl; R ⁸ is independently at each occurrence selected from the group comprising: halo, C ₁ -C ₆ - alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; wherein where R ⁸ is heterocycloalkyl, phenyl or heteroaryl, R ⁸ is optionally substituted where chemically possible with one or more R ^8c groups; R ^8c is independently selected at each occurrence from: halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , C ₁ -C ₆ -alkylene-NR ⁶ R ¹⁰ , -OR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ ; R ⁹ is independently at each occurrence selected from the group comprising: =O, =S, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -NR ¹¹ R ¹² , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, 4-, 5- or 6- membered heterocycloalkyl, C _2-6 -alkenyl C _2-6 -alkynyl and C ₁ -C ₃ -alkylene-R ^9a ; wherein R ^9a is selected from OR ⁶ , SR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ NR ⁶ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ , CONR ⁶ R ⁶ , 4-, 5- or 6- membered heterocycloalkyl, and cyclopropyl; R ¹⁰ is independently selected at each occurrence from the group comprising: H, C ₁ -C ₆ - alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ^10a , C _3-8 cycloalkyl, 4-, 5-, 6-, 7- or 8- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; wherein R ^10a is independently selected at each occurrence from C _3-8 cycloalkyl, OR ⁶ , SR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ , CONR ⁶ R ⁶ , phenyl, 5- or 6- membered heteroaryl, and 5- or 6- membered heterocycloalkyl; R ¹² is 6-membered heterocycloalkyl; wherein said heterocycloalkyl is optionally substituted with at least one R ¹³ group; R ¹³ is independently at each occurrence selected from: =O, =S, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - haloalkyl, -OR ⁶ , cyano, nitro, -NR ⁶ R ⁷ , -SR ⁶ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ⁶ , - S(O) ₂ R ⁶ , -S(O) ₂ NR ⁶ R ⁶ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl and C ₁ -C ₃ -alkylene-R ^13a ; wherein R ^13a is selected from OR ⁶ , SR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ and CONR ⁶ R ⁶ ; R ¹⁴ is selected from H and C ₁ -C ₃ -alkylene-R ^14a ; wherein R ^14a is selected from OR ⁶ , SR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ , CONR ⁶ R ⁶ , C _3-8 cycloalkyl, or 4-, 5-, 6-, 7- or 8- membered heterocycloalkyl; and n is an integer selected from 0, 1, 2 and 3; wherein any aforementioned alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, heterocycloalkyl, phenyl, heteroaryl, alkylene, alkenylene, alkynylene, C(O)-alkyl and S(O) ₂ -alkyl is optionally substituted, where chemically possible, by 1 to 4 substituents which are each independently selected at each occurrence from the group consisting of: =O; =NR ^a , =NOR ^a , C ₁ -C ₄ -alkyl, halo, nitro, cyano, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ - alkynyl, NR ^a R ^b , S(O) ₂ R ^a , S(O)R ^a , S(O)(NR ^a )R ^a , S(O) ₂ NR ^a R ^a , CO ₂ R ^a , C(O)R ^a , CONR ^a R ^a , OR ^a and SR ^a ; wherein R ^a is independently selected from H and C ₁ -C ₄ -alkyl; and R ^b is independently selected from H, C ₁ -C ₄ -alkyl, C(O)-C ₁ -C ₄ -alkyl and S(O) ₂ -C ₁ -C ₄ -alkyl. [0011] In an embodiment of the first aspect, there is provided a compound of formula (Ib) or pharmaceutically acceptable salt thereof: wherein Y is -C(O)-, -C(S)-, -C(=NR ⁶ )-; -L ¹ - is absent or a linker selected from C ₁ alkylene, C ₂ -alkenylene, or C ₂ -alkynylene; -L ² - is selected from -C _1-3 -alkylene-, -C _0-3 -alkylene-C(O)-C _0-3 -alkylene-, -C _1-3 -alkylene- NR ⁶ -C _0-3 -alkylene-, -C _1-3 -alkylene-NR ⁶ -C(O)-C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)NR ⁶ -C _0-3 - alkylene-, -C _0-3 -alkylene-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene- L ^2a -C(O)-C _0-3 -alkylene-, and - C _0-3 -alkylene-L ^2a -C(O)NR ⁶ - C _0-3 -alkylene-; -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 -alkylene-, and - C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-; -L ^2a - is selected from phenyl, 5- or 6- membered heteroaryl, 4-, 5- or 6- membered heterocycloalkyl, or C ₅ or C ₆ cycloalkyl; -L ³ - is absent or is selected from -NR ⁶ -NR ⁶ -C(O)-C _0-3 -alkylene, -NR ⁶ -C(O)-C _0-3 -alkylene, -C(O)-C _0-3 -alkylene, -C(O)NR ⁶ -C _0-3 -alkylene, and -NR ⁶ -C _0-3 -alkylene; X ¹ , X ² , X ³ and X ⁴ are each independently selected from carbon and nitrogen wherein no more than two of X ¹ , X ² , X ³ and X ⁴ may be nitrogen, R ¹ is selected from the group comprising: C ₁ or C ₂ alkyl, C ₁ or C ₂ haloalkyl, and C ₁ or C ₂ alkylene-R ^1a ; wherein R ^1a is selected from OR ⁶ , SR ⁶ , NR ⁶ R ⁷ , CO ₂ R ⁶ and CONR ⁶ R ⁶ ; R ² is selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl, and said phenyl, heteroaryl or cycloalkyl is optionally fused to or substituted with a group selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cycloalkyl is optionally substituted with at least one R ⁹ group; R ³ , R ⁶ and R ¹¹ are each independently at each occurrence selected from the group comprising: H and C ₁ -C ₆ -alkyl; R ^4a is a group capable of reacting with a cysteine residue to form a C-S bond, wherein the carbon atom of the C-S bond is present in the R ^4a group and the sulfur atom of the C-S bond is from the SH of the cysteine residue R ⁴ is independently at each occurrence selected from the group comprising: halo, C ₁ -C ₆ - alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, phenyl and 5- or 6- membered heteroaryl; R ⁵ is absent or is selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , -C _0-3 - alkylene-NR ⁶ R ¹⁴ , -OR ¹⁰ , phenyl, 5- or 6- membered heteroaryl; 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group; wherein when the X ¹ , X ² , X ³ or X ⁴ onto which R ⁵ is substituted is nitrogen, R ⁵ is selected such that R ⁵ is attached to said nitrogen atom via a carbon atom of R ⁵ ; R ⁷ is independently at each occurrence selected from the group comprising: H, C ₁ -C ₆ - alkyl, C(O)-C ₁ -C ₆ -alkyl and S(O) ₂ -C ₁ -C ₆ -alkyl; R ⁸ is independently at each occurrence selected from the group comprising: halo, C ₁ -C ₆ - alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; wherein where R ⁸ is heterocycloalkyl, phenyl or heteroaryl, R ⁸ is optionally substituted where chemically possible with one or more R ^8c groups; R ^8c is independently selected at each occurrence from: halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , C ₁ -C ₆ -alkylene-NR ⁶ R ¹⁰ , -OR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ ; R ⁹ is independently at each occurrence selected from the group comprising: =O, =S, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -NR ¹¹ R ¹² , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, 4-, 5- or 6- membered heterocycloalkyl, C _2-6 -alkenyl C _2-6 -alkynyl and C ₁ -C ₃ -alkylene-R ^9a ; wherein R ^9a is selected from OR ⁶ , SR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ NR ⁶ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ , CONR ⁶ R ⁶ , 4-, 5- or 6- membered heterocycloalkyl, and cyclopropyl; R ¹⁰ is independently selected at each occurrence from the group comprising: H, C ₁ -C ₆ - alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ^10a , C _3-8 cycloalkyl, 4-, 5-, 6-, 7- or 8- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; wherein R ^10a is independently selected at each occurrence from C _3-8 cycloalkyl, OR ⁶ , SR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ , CONR ⁶ R ⁶ , phenyl, 5- or 6- membered heteroaryl, and 5- or 6- membered heterocycloalkyl; R ¹² is 6-membered heterocycloalkyl; wherein said heterocycloalkyl is optionally substituted with at least one R ¹³ group; R ¹³ is independently at each occurrence selected from: =O, =S, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - haloalkyl, -OR ⁶ , cyano, nitro, -NR ⁶ R ⁷ , -SR ⁶ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ⁶ , - S(O) ₂ R ⁶ , -S(O) ₂ NR ⁶ R ⁶ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl and C ₁ -C ₃ -alkylene-R ^13a ; wherein R ^13a is selected from OR ⁶ , SR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ and CONR ⁶ R ⁶ ; R ¹⁴ is selected from H and C ₁ -C ₃ -alkylene-R ^14a ; wherein R ^14a is selected from OR ⁶ , SR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ , CONR ⁶ R ⁶ , C _3-8 cycloalkyl, or 4-, 5-, 6-, 7- or 8- membered heterocycloalkyl; and n is an integer selected from 0, 1, 2 and 3; wherein any aforementioned alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, heterocycloalkyl, phenyl, heteroaryl, alkylene, alkenylene, alkynylene, C(O)-alkyl and S(O) ₂ -alkyl is optionally substituted, where chemically possible, by 1 to 4 substituents which are each independently selected at each occurrence from the group consisting of: =O; =NR ^a , =NOR ^a , C ₁ -C ₄ -alkyl, halo, nitro, cyano, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ - alkynyl, NR ^a R ^b , S(O) ₂ R ^a , S(O)R ^a , S(O)(NR ^a )R ^a , S(O) ₂ NR ^a R ^a , CO ₂ R ^a , C(O)R ^a , CONR ^a R ^a , OR ^a and SR ^a ; wherein R ^a is independently selected from H and C ₁ -C ₄ -alkyl; and R ^b is independently selected from H, C ₁ -C ₄ -alkyl, C(O)-C ₁ -C ₄ -alkyl and S(O) ₂ -C ₁ -C ₄ -alkyl. [0012] It may be that when R ² is naphthyl (optionally substituted with at least one R ⁸ group), either (a) -L ² - is selected from -C _1-3 -alkylene-NR ⁶ -C _0-3 -alkylene-, -C _1-3 -alkylene-NR ⁶ -C(O)- L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene- L ^2a -C(O)-C _0-3 - alkylene-, -C _0-3 -alkylene-L ^2a -C(O)NR ⁶ -C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)-L ^2a -C _{0- 3} -alkylene-, and -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-; or (b) R ⁵ is selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , -C _0-3 - alkylene-NR ⁶ R ¹⁴ , -OR ¹⁰ , phenyl, 5- or 6- membered heteroaryl; 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. [0013] It may be that when R ² is naphthyl (optionally substituted with at least one R ⁸ group), either (a) -L ² - is selected from -C _0-3 -alkylene-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene- L ^2a -C(O)- C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C(O)NR ⁶ -C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)- L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-; or (b) R ⁵ is selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , -C _0-3 - alkylene-NR ⁶ R ¹⁴ , -OR ¹⁰ , phenyl, 5- or 6- membered heteroaryl; 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. [0014] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (IIa): wherein L ¹ , L ² , L ³ , X ¹ , X ² , X ⁴ , R ¹ , R ² , R ^4a , R ⁴ , R ⁵ and n are as described above for formula (I), formula (Ia) or formula (Ib). [0015] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (IIb): wherein L ¹ , L ² , L ³ , X ¹ , X ³ , X ⁴ , R ¹ , R ² , R ^4a , R ⁴ , R ⁵ and n are as described above for formula (I), formula (Ia) or formula (Ib). [0016] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (IIIa): wherein L ¹ , L ² , L ³ , R ¹ , R ² , R ^4a , R ⁴ and R ⁵ are as described above for formula (I), formula (Ia) or formula (Ib) and wherein n1 is an integer selected from 0, 1, 2 or 3. [0017] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (IIIb): wherein L ¹ , L ² , L ³ , R ¹ , R ² , R ^4a , R ⁴ and R ⁵ are as described above for formula (I), formula (Ia) or formula (Ib) and wherein n1 is an integer selected from 0, 1, 2 or 3. [0018] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (IVa) : Wherein Y, L ² , L ³ , X ¹ , X ² , X ⁴ , R ¹ , R ² , R ³ , R ^4a , R ⁴ , R ⁵ and n are as described above for formula (I), formula (Ia) or formula (Ib). [0019] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (Ivb): wherein Y, L ² , L ³ , X ¹ , X ³ , X ⁴ , R ¹ , R ² , R ³ , R ^4a , R ⁴ , R ⁵ and n are as described above for formula (I), formula (Ia) or formula (Ib). [0020] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (Va): wherein L ² , L ³ , X ¹ , X ² , X ⁴ , R ¹ , R ^4a , R ⁴ , R ⁵ , R ⁸ and n are as described above for formula (I), formula (Ia) or formula (Ib) and wherein m is an integer independently selected from 0, 1, 2, 3, 4, 5, 6, and 7. [0021] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (Vb): Wherein L ² , L ³ , X ¹ , X ³ , X ⁴ , R ¹ , R ^4a , R ⁴ , R ⁵ , R ⁸ and n are as described above for formula (I), formula (Ia) or formula (Ib) and wherein m is an integer independently selected from 0, 1, 2, 3, 4, 5, 6, and 7. [0022] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (VIa): wherein L ² , L ³ , R ¹ , R ^4a , R ⁴ , R ⁵ and R ⁸ are as described above for formula (I), formula (Ia) or formula (Ib); and wherein n1 is an integer selected from 0, 1, 2 or 3; and m is an integer independently selected from 0, 1, 2, 3, 4, 5, 6, and 7. [0023] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (Vib): wherein L ² , L ³ , R ¹ , R ^4a , R ⁴ , R ⁵ and R ⁸ are as described above for formula (I), formula (Ia) or formula (Ib); and wherein n1 is an integer selected from 0, 1, 2 or 3; and m is an integer independently selected from 0, 1, 2, 3, 4, 5, 6, and 7. [0024] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (VIIa): wherein L ² , L ³ , X ¹ , X ² , X ⁴ , R ¹ , R ^4a , R ⁴ , R ⁵ , R ⁸ and n are as described above for formula (I), formula (Ia) or formula (Ib) and wherein m is an integer independently selected from 0, 1, 2, 3, 4, and 5. [0025] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (VIIb): wherein L ² , L ³ , X ¹ , X ³ , X ⁴ , R ¹ , R ^4a , R ⁴ , R ⁵ , R ⁸ and n are as described above for formula (I), formula (Ia) or formula (Ib) and wherein m is an integer independently selected from 0, 1, 2, 3, 4, and 5. [0026] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (VIIc) or (VIId): Wherein L ² , L ³ , X ¹ , X ² , X ³ , X ⁴ , R ¹ , R ^4a , R ⁴ , R ⁵ , R ⁸ and n are as described above for formula (I), formula (Ia) or formula (Ib); R ^8e is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and - SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; p3 is an integer selected from 1, 2 and 3; and wherein m is an integer independently selected from 0, 1, 2, 3, 4, and 5. [0027] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (VIIIa): wherein L ² , L ³ , R ¹ , R ^4a , R ⁴ , R ⁵ and R ⁸ are as described above for formula (I), formula (Ia) or formula (Ib); and wherein n1 is an integer selected from 0, 1, 2 or 3; and m is an integer independently selected from 0, 1, 2, 3, 4, and 5. [0028] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (VIIIb): wherein L ² , L ³ , R ¹ , R ^4a , R ⁴ , R ⁵ and R ⁸ are as described above for formula (I), formula (Ia) or formula (Ib); and wherein n1 is an integer selected from 0, 1, 2 or 3; and m is an integer independently selected from 0, 1, 2, 3, 4, and 5. [0029] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (VIIIc) or (VIIId): wherein L ² , L ³ , R ¹ , R ^4a , R ⁴ , R ⁵ , R ⁸ and n are as described above for formula (I), formula (Ia) or formula (Ib); R ^8e is independently at each occurrence selected from halo, C ₁ -C ₆ - alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and -SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; p3 is an integer selected from 1, 2 and 3; and wherein m is an integer independently selected from 0, 1, 2, 3, 4, and 5. [0030] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (IXa): wherein L ² , L ³ , ^{1 2 4 1 4a 4 5} X , X , X , R , R , R , R , R ⁸ and n are as described above for formula (I), formula (Ia) or formula (Ib); wherein R ^2a is selected from a 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; wherein p is an integer independently selected from 0, 1, 2, 3, 4, and 5; and wherein q is an integer independently selected from 0, 1, 2, 3, and 4. [0031] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (IXb): wherein L ² , L ³ , X ¹ , X ³ , X ⁴ , R ¹ , R ^4a , R ⁴ , R ⁵ , R ⁸ and n are as described above for formula (I), formula (Ia) or formula (Ib); wherein R ^2a is selected from a 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; wherein p is an integer independently selected from 0, 1, 2, 3, 4, and 5; and wherein q is an integer independently selected from 0, 1, 2, 3, and 4. [0032] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (IXc) or (IXd): wherein L ² , L ³ , X ¹ , X ² , X ³ , X ⁴ , R ¹ , R ^4a , R ⁴ , R ⁵ , R ⁸ and n are as described above for formula (I), formula (Ia) or formula (Ib); wherein R ^2a is selected from a 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; R ^8e is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ - C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and -SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; p is an integer independently selected from 0, 1, 2, 3, 4, and 5; p3 is an integer selected from 1, 2 and 3; and wherein q is an integer independently selected from 0, 1, 2, 3, and 4. [0033] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (Xa): wherein L ² , L ³ , R ¹ , R ^4a , R ⁴ , R ⁵ and R ⁸ are as described above for formula (I), formula (Ia) or formula (Ib); and wherein R ^2a is selected from a 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; n1 is an integer selected from 0, 1, 2 or 3; wherein p is an integer independently selected from 0, 1, 2, 3, 4, and 5; and wherein q is an integer independently selected from 0, 1, 2, 3, and 4. [0034] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (Xb): wherein L ² , L ³ , R ¹ , R ^4a , R ⁴ , R ⁵ and R ⁸ are as described above for formula (I), formula (Ia) or formula (Ib); and wherein R ^2a is selected from a 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; n1 is an integer selected from 0, 1, 2 or 3; wherein p is an integer independently selected from 0, 1, 2, 3, 4, and 5; and wherein q is an integer independently selected from 0, 1, 2, 3, and 4. [0035] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (Xc):

wherein L ² , L ³ , R ¹ , R ^4a , R ⁴ , R ⁵ and R ⁸ are as described above for formula (I), formula (Ia) or formula (Ib); and wherein R ^2a is selected from a 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; n1 is an integer selected from 0, 1, 2 or 3; R ^8e is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ - C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and -SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; p is an integer independently selected from 0, 1, 2, 3, 4, and 5; p3 is an integer selected from 1, 2 and 3; and wherein q is an integer independently selected from 0, 1, 2, 3, and 4. [0036] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (XIa): wherein L ² , L ³ , R ¹ , R ^4a , R ⁴ , R ⁵ and R ⁸ are as described above for formula (I), formula (Ia) or formula (Ib); n1 is an integer selected from 0, 1, 2 or 3; wherein Q ¹ , Q ² and Q ³ are each independently selected from carbon, nitrogen and sulfur, wherein no more than one of Q ¹ , Q ² and Q ³ is sulfur, and if one of Q ¹ , Q ² and Q ³ is sulfur, at least one of the other two of Q ¹ , Q ² and Q ³ is carbon; wherein p is an integer independently selected from 0, 1, 2, 3, 4, and 5; wherein q is an integer independently selected from 0, 1, 2, 3, and 4; and wherein r is an integer independently selected from 0, 1 and 2. [0037] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (XIIb): wherein L ² , L ³ , R ¹ , R ^4a , R ⁴ , R ⁵ and R ⁸ are as described above for formula (I), formula (Ia) or formula (Ib); n1 is an integer selected from 0, 1, 2 or 3; wherein Q ¹ , Q ² and Q ³ are each independently selected from carbon, nitrogen and sulfur, wherein no more than one of Q ¹ , Q ² and Q ³ is sulfur, and if one of Q ¹ , Q ² and Q ³ is sulfur, at least one of the other two of Q ¹ , Q ² and Q ³ is carbon; wherein p is an integer independently selected from 0, 1, 2, 3, 4, and 5; wherein q is an integer independently selected from 0, 1, 2, 3, and 4; and wherein r is an integer independently selected from 0, 1 and 2. [0038] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (XIIc) or (XIId): wherein L ² , L ³ , R ¹ , R ^4a , R ⁴ , R ⁵ and R ⁸ are as described above for formula (I), formula (Ia) or formula (Ib); n1 is an integer selected from 0, 1, 2 or 3; wherein Q ¹ , Q ² and Q ³ are each independently selected from carbon, nitrogen and sulfur, wherein no more than one of Q ¹ , Q ² and Q ³ is sulfur, and if one of Q ¹ , Q ² and Q ³ is sulfur, at least one of the other two of Q ¹ , Q ² and Q ³ is carbon; R ^8e is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and - SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; p is an integer independently selected from 0, 1, 2, 3, 4, and 5; p3 is an integer selected from 1, 2 and 3; q is an integer independently selected from 0, 1, 2, 3, and 4; and wherein r is an integer independently selected from 0, 1 and 2. [0039] In certain embodiments, the compound of formula (I), formula (Ia) or formula (Ib) is a compound of formula (XIIIa), (XIIIb), (XIIIc) or (XIIId): wherein L ² , L ³ , R ¹ , R ^4a , R ⁴ , R ⁵ and R ⁸ are as described above for formula (I), formula (Ia) or formula (Ib); n1 is an integer selected from 0, 1, 2 or 3; wherein Q ¹ , Q ² and Q ³ are each independently selected from carbon, nitrogen and sulfur, wherein no more than one of Q ¹ , Q ² and Q ³ is sulfur, and if one of Q ¹ , Q ² and Q ³ is sulfur, at least one of the other two of Q ¹ , Q ² and Q ³ is carbon; R ^8e is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and - SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; p is an integer independently selected from 0, 1, 2, 3, 4, and 5; q is an integer independently selected from 0, 1, 2, 3, and 4; and wherein r is an integer independently selected from 0, 1 and 2. [0040] The following embodiments apply to compounds of any of formulae (I) to (XIII) (including Formulae labelled either a), b), c) or d)). These embodiments are independent and interchangeable. Any one embodiment may be combined with any other embodiment, where chemically allowed. In other words, any of the features described in the following embodiments may (where chemically allowable) be combined with the features described in one or more other embodiments. In particular, where a compound is exemplified or illustrated in this specification, any two or more of the embodiments listed below, expressed at any level of generality, which encompass that compound may be combined to provide a further embodiment which forms part of the present disclosure. [0041] It may be that Y is -C(S)-. It may be that Y is -C(=NR ⁶ )-. Preferably, Y is -C(O)-. [0042] -L ¹ - may be absent, -CH ₂ -, -CH ₂ CH ₂ - or -CHCH-. -L ¹ - may be absent or -CH ₂ -. - L ¹ - may be -CH ₂ -, -CH ₂ CH ₂ - or -CHCH-. Preferably, -L ¹ - is absent. [0043] It may be that Y is -C(O)- and -L ¹ - is absent. [0044] -L ² - is selected from -C _1-3 -alkylene-, -C _0-3 -alkylene-C(O)-C _0-3 -alkylene-, -C _1-3 - alkylene-NR ⁶ -C _0-3 -alkylene-, -C _1-3 -alkylene-NR ⁶ -C(O)-C _0-3 -alkylene-, -C _1-3 -alkylene-NR ⁶ - C(O)-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)NR ⁶ -C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C _0-3 - alkylene-, -C _0-3 -alkylene- L ^2a -C(O)-C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C(O)NR ⁶ - C _0-3 - alkylene-; -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 - alkylene-. L ² - may be selected from -C _1-3 -alkylene-NR ⁶ -C(O)-L ^2a -C _0-3 -alkylene-, -C _0-3 - alkylene-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene- L ^2a -C(O)-C _0-3 -alkylene-, and -C _0-3 -alkylene- L ^2a -C(O)NR ⁶ - C _0-3 -alkylene-; -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene- C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-. [0045] -L ² - may be selected from -C _1-3 -alkylene-, -C _0-3 -alkylene-C(O)-C _0-3 -alkylene-, -C _1- 3-alkylene-NR ⁶ -C _0-3 -alkylene-, -C _1-3 -alkylene-NR ⁶ -C(O)-C _0-3 -alkylene-, -C _0-3 -alkylene- C(O)NR ⁶ -C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene- L ^2a -C(O)-C _0-3 - alkylene-, -C _0-3 -alkylene-L ^2a -C(O)NR ⁶ - C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 - alkylene-, and -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-. L ² - may be selected from -C _0-3 - alkylene-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene- L ^2a -C(O)-C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a - C(O)NR ⁶ - C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene- C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-. [0046] -L ² - may be selected from -C _0-3 -alkylene-C(O)-C _0-3 -alkylene-, -C _1-3 -alkylene- NR ⁶ -C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)NR ⁶ -C _0-3 -alkylene-,-C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C0- 3-alkylene-, -C _1-3 -alkylene-NR ⁶ -C(O)-L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 - alkylene-. -L ² - may be -C _0-3 -alkylene-C(O)-C _0-3 -alkylene-, e.g. -CH ₂ CH ₂ C(O)-. -L ² - may be -C _1-3 -alkylene-NR ⁶ -C _0-3 -alkylene-, e.g. -CH ₂ CH ₂ CH ₂ NH-. -L ² - may be -C _0-3 -alkylene- C(O)NR ⁶ -C _0-3 -alkylene-, e.g. -CH ₂ CH ₂ C(O)NH-. -L ² - may be -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a - C _0-3 -alkylene-, e.g. -CH ₂ CH ₂ C(O)NH-azetidinyl-. -L ² - may be -C _1-3 -alkylene-NR ⁶ -C(O)- L ^2a -C _0-3 -alkylene-, e.g. -CH ₂ NHC(O)-pyrrolidinyl-, -CH ₂ NHC(O)-cyclopropyl- or - CH ₂ CH ₂ NHC(O)-cyclopropyl-. -L ² may be -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 -alkylene-, e.g. - CH ₂ CH ₂ C(O)-L ^2a -. [0047] -L ² - may be selected from -C _0-3 -alkylene-C(O)-C _0-3 -alkylene-, -C _0-3 -alkylene- C(O)NR ⁶ -C _0-3 -alkylene- and -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 -alkylene-. -L ² - may be -C _0-3 - alkylene-C(O)-C _0-3 -alkylene-, e.g. -CH ₂ CH ₂ C(O)-. -L ² - may be -C _0-3 -alkylene-C(O)NR ⁶ - C _0-3 -alkylene-, e.g. -CH ₂ CH ₂ C(O)NH-. -L ² may be -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 -alkylene-, e.g. -CH ₂ CH ₂ C(O)-L ^2a -. [0048] -L ² - may be selected from -C _1-3 -alkylene-NR ⁶ -C(O)-L ^2a -C _0-3 -alkylene-, -C _0-3 - alkylene-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene- L ^2a -C(O)-C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a - C(O)NR ⁶ -C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene- C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-. [0049] -L ² - may be selected from -C _0-3 -alkylene-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene- L ^2a - C(O)-C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C(O)NR ⁶ -C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)-L ^2a - C _0-3 -alkylene-, and -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-. [0050] -L ^2a - is selected from phenyl, 5- or 6- membered heteroaryl, 4-, 5- or 6- membered heterocycloalkyl, or C ₅ or C ₆ cycloalkyl. -L ^2a - may be a 4-, 5- or 6- membered heterocycloalkyl, e.g. pyrrolidinyl, piperazinyl or azetidinyl. -L ^2a - may be a C ₅ or C ₆ cycloalkyl. [0051] -L ^2a - may be selected from phenyl, 5- or 6- membered heteroaryl, 4-, 5- or 6- membered heterocycloalkyl, or C ₅ or C ₆ cycloalkyl. -L ^2a - may be a 4-, 5- or 6- membered heterocycloalkyl, e.g. piperazinyl or azetidinyl. -L ^2a - may be a C ₅ or C ₆ cycloalkyl. [0052] -L ^2a - may be selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl, or C ₅ or C ₆ cycloalkyl. -L ^2a - may be a 5- or 6- membered heterocycloalkyl, e.g. piperazinyl. -L ^2a - may be a C ₅ or C ₆ cycloalkyl. [0053] -L ^2a - may be selected from: and [0054] -L ^2a - may be selected from: [0055] L ^2a - may be selected from: and [0056] -L ³ - is absent or is independently selected from -NR ⁶ -NR ⁶ -C(O)-C _0-3 -alkylene, - NR ⁶ -C(O)-C _0-3 -alkylene, -C(O)-C _0-3 -alkylene, -C(O)NR ⁶ -C _0-3 -alkylene, and -NR ⁶ -C _0-3 - alkylene. [0057] -L ³ - may be absent. -L ³ - may be -NR ⁶ -NR ⁶ -C(O)-C _0-3 -alkylene, e.g. -NH-NH- C(O)-. -L ³ - may be -C(O)-C _0-3 -alkylene, e.g. -C(O)-. -L ³ - may be -NR ⁶ -C _0-3 -alkylene, e.g. -NH- or -NH-CH ₂ -. [0058] -L ² -L ³ - may have an atom length of at least 4 atoms, at least 5 atoms, at least 6 atoms, at least 7 atoms or at least 8 atoms. [0059] For the absence of doubt, the atom length of the linkers formed by -L ² - and -L ³ - together is the number of atoms in a continuous chain from the carbon atom of the ring comprising X ¹ , X ² , X ³ , and X ⁴ onto which -L ² - is substituted to the atom of R ^4a to which - L ² - or -L ³ - is attached. The length does not include any substituents or branching that might be present on the chain. [0060] It may be that -L ² - is -C _0-3 -alkylene-C(O)-C _0-3 -alkylene- (e.g. -CH ₂ CH ₂ C(O)-) and -L ³ - is -NR ⁶ -NR ⁶ -C(O)-C _0-3 -alkylene (e.g. -NH-NH-C(O)-). It may be that -L ² - is -C _0-3 - alkylene-C(O)NR ⁶ -C _0-3 -alkylene- (e.g. -CH ₂ CH ₂ C(O)NH-) and -L ³ - is -NR ⁶ -C _0-3 -alkylene (e.g. -NH- or -NH-CH ₂ -). It may be that -L ² - is -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 -alkylene- (e.g. -CH ₂ CH ₂ C(O)-L ^2a -) and -L ³ - is absent. It may be that -L ² is -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 - alkylene- (e.g. -CH ₂ CH ₂ C(O)-L ^2a -) and -L ³ - is -C(O)-C _0-3 -alkylene (e.g. -C(O)-). It may be that -L ² - is -C _1-3 -alkylene-NR ⁶ -C _0-3 -alkylene- (e.g. -CH ₂ CH ₂ CH ₂ NH-) and -L ³ - is -C(O)-C0- 3-alkylene (e.g. -C(O)-). It may be that -L ² - is -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 -alkylene- (e.g. -CH ₂ CH ₂ C(O)NH-azetidinyl-) and -L ³ - is -C(O)-C _0-3 -alkylene (e.g. -C(O)-). It may be that -L ² - is -C _1-3 -alkylene-NR ⁶ -C(O)-L ^2a -C _0-3 -alkylene- (e.g. -CH ₂ NHC(O)-pyrrolidinyl-) and -L ³ - is -NR ⁶ -C _0-3 -alkylene (e.g. -NH-). [0061] -L ² -L ³ - may be selected from:

and [0062] -L ² -L ³ - may be selected from:

and [0063] -L ² -L ³ - may be selected from:

, and [0064] X ³ may be carbon, and X ¹ , X ² and X ⁴ may be each independently selected from carbon and nitrogen, and no more than two of X ¹ , X ² , and X ⁴ may be nitrogen. It may be that each of X ¹ , X ² , and X ⁴ is carbon. It may be that at least one of X ¹ , X ² and X ⁴ is nitrogen. It may be that a single one of X ¹ , X ² and X ⁴ is nitrogen. It may be that X ⁴ is nitrogen and each of X ¹ and X ² is carbon. It may be that each of X ¹ , X ² and X ³ is carbon. [0065] X ² may be carbon, and X ¹ , X ³ and X ⁴ may be each independently selected from carbon and nitrogen, and no more than two of X ¹ , X ³ , and X ⁴ may be nitrogen. It may be that each of X ¹ , X ³ , and X ⁴ is carbon. It may be that at least one of X ¹ , X ³ and X ⁴ is nitrogen. It may be that a single one of X ¹ , X ³ and X ⁴ is nitrogen. It may be that X ⁴ is nitrogen and each of X ¹ and X ³ is carbon. It may be that each of X ¹ , X ² and X ³ is carbon. [0066] The ring comprising X ¹ , X ² , X ³ , and X ⁴ may be: or [0067] The ring comprising X ¹ , X ² , X ³ , and X ⁴ may be: [0068] The ring comprising X ¹ , X ² , X ³ , and X ⁴ may be: [0069] The ring comprising X ¹ , X ² , X ³ , and X ⁴ may be: [0070] The ring comprising X ¹ , X ² , X ³ , and X ⁴ may be: [0071] The ring comprising X ¹ , X ² , X ³ , and X ⁴ may be: [0072] The ring comprising X ¹ , X ² , X ³ and X ⁴ may be: [0073] The ring comprising X ¹ , X ² , X ³ and X ⁴ may be: [0074] R ¹ may be C ₁ or C ₂ alkyl, e.g. methyl or ethyl. R ¹ may be C ₁ or C ₂ haloalkyl, e.g. CF ₃ , CH ₂ CF ₃ , CH(CF ₃ )CH ₃ . R ¹ may be C ₁ or C ₂ alkylene-R ^1a , wherein R ^1a is selected from OR ⁶ , SR ⁶ , NR ⁶ R ⁷ , CO ₂ R ⁶ and CONR ⁶ R ⁶ , e.g. CH ₂ -R ^1a or CH ₂ CH ₂ R ^1a . Preferably, R ¹ is methyl. [0075] It may be that -L ¹ - is absent and R ¹ is C ₁ or C ₂ alkyl. It may be that L ¹ is absent and R ¹ is methyl. [0076] It may be that R ² is selected from phenyl, 5- or 6- membered heteroaryl; where said phenyl or heteroaryl is optionally fused to or substituted with a group selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cycloalkyl is optionally substituted with at least one R ⁹ group. [0077] It may be that R ² is selected from phenyl, 5- or 6- membered heteroaryl; where said phenyl or heteroaryl is optionally fused to or substituted with a group selected from phenyl, and 5- or 6- membered heteroaryl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group. [0078] It may be that R ² is selected from the group comprising phenyl, biphenyl, phenylpyrrolyl, phenylthiophenyl, pyridyl, naphthyl, indolyl, benzofuryl, benzothiophenyl, and quinolinyl. It may be that R ² is phenyl, biphenyl, phenylpyrrolyl, phenylthiophenyl or naphthyl. It may be that R ² is phenyl, biphenyl or naphthyl. R ² may be naphthyl, e.g. naphth-2-yl. R ² may be phenyl. R ² may be biphenyl. [0079] It may be that R ² has the structure: wherein m is an integer independently selected from 0, 1, 2, 3, 4, 5, 6, and 7. [0080] It may be that R ² has the structure: [0081] It may be that R ² has the structure: [0082] It may be that R ² has the structure: [0083] Where R ² has a structure as described in any of the five paragraphs immediately preceding this paragraph, it may be that: (a) -L ² - is selected from -C _1-3 -alkylene-NR ⁶ -C _0-3 -alkylene-, -C _1-3 -alkylene-NR ⁶ -C(O)- L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene- L ^2a -C(O)-C _0-3 - alkylene-, and -C _0-3 -alkylene-L ^2a -C(O)NR ⁶ - C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)- L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-; or (b) R ⁵ is selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , -C _0-3 - alkylene-NR ⁶ R ¹⁴ , -OR ¹⁰ , phenyl, 5- or 6- membered heteroaryl; 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. [0084] It may be that R ² has the structure: wherein p is an integer selected from 0, 1, 2, 3, 4 and 5. In these embodiments, it may be that R ⁸ is independently selected at each occurrence from the group comprising: halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , - S(O) ₂ NR ⁶ R ¹⁰ , C _2-6 -alkenyl, C _2-6 -alkynyl, and 5- or 6- membered heterocycloalkyl. In these embodiments, it may be that R ⁸ is independently selected at each occurrence from the group comprising: halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, - NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _2-6 - alkenyl, C _2-6 -alkynyl. R ⁸ may be independently selected at each occurrence from the group comprising: halo, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, -OR ¹⁰ , cyano, and -NR ⁶ R ⁷ . [0085] It may be that R ² has the structure: wherein R ^8a is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _2-6 -alkenyl, C _2-6 -alkynyl; R ^8b is independently at each occurrence selected from C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkylene-R ¹⁰ , halo, nitro, cyano, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, NR ⁶ R ⁷ , S(O) ₂ R ¹⁰ , S(O)R ¹⁰ , S(O) ₂ NR ⁶ R ¹⁰ , CO ₂ R ¹⁰ , C(O)R ¹⁰ , CONR ⁶ R ¹⁰ , OR ¹⁰ , SR ¹⁰ , 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; p1 is an integer selected from 0, 1, 2, 3 and 4; and p2 is an integer selected from 0, 1, 2, 3, 4 and 5. [0086] It may be that R ² has the structure: wherein R ^8b is independently at each occurrence selected from C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkylene-R ¹⁰ , halo, nitro, cyano, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ - C ₄ -alkynyl, NR ⁶ R ⁷ , S(O) ₂ R ¹⁰ , S(O)R ¹⁰ , S(O) ₂ NR ⁶ R ¹⁰ , CO ₂ R ¹⁰ , C(O)R ¹⁰ , CONR ⁶ R ¹⁰ , OR ¹⁰ , SR ¹⁰ , 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; R ^8e is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ - C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and -SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; p2 is an integer selected from 0, 1, 2, 3, 4 and 5; and p3 is an integer selected from 1, 2 and 3. [0087] It may be that R ² has the structure: wherein R ^8a is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _2-6 -alkenyl, C _2-6 -alkynyl; R ^8b is independently at each occurrence selected from C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkylene-R ¹⁰ halo, nitro, cyano, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, NR ⁶ R ⁷ , S(O) ₂ R ¹⁰ , S(O)R ¹⁰ , S(O) ₂ NR ⁶ R ¹⁰ , CO ₂ R ¹⁰ , C(O)R ¹⁰ , CONR ⁶ R ¹⁰ , OR ¹⁰ , SR ¹⁰ , 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; p1 is an integer selected from 0, 1, 2, 3 and 4; and p2 is an integer selected from 0, 1, 2, 3, 4 and 5. [0088] It may be that R ² has the structure: wherein R ^8e is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and -SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; R ^8b is independently at each occurrence selected from C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkylene-R ¹⁰ halo, nitro, cyano, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, NR ⁶ R ⁷ , S(O) ₂ R ¹⁰ , S(O)R ¹⁰ , S(O) ₂ NR ⁶ R ¹⁰ , CO ₂ R ¹⁰ , C(O)R ¹⁰ , CONR ⁶ R ¹⁰ , OR ¹⁰ , SR ¹⁰ , 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; p2 is an integer selected from 0, 1, 2, 3, 4 and 5; and p3 is an integer selected from 1, 2 and 3. [0089] It may be that R ² has the structure: wherein Q ¹ , Q ² and Q ³ are each independently selected from carbon, nitrogen and sulfur; wherein no more than one of Q ¹ , Q ² and Q ³ is sulfur, and if one of Q ¹ , Q ² or Q ³ is sulfur, at least one of the other two of Q ¹ , Q ² and Q ³ is carbon; wherein R ^8a is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, - OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , - S(O) ₂ NR ⁶ R ⁶ , C _2-6 -alkenyl, C _2-6 -alkynyl; wherein p1 is an integer selected from 0, 1, 2, 3 and 4; and wherein r is an integer independently selected from 0, 1 and 2. [0090] It may be that R ² has the structure: wherein Q ¹ , Q ² and Q ³ are each independently selected from carbon, nitrogen and sulfur; wherein no more than one of Q ¹ , Q ² and Q ³ is sulfur, and if one of Q ¹ , Q ² or Q ³ is sulfur, at least one of the other two of Q ¹ , Q ² and Q ³ is carbon; wherein R ^8e is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ - C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and -SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; wherein p3 is an integer selected 1, 2 and 3; and wherein r is an integer independently selected from 0, 1 and 2. [0091] It may be that R ² has the structure: or wherein Q ¹ , Q ² and Q ³ are each independently selected from carbon, nitrogen and sulfur; wherein no more than one of Q ¹ , Q ² and Q ³ is sulfur, and if one of Q ¹ , Q ² or Q ³ is sulfur, at least one of the other two of Q ¹ , Q ² and Q ³ is carbon; wherein R ^8e is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ - C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and -SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; wherein p3 is an integer selected 1, 2 and 3; and wherein r is an integer independently selected from 0, 1 and 2. [0092] Q ¹ , Q ² and Q ³ may be independently selected from carbon, nitrogen and sulfur. In these embodiments, no more than one of Q ¹ , Q ² and Q ³ is sulfur, and if one of Q ¹ , Q ² and Q ³ is sulfur, at least one of the other two of Q ¹ , Q ² and Q ³ is carbon. It may be that a single one of Q ¹ , Q ² and Q ³ is nitrogen. It may be that Q ¹ is nitrogen and each of Q ² and Q ³ is carbon. It may be that Q ² is nitrogen and each of Q ¹ and Q ³ is carbon. It may be that at least one of Q ¹ , Q ² and Q ³ is nitrogen. It may that two of Q ¹ , Q ² and Q ³ are nitrogen. It may be that Q ¹ and Q ² are nitrogen and Q ³ is carbon. It may be that Q ² and Q ³ are nitrogen and Q ¹ is carbon. It may be that Q ² is sulfur and Q ¹ and Q ³ are carbon. [0093] The ring comprising Q ¹ , Q ² and Q ³ may be: , wherein R ^8d is independently selected from H, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 - alkynyl. [0094] The ring comprising Q ¹ , Q ² and Q ³ may be: , wherein R ^8d is independently selected from H, halo, C ₁ -C ₆ -alkyl, C ₁ - C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 - alkynyl. [0095] The ring comprising Q ¹ , Q ² and Q ³ may be: wherein R ^8d is independently selected from H, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 - alkynyl. [0096] The ring comprising Q ¹ , Q ² and Q ³ may be: [0097] Illustrative examples of rings comprising Q ¹ , Q ² and Q ³ include:

and [0098] It may be that R ² has the structure: wherein R ^8a is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _2-6 -alkenyl, C _2-6 -alkynyl; R ^8b is independently at each occurrence selected from C ₁ -C ₄ -alkyl, halo, nitro, cyano, C ₁ -C ₄ - haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, NR ^a R ^b , S(O) ₂ R ^a , S(O)R ^a , S(O)(NR ^a )R ^a , S(O) ₂ NR ^a R ^a , CO ₂ R ^a , C(O)R ^a , CONR ^a R ^a , OR ^a and SR ^a ; R ^8d is independently selected from H, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, - NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl; p1 is an integer selected from 0, 1, 2, 3 and 4; and r1 is an integer selected from 0, 1 and 2. [0099] It may be that R ² has the structure: wherein R ^8a is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _2-6 -alkenyl, C _2-6 -alkynyl; R ^8b is independently at each occurrence selected from C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkylene-R ¹⁰ halo, nitro, cyano, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, NR ⁶ R ⁷ , S(O) ₂ R ¹⁰ , S(O)R ¹⁰ , S(O) ₂ NR ⁶ R ¹⁰ , CO ₂ R ¹⁰ , C(O)R ¹⁰ , CONR ⁶ R ¹⁰ , OR ¹⁰ , SR ¹⁰ , 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; R ^8d is independently selected from H, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , - S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; p1 is an integer selected from 0, 1, 2, 3 and 4; and r1 is an integer selected from 0, 1 and 2. [00100] It may be that R ² has the structure: wherein R ^8d is independently selected from H, halo, C ₁ -C ₆ -alkyl, C ₁ - C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 - alkynyl, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; R ^8e is independently at each occurrence selected from halo, C ₁ - C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and -SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; R ^8b is independently at each occurrence selected from C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkylene-R ¹⁰ halo, nitro, cyano, C ₁ -C ₄ - haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, NR ⁶ R ⁷ , S(O) ₂ R ¹⁰ , S(O)R ¹⁰ , S(O) ₂ NR ⁶ R ¹⁰ , CO ₂ R ¹⁰ , C(O)R ¹⁰ , CONR ⁶ R ¹⁰ , OR ¹⁰ , SR ¹⁰ , 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; p3 is an integer selected from 1, 2 and 3; and r1 is an integer selected from 0, 1 and 2. [00101] It may be that R ² has the structure: wherein R ^8a is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _2-6 -alkenyl, C _2-6 -alkynyl; R ^8b is independently at each occurrence selected from C ₁ -C ₄ -alkyl, halo, nitro, cyano, C ₁ -C ₄ - haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, NR ^a R ^b , S(O) ₂ R ^a , S(O)R ^a , S(O)(NR ^a )R ^a , S(O) ₂ NR ^a R ^a , CO ₂ R ^a , C(O)R ^a , CONR ^a R ^a , OR ^a and SR ^a ; R ^8d is independently selected from H, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, - NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl; p1 is an integer selected from 0, 1, 2, 3 and 4; and r1 is an integer selected from 0, 1 and 2. [00102] It may be that R ² has the structure: wherein R ^8a is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _2-6 -alkenyl, C _2-6 -alkynyl; R ^8b is independently at each occurrence selected from C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkylene-R ¹⁰ halo, nitro, cyano, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, NR ⁶ R ⁷ , S(O) ₂ R ¹⁰ , S(O)R ¹⁰ , S(O) ₂ NR ⁶ R ¹⁰ , CO ₂ R ¹⁰ , C(O)R ¹⁰ , CONR ⁶ R ¹⁰ , OR ¹⁰ , SR ¹⁰ , 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; R ^8d is independently selected from H, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , - S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; p1 is an integer selected from 0, 1, 2, 3 and 4; and r1 is an integer selected from 0, 1 and 2. [00103] It may be that R ² has the structure: wherein R ^8b is independently at each occurrence selected from C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkylene-R ¹⁰ halo, nitro, cyano, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, NR ⁶ R ⁷ , S(O) ₂ R ¹⁰ , S(O)R ¹⁰ , S(O) ₂ NR ⁶ R ¹⁰ , CO ₂ R ¹⁰ , C(O)R ¹⁰ , CONR ⁶ R ¹⁰ , OR ¹⁰ , SR ¹⁰ , 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; R ^8d is independently selected from H, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ - C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , - S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; R ^8e is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ - C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and -SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; p3 is an integer selected from 1, 2 and 3; and r1 is an integer selected from 0, 1 and 2. [00105] It may be that R ² has the structure: wherein R ^8a is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _2-6 -alkenyl, C _2-6 -alkynyl; R ^8b is independently at each occurrence selected from C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkylene-R ¹⁰ halo, nitro, cyano, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, NR ⁶ R ⁷ , S(O) ₂ R ¹⁰ , S(O)R ¹⁰ , S(O) ₂ NR ⁶ R ¹⁰ , CO ₂ R ¹⁰ , C(O)R ¹⁰ , CONR ⁶ R ¹⁰ , OR ¹⁰ , SR ¹⁰ , 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; R ^8d is independently selected from H, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , - S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl, p1 is an integer selected from 0, 1, 2, 3 and 4; and r1 is an integer selected from 0, 1 and 2. [00106] It may be that R ² has the structure: wherein R ^8a is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _2-6 -alkenyl, C _2-6 -alkynyl; R ^8b is independently at each occurrence selected from C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkylene-R ¹⁰ halo, nitro, cyano, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, NR ⁶ R ⁷ , S(O) ₂ R ¹⁰ , S(O)R ¹⁰ , S(O) ₂ NR ⁶ R ¹⁰ , CO ₂ R ¹⁰ , C(O)R ¹⁰ , CONR ⁶ R ¹⁰ , OR ¹⁰ , SR ¹⁰ ; R ^8d is independently selected from H, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, - NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, p1 is an integer selected from 0, 1, 2, 3 and 4; and r1 is an integer selected from 0, 1 and 2. [00107] It may be that R ² has the structure: wherein R ^8b is independently at each occurrence selected from C ₁ -C ₄ - alkyl, C ₁ -C ₄ -alkylene-R ¹⁰ halo, nitro, cyano, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, NR ⁶ R ⁷ , S(O) ₂ R ¹⁰ , S(O)R ¹⁰ , S(O) ₂ NR ⁶ R ¹⁰ , CO ₂ R ¹⁰ , C(O)R ¹⁰ , CONR ⁶ R ¹⁰ , OR ¹⁰ , SR ¹⁰ , 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; R ^8d is independently selected from H, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , - OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , - S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; R ^8e is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ - C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and -SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; p3 is an integer selected from 1, 2 and 3; and r1 is an integer selected from 0, 1 and 2. [00108] It may be that R ² has the structure: or wherein R ^8b is independently at each occurrence selected from C ₁ -C ₄ -alkyl, C ₁ -C ₄ - alkylene-R ¹⁰ halo, nitro, cyano, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, NR ⁶ R ⁷ , S(O) ₂ R ¹⁰ , S(O)R ¹⁰ , S(O) ₂ NR ⁶ R ¹⁰ , CO ₂ R ¹⁰ , C(O)R ¹⁰ , CONR ⁶ R ¹⁰ , OR ¹⁰ , SR ¹⁰ , 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; R ^8d is independently selected from H, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , - OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , - S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl; R ^8e is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ - C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and -SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; p3 is an integer selected from 1, 2 and 3; and r1 is an integer selected from 0, 1 and 2. [00109] R ² may be selected from: wherein m is an integer selected from 1 and 2; p is an integer independently selected from 0, 1 and 2; and q is an integer independently selected from 0 and 1. [00110] R ² may be selected from: wherein R ^8e is independently at each occurrence selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and - SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group; m is an integer selected from 1 and 2; p is an integer independently selected from 0, 1 and 2; and w is an integer independently selected from 0, 1, 2 and 3. [00111] R ² may be R ² m ² ay be . R may be R ² m ^{2 2} ay be R may be R may be . R ² may b ² e . R may be . R ² may be . R ² may be . R ² may be . R ² may ² be . R may be . R ² may be . R ² may be . R ² may be . R ² may be . R ² may be . R ² may be [00112] R ² may be selected from: and [00113] R ² may be . R ² may be . R ² may be R ² may be [00114] R ² may be . R ² may be . R ² may be . R ² may be ² . R may be R ² may be . R ² may be . R ² may be . R ² may be . R ² may be ² . R may be . R ² may be . R ² may be . R ² may be [00115] Illustrative R ² groups include:

[00116] Further illustrative R ² groups include:

[00117] Further illustrative R ² groups include: and [00118] It may be that when R ⁵ is absent and -L ² -L ³ -R ^4a is , R ² may be selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl, and said heteroaryl or cycloalkyl is optionally fused to or substituted with a group selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl, and said phenyl is optionally fused to a group selected from 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl; or said phenyl is optionally substituted with a group selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cycloalkyl is optionally substituted with at least one R ⁹ group. [00119] It may be that when R ² is naphthyl (optionally substituted with at least one R ⁸ group), either (a) -L ² - is selected from -C _1-3 -alkylene-NR ⁶ -C _0-3 -alkylene-, -C _1-3 -alkylene-NR ⁶ - C(O)-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene- L ^2a - C(O)-C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C(O)NR ⁶ - C _0-3 -alkylene-, -C _0-3 - alkylene-C(O)-L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 - alkylene-; or (b) R ⁵ is selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , -C _0-3 - alkylene-NR ⁶ R ¹⁴ , -OR ¹⁰ , phenyl, 5- or 6- membered heteroaryl; 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. [00120] It may be that R ³ is H. It may be that R ³ is -C _1-6 alkyl, e.g. methyl, ethyl, propyl. It may be that R ³ is H and Y is -C(O)-. It may be that L ¹ is absent, R ³ is H and Y is -C(O)- . [00121] R ^4a is a group capable of reacting with a cysteine residue to form a C-S bond, wherein the carbon atom of the C-S bond is present in the R ^4a group and the sulfur atom of the C-S bond is from the SH of the cysteine residue. [00122] R ^4a may be selected from: a Michael acceptor, α-halocarbonyl, C _1-4 -alkylene- CN. R ^4a may be a Michael acceptor, e.g. -C(O)-alkenyl, -C(O)alkynyl, or -alkenyl- C(O)O-C _1-4 alkyl. R ^4a may be a α-halocarbonyl, e.g. -C(O)-CHFCl. R ^4a may be a C _1-4 - alkylene-CN, e.g. -CH ₂ CN, -CH(CH ₃ )CN, or -C(cyclopropyl)CN. R ^4a may be . R ^4a ma ^4a y be . R may be R ^4a may be . R ^4a m ^4a ay be . R may be R ^4a may be . R ^4a may be . R ^4a may be R ^4a may be R ^4a may be R ^4a may be . R ^4a may be . R ^4a may be [00123] R ^4a may be selected from the group comprising:

and [00124] R ^4a may be selected from the group comprising: , and [00125] R ^4a may be: [00126] It may be that when R ⁵ is absent and R ² is phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl, and said phenyl, heteroaryl or cycloalkyl is fused to a group selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl (optionally substituted with at least one R ⁸ group), -L ² - is selected from -C _1-3 -alkylene-NR ⁶ -C _0-3 - alkylene-, -C _1-3 -alkylene-NR ⁶ -C(O)-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C _0-3 -alkylene-, - C _0-3 -alkylene- L ^2a -C(O)-C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C(O)NR ⁶ - C _0-3 -alkylene-, -C _0-3 - alkylene-C(O)-L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-. [00127] It may be that when R ⁵ is absent and R ² is phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl, and said phenyl, heteroaryl or cycloalkyl is fused to a group selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl (optionally substituted with at least one R ⁸ group), -L ² - is selected from -C _0-3 -alkylene-L ^2a -C _0-3 - alkylene-, -C _0-3 -alkylene- L ^2a -C(O)-C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C(O)NR ⁶ - C _0-3 - alkylene-, -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 - alkylene-. [00128] It may be that when R ⁵ is absent and R ² is phenyl fused to a group selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl (optionally substituted with at least one R ⁸ group), -L ² - is selected from -C ₁ - 3-alkylene-NR ⁶ -C _0-3 -alkylene-, -C _1-3 -alkylene-NR ⁶ -C(O)-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene- L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene- L ^2a -C(O)-C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C(O)NR ⁶ - C _0- 3-alkylene-, -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 - alkylene-. [00129] It may be that when R ⁵ is absent and R ² is phenyl fused to a group selected from phenyl, 5- or 6- membered heteroaryl, 5- or 6- membered heterocycloalkyl or C ₅ or C ₆ cycloalkyl (optionally substituted with at least one R ⁸ group), -L ² - is selected from -C _{0- 3} -alkylene-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene- L ^2a -C(O)-C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a - C(O)NR ⁶ - C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)-L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene- C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-. [00130] It may be that when R ⁵ is absent and R ² is naphthyl (optionally substituted with at least one R ⁸ group), -L ² - is selected from -C _1-3 -alkylene-NR ⁶ -C _0-3 -alkylene-, -C _1-3 - alkylene-NR ⁶ -C(O)-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C _0-3 -alkylene-, -C _0-3 -alkylene- L ^2a -C(O)-C _0-3 -alkylene-, -C _0-3 -alkylene-L ^2a -C(O)NR ⁶ - C _0-3 -alkylene-, -C _0-3 -alkylene-C(O)- L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-. [00131] It may be that when R ⁵ is absent and R ² is naphthyl (optionally substituted with at least one R ⁸ group), -L ² - is selected from -C _0-3 -alkylene-L ^2a -C _0-3 -alkylene-, -C _0-3 - alkylene- L ^2a -C(O)-C _0-3 -alkylene-, and -C _0-3 -alkylene-L ^2a -C(O)NR ⁶ - C _0-3 -alkylene-, -C _0-3 - alkylene-C(O)-L ^2a -C _0-3 -alkylene-, and -C _0-3 -alkylene-C(O)NR ⁶ -L ^2a -C _0-3 -alkylene-. [00132] R ⁴ may be independently selected at each occurrence from the group comprising: halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _2-6 -alkenyl, C _2-6 - alkynyl. R ⁴ may be independently selected at each occurrence from the group comprising: halo, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, -OR ¹⁰ , cyano, nitro and -NR ⁶ R ⁷ . [00133] When present, R ⁵ may be attached to the ring via X ² or X ³ . When present, R ⁵ may be attached to the ring via X ² . When present, R ⁵ may be attached to the ring via X ³ . [00134] When present, R ⁵ may be attached to the ring via X ³ , and X ³ may be carbon. When present, R ⁵ may be attached to the ring via X ³ , and X ³ may be nitrogen. When present, R ⁵ may be attached to the ring via X ³ , and X ³ may be carbon. [00135] R ⁵ is absent or is selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , - C _0-3 -alkylene-NR ⁶ R ¹⁴ , -OR ¹⁰ , phenyl, 5- or 6- membered heteroaryl; 4-, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. [00136] R ⁵ is absent or is selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , - C _0-3 -alkylene-NR ⁶ R ¹⁴ , -OR ¹⁰ , phenyl, 5- or 6- membered heteroaryl; 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. [00137] It may be that when R ² is naphthyl and -L ² -L ³ -R ^4a is , R ⁵ is selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , - C(O)R ¹² , -C _0-3 -alkylene-NR ⁶ R ¹⁴ , -OR ¹⁰ , phenyl, 5- or 6- membered heteroaryl; 4-, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. [00138] It may be that when R ² is naphthyl and -L ² -L ³ -R ^4a is , R ⁵ is selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , - C(O)R ¹² , -C _0-3 -alkylene-NR ⁶ R ¹⁴ , -OR ¹⁰ , phenyl, 5- or 6- membered heteroaryl; 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. [00139] R ⁵ may be selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , -C _0-3 - alkylene-NR ⁶ R ¹⁴ , -OR ¹⁰ , phenyl, 5- or 6- membered heteroaryl; 4-, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. [00140] R ⁵ may be selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , -C _0-3 - alkylene-NR ⁶ R ¹⁴ , -OR ¹⁰ , phenyl, 5- or 6- membered heteroaryl; 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. [00141] R ⁵ may be selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , -C _0-3 - alkylene-NR ⁶ R ¹⁴ , phenyl, 6- membered heteroaryl; 4-, 5-, 6-, 7- or 8- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group may be optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl may be optionally substituted with at least one R ⁹ group. [00142] R ⁵ may be selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , -C _0-3 - alkylene-NR ⁶ R ¹⁴ , phenyl, 6- membered heteroaryl; 5-, 6-, 7- or 8- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group may be optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl may be optionally substituted with at least one R ⁹ group. [00143] R ⁵ may be selected from the group comprising: -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² and -C _{0- 3} -alkylene-NR ⁶ R ¹⁴ _. R ⁵ may be -C(O)NR ⁶ R ¹⁴ , e.g. -C(O)NHR ¹⁴ or -C(O)N(CH ₃ )R ¹⁴ . R ⁵ may be -C(O)R ¹² , e.g. -C(O)-piperidyl or -C(O)-piperazinyl. R ⁵ may be -C _0-3 -alkylene- NR ⁶ R ¹⁴ , e.g. -NHR ¹⁴ , -CH ₂ NHR ¹⁴ or -CH ₂ CH ₂ NHR ¹⁴ . [00144] R ⁵ may be selected from the group comprising -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , 4-, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. In embodiments, the heterocycloalkyl or cyclopropyl group is a saturated ring system. [00145] R ⁵ may be selected from the group comprising -C(O)NR ⁶ R ¹⁴ , -C(O)R ¹² , 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. In embodiments, the heterocycloalkyl or cyclopropyl group is a saturated ring system. [00146] R ⁵ may be selected from the group comprising phenyl, 6- membered heteroaryl, 4-, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. [00147] R ⁵ may be selected from the group comprising phenyl, 6- membered heteroaryl, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group; or wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. [00148] R ⁵ may be selected from the group comprising 4-, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. In embodiments, the heterocycloalkyl or cyclopropyl group is a saturated ring system. [00149] R ⁵ may be selected from the group comprising 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl and cyclopropyl; wherein any said heterocycloalkyl or cyclopropyl is optionally substituted with at least one R ⁹ group. In embodiments, the heterocycloalkyl or cyclopropyl group is a saturated ring system. [00150] R ⁵ may be selected from the group comprising phenyl and 6- membered heteroaryl; wherein any said phenyl or heteroaryl group is optionally substituted with at least one R ⁸ group. [00151] R ⁵ may be cyclopropyl; wherein said cyclopropyl is optionally substituted with at least one R ⁹ group. [00152] R ⁵ may be a 4-, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl; wherein said heterocycloalkyl is optionally substituted with at least one R ⁹ group. R ⁵ may be 5-, 6- or 7- or 8- membered heterocycloalkyl; wherein said heterocycloalkyl is optionally substituted with at least one R ⁹ group. R ⁵ may be a 6- or 7- membered heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with at least one R ⁹ group. Preferably, R ⁵ is a 6- membered heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with at least one R ⁹ group. [00153] R ⁵ may be a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl; wherein said heterocycloalkyl is optionally substituted with at least one R ⁹ group. R ⁵ may be 5-, 6- or 7- or 8- membered heterocycloalkyl; wherein said heterocycloalkyl is optionally substituted with at least one R ⁹ group. R ⁵ may be a 6- or 7- membered heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with at least one R ⁹ group. Preferably, R ⁵ is a 6- membered heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with at least one R ⁹ group. [00154] When R ⁵ is a heterocycloalkyl group, said heterocycloalkyl group may include at least two heteroatoms. It may be that said heterocycloalkyl group includes one N atom and at least one other heteroatom independently selected from O, N and S. It may be that said heterocycloalkyl group contains two N atoms. It may be that the heterocycloalkyl group does not contain S or O. Alternatively, when R ⁵ is a heterocycloalkyl group, said heterocycloalkyl group may include one heteroatom. It may be that said heteroatom is a N atom. [00155] When R ⁵ is a heterocycloalkyl group having at least one N atom in the ring, it may be that said heterocycloalklyl group is attached to the X ⁴ group via the N atom. [00156] R ⁵ may be phenyl, pyridyl, pyrazyl, pyrazolyl, pyridazyl, pyrimidyl, pyrrolidyl, imidazolinyl, pyrazolidyl, tetrahydrothiophenyl, dihydropyrrolyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyran, tetrahydropyridyl, azepanyl, diazepanyl, azaspiroheptanyl, diazaspiroheptanyl, azabicycloheptyl, diazabicycloheptyl, diazabicyclooctyl, octahydropyrrolopyrazyl, azetidinyl, cyclopropyl, -C(O)R ¹² or - C(O)NR ⁶ R ¹⁴ . R ⁵ may be phenyl, pyridyl, pyrazyl, pyridazyl, pyrimidyl, pyrrolidyl, imidazolinyl, pyrazolidyl, tetrahydrothiophenyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyran, azepanyl, diazepanyl, azaspiroheptanyl, diazaspiroheptanyl, diazabicyclooctyl, azetidinyl, cyclopropyl, -C(O)R ¹² or -C(O)NR ⁶ R ¹⁴ . R ⁵ may be phenyl, pyridyl, pyrrolidyl, piperidyl, piperazinyl, thiomorpholinyl, morpholinyl, diazepanyl, diazespiroheptanyl, diazabicyclooctyl, azetidinyl, cyclopropyl, -C(O)R ¹² or - C(O)NR ⁶ R ¹⁴ . R ⁵ may be pyridyl, piperidyl, piperazinyl, thiomorpholinyl, morpholinyl, diazepanyl, diazabicyclooctyl, azetidinyl, -C(O)R ¹² , -C(O)NR ⁶ R ¹⁴ or -C _0-3 -alkylene- NR ⁶ R ¹⁴ . R ⁵ may be piperazinyl. [00157] R ⁵ may be phenyl, pyridyl, pyrazyl, pyrazolyl, pyridazyl, pyrimidyl, pyrrolidyl, imidazolinyl, pyrazolidyl, tetrahydrothiophenyl, dihydropyrrolyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyran, tetrahydropyridyl, azepanyl, diazepanyl, azaspiroheptanyl, diazaspiroheptanyl, azabicycloheptyl, diazabicycloheptyl, diazabicyclooctyl, octahydropyrrolopyrazyl, cyclopropyl, -C(O)R ¹² or -C(O)NR ⁶ R ¹⁴ . R ⁵ may be phenyl, pyridyl, pyrazyl, pyridazyl, pyrimidyl, pyrrolidyl, imidazolinyl, pyrazolidyl, tetrahydrothiophenyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyran, azepanyl, diazepanyl, azaspiroheptanyl, diazaspiroheptanyl, cyclopropyl, -C(O)R ¹² or -C(O)NR ⁶ R ¹⁴ . R ⁵ may be phenyl, pyridyl, pyrrolidyl, piperidyl, piperazinyl, thiomorpholinyl, morpholinyl, diazepanyl, diazespiroheptanyl, cyclopropyl, - C(O)R ¹² or -C(O)NR ⁶ R ¹⁴ . R ⁵ may be pyridyl, piperidyl, piperazinyl, thiomorpholinyl, morpholinyl, diazepanyl, -C(O)R ¹² , -C(O)NR ⁶ R ¹⁴ or -C _0-3 -alkylene-NR ⁶ R ¹⁴ . R ⁵ may be piperazinyl. [00158] R ⁵ may be phenyl, pyridyl, pyrazyl, pyrazolyl, pyridazyl, pyrimidyl, pyrrolidyl, imidazolinyl, pyrazolidyl, tetrahydrothiophenyl, dihydropyrrolyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyran, tetrahydropyridyl, azepanyl, diazepanyl, azaspiroheptanyl, diazaspiroheptanyl, azabicycloheptyl, diazabicycloheptyl, diazabicyclooctyl, octahydropyrrolopyrazyl, azetidinyl or cyclopropyl. R ⁵ may be phenyl, pyridyl, pyrazyl, pyridazyl, pyrimidyl, pyrrolidyl, imidazolinyl, pyrazolidyl, tetrahydrothiophenyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyran, azepanyl, diazepanyl, azaspiroheptanyl, diazaspiroheptanyl, diazabicyclooctyl, azetidinyl, or cyclopropyl. R ⁵ may be phenyl, pyridyl, pyrrolidyl, piperidyl, piperazinyl, thiomorpholinyl, morpholinyl, diazepanyl, diazespiroheptanyl, diazabicyclooctyl, azetidinyl, or cyclopropyl. R ⁵ may be pyridyl, piperidyl, piperazinyl, thiomorpholinyl, morpholinyl, diazabicyclooctyl, azetidinyl or diazepanyl. R ⁵ may be piperazinyl. [00159] R ⁵ may be phenyl, pyridyl, pyrazyl, pyrazolyl, pyridazyl, pyrimidyl, pyrrolidyl, imidazolinyl, pyrazolidyl, tetrahydrothiophenyl, dihydropyrrolyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyran, tetrahydropyridyl, azepanyl, diazepanyl, azaspiroheptanyl, diazaspiroheptanyl, azabicycloheptyl, diazabicycloheptyl, diazabicyclooctyl, octahydropyrrolopyrazyl, or cyclopropyl. R ⁵ may be phenyl, pyridyl, pyrazyl, pyridazyl, pyrimidyl, pyrrolidyl, imidazolinyl, pyrazolidyl, tetrahydrothiophenyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyran, azepanyl, diazepanyl, azaspiroheptanyl, diazaspiroheptanyl, or cyclopropyl. R ⁵ may be phenyl, pyridyl, pyrrolidyl, piperidyl, piperazinyl, thiomorpholinyl, morpholinyl, diazepanyl, diazespiroheptanyl or cyclopropyl. R ⁵ may be pyridyl, piperidyl, piperazinyl, thiomorpholinyl, morpholinyl, or diazepanyl. R ⁵ may be piperazinyl. [00160] R ⁵ may be phenyl, pyridyl, pyrazyl, pyridazyl, pyrimidyl or azetidinyl. R ⁵ may be phenyl, pyridyl, pyrazyl, pyridazyl, pyrimidyl. R ⁵ may be phenyl or pyridyl. [00161] R ⁵ may be pyrrolidyl, imidazolinyl, pyrazolidyl, tetrahydrothiophenyl, dihydropyrrolyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyran, tetrahydropyridyl, azepanyl, diazepanyl, azaspiroheptanyl, diazaspiroheptanyl, azabicycloheptyl, diazabicycloheptyl, diazabicyclooctyl, octahydropyrrolopyrazyl, or azetidinyl. R ⁵ may be pyrrolidyl, imidazolinyl, pyrazolidyl, tetrahydrothiophenyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyran, azepanyl, diazepanyl, azaspiroheptanyl, diazabicyclooctyl, azetidinyl or diazaspiroheptanyl. R ⁵ may be pyrrolidyl, piperidyl, piperazinyl, thiomorpholinyl, morpholinyl, diazepanyl, diazabicyclooctyl, azetidinyl or diazespiroheptanyl. R ⁵ may be piperidyl, piperazinyl, thiomorpholinyl, morpholinyl, diazabicyclooctyl, azetidinyl or diazepanyl. R ⁵ may be piperazinyl. [00162] R ⁵ may be pyrrolidyl, imidazolinyl, pyrazolidyl, tetrahydrothiophenyl, dihydropyrrolyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyran, tetrahydropyridyl, azepanyl, diazepanyl, azaspiroheptanyl, diazaspiroheptanyl, azabicycloheptyl, diazabicycloheptyl, diazabicyclooctyl, or octahydropyrrolopyrazyl. R ⁵ may be pyrrolidyl, imidazolinyl, pyrazolidyl, tetrahydrothiophenyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyran, azepanyl, diazepanyl, azaspiroheptanyl, or diazaspiroheptanyl. R ⁵ may be pyrrolidyl, piperidyl, piperazinyl, thiomorpholinyl, morpholinyl, diazepanyl, or diazespiroheptanyl. R ⁵ may be piperidyl, piperazinyl, thiomorpholinyl, morpholinyl, or diazepanyl. R ⁵ may be piperazinyl. [00163] R ⁵ may be imidazolinyl, pyrazolidyl, piperazinyl, morpholinyl, thiomorpholinyl, diazepanyl, diazabicyclooctyl, azetidinyl or diazaspiroheptanyl. R ⁵ may be piperazinyl, thiomorpholinyl, morpholinyl, diazepanyl, diazabicyclooctyl, azetidinyl or diazespiroheptanyl. R ⁵ may be piperazinyl. [00164] R ⁵ may be imidazolinyl, pyrazolidyl, piperazinyl, morpholinyl, thiomorpholinyl, diazepanyl, or diazaspiroheptanyl. R ⁵ may be piperazinyl, thiomorpholinyl, morpholinyl, diazepanyl, or diazespiroheptanyl. R ⁵ may be piperazinyl. [00165] R ⁵ may be selected from: phenyl, pyridyl, piperidine substituted with R ^9b , piperazine substituted with R ^9b , diazabicycloheptyl substituted with R ^9b , diazabicyclooctyl substituted with R ^9b , azetidinyl substituted with R ^9b , tetrahydropyridyl, morpholine, thiomorpholine, 1,4-diazepanyl, pyrrolidinyl, cyclopropyl and diazaspiroheptanyl; wherein, when R ⁵ is phenyl or pyridyl, R ⁵ may be substituted where chemically possible with 0, 1, 2, 3, 4, or 5 R ⁸ groups; and wherein, when R ⁵ is piperidine substituted with R ^9b , piperazine substituted with R ^9b , diazabicycloheptyl substituted with R ^9b , diazabicyclooctyl substituted with R ^9b , tetrahydropyridyl, morpholine, thiomorpholine, 1,4-diazepanyl, pyrrolidinyl, cyclopropyl or diazaspiroheptanyl, R ⁵ may be substituted where chemically possible with 0, 1, 2, 3, 4, 5, or 6 R ⁹ groups. [00166] R ⁵ may be selected from: phenyl, pyridyl, piperidine substituted with R ^9b , piperazine substituted with R ^9b , diazabicycloheptyl substituted with R ^9b , diazabicyclooctyl substituted with R ^9b , tetrahydropyridyl, morpholine, thiomorpholine, 1,4-diazepanyl, pyrrolidinyl, cyclopropyl and diazaspiroheptanyl; wherein, when R ⁵ is phenyl or pyridyl, R ⁵ may be substituted where chemically possible with 0, 1, 2, 3, 4, or 5 R ⁸ groups; and wherein, when R ⁵ is piperidine substituted with R ^9b , piperazine substituted with R ^9b , diazabicycloheptyl substituted with R ^9b , diazabicyclooctyl substituted with R ^9b , tetrahydropyridyl, morpholine, thiomorpholine, 1,4-diazepanyl, pyrrolidinyl, cyclopropyl or diazaspiroheptanyl, R ⁵ may be substituted where chemically possible with 0, 1, 2, 3, 4, 5, or 6 R ⁹ groups.

R ⁵ may be R ⁵ may b ^{5 5} e . R may be . R may be . R ⁵ may be . R ⁵ may be ⁵ . R may be . R ⁵ m ^{5 5 5} ay be R may be R may be . R may be . R ⁵ may be . R ⁵ may be . R ⁵ may be R ⁵ may be . R ⁵ may be ^{5 5} . R may be . R may be x is selected from 0, 1, 2, 3, 4, 5 or 6; y is selected from 0, 1, 2, 3, 4, or 5; and w is selected from 0, 1 or 2. [00167] R ⁵ may be selected from:

[00168] R ⁵ may be selected from:

. [00169] R ⁵ may be selected from: piperidine substituted with R ^9b , piperazine substituted with R ^9b , diazabicyclooctyl substituted with R ^9b , azetidinyl substituted with R ^9b , morpholine, thiomorpholine, 1,4-diazepanyl, pyrrolidinyl, and diazaspiroheptanyl; wherein R ⁵ may be substituted where chemically possible with 0, 1, 2, 3, 4, 5, or 6 R ⁹ groups. [00170] R ⁵ may be selected from: piperidine substituted with R ^9b , piperazine substituted with R ^9b , morpholine, thiomorpholine, 1,4-diazepanyl, pyrrolidinyl, and diazaspiroheptanyl; wherein R ⁵ may be substituted where chemically possible with 0, 1, 2, 3, 4, 5, or 6 R ⁹ groups. R ⁵ may be . R ⁵ may be . R ⁵ may be R ⁵ may be . R ⁵ may be . R ⁵ may be . R ⁵ may be . R ⁵ may be . R ⁵ may be . R ⁵ may be x is selected from 0, 1, 2, 3, 4, 5 or 6 and w is selected from 0, 1 or 2. [00171] R ⁵ may be selected from: piperidine substituted with R ^9b , piperazine substituted with R ^9b , morpholine or thiomorpholine; wherein R ⁵ may be substituted where chemically possible with 0, 1, 2, 3, 4, 5, or 6 R ⁹ groups. [00172] R ⁵ may be selected from: piperazine substituted with R ^9b , morpholine or thiomorpholine; wherein R ⁵ may be substituted where chemically possible with 0, 1, 2, 3, 4, 5, or 6 R ⁹ groups. [00173] R ⁵ may be wherein Z is NR ^9b , O or S(O) _q ; wherein x is selected from 0, 1, 2, 3, 4, 5 or 6 and q is selected from 0, 1 or 2. It may be that Z is NR ^9b . It may be that Z is O. It may be that Z is S(O)q. [00174] R ⁵ may be: wherein x is selected from 0, 1, 2, 3, 4, 5 or 6, and R ^9b is selected from the group comprising: C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , - S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, 4-, 5- or 6- membered heterocycloalkyl, C _2-6 -alkenyl C _2-6 -alkynyl and C ₂ -C ₃ -alkylene-R ^9a . x may be 1. x may be 0. R ^9b may be selected from the group comprising: H, C _1-4 alkyl, C(O)R ¹⁰ , and C ₂ -C ₃ - alkylene-R ^9a Preferably, R ^9b is C _1-4 alkyl. [00175] R ⁵ may be: wherein L ⁵ is selected from -CH ₂ - and -CH ₂ CH ₂ -; and wherein R ^9b is selected from the group comprising: C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, 4-, 5- or 6- membered heterocycloalkyl, C _2-6 -alkenyl C _2-6 -alkynyl and C ₂ -C ₃ -alkylene-R ^9a . L ⁵ may be -CH ₂ CH ₂ -. R ^9b may be selected from the group comprising: H, C _1-4 alkyl, C(O)R ¹⁰ , and C ₂ -C ₃ - alkylene-R ^9a Preferably, R ^9b is C _1-4 alkyl. [00176] Illustrative R ⁵ groups include:

[00177] Further illustrative R ⁵ groups include:

. [00178] Further illustrative R ⁵ groups include: and [00179] Further illustrative R ⁵ groups include:

[00180] R ⁶ may be H. R ⁶ may be -C _1-6 alkyl, e.g. methyl, ethyl, propyl. [00181] R ⁷ may be independently selected at each occurrence from the group comprising: H and C ₁ -C ₆ -alkyl. It may be that R ⁷ is H. It may be that R ⁷ is -C _1-6 alkyl, e.g. methyl, ethyl, propyl. [00182] R ⁸ may be independently at each occurrence selected from the group comprising: halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , cyano, nitro, - NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, phenyl and 5- or 6- membered heteroaryl. R ⁸ may be independently selected at each occurrence from the group comprising: halo, C ₁ -C ₆ - alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _2-6 -alkenyl, C _2-6 -alkynyl, phenyl and 6-membered heteroaryl. R ⁸ may be independently selected at each occurrence from the group comprising: halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _2-6 -alkenyl, C _2-6 - alkynyl, 5- or 6- membered heterocycloalkyl, phenyl and 6- membered heteroaryl; wherein R ⁸ is optionally substituted where chemically possible with one or more R ^8c groups. [00183] R ⁸ may be independently selected at each occurrence from the group comprising: halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _2-6 -alkenyl, C _2-6 - alkynyl, wherein R ⁸ is optionally substituted where chemically possible with one or more R ^8c groups. R ⁸ may be independently selected at each occurrence from the group comprising: halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ⁶ , C _2-6 -alkenyl, C _2-6 - alkynyl. R ⁸ may be independently selected at each occurrence from the group comprising: halo, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , 5- or 6- membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl; wherein R ⁸ is optionally substituted where chemically possible with one or more R ^8c groups. R ⁸ may be independently selected at each occurrence from the group comprising: halo, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , phenyl and 6-membered heteroaryl. R ⁸ may be independently selected at each occurrence from the group comprising: halo, C ₁ - C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, -OR ¹⁰ , cyano, and -NR ⁶ R ⁷ . [00184] R ^8a may be independently selected at each occurrence from the group comprising: halo, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, -OR ¹⁰ , cyano, and -NR ⁶ R ⁷ . [00185] R ^8b may be independently selected at each occurrence from the group comprising: halo, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, -OR ^a , cyano, and -NR ^a R ^b . [00186] R ^8c may be independently selected at each occurrence from: halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , C ₁ -C ₆ -alkylene-NR ⁶ R ¹⁰ , -OR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ . [00187] R ^8d may be selected from H, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene- R ¹⁰ , -OR ¹⁰ , cyano, nitro, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , - S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl. R ^8d may be selected from H, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , C(O)R ¹⁰ , C(O)NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl, phenyl and 5- or 6- membered heteroaryl. [00188] R ^8e may be independently selected at each occurrence from selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , -NR ⁶ R ⁶ , -NR ^8f R ^8f and -SR ¹⁰ , wherein the two R ^8f groups together form a 5-, 6-, 7-, 8-, 9- or 10- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group. R ^8e may be independently selected at each occurrence from selected from halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - alkylene-R ¹⁰ , -OR ¹⁰ , and -NR ^8f R ^8f , wherein the two R ^8f groups together form a 5- or 6- membered heterocycloalkyl ring comprising the N atom of the -NR ^8f R ^8f group. R ^8e may be independently selected at each occurrence from selected from halo, C ₁ -C ₆ -alkyl, C ₁ - C ₆ -alkylene-R ¹⁰ and -OR ¹⁰ . R ^8e may be independently selected at each occurrence from selected from C ₁ -C ₆ -alkylene-R ¹⁰ , -OR ¹⁰ , and -NR ^8f R ^8f , wherein the two R ^8f groups together form a 5- or 6- membered heterocycloalkyl ring comprising the N atom of the - NR ^8f R ^8f group. [00189] It may be that at least one instance of R ^8e is -OR ¹⁰ , e.g. -OCH ₃ or -OCH(CH ₃ ) ₂ . It may be that all instances of R ^8e are -OR ¹⁰ , e.g. -OCH ₃ or -OCH(CH ₃ ) ₂ . [00190] R ⁹ may be independently at each occurrence selected from the group comprising: =O, =S, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ⁶ , cyano, nitro, -NR ⁶ R ⁷ , - NR ¹¹ R ¹² , -SR ⁶ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ⁶ , -S(O) ₂ R ⁶ , -S(O) ₂ NR ⁶ R ⁶ , C _3-6 cycloalkyl, 4-, 5- or 6- membered heterocycloalkyl, C _2-6 -alkenyl C _2-6 -alkynyl and C ₁ -C ₃ - alkylene-R ^9a ; wherein R ^9a may be selected from OR ⁶ , SR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ NR ⁶ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ , CONR ⁶ R ⁶ , and cyclopropyl. [00191] R ⁹ may be independently at each occurrence selected from the group comprising: =O, =S, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ¹⁰ , cyano, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , -S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, 4-, 5- or 6- membered heterocycloalkyl, and C ₁ -C ₃ -alkylene-R ^9a . R ⁹ may be independently at each occurrence selected from the group comprising: =O, halo, C ₁ -C ₄ -alkyl, C ₁ -C ₄ - haloalkyl, -OR ¹⁰ , cyano, -NR ⁶ R ⁷ , -SR ¹⁰ , C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O) ₂ R ¹⁰ , - S(O) ₂ NR ⁶ R ¹⁰ , and C ₁ -C ₃ -alkylene-R ^9a . [00192] R ⁹ may be independently at each occurrence selected from the group comprising: =O, =S, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ⁶ , cyano, -NR ⁶ R ⁷ , -SR ⁶ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ⁶ , -S(O) ₂ R ⁶ , -S(O) ₂ NR ⁶ R ⁶ , C _3-6 cycloalkyl, 4-, 5- or 6- membered heterocycloalkyl, and C ₁ -C ₃ -alkylene-R ^9a . R ⁹ may be independently at each occurrence selected from the group comprising: =O, halo, C ₁ -C ₄ -alkyl, C ₁ -C ₄ - haloalkyl, -OR ⁶ , cyano, -NR ⁶ R ⁷ , -SR ⁶ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O) ₂ R ⁶ , - S(O) ₂ NR ⁶ R ⁶ , and C ₁ -C ₃ -alkylene-R ^9a . [00193] R ^9a may be independently selected at each occurrence from OR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ , CONR ⁶ R ⁶ , 4-, 5- or 6- membered heterocycloalkyl, and cyclopropyl. R ^9a may be independently selected at each occurrence from OR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ Ph, CO ₂ R ⁶ and cyclopropyl. [00194] R ^9a may be independently selected at each occurrence from OR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ , CONR ⁶ R ⁶ , and cyclopropyl. R ^9a may be independently selected at each occurrence from OR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ Ph, CO ₂ R ⁶ and cyclopropyl. [00195] R ^9b may be independently at each occurrence selected from the group comprising: H, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , - S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, 4-, 5- or 6- membered heterocycloalkyl, C _2-6 - alkenyl C _2-6 -alkynyl and C ₂ -C ₃ -alkylene-R ^9a . R ^9b may be independently at each occurrence selected from the group comprising: H, C ₁ -C ₄ -alkyl, C(O)R ¹⁰ , C(O)OR ¹⁰ , - S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, and C ₂ -C ₃ -alkylene-R ^9a . R ^9b may be selected from the group comprising: H, C _1-4 alkyl, C(O)R ¹⁰ , and C ₂ -C ₃ -alkylene-R ^9a . R ^9b may be H. R ^9b may be C ₁ -C ₄ -alkyl, e.g. methyl, ethyl, propyl. R ^9b may be C(O)R ¹⁰ , e.g. C(O)Me, C(O)Et. R ^9b may be C ₂ -C ₃ -alkylene-R ^9a ¸e.g. CH ₂ CH ₂ R ^9a , CH ₂ CH ₂ CH ₂ R9 ^a . [00196] R ^9b may be independently at each occurrence selected from the group comprising: H, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ⁶ , - S(O) ₂ R ⁶ , -S(O) ₂ NR ⁶ R ⁶ , C _3-6 cycloalkyl, 4-, 5- or 6- membered heterocycloalkyl, C _2-6 - alkenyl C _2-6 -alkynyl and C ₂ -C ₃ -alkylene-R ^9a . R ^9b may be independently at each occurrence selected from the group comprising: H, C ₁ -C ₄ -alkyl, C(O)R ⁶ , C(O)OR ⁶ , - S(O) ₂ R ⁶ , -S(O) ₂ NR ⁶ R ⁶ , C _3-6 cycloalkyl, and C ₂ -C ₃ -alkylene-R ^9a . R ^9b may be selected from the group comprising: H, C _1-4 alkyl, C(O)R ⁶ , and C ₂ -C ₃ -alkylene-R ^9a . R ^9b may be H. R ^9b may be C ₁ -C ₄ -alkyl, e.g. methyl, ethyl, propyl. R ^9b may be C(O)R ⁶ , e.g. C(O)Me, C(O)Et. R ^9b may be C ₂ -C ₃ -alkylene-R ^9a ¸e.g. CH ₂ CH ₂ R ^9a , CH ₂ CH ₂ CH ₂ R9 ^a . [00197] R ^9b may be independently at each occurrence selected from the group comprising: C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C(O)R ¹⁰ , C(O)OR ¹⁰ , C(O)NR ⁶ R ¹⁰ , -S(O)R ¹⁰ , - S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, 4-, 5- or 6- membered heterocycloalkyl, C _2-6 - alkenyl C _2-6 -alkynyl and C ₂ -C ₃ -alkylene-R ^9a . R ^9b may be independently at each occurrence selected from the group comprising: C ₁ -C ₄ -alkyl, C(O)R ¹⁰ , C(O)OR ¹⁰ , - S(O) ₂ R ¹⁰ , -S(O) ₂ NR ⁶ R ¹⁰ , C _3-6 cycloalkyl, and C ₂ -C ₃ -alkylene-R ^9a . R ^9b may be selected from the group comprising: C _1-4 alkyl, C(O)R ¹⁰ , and C ₂ -C ₃ -alkylene-R ^9a . R ^9b may be C ₁ - C ₄ -alkyl, e.g. methyl, ethyl, propyl. R ^9b may be C(O)R ¹⁰ , e.g. C(O)Me, C(O)Et. R ^9b may be C ₂ -C ₃ -alkylene-R ^9a ¸e.g. CH ₂ CH ₂ R ^9a , CH ₂ CH ₂ CH ₂ R9 ^a . [00198] R ¹⁰ may be independently selected at each occurrence from the group comprising: H, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₀ -C ₆ -alkylene-R ^10a , C _3-8 cycloalkyl, and 4-, 5-, 6-, 7- or 8- membered heterocycloalkyl. R ¹⁰ may be independently selected at each occurrence from the group comprising: H, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, and C ₀ -C ₆ - alkylene-R ^10a . R ¹⁰ may be independently selected at each occurrence from the group comprising: H, C ₁ -C ₄ -alkyl, and C ₀ -C ₃ -alkylene-R ^10a . It may be that R ¹⁰ is H. It may be that R ¹⁰ is -C _1-4 alkyl, e.g. methyl, ethyl, propyl. R ¹⁰ may be C ₀ -C ₃ -alkylene-R ^10a , e.g. - R ^10a , -CH ₂ R ^10a , -CH ₂ CH ₂ R ^10a or -CH ₂ CH ₂ CH ₂ R ^10a . [00199] R ¹⁰ may be independently selected at each occurrence from the group comprising: H, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkylene-R ^10a , C _3-8 cycloalkyl, and 4-, 5-, 6-, 7- or 8- membered heterocycloalkyl. R ¹⁰ may be independently selected at each occurrence from the group comprising: H, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, and C ₁ -C ₆ - alkylene-R ^10a . R ¹⁰ may be independently selected at each occurrence from the group comprising: H, C ₁ -C ₄ -alkyl, and C ₁ -C ₃ -alkylene-R ^10a . It may be that R ¹⁰ is H. It may be that R ¹⁰ is -C _1-4 alkyl, e.g. methyl, ethyl, propyl. R ¹⁰ may be C ₁ -C ₃ -alkylene-R ^10a , e.g. - CH ₂ R ^10a , -CH ₂ CH ₂ R ^10a or -CH ₂ CH ₂ CH ₂ R ^10a . [00200] R ^10a may be independently selected at each occurrence from cyclopropyl, OR ⁶ , S(O) ₂ R ⁶ , NR ⁶ R ⁷ , CO ₂ R ⁶ and CONR ⁶ R ⁶ . R ^10a may be independently selected at each occurrence from OR ⁶ , NR ⁶ R ⁷ , and CO ₂ R ⁶ . [00201] R ¹¹ may be H. R ¹¹ may be -C _1-6 alkyl, e.g. methyl, ethyl, propyl. [00202] R ¹² may be selected from the group comprising: piperidyl, piperazyl, morpholinyl, and tetrahydropyran, optionally substituted with at least one R ¹³ group. It may be that R ¹² is piperidyl or piperazyl, optionally substituted with at least one R ¹³ group. [00203] R ¹³ may be independently at each occurrence selected from: =O, =S, halo, C ₁ - C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, -OR ⁶ , cyano, nitro, -NR ⁶ R ⁷ , -SR ⁶ , C(O)R ⁶ , C(O)OR ⁶ , C(O)NR ⁶ R ⁶ , -S(O)R ⁶ , -S(O) ₂ R ⁶ , -S(O) ₂ NR ⁶ R ⁶ , and C ₁ -C ₃ -alkylene-R ^13a ; wherein R ^13a is selected from OR ⁶ , SR ⁶ , S(O) ₂ R ⁶ , S(O) ₂ Ph, NR ⁶ R ⁷ , CO ₂ R ⁶ and CONR ⁶ R ⁶ . R ¹³ may be independently at each occurrence selected from: =O, halo, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, -OR ⁶ , cyano, -NR ⁶ R ⁷ , C(O)R ⁶ , C(O)OR ⁶ , and C(O)NR ⁶ R ⁶ . [00204] R ¹⁴ may be H. R ¹⁴ may be C _1- C ₃ -alkylene-R ^14a , e.g. -CH ₂ R ^14a , -CH ₂ CH ₂ R ^14a or - CH ₂ CH ₂ CH ₂ R ^14a . [00205] R ^14a may be selected from OR ⁶ , S(O) ₂ R ⁶ , NR ⁶ R ⁷ , CO ₂ R ⁶ and CONR ⁶ R ⁶ . R ^14a may be selected from OR ⁶ , NR ⁶ R ⁷ , and CO ₂ R ⁶ . R ^14a may be OR ⁶ , e.g. OH or OMe. R ^14a may be NR ⁶ R ⁷ , e.g. NH2, NHMe or NMe2. R ^14a may be CO ₂ R ⁶ , e.g. C(O)OH, C(O)OMe or C(O)OEt. [00206] R ¹⁵ may be independently selected at each occurrence from H, C _1-4 alkyl, C _1-4 haloalkyl and phenyl. R ¹⁵ may be independently selected at each occurrence from H and C _1-4 alkyl. R ¹⁵ may be H. R ¹⁵ may be -C _1-6 alkyl, e.g. methyl, ethyl, propyl. R ¹⁵ may be C _1-4 haloalkyl, e.g. trifluoromethyl. R ¹⁵ may be phenyl [00207] R ¹⁶ may be independently selected at each occurrence from H and C _1-4 alkyl, or the two R ¹⁶ groups together may form a cyclopropyl ring system. [00208] m may be 0. m may be an integer selected from 1, 2, 3, 4, 5, 6, and 7. m may be an integer selected from 0, 1, 2, 3, and 4. m may be an integer selected from 0, 1, and 2. Preferably, however, m is 0 or 1. [00209] n may be 0. Preferably, however, n is an integer selected from 1, 2, 3 and 4. n may be an integer selected from 1, 2 and 3. n may be 0 or 1. n may be 1. [00210] n1 may be 0. n1 may be an integer selected from 1 and 2. n1 may be 1. [00211] p may be 0. p may be an integer selected from 1, 2, 3, 4, and 5. p may be an integer selected from 0, 1, and 2. Preferably, however, p is 0 or 1. [00212] p3 may be an integer selected from 1, 2 or 3. p3 may be selected from 1 or 2. It may be that p3 is 1. It may be that p3 is 2. [00213] q may be 0. Q may be an integer selected from 1, 2, 3, and 4. Q may be an integer selected from 0, 1, and 2. Preferably, however, q is 0 or 1. [00214] r may be 0. R may be an integer selected from 1 and 2. Preferably, however, r is 0 or 1. [00215] x may be 0, 1, 2 or 3. X may be 0. X may be 1. X may be 2. X may be 3. [00216] y may be 0, 1, 2 or 3. Y may be 0. Y may be 1. Y may be 2. Y may be 3. [00217] The compounds of formulae (I), (Ia) or (Ib) may be selected from:

DETAILED DESCRIPTION [00218] The chemical terms used in the specification have their generally accepted meanings in the art. [00219] The term C _m -C _n refers to a group with m to n carbon atoms. [00220] The term “halo” refers to fluoro, chloro, bromo and iodo. [00221] The term “alkyl” refers to a linear or branched saturated monovalent hydrocarbon chain. For example, C ₁ -C ₆ -alkyl may refer to methyl, ethyl, n-propyl, iso- propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl and n-hexyl. The alkyl groups may be unsubstituted or substituted by one or more substituents. Specific substituents for each alkyl group independently may be fluorine, OR ^a or NHR ^a . [00222] The term “alkylene” refers to a linear saturated divalent hydrocarbon chain. The alkylene groups may be unsubstituted or substituted by one or more substituents. Specific substituents for each alkylene group independently may be C ₁ -C ₄ -alkyl, fluorine, OR ^a or NHR ^a . [00223] The term “haloalkyl” refers to a hydrocarbon group substituted with at least one halogen atom independently chosen at each occurrence from: fluorine, chlorine, bromine and iodine. The halogen atom may be present at any position on the hydrocarbon chain. For example, C ₁ -C ₆ -haloalkyl may refer to chloromethyl, fluoromethyl, trifluoromethyl, chloroethyl e.g.1-chloroethyl and 2-chloroethyl, trichloroethyl e.g.1,2,2-trichloroethyl, 2,2,2-trichloroethyl, fluoroethyl e.g.1-fluoroethyl and 2-fluoroethyl, trifluoroethyl e.g.1,2,2-trifluoroethyl and 2,2,2-trifluoroethyl, chloropropyl, trichloropropyl, fluoropropyl, trifluoropropyl. A haloalkyl group may be a fluoroalkyl group, i.e. a hydrocarbon chain substituted with at least one fluorine atom. Thus, a haloalkyl group may have any amount of halogen substituents. The group may contain a single halogen substituent, it may have two or three halogen substituents, or it may be saturated with halogen substituents. [00224] The term “alkenyl” refers to a branched or linear hydrocarbon group containing at least one double bond. The double bond(s) may be present as the E or Z isomer. The double bond may be at any possible position of the hydrocarbon chain; for example, “C ₂ -C ₆ -alkenyl” may refer to ethenyl, propenyl, butenyl, butadienyl, pentenyl, pentadienyl, hexenyl and hexadienyl. The alkenyl groups may be unsubstituted or substituted by one or more substituents. Specific substituents for any saturated carbon atom in each alkenyl group independently may be fluorine, OR ^a or NHR ^a . [00225] The term “alkynyl” refers to a branched or linear hydrocarbon chain containing at least one triple bond. The triple bond may be at any possible position of the hydrocarbon chain. For example, “C ₂ -C ₆ -alkynyl” may refer to ethynyl, propynyl, butynyl, pentynyl and hexynyl. The alkynyl groups may be unsubstituted or substituted by one or more substituents. Specific substituents for any saturated carbon atom in each alkynyl group independently may be fluorine, OR ^a or NHR ^a . [00226] The term “cycloalkyl” refers to a saturated hydrocarbon ring system containing, for example, 3, 4, 5 or 6 carbon atoms. For example, “C3-C ₆ -cycloalkyl” may refer to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. The cycloalkyl groups may be unsubstituted or substituted by one or more substituents. Specific substituents for each cycloalkyl group independently may be fluorine, OR ^a or NHR ^a . [00227] The term “heterocycloalkyl” may refer to a monocyclic or bicyclic saturated or partially saturated group having the indicated number of atoms in the ring system and comprising 1, 2 or 3 heteroatoms independently selected from O, S and N in the ring system (in other words 1, 2 or 3 of the atoms forming the ring system are selected from O, S and N). By saturated (or fully saturated) it is meant that the ring does not comprise any double bonds. By partially saturated it is meant that the ring may comprise one or two double bonds. This applies particularly to monocyclic rings with from 5 to 6 members. The double bond will typically be between two carbon atoms but may be between a carbon atom and a nitrogen atom. Examples of heterocycloalkyl groups include; piperidine, piperazine, morpholine, thiomorpholine, pyrrolidine, tetrahydrofuran, tetrahydrothiophene, dihydrofuran, tetrahydropyran, dihydropyran, dioxane, azepine. A heterocycloalkyl group may be unsubstituted or substituted by one or more substituents. Specific substituents for any saturated carbon atom in each heterocycloalkyl group may independently be fluorine, OR ^a or NHR ^a . [00228] Aryl groups may be any aromatic carbocyclic ring system (i.e. a ring system containing 2(2n + 1)π electrons). Aryl groups may have from 6 to 12 carbon atoms in the ring system. Aryl groups will typically be phenyl groups. Aryl groups may be naphthyl groups or biphenyl groups. [00229] In any of the above aspects and embodiments, heteroaryl groups may be any aromatic (i.e. a ring system containing 2(2n + 1)π electrons) 5-10 membered ring system comprising from 1 to 4 heteroatoms independently selected from O, S and N (in other words from 1 to 4 of the atoms forming the ring system are selected from O, S and N). Thus, any heteroaryl groups may be independently selected from: 5 membered heteroaryl groups in which the heteroaromatic ring is substituted with 14 heteroatoms independently selected from O, S and N; and 6-membered heteroaryl groups in which the heteroaromatic ring is substituted with 1-3 (e.g.1-2) nitrogen atoms; 9-membered bicyclic heteroaryl groups in which the heteroaromatic system is substituted with 1-4 heteroatoms independently selected from O, S and N; 10-membered bicyclic heteroaryl groups in which the heteroaromatic system is substituted with 1-4 nitrogen atoms. Specifically, heteroaryl groups may be independently selected from: pyrrole, furan, thiophene, pyrazole, imidazole, oxazole, isoxazole, triazole, oxadiazole, thiadiazole, tetrazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, indole, isoindole, benzofuran, isobenzofuran, benzothiophene, indazole, benzimidazole, benzoxazole, benzothiazole, benzisoxazole, purine, quinoline, isoquinoline, cinnoline, quinazoline, quinoxaline, pteridine, phthalazine, naphthyridine. [00230] It may be that, in any group which is an aryl or heteroaryl group, that aryl or heteroaryl group is unsubstituted or is optionally substituted, where chemically possible, by 1 to 5 substituents which are each independently selected at each occurrence from: halo, nitro, cyano, NR ^a R ^a , NR ^a S(O) ₂ R ^a , NR ^a C(O)R ^a , NR ^a CONR ^a R ^a , NR ^a CO ₂ R ^a , OR ^a , SR ^a , S(O)R ^a , S(O) ₂ OR ^a , S(O) ₂ R ^a , S(O) ₂ NR ^a R ^a _, CO ₂ R ^a C(O)R ^a , CONR ^a R ^a , CR ^b R ^b NR ^a R ^a , CR ^b R ^b OR ^a , C ₁ -C ₄ -alkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl and C ₁ - C ₄ -haloalkyl; wherein R ^a and R ^b are as described above for formula I. [00231] Compounds of the invention containing one or more asymmetric carbon atoms can exist as two or more stereoisomers. Where a compound of the invention contains a double bond such as a C=C or C=N group, geometric cis/trans (or Z/E) isomers are possible. Where structural isomers are interconvertible via a low energy barrier, tautomeric isomerism (‘tautomerism’) can occur. This can take the form of proton tautomerism in compounds of the invention containing, for example, an imino, keto, or oxime group, or so- called valence tautomerism in compounds which contain an aromatic moiety. It follows that a single compound may exhibit more than one type of isomerism. [00232] Included within the scope of the present invention are all stereoisomers, geometric isomers and tautomeric forms of the compounds of the invention, including compounds exhibiting more than one type of isomerism, and mixtures of one or more thereof. [00233] The compounds of the invention may be obtained, stored and/or used in the form of a pharmaceutically acceptable salt. Suitable salts include, but are not limited to, salts of acceptable inorganic acids such as hydrochloric, sulfuric, phosphoric, nitric, carbonic, boric, sulfamic, and hydrobromic acids, or salts of pharmaceutically acceptable organic acids such as acetic, propionic, butyric, tartaric, maleic, hydroxymaleic, fumaric, malic, citric, lactic, mucic, gluconic, benzoic, succinic, oxalic, phenylacetic, methanesulfonic, toluenesulfonic, benzenesulfonic, salicylic, sulfanilic, aspartic, glutamic, edetic, stearic, palmitic, oleic, lauric, pantothenic, tannic, ascorbic and valeric acids. Suitable salts also include salts of inorganic and organic bases, e.g. counterions such as Na, Ca, K, Li, Mg, ammonium, trimethylsulfonium. The compounds may also be obtained, stored and/or used in the form of an N-oxide. Also included are acid addition salts or base salts wherein the counter ion is optically active; for example, d-lactate or l- lysine, or racemic; for example, dl-tartrate or dl-arginine. [00234] Cis/trans isomers may be separated by conventional techniques well known to those skilled in the art, for example, chromatography and fractional crystallisation. [00235] Conventional techniques for the preparation/isolation of individual enantiomers when necessary include chiral synthesis from a suitable optically pure precursor or resolution of the racemate (or the racemate of a salt or derivative) using, for example, chiral high pressure liquid chromatography (HPLC). Thus, chiral compounds of the invention (and chiral precursors thereof) may be obtained in enantiomerically-enriched form using chromatography, typically HPLC, on an asymmetric resin with a mobile phase consisting of a hydrocarbon, typically heptane or hexane, containing from 0 to 50% by volume of isopropanol, typically from 2% to 20%, and for specific examples, 0 to 5% by volume of an alkylamine e.g.0.1% diethylamine. Concentration of the eluate affords the enriched mixture. [00236] Alternatively, the racemate (or a racemic precursor) may be reacted with a suitable optically active compound, for example, an alcohol, or, in the case where the compound of the invention contains an acidic or basic moiety, a base or acid such as 1- phenylethylamine or tartaric acid. The resulting diastereomeric mixture may be separated by chromatography and/or fractional crystallisation and one or both of the diastereoisomers converted to the corresponding pure enantiomer(s) by means well known to a skilled person. [00237] When any racemate crystallises, crystals of two different types are possible. The first type is the racemic compound (true racemate) referred to above wherein one homogeneous form of crystal is produced containing both enantiomers in equimolar amounts. The second type is the racemic mixture or conglomerate wherein two forms of crystal are produced in equimolar amounts each comprising a single enantiomer. [00238] While both of the crystal forms present in a racemic mixture have identical physical properties, they may have different physical properties compared to the true racemate. Racemic mixtures may be separated by conventional techniques known to those skilled in the art – see for example, “Stereochemistry of Organic Compounds” by E. L. Eliel and S. H. Wilen (Wiley, 1994). [00239] It is to be understood that the present invention encompasses all isomeric forms and mixtures thereof that possess PLpro inhibitory activity. [00240] Methods for the determination of stereochemistry and the separation of stereoisomers are well-known in the art (see discussion in “Advanced Organic Chemistry”, 7th edition J. March, John Wiley and Sons, New York, 2013). [00241] Compounds of the Formula (I) containing an amine function may also form Noxides. A reference herein to a compound of the Formula (I) that contains an amine function also includes the N-oxide. Where a compound contains several amine functions, one or more than one nitrogen atom may be oxidised to form an N-oxide. Particular examples of N-oxides are the N-oxides of a tertiary amine or a nitrogen atom of a nitrogen-containing heterocycle. N-Oxides can be formed by treatment of the corresponding amine with an oxidizing agent such as hydrogen peroxide or a per-acid (e.g. a peroxycarboxylic acid); this is described in general textbooks such as Advanced Organic Chemistry, by J. March referred to above. N-oxides can be made in a variety of ways which are known to the skilled person; for example, by reacting the amine compound with m-chloroperoxybenzoic acid (mCPBA) in a solvent such as dichloromethane. [00242] The present invention also encompasses compounds of the invention as defined herein which comprise one or more isotopic substitutions. For example, H may be in any isotopic form, including 1H, 2H(D), and 3H (T); C may be in any isotopic form, including 12C, 13C, and 14C; and O may be in any isotopic form, including 16O and18O; and the like. Similarly, isotopic variants of N, S and P may be utilised. [00243] The term ‘Michael acceptor’ as used herein refers to an α,β-unsaturated carbonyl or α,β-unsaturated nitrile moiety capable of reacting with a resonance- stabilised nucleophile (i.e. a so-called ‘Michael donor’) in a Michael addition reaction. For example, the Michael acceptor of R ^4a may react with a cysteine residue in a Michael addition reaction to form a C-S bond, wherein the carbon atom of the C-S bond is present in the Michael acceptor and the sulfur atom of the C-S bond is from the SH of the cysteine residue (i.e. the Michael donor). [00244] Throughout the description and claims of this specification, the words “comprise” and “contain” and variations of them mean “including but not limited to”, and they are not intended to (and do not) exclude other moieties, additives, components, integers or steps. Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise. [00245] Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise. [00246] Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. [00247] The reader's attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference. [00248] According to another aspect of the present inventions, there is provided a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, in association with one or more pharmaceutically acceptable excipients. [00249] Compounds of the invention have been described throughout the present application as a compound or a salt of a compound. It would be understood by the skilled person that a compound can be converted into a salt and a salt can be converted into a compound, in other words the free acid or free base corresponding to the salt. Accordingly, where a compound is disclosed or where a salt is disclosed, the present invention also includes the corresponding salt form, free acid form or free base form, as appropriate. [00250] The compounds of the present invention are inhibitors of PLpro. As discussed above, PLpro plays a key role in viral replication. In particular, PLpro resides within viral polyprotein and is responsible for processing the polyprotein into its functional units. These functional units in turn assemble into complexes to execute viral RNA synthesis. Without wishing to be bound by theory, it is thought that selective inhibition of PLpro can prevent viral replication and can thus be used in the treatment of viral infections. [00251] Viral infections which can be treated using compounds of Formula (I) and compositions containing compounds of Formula (I) may include those caused by coronaviruses, rotaviruses, noroviruses, enteroviruses, hepatitis viruses (e.g. HAV, HBV, HCV), herpesviruses, papillomaviruses, arboviruses (e.g. West Nile virus, Zika virus, Dengue virus), ebolaviruses, rabies virus, or rubella virus. It may be that the viral infection in caused by coronaviruses. For example, the viral infection may be caused by one or more of the following: severe acute respiratory syndrome coronavirus (SARS- CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus OC43 (HCoV- OC43), human coronavirus HKU1 (HCoV-HKU1), human coronavirus 229E (HCoV- 229E), and human coronavirus NL63 (HCoV-NL63). [00252] In one aspect, the present invention provides a compound of formula (I) or pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the compound of formula (I) or pharmaceutically acceptable salt thereof for use in the inhibition of PLpro activity. [00253] In a further aspect, the compounds or compositions of the present invention may be for use in a method of treating and/or preventing a disease or disorder caused by coronaviruses, rotaviruses, noroviruses, enteroviruses, hepatitis viruses (e.g. HAV, HBV, HCV, HDV, HEV), herpesviruses, papillomaviruses, arboviruses (e.g. West Nile virus, Zika virus, Dengue virus), ebolaviruses, rabies virus, or rubella virus. It may be that the disease or disorder is selected from: coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), common cold, other coronavirus infections, gastroenteritis, viral meningitis, polio, hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E, infectious mononucleosis, human cytomegalovirus, chickenpox, viral warts, oral herpes, genital herpes, HSV encephalitis, West Nile fever, Zika fever, Dengue fever, Japanese encephalitis, tick- borne encephalitis, yellow fever, Ebola virus disease, rabies, and rubella. [00254] It may be that the disease or disorder is caused by coronaviruses. It may be that the disease or disorder is selected from: coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), common cold, or other coronavirus infections. [00255] The compounds of Formula (I) may be presented in dosage forms which are suitable for oral use (for example as tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixirs), or they may be suitable for topical use (for example as creams, ointments, gels, or aqueous or oily solutions or suspensions). Other suitable dosage forms also include those intended for administration by inhalation (for example as a finely divided powder or a liquid aerosol), for administration by insufflation (for example as a finely divided powder) or for parenteral administration (for example as a sterile aqueous or oily solution for intravenous, subcutaneous, intramuscular, intraperitoneal or intramuscular dosing or as a suppository for rectal dosing). In a preferred embodiment oral or intravenous administration is preferred, with intravenous administration being most preferred. [00256] Oral dosage formulations may contain, together with the active compound, one or more of the following excipients: diluents, lubricants, binding agents, desiccants, sweeteners, flavourings, colouring agents, wetting agents, and effervescing agents. [00257] Compound of formula (I) are inhibitors of PLpro and the present invention therefore provides a method of inhibiting viral PLpro activity in vitro or in vivo. This method comprises contacting a cell with an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, hydrate or solvate thereof, or contacting a cell with a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof. [00258] Accordingly, in one aspect of the invention, there is provided a method of inhibiting viral PLpro activity in vitro or in vivo, the method comprising contacting a cell with an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof; or contacting a cell with a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof. [00259] In another aspect, the present invention provides a method for the prevention or treatment of viral infection in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof; or administering to said patient a therapeutically effective amount of a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof. [00260] In another aspect, the present invention provides a method for the prevention or treatment of a disease or disorder, said method comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof; or administering to a patient in need of such treatment a therapeutically effective amount of a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof. [00261] It may be that the disease or disorder is selected from: coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), common cold, other coronavirus infections, gastroenteritis, viral meningitis, polio, hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E, infectious mononucleosis, human cytomegalovirus, chickenpox, viral warts, oral herpes, genital herpes, HSV encephalitis, West Nile fever, Zika fever, Dengue fever, Japanese encephalitis, tick-borne encephalitis, yellow fever, Ebola virus disease, rabies, and rubella. It may be that the disease or disorder is selected from: coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), common cold, or other coronavirus infections. [00262] In another aspect, the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition containing a compound of formula (I) or a pharmaceutically acceptable salt thereof, for use in therapy. [00263] In another aspect, the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing a compound of formula (I) or a pharmaceutically acceptable salt thereof, for use in the treatment of a viral infection. The treatment may be curative or preventative i.e. prophylactic. Preferably, the treatment is curative; this means that the treatment reduces the overall level of viral infection EXAMPLES The following compounds represent examples of compounds which can be synthesised in accordance with the invention. Some of the compounds were also tested in a biological assay and the results are presented below. The compounds show activity as inhibitors of papain-like protease (PLpro) and thus have utility in the treatment of viral infections, particularly coronaviruses infections. General Experimental Throughout this document the following abbreviations have been used: DCM – dichloromethane DIPEA – N,N-diisopropylethylamine DMF – N,N-dimethylformamide DMSO – dimethyl sulfoxide FCC – Flash Column Chromatography HBTU – N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate THF – tetrahydrofuran RT – room temperature R _T – retention time RuPhos – dicyclohexyl(2',6'-diisopropoxy-[1,1'-biphenyl]-2-yl)phosphi ne SCX – Strong Cation Exchange Xphos Pd G2 – chloro(2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl -1,1′-biphenyl)[2-(2′- amino-1,1′-biphenyl)]palladium(II) All intermediate materials used that are not described were obtained from commercial sources or have been previously described. Analytical Methods All ¹ H NMR spectra were obtained on a Bruker AVI 500 with 5 mm QNP. Chemical shifts are expressed in parts per million (δ) and are referenced to the solvent. Coupling constants J are expressed in Hertz (Hz). LC-MS were obtained on a Waters Alliance ZQ using the methods detailed below. Wavelengths were 254 and 210 nm. Method A Column: YMC-Triart C18, 2.0 × 50 mm, 5 µm. Flow rate: 0.8 mL/min. Injection volume: 6 µL. Mobile Phase: A = water, B = acetonitrile, C = 1:1 water:acetonitrile + 1.0% formic acid Method B Column: YMC-Triart C18, 2.0 × 50 mm, 5 µm. Flow rate: 0.8 mL/min. Injection volume: 6 µL. Mobile Phase: A = water, B = acetonitrile, C = 1:1 water:acetonitrile + 1.0% ammonia (aq.) General Procedure 1 The required amine (0.75-1 mmol) was added to the desired solvent, and to this was added the required carboxylic acid (1 mmol), HBTU (1 mmol) and DIPEA (3 mmol). The mixture was stirred under nitrogen at the described temperature for the described length of time. The described work-up and purification procedures were then followed to afford desired material. Example 1: Methyl (E)-4-[2-[3-[4-(4-methylpiperazin-1-yl)-2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoyl]hydrazino]-4-oxo-b ut-2-enoate Step A: Benzyl 5-bromo-2-iodo-benzoate Benzyl bromide (14.9 mL, 125.42 mmol), 5-bromo-2-iodo-benzoic acid (41 g, 125.4 mmol) and potassium carbonate (22.53 g, 163.04 mmol) were added to DMF (100 mL) and stirred for 4 days. The reaction was quenched with water (800 ml) extracted with petroleum ether (2 x 800 ml), dried and solvent evaporated to afford benzyl 5- bromo-2-iodo-benzoate (42.0 g, 80%) as a slightly yellow liquid. ¹ H NMR (500 MHz, CDCl ₃ ) δ = 7.92 (d, J=2.1 Hz, 1H), 7.83 (d, J=8.5 Hz, 1H), 7.49-7.44 (m, 2H), 7.43-7.31 (m, 3H), 7.30-7.24 (m, 1H), 5.37 (s, 2H). Step B: Benzyl 5-bromo-2-[(E)-3-methoxy-3-oxo-prop-1-enyl]benzoate Palladium(II) acetate (2.64 g, 11.8 mmol) then sodium hydrogen carbonate (24.7 g, 294 mmol) were added to a mixture of benzyl 5-bromo-2-iodo-benzoate (49.0 g, 118 mmol) and methyl acrylate (11.1 g, 129 mmol) in DMF (300 mL) to give a clear orange solution. Tetrabutylammonium chloride (81.6 g, 294 mmol) was added in one portion as a solid and the mixture was heated at 70 °C for 2 hours to afford a black solution. The mixture was diluted with water (400 ml), then extracted with diethyl ether. Purification by FCC (eluting with 60-100% diethyl ether in petroleum ether) gave benzyl 5-bromo-2-[(E)- 3-methoxy-3-oxo-prop-1-enyl]benzoate (22.7 g, 51%) as a yellow gum. ¹ H NMR (500 MHz, CDCl ₃ ) δ = 8.41-8.33 (m, 1H), 8.11 (d, J=2.1, 1H), 7.66 (dd, J=2.0, 8.4, 1H), 7.48- 7.43 (m, 3H), 7.43-7.35 (m, 3H), 6.29 (d, J=15.9, 1H), 5.37 (s, 2H), 3.80 (s, 3H). Step C: Benzyl 2-[(E)-3-methoxy-3-oxo-prop-1-enyl]-5-(4-methylpiperazin-1-y l)benzoate Palladium(II) acetate (23 mg, 102 μmol) was added to a degassed solution of benzyl 5- bromo-2-[(E)-3-methoxy-3-oxo-prop-1-enyl]benzoate (381 mg, 1.0 mmol), 1- methylpiperazine (112 mg, 1.1 mmol), RuPhos (95 mg, 204 μmol) and caesium carbonate (496 mg, 1.5 mmol) in anhydrous 1,4-dioxane (20 mL) and heated to 100 °C overnight under nitrogen. The reaction mixture was cooled to RT, diluted with 60% diethyl ether in petrol (80 mL), stirred for 10 mins and the reaction mixture filtered. The filtrate was collected and concentrated under reduced pressure to afford crude material which was purified by FCC (eluting with 5-30% MeOH in ethyl acetate to afford benzyl 2- [(E)-3-methoxy-3-oxo-prop-1-enyl]-5-(4-methylpiperazin-1-yl) benzoate as a yellow oil (255 mg, 64%). ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.36 (d, J=15.9, 1H), 8.85 (d, J=8.8, 1H), 7.46 (br d, J=7.2, 2H), 7.41-7.33 (m, 4H), 7.01 (dd J=8.7, 2.6, 1H), 6.22 (d, J=15.9, 1H), 5.38 (s, 2H), 3.77 (s, 3H), 3.33-3.27 (m, 4H), 2.58-2.52 (m, 4H), 2.35 (s, 3H). LC-MS (Method B): RT = 4.09 min, m/z = 395.6 [M+H] ⁺ . Step D: 2-(3-Methoxy-3-oxo-propyl)-5-(4-methylpiperazin-1-yl)benzoic acid A solution of benzyl 2-[(E)-3-methoxy-3-oxo-prop-1-enyl]-5-(4-methylpiperazin-1- yl)benzoate (255 mg, 646 μmol) in methanol (10 mL) was evacuated and the atmosphere replaced with nitrogen three times and left under nitrogen. Palladium hydroxide, 20% on carbon (91 mg, 65 μmol, 10% purity) was added to the reaction mixture, evacuated three times (vacuum/nitrogen), evacuated with vacuum, and then left under an atmosphere of hydrogen overnight at RT. The reaction mixture was filtered through a methanol pre-washed pad of celite, washed with methanol (2 x 20 mL) and the filtrate concentrated under reduced pressure, slurried in DCM/diethyl ether then diethyl ether/petroleum ether (1:1, 5 mL) and concentrated to afford 2-(3-methoxy-3-oxo- propyl)-5-(4-methylpiperazin-1-yl)benzoic acid (189 mg, 95%) as an off white solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ = 12.80 (br s, 1H), 7.30 (d, J=2.6, 1H), 7.14 (d, J=8.4, 1H), 7.05 (dd, J=2.5, 8.5, 1H), 3.57 (s, 3H), 3.13-3.11 (m, 4H), 3.05 (t, J=7.7, 2H), 2.56-2.54 (m, 2H), 2.46–2.44 (m, 4H), 2.22 (s, 3H). LC-MS (Method B): R _T = 0.46 min, m/z = 307.5 [M+H] ⁺ . Step E: Methyl 3-[4-(4-methylpiperazin-1-yl)-2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoate DIPEA (422 μL, 2.5 mmol) followed by HBTU (280 mg, 0.74 mmol) were added to a solution of (R)-(+)-1-(1-naphthyl)ethylamine (99 μL, 617 μmol) and 2-(3-methoxy-3-oxo- propyl)-5-(4-methylpiperazin-1-yl)benzoic acid (189 mg, 616 μmol) in DMF (5 mL) and stirred at RT for 1.5 hours. The reaction mixture was quenched with water (30 mL) and extracted with ethyl acetate (3 x 50 mL). The combined extracts were washed with 1:1 water/brine (2 x 20 mL), dried (MgSO ₄ ) and concentrated under reduced pressure to afford crude material. Purification by FCC (eluting with 5-60% MeOH in ethyl acetate) gave methyl 3-[4-(4-methylpiperazin-1-yl)-2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoate (236 mg, 79%) as a white solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ = 8.90 (d, J=7.9, 1H), 8.24 (d, J=8.4, 1H), 7.96 (d, J=7.9, 1H), 7.84 (d, J=8.2, 1H), 7.63 - 7.47 (m, 4H), 7.10 (d, J=8.5, 1H), 6.94 (dd, J=2.2, 8.3, 1H), 6.86 (d, J=2.3, 1H), 5.92 - 5.85 (m, 1H), 3.56 (s, 3H), 3.23 - 3.00 (m, 4H), 2.87 - 2.75 (m, 2H), 2.36 - 2.20 (m, 2H), 1.59 (d, J=6.9, 3H). LC-MS (Method B): RT = 3.71 min, m/z = 460.6 [M+H] ⁺ . Step F: 2-(3-Hydrazino-3-oxo-propyl)-5-(4-methylpiperazin-1-yl)-N-[( 1R)-1-(1- naphthyl)ethyl]benzamide Hydrazine hydrate (0.5 mL, 5.14 mmol, 50% purity) was added to a solution of methyl 3- [4-(4-methylpiperazin-1-yl)-2-[[(1R)-1-(1-naphthyl)ethyl]car bamoyl]phenyl]propanoate (66 mg, 144 μmol) in ethanol (5 mL) and heated to 90 °C for 5.5 hours under nitrogen. The reaction mixture was concentrated under reduced pressure, diluted with DCM (5 mL) then DCM/diethyl ether (1:1, 2 x 5 mL) and concentrated under reduced pressure to afford a white solid. The white solid was slurried with diethyl ether (3 x 5 mL), solvent decanted and the resulting solid dried under vacuum overnight to afford 2-(3-hydrazino- 3-oxo-propyl)-5-(4-methylpiperazin-1-yl)-N-[(1R)-1-(1-naphth yl)ethyl] benzamide (55 mg, 82%) as a white solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 8.92 (d, J=7.7, 1H), 8.89 (br s, 1H), 8.24 (d, J=8.5, 1H), 7.96 (d, J=8.1, 1H), 7.84 (d, J=8.2, 1H), 7.65-7.58 (m, 2H), 7.57-7.50 (m, 2H), 7.08 (d, J=8.4, 1H), 6.92 (dd, J=2.0, 8.4, 1H), 6.82 (d, J=1.8, 1H), 5.89 (quin, J=7.0, 1H), 4.13 (br s, 2H), 3.11-3.09 (m, 4H), 2.79 (br t, J=7.7, 2H), 2.45- 2.43 (m, 4H), 2.28 (br t, J=7.9, 2H), 2.22 (s, 3H), 1.59 (d, J=6.9, 3H). LC-MS (Method B): R _T = 2.99 min, m/z = 460.6 [M+H] ⁺ . Step G: Methyl (E)-4-[2-[3-[4-(4-methylpiperazin-1-yl)-2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoyl]hydrazino]-4-oxo-b ut-2-enoate DIPEA (52 μL, 300 μmol) followed by HBTU (46 mg, 120 μmol) were added to a solution of 2-(3-hydrazino-3-oxo-propyl)-5-(4-methylpiperazin-1-yl)-N-[( 1R)-1-(1- naphthyl)ethyl]benzamide (46 mg, 100 μmol) and (E)-4-methoxy-4-oxobut-2-enoic acid (14 mg, 110 μmol) in DCM (3 mL) and stirred for 5 hours at RT under nitrogen. The reaction mixture was recharged with (E)-4-methoxy-4-oxobut-2-enoic acid (14 mg, 110 μmol) and HBTU (46 mg, 120 μmol) and stirred overnight at RT. The reaction mixture was diluted with DCM (10 mL) and extracted with water (20 mL). The aqueous was washed with DCM (2 x 10 mL) and the washings combined with the original organic layer, extracted with sat. aq. NaHCO ₃ (2 x 10 mL), brine (10 mL), dried (MgSO ₄ ) and concentrated under reduced pressure to afford crude material. Purification by FCC (eluting with 10-80% MeOH/ethyl acetate) gave methyl (E)-4-[2-[3-[4-(4-methylpiperazin- 1-yl)-2-[[(1R)-1-(1-naphthyl)ethyl]carbamoyl]phenyl]propanoy l]hydrazino]-4-oxo-but-2- enoate (18 mg, 30%) as an off white solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ = 10.55 (br s, 1H), 10.16 (br s, 1H), 8.89 (br d, J=7.2, 1H), 8.24 (d, J=8.7, 1H), 7.96 (d, J=7.5, 1H), 7.83 (br d, J=8.4, 1H), 7.64-7.49 (m, 4H), 7.13 (d, J=8.4, 1H), 7.08 (d, J=15.6, 1H), 6.95-6.89 (m, 1H), 6.86-6.81 (m, 1H), 6.69 (d, J=15.6, 1H), 5.96-5.83 (m, 1H), 3.80-3.65 (m, 4H), 3.11 (br s, 4H), 2.83 (br s, 2H), 2.44 (br s, 4H), 2.22 (s, 2H), 1.59 (br d, J=7.0, 3H). LC-MS (Method B): R _T = 2.61 min, m/z = 571.0 [M+H] ⁺ . Example 2: Methyl (E)-4-[2-[3-[4-(1-methyl-4-piperidyl)-2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoyl]hydrazino]-4-oxo-b ut-2-enoate Step A: Benzyl 2-[(E)-3-methoxy-3-oxo-prop-1-enyl]-5-(1-methyl-3,6-dihydro- 2H-pyridin- 4-yl)benzoate Xphos Pd G2 (353 mg, 450 μmol) was added to a degassed solution of 1-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H -pyridine (2.65 g, 11.8 mmol), benzyl 5-bromo-2-[(E)-3-methoxy-3-oxo-prop-1-enyl]benzoate (3.37 g, 8.90 mmol) (Example 1, Step B), potassium phosphate tribasic (5.72 g, 26.9 mmol) in 1,4- dioxane (30 mL) and water (8 mL) and the reaction mixture heated to 60 °C for 2 hours under nitrogen. The reaction mixture was allowed to cool to RT and diluted with water (100 mL) and ethyl acetate (2 x 70 mL). The phases were separated, and the organic phase washed with brine (100 mL), dried (MgSO ₄ ) and concentrated under reduced pressure to afford crude. Crude was purified by FCC (eluting with 0-25% ethyl acetate in petroleum ether, followed by 0-100% MeOH in ethyl acetate) to afford benzyl 2-[(E)-3- methoxy-3-oxo-prop-1-enyl]-5-(1-methyl-3,6-dihydro-2H-pyridi n-4-yl)benzoate as a yellow oil (1.40 g, 40%). ¹ H NMR (500 MHz, CDCl ₃ ) δ = 8.42 (d, J=15.9, 1H), 7.99 (d, J=1.4, 1H), 7.58-7.52 (m, 2H), 7.46 (d, J=7.2, 2H), 7.41-7.32 (m, 3H), 6.30 (d, J=16.0, 1H), 6.20-6.15 (m, 1H), 5.38 (s, 2H), 3.79 (s, 3H), 3.13 (br d, J=3.1, 2H), 2.70-2.64 (m, 2H), 2.61-2.55 (m, 2H), 2.41 (s, 3H). LC-MS (Method B): RT = 4.44 min, m/z = 392.3 [M+H] ⁺ . Step B-E: Methyl (E)-4-[2-[3-[4-(1-methyl-4-piperidyl)-2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoyl]hydrazino]-4-oxo-b ut-2-enoate Procedures followed in a similar manner to procedures towards methyl (E)-4-[2-[3-[4-(4- methylpiperazin-1-yl)-2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoyl]hydrazino]-4-oxo-b ut-2-enoate (Example 1, Steps D-G) – using benzyl 2-[(E)-3-methoxy-3-oxo-prop-1-enyl]-5-(1-methyl-3,6-dihydro- 2H-pyridin-4-yl)benzoate in Step B – to afford methyl (E)-4-[2-[3-[4-(1-methyl-4- piperidyl)-2-[[(1R)-1-(1-naphthyl)ethyl]carbamoyl]phenyl]pro panoyl]hydrazino]-4-oxo-but- 2-enoate. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ = 10.54 (br s, 1H), 10.15 (br s, 1H), 9.01-8.86 (m, 1H), 8.30-8.19 (m, 1H), 8.02-7.89 (m, 1H), 7.88-7.80 (m, 1H), 7.67-7.45 (m, 5H), 7.23 (s, 2H), 7.15 (s, 1H), 7.08 (br d, J=15.8, 1H), 6.68 (br d, J=15.8, 1H), 5.98-5.86 (m, 1H), 3.75 (s, 3H), 2.95-2.81 (m, 5H), 2.19 (s, 3H), 1.99-1.90 (m, 2H), 1.74-1.62 (m, 5H), 1.60 (br d, J=6.7, 3H). LC-MS (Method B): R _T = 2.89 min, m/z = 569.6 [M-H]-. Example 3: tert-Butyl 4-[4-[3-[2-[(E)-4-methoxy-4-oxo-but-2-enoyl]hydrazino]-3-oxo - propyl]-3-[[(1R)-1-(1-naphthyl)ethyl]carbamoyl]phenyl]-1,4-d iazepane-1-carboxylate

Oxalyl chloride (65 μL, 748 μmol) followed by DMF (10 μL, 129 μmol) were added to a solution of (E)-4-methoxy-4-oxobut-2-enoic acid (94 mg, 721 μmol) in DCM (20 mL) and stirred at RT for 20 mins under nitrogen. The reaction mixture was cooled to -78 °C, then DIPEA (250 μL, 1.46 mmol) added followed by a solution of tert-butyl 4-[4-(3- hydrazino-3-oxo-propyl)-3-[[(1R)-1-(1-naphthyl)ethyl]carbamo yl]phenyl]-1,4-diazepane- 1-carboxylate (269 mg, 481 μmol) – prepared in a similar manner to 2-(3-hydrazino-3- oxo-propyl)-5-(4-methylpiperazin-1-yl)-N-[(1R)-1-(1-naphthyl )ethyl]benzamide (Example 1, Step F), using the required commercially available secondary amine in Step C – in DCM (5 mL). The reaction mixture was stirred for 5 mins, allowed to warm to RT and stirred for a further 1 hour. The reaction mixture was diluted with DCM (20 mL) and water (50 mL) and the resulting layers separated. The aqueous was further washed with DCM (2 x 20 mL) and the washings combined with the original organic layer, dried (MgSO ₄ ) and concentrated under reduced pressure to afford crude material. Purification by FCC (eluting with 0-20% MeOH in ethyl acetate) gave tert-butyl 4-[4-[3-[2-[(E)-4- methoxy-4-oxo-but-2-enoyl]hydrazino]-3-oxo-propyl]-3-[[(1R)- 1-(1- naphthyl)ethyl]carbamoyl]phenyl]-1,4-diazepane-1-carboxylate (145 mg, 42%) as a yellow solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ = 10.54 (s, 1H), 10.15 (s, 1H), 8.82-8.72 (m, 1H), 8.24 (d, 8.5, 1H), 7.96 (d, J=8.1, 1H), 7.84 (d, J=8.1, 1H), 7.66-7.57 (m, 2H), 7.56-7.50 (m, 2H), 7.12-7.05 (m (contains d, J=15.6, 1H), 2H), 6.78-6.71 (m, 1H), 6.69 (d, J=15.6, 1H), 6.63-6.57 (m, 1H), 5.89 (quin, J=7.1, 1H), 3.75 (s, 3H), 3.57-3.44 (m, 6H), 3.25-3.12 (m, 2H), 2.85-2.76 (m, 2H), 2.46-2.41 (m, 2H), 1.84-1.74 (m, 2H), 1.69 (br d, J=6.9, 3H), 1.32-1.21 (m, 9H). LC-MS (Method B): R _T = 2.76 min, m/z = 672.5 [M+H] ⁺ . Further Examples The following examples were prepared in a similar manner to tert-butyl 4-[4-[3-[2-[(E)-4- methoxy-4-oxo-but-2-enoyl]hydrazino]-3-oxo-propyl]-3-[[(1R)- 1-(1- naphthyl)ethyl]carbamoyl]phenyl]-1,4-diazepane-1-carboxylate (Example 3), using the required commercially available carboxylic acid. Regioisomeric examples were synthesised from commercially available 4-bromo-2-iodo-benzoic acid.

Example 10: Methyl (E)-4-[2-[3-[4-(1,4-diazepan-1-yl)-2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoyl]hydrazino]-4-oxo-b ut-2-enoate hydrochloride salt

Hydrogen chloride solution, 4N in 1,4-dioxane (0.1 mL) was added to a solution of tert- butyl 4-[4-[3-[2-[(E)-4-methoxy-4-oxo-but-2-enoyl]hydrazino]-3-oxo -propyl]-3-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]-1,4-diazepane-1-carboxylate (44 mg, 65 μmol) (Example 3) in DCM (3 mL) and 1,4-dioxane (1 mL) and stirred at RT overnight. The reaction mixture was recharged with hydrogen chloride solution, 4N in 1,4-dioxane (0.1 mL) and stirred for a further 5 hours. The reaction mixture was concentrated under reduced pressure to afford an off-white solid which was slurried in diethyl ether (10 mL) and stirred overnight at RT. The slurry was filtered and dried under vacuum filtration to afford methyl (E)-4-[2-[3-[4-(1,4-diazepan-1-yl)-2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoyl]hydrazino]-4-oxo-b ut-2-enoate hydrochloride salt (37 mg, 84%) as an off white solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ = 10.56 (s, 1H), 10.17 (s, 1H), 8.87 (br d, J=7.8, 1H), 8.84-8.67 (m, 2H), 8.24 (br d, J=8.5, 1H), 7.96 (d, J=7.8, 1H), 7.84 (d, J=7.8, 1H), 7.70-7.50 (m, 4H), 7.13 (d, J=8.5, 1H), 7.09 (d, J=15.9, 1H), 6.80-6.75 (m, 1H), 6.69 (d, J=15.3, 1H), 6.65 (br s, 1H), 5.96-5.82 (m, 1H), 3.75 (s, 3H), 3.69-3.67 (m, 3H), 3.25-3.18 (m, 2H), 3.15-3.07 (m, 2H), 2.87-2.78 (m, 2H), 2.49- 2.43 (m, 2H), 2.05 (br d, 2H), 1.60 (br d, J=6.6, 3H). LC-MS (Method B): R _T = 2.46 min, m/z = 570.5 [M-H]-. The following examples were prepared in a similar manner to methyl (E)-4-[2-[3-[4-(1,4- diazepan-1-yl)-2-[[(1R)-1-(1-naphthyl)ethyl]carbamoyl]phenyl ]propanoyl]hydrazino]-4- oxo-but-2-enoate hydrochloride salt (Example 10), using the intermediate example described.

Example 12: Methyl (E)-4-[2-[3-[4-[4-(cyclopropylmethyl)piperazin-1-yl]-2-[[(1R )-1-(3,4- dimethoxyphenyl) ethyl]carbamoyl]phenyl]propanoyl]hydrazino]-4-oxo-but-2-enoa te Step A: Methyl 3-[2-[[(1R)-1-(3,4-dimethoxyphenyl)ethyl]carbamoyl]-4-pipera zin-1-yl- phenyl]propanoate hydrochloride salt tert-Butyl 4-[3-[[(1R)-1-(3,4-dimethoxyphenyl)ethyl]carbamoyl]-4-(3-met hoxy-3-oxo- propyl)phenyl]piperazine-1-carboxylate (1.39 g, 2.50 mmol) – prepared in a similar manner to methyl 3-[4-(4-methylpiperazin-1-yl)-2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoate (Example 1, Step E), using the required commercially available secondary amine in Step C – was dissolved in DCM (2 ml). To this was added hydrogen chloride solution, 4N in 1,4-dioxane (10 mL) and the mixture was stirred for 20 mins. The reaction was diluted with diethyl ether (70 ml) and stirred for 20 mins before being filtered under nitrogen to afford methyl 3-[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]-4-piperazin-1-yl-phenyl]pro panoate (1.20 g, 98%) as a white solid. LC-MS (Method B): RT = 2.89 min, m/z = 454.4 [M-H]-. Step B: Methyl 3-[4-[4-(cyclopropylmethyl)piperazin-1-yl]-2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]propanoate Bromomethyl cyclopropane (572 mg, 4.24 mmol), methyl 3-[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]-4-piperazin-1-yl-phenyl]pro panoate hydrochloride salt (1.39 g, 2.83 mmol) and potassium carbonate (585 mg, 4.24 mmol) were added to DMF (25 mL) and heated at 50 °C for 5 hours. The reaction was quenched with water (50 ml), extracted with diethyl ether (100 ml), dried and solvent evaporated to afford a yellow gum. To this was added 60% diethyl ether in petroleum ether and the mixture was left standing overnight to afford a solid which was sonicated with 60% diethyl ether in petroleum ether to afford a solid which was filtered to give methyl 3-[4-[4- (cyclopropylmethyl)piperazin-1-yl]-2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]propanoate (850 mg, 58%) as a white solid. LC-MS (Method B): R _T = 3,35 min, m/z = 508.5 [M-H]-. Step C: 5-[4-(Cyclopropylmethyl)piperazin-1-yl]-N-[(1R)-1-(3,4-dimet hoxyphenyl)ethyl]- 2-(3-hydrazino-3-oxo-propyl)benzamide Methyl 3-[4-[4-(cyclopropylmethyl)piperazin-1-yl]-2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]propanoate (850 mg, 1.67 mmol) and hydrazine hydrate (2 ml) were added to ethanol (20 mL) and heated at reflux for 5 hours. The mixture was evaporated to afford a solid which was dissolved in DCM (1 mL) and diluted with 60% diethyl ether in petroleum ether to afford a solid which was filtered and dried to give 5-[4-(cyclopropylmethyl)piperazin-1-yl]-N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]-2-(3-hydrazino-3-oxo-propyl)benzamide (500 mg, 59%) as a white solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ = 7.42 (s, 1H), 7.11 (d, J=8.9, 1H), 6.97-6.92 (m, 2H), 6.92-6.85 (m, 3H), 6.57 (br d, J=7.9, 1H), 5.26 (quin, J=7.2, 1H), 3.90 (s, 3H), 3.89-3.87 (m, 3H), 3.75 (br d, J=2.1, 2H), 3.23-3.16 (m, 4H), 2.91 (qt, J=7.1, 14.6, 2H), 2.71-2.64 (m, 4H), 2.56-2.44 (m, 2H), 2.31 (d, J=6.7, 2H), 1.57-1.56 (m, 3H), 0.95-0.83 (m, 1H), 0.57-0.52 (m, 2H), 0.13 (q, J=4.8, 2H). LC-MS (Method B): RT = 2.71 min, m/z = 508.4 [M-H]-. Step D: Methyl (E)-4-[2-[3-[4-[4-(cyclopropylmethyl)piperazin-1-yl]-2-[[(1R )-1-(3,4- dimethoxyphenyl) ethyl]carbamoyl]phenyl]propanoyl]hydrazino]-4-oxo-but-2-enoa te (E)-4-Methoxy-4-oxo-but-2-enoic acid (30.6 mg, 235 μmol) was dissolved in (10 mL) to this was added triethylamine (82.1 μL, 588 μmol) and then oxalyl chloride (20.5 μL, 235.46 μmol) along with 1 drop of DMF. The reaction was stirred for 10 mins under nitrogen. The reaction was cooled to -78 °C and to this was added 5-[4- (cyclopropylmethyl)piperazin-1-yl]-N-[(1R)-1-(3,4-dimethoxyp henyl)ethyl]-2-(3-hydrazino- 3-oxo-propyl)benzamide (100 mg, 196 μmol) and the bath was removed and the mixture was stirred for 2 hours. The reaction was quenched with water (50 mL), extracted with DCM (50 mL), dried and solvent evaporated to afford a solid. Purification by FCC (eluting with ethyl acetate and then 30% MeOH in ethyl acetate) gave methyl (E)-4-[2-[3- [4-[4-(cyclopropylmethyl)piperazin-1-yl]-2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl] propanoyl]hydrazino]-4-oxo-but-2-enoate (38 mg, 31%) as a white solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ = 10.52-10.33 (m, 1H), 10.06 (br s, 1H), 8.54 (br d, J=8.2, 1H), 7.03 (br d, J=8.5, 1H), 6.96 (d, J=15.6, 1H), 6.90 (s, 1H), 6.84 (br s, 1H), 6.80 (brs, 2H), 6.71 (br d, J=2.4, 1H), 6.57 (d, J=15.6, 1H), 5.09- 4.71 (m, 1H), 3.72-3.49 (m, 6H), 3.22 (s, 3H), 3.12-2.94 (m, 4H), 2.69 (br d, J=7.6, 2H), 2.54-2.48 (br s, 4H), 2.38-2.32 (m, 2H), 2.12 (br d, J=6.7, 2H), 1.31 (br d, J=7.0, 3H), 0.76 (br s, 1H), 0.38 (br d, J=6.7, 2H), 0.06--0.15 (m, 2H). LC-MS (Method B): R _T = 2.18 min, m/z = 620.5 [M-H]-. The following examples were prepared in a similar manner to methyl (E)-4-[2-[3-[4-[4- (cyclopropylmethyl)piperazin-1-yl]-2-[[(1R)-1-(3,4-dimethoxy phenyl) ethyl]carbamoyl]phenyl] propanoyl]hydrazino]-4-oxo-but-2-enoate (Example 12), using the required commercially available primary amine, and the required commercially available secondary amine.

Example 16: 5-[4-(Cyclopropylmethyl)piperazin-1-yl]-N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]-2-[3-oxo-3-(2-prop-2-enoylhydrazino)p ropyl]benzamide 5-[4-(Cyclopropylmethyl)piperazin-1-yl]-N-[(1R)-1-(3,4-dimet hoxyphenyl)ethyl]-2-(3- hydrazino-3-oxo-propyl)benzamide (100 mg, 196 μmol) (Example 12, Step D) was added to DCM (10 mL). To this was added triethylamine (41.0 μL, 294 μmol) and then prop-2-enoyl chloride (19.2 μL, 235 μmol) and the mixture was stirred overnight to afford a solid. The reaction was quenched with water (20 ml) and stirred, the undissolved solid was filtered to afford 5-[4-(cyclopropylmethyl)piperazin-1-yl]-N-[(1R)-1- (3,4-dimethoxyphenyl)ethyl]-2-[3-oxo-3-(2-prop-2-enoylhydraz ino)propyl]benzamide (24 mg, 22%) as a white solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ = 9.97 (s, 1H), 9.84 (s, 1H), 8.55 (br d, J=8.2, 1H), 7.04 (d, J=8.5, 1H), 6.93 (s, 1H), 6.84 (br dd, J=2.4, 8.2, 1H), 6.82-6.79 (m, 2H), 6.74-6.70 (m, 1H), 6.26-6.13 (m, 1H), 6.12-6.05 (m, 1H), 5.61 (dd, J=2.0, 10.2, 1H), 4.95-4.03 (m, 1H), 3.66 (s, 3H), 3.65-3.62 (m, 3H), 3.04 (br s, 4H), 2.71 (br t, J=7.3, 2H), 2.48 (br s, 4H), 2.38-2.28 (m, 2H), 2.17-2.10 (m, 2H), 1.32 (d, J=7.0, 3H), 0.84 - 0.66 (m, 1H), 0.39 (br d, J=7.9, 2H), 0.00 (br d, J=4.6, 2H). LC-MS (Method B): RT = 2.64 min, m/z = 562.5 (M-H)-. Example 17: Methyl (E)-4-[2-[3-[2-[[(1R)-1-[3-methoxy-5-(1-methylpyrazol-4- yl)phenyl]ethyl]carbamoyl]phenyl]propanoyl]hydrazino]-4-oxo- but-2-enoate Step A: (NE,S)-N-[(3-Bromo-5-methoxy-phenyl)methylene]-2-methyl-prop ane-2- sulfinamide (S)-2-Methylpropane-2-sulfinamide (29.0 g, 239 mmol) and 3-bromo-5-methoxy- benzaldehyde (49.0 g, 228 mmol) were added to DCM (100 mL) and stirred until solids dissolved. To this was added cesium carbonate (74.2 g, 228 mmol) and the mixture was stirred at reflux for 2 hours. The reaction was then cooled and diluted with diethyl ether (100 mL) with stirring. The resulting precipitate was removed by filtration, then the liquor concentrated to afford (NE,S)-N-[(3-bromo-5-methoxy-phenyl)methylene]-2-methyl- propane-2-sulfinamide (65.0 g, 89%) as a yellow gum. ¹ H NMR (500 MHz, CDCl ₃ ) δ = 8.47 (s, 1H), 7.58 (t, J=1.4, 1H), 7.29 (dd, J=1.3, 2.1, 1H), 7.20 (t, J=2.1, 1H), 3.85 (s, 3H), 1.27 (s, 9H). Step B: (S)-N-[(1R)-1-(3-Bromo-5-methoxy-phenyl)ethyl]-2-methyl-prop ane-2- sulfinamide (NE,S)-N-[(3-Bromo-5-methoxy-phenyl)methylene]-2-methyl-prop ane-2-sulfinamide (21.0 g, 66.0 mmol) was dissolved in DCM (170 mL) and cooled to 0 °C, then methylmagnesium bromide solution (3.0 M, 28.6 mL) was slowly added to the mixture to afford a yellow solution. The reaction was allowed to warm to RT, then stirred overnight. The reaction was carefully quenched with ammonium chloride (sat. aq., 150 mL) and water (100 mL), the DCM layer was obtained, dried and solvent evaporated to afford a yellow gum. The gum was dissolved in 20% diethyl ether in petroleum ether and stirred to afford a solid which was filtered and dried to give (S)-N-[(1R)-1-(3-bromo-5- methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfinamide (17.8 g, 81%) as a white solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ = 7.09-7.03 (m, 1H), 6.95 (t, J=2.0, 1H), 6.84-6.76 (m, 1H), 4.50 (dd, J=3.2,6.7, 1H), 3.79 (s, 3H), 3.28 (br d, J=2.7, 1H), 1.53-1.48 (m, 3H), 1.24- 1.18 (m, 9H). Step C: (1R)-1-[3-Methoxy-5-(1-methylpyrazol-4-yl)phenyl]ethanamine Xphos Pd G2 (588 mg, 748 μmol) was added to a degassed solution of 1-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (7.47 g, 35.9 mmol) , (S)-N-[(1R)- 1-(3-bromo-5-methoxy-phenyl)ethyl]-2-methyl-propane-2-sulfin amide (10.0 g, 29.9 mmol) and potassium phosphate tribasic (19.7 g, 92.7 mmol) in 1,4-dioxane (171 mL) water (34 mL) and the reaction mixture was stirred at 70 °C for 1 hour to afford a black mixture. This was quenched with water (100 mL), extracted with diethyl ether (2 x 150 mL) dried and solvent evaporated to afford a black gum. This was dissolved in diethyl ether (250 mL) and hydrogen chloride solution, 4N in 1,4-dioxane (17.5 mL) was added with stirring to afford a dark grainy solid. This was filtered to afford (1R)-1-[3- methoxy-5-(1-methylpyrazol-4-yl)phenyl]ethanamine hydrochloride salt, which was used in subsequent steps. To obtain the free base, the product salt was then dissolved into water (200 mL) and extracted with diethyl ether (200 mL). The dark aqueous layer was filtered to afford a yellow solution. The aqueous was then basified to pH 14 with solid NaOH, extracted with diethyl ether (2 x 250 mL), dried and solvent evaporated to afford (1R)-1-[3-methoxy-5-(1-methylpyrazol-4-yl)phenyl]ethanamine (5.93 g, 86%) as a yellow liquid. LC-MS (Method B): R _T = 3.03 min, m/z = 232.4 [M+H] ⁺ . Step D: Methyl 3-[2-[[(1R)-1-[3-methoxy-5-(1-methylpyrazol-4- yl)phenyl]ethyl]carbamoyl]phenyl]propanoate HBTU (974 mg, 2.57 mmol) was added to a solution of (1R)-1-[3-methoxy-5-(1- methylpyrazol-4-yl)phenyl]ethanamine hydrochloride salt (675 mg, 2.22 mmol), 2-(3- methoxy-3-oxo-propyl)benzoic acid (486 mg, 2.33 mmol) and DIPEA (2.00 mL, 11.7 mmol) in DCM (50 mL) and the reaction mixture allowed to stir at RT overnight. Water (80 mL) and DCM (100 mL) were added, and the phases separated. The organic phase was dried over sodium sulfate and the solvent removed in vacuo. Purification by FCC (eluting with 0-50% MeOH in ethyl acetate) gave methyl 3-[2-[[(1R)-1-[3-methoxy-5-(1- methylpyrazol-4-yl)phenyl]ethyl]carbamoyl]phenyl]propanoate (623 mg, 63%) as a colourless oil. LC-MS (Method B): RT = 3.66 min, m/z = 420.7 [M-H]-. Step E: 2-(3-Hydrazino-3-oxo-propyl)-N-[(1R)-1-[3-methoxy-5-(1-methy lpyrazol-4- yl)phenyl]ethyl]benzamide Hydrazine hydrate (2.00 mL, 50% purity) was added to a solution of methyl 3-[2-[[(1R)-1- [3-methoxy-5-(1-methylpyrazol-4-yl)phenyl]ethyl]carbamoyl]ph enyl]propanoate (623 mg, 1.48 mmol) in ethanol (80 mL) and the reaction mixture heated to 90 °C and allowed to stir at this temperature overnight. The reaction mixture was allowed to cool to RT and the solvent removed in vacuo. Purification by FCC (eluting with 0-100% MeOH in ethyl acetate) gave a white solid. Purification by trituration with diethyl ether gave 2-(3- hydrazino-3-oxo-propyl)-N-[(1R)-1-[3-methoxy-5-(1-methylpyra zol-4- yl)phenyl]ethyl]benzamide (437 mg, 70%) as a white crystalline solid. LC-MS (Method B): RT = 3.44 min, m/z = 420.7 [M-H]-. Step F: Methyl (E)-4-[2-[3-[2-[[(1R)-1-[3-methoxy-5-(1-methylpyrazol-4- yl)phenyl]ethyl]carbamoyl]phenyl]propanoyl]hydrazino]-4-oxo- but-2-enoate Oxalyl chloride (59.2 μL, 681 μmol,) was added to a solution of (E)-4-methoxy-4-oxo- but-2-enoic acid (89 mg, 681 μmol) and DMF (5 drops) in DCM (10 mL) and the reaction mixture allowed to stir at RT for 10 mins. The reaction mixture was cooled to -78 °C and a solution of 2-(3-hydrazino-3-oxo-propyl)-N-[(1R)-1-[3-methoxy-5-(1-methy lpyrazol-4- yl)phenyl]ethyl]benzamide (287 mg, 681 μmol) in DCM (5 mL) added. The reaction mixture was taken out of the cooling bath and allowed to stir for 10 mins. Water (75 mL) and DCM (75 mL) were added, and the phases separated. The organic phase was dried over sodium sulfate and the solvent removed in vacuo. Purification by FCC (eluting with 0-50% MeOH in ethyl acetate) gave methyl (E)-4-[2-[3-[2-[[(1R)-1-[3-methoxy-5-(1- methylpyrazol-4-yl)phenyl]ethyl]carbamoyl]phenyl] propanoyl]hydrazino]-4-oxo-but-2- enoate (143 mg, 35%) as a white solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 10.54 (br s, 1H), 10.19 (br s, 1H), 8.76 (d, J=8.0, 1H), 8.11 (s, 1H), 7.85 (s, 1H), 7.39-7.27 (m, 4H), 7.18 (br s, 1H), 7.06 (d, J=15.5, 1H), 7.00 (br s, 1H), 6.82 (br s, 1H), 6.68 (d, J=15.5, 1H), 5.13 (quin, J=7.0, 1H), 3.86 (s, 3H), 3.79 (s, 3H), 3.75 (s, 3H), 2.95-2.92 (m, 2H), 2.90 (br s, 1H), 2.74 (br s, 1H), 1.45 (d, J=7.0, 3H). LC-MS (Method B): RT = 3.28 min, m/z = 532.9 [M-H]-. Further Examples The following examples were prepared in a similar manner to methyl (E)-4-[2-[3-[2- [[(1R)-1-[3-methoxy-5-(1-methylpyrazol-4- yl)phenyl]ethyl]carbamoyl]phenyl]propanoyl]hydrazino]-4-oxo- but-2-enoate (Example 17), using 2-(3-methoxy-3-oxo-propyl)-5-(4-methylpiperazin-1-yl)benzoic acid (Example 1, Step D) in Step D and the required carboxylic acid in Step F.

Example 20: 2-[2-[(2-Chloro-2-fluoro-acetyl)amino]ethyl]-N-[(1R)-1-(1- naphthyl)ethyl]benzamide Step A: 3-[2-[[(1R)-1-(1-naphthyl)ethyl]carbamoyl]phenyl]propanoate Used General Procedure 1 with (R)-(+)-1-(1-naphthyl)ethylamine (620 μL, 3.87 mmol) and 2-(3-methoxy-3-oxo-propyl)benzoic acid (805 mg, 3.87 mmol) in DMF (40 mL) at RT for 60 hours. The reaction mixture was quenched with water (100 mL) to give a milky saturated solution which was stirred for 30 mins. The resulting solid was filtered and dried under vacuum filtration to afford a wet brown solid. Solid was taken up in DCM (20 mL) and the resulting aqueous layer decanted. The remaining solvent was concentrated under reduced pressure to afford crude material. Purification by FCC (eluting with 10-60% ethyl acetate in petroleum ether) gave methyl 3-[2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoate (927 mg, 65%) as a white solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ = 8.25 (d, J=8.5, 1H), 7.88 (d, J=8.2, 1H), 7.81 (d, J=8.1, 1H), 7.58 (br d, J=7.2, 2H), 7.54-7.50 (m, 1H), 7.49-7.45 (m, 1H), 7.33-7.27 (m, 2H), 7.22 (d, J=7.5, 1H), 7.18-7.14 (m, 1H), 6.37 (br d, J=7.6, 1H), 6.14 (quin, J=7.2, 1H), 3.62 (s, 3H), 3.15-3.02 (m, 2H), 2.77-2.64 (m, 2H), 1.80 (d, J=6.7, 3H). LC-MS (Method B): RT = 3.99 min, m/z = 360.6 [M-H]-. Step B: 3-[2-[[(1R)-1-(1-naphthyl)ethyl]carbamoyl]phenyl]propanoic acid Lithium hydroxide monohydrate (1.51 g, 36.0 mmol) was added to a solution of methyl 3-[2-[[(1R)-1-(1-naphthyl)ethyl]carbamoyl]phenyl]propanoate (2.60 g, 7.19 mmol) in THF (20 mL) and water (20 mL) and the reaction mixture allowed to stir at RT overnight. Diethyl ether (75 mL) and water (75 mL were added and the phases separated. The aqueous phase was acidified by addition of a 2M aqueous solution of HCl and the resulting precipitate was filtered and dried under vacuum to give 3-[2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoic acid (2.10 g, 84%) as a white solid, which was used directly in subsequent steps without further purification. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 12.09 (br s, 1H), 8.98 (d, J=8.0, 1H), 8.24 (d, J=8.0, 1H), 7.96 (d, J=7.5, 1H), 7.84 (d, J=8.0, 1H), 7.64 (d, J=7.0, 1H), 7.60 (m, 1H), 7.56-7.49 (m, 2H), 7.37-7.24 (m, 4H), 5.93 (quin, J=7.0, 1H), 2.91 (t, J=8.0, 2H), 1.59 (d, J=7.0, 3H).2H obscured by DMSO. Step C: tert-Butyl N-[2-[2-[[(1R)-1-(1-naphthyl)ethyl]carbamoyl]phenyl]ethyl]ca rbamate Diphenylphosphoryl azide (1.86 mL, 8.58 mmol) was added to a solution of 3-[2-[[(1R)- 1-(1-naphthyl)ethyl]carbamoyl]phenyl]propanoic acid (1.49 g, 4.29 mmol) and triethylamine (1.20 mL, 8.58 mmol) in tert-butanol (20 mL) and the reaction mixture heated to 60 °C overnight. The reaction mixture was allowed to cool to RT and the solvent removed in vacuo. DCM (100 mL) and an aqueous solution of citric acid (100 mL) was added. The phases were separated, and the organic phase washed with brine (100 mL) and dried (Na ₂ SO ₄ ). The solvent was removed in vacuo and purification by FCC (eluting with 0-50% ethyl acetate in petroleum ether) gave tert-butyl N-[2-[2-[[(1R)- 1-(1-naphthyl)ethyl]carbamoyl]phenyl]ethyl]carbamate (1.13 g, 63%) as a colourless oil. LC-MS (Method B): RT = 4.04 min, m/z = 417.3 [M-H]-. Step D: 2-(2-Aminoethyl)-N-[(1R)-1-(1-naphthyl)ethyl]benzamide hydrochloride salt Hydrogen chloride solution, 4N in 1,4-dioxane (10 mL) was added to a solution of tert- butyl N-[2-[2-[[(1R)-1-(1-naphthyl)ethyl]carbamoyl]phenyl]ethyl]ca rbamate (1.80 g, 4.29 mmol) in DCM (10 mL) and the reaction mixture allowed to stir at RT for 2 hours. The solvent was removed in vacuo which gave 2-(2-aminoethyl)-N-[(1R)-1-(1- naphthyl)ethyl]benzamide hydrochloride salt (487 mg, 32%) as a white solid after trituration with diethyl ether. LC-MS (Method B): RT = 4.10 min, m/z = 319.3 [M+H] ⁺ . Step E: 2-[2-[(2-Chloro-2-fluoro-acetyl)amino]ethyl]-N-[(1R)-1-(1- naphthyl)ethyl]benzamide Used General Procedure 1 with 2-(2-aminoethyl)-N-[(1R)-1-(1-naphthyl)ethyl]benzamide hydrochloride salt (90 mg, 254 μmol) and sodium chloro(fluoro) acetate (38 mg, 279 μmol) in DCM (20 mL) at RT for 2 hours. Water (75 mL) and DCM (75 mL) were added, and the phases separated. The organic phase was dried (Na2SO4) and the solvent removed in vacuo. Purification by FCC (eluting with 0-20% MeOH in ethyl acetate) gave 2-[2-[(2-chloro-2-fluoro-acetyl)amino]ethyl]-N-[(1R)-1-(1-na phthyl)ethyl]benzamide (16 mg, 15%) as a white solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 9.02 (d, J=8.0, 1H), 8.88 (br t, J=5.0, 1H), 8.23 (d, J=8.5, 1H), 7.97 (d, J=8.0, 1H), 7.85 (d, J=8.0, 1H), 7.64-7.59 (m, 2H), 7.57-7.50 (m, 2H), 7.40-7.36 (m, 2H), 7.31-7.28 (m, 2H), 6.68 (d, J=49.5, 1H), 5.94 (quin, J=7.0, 1H), 3.37 (m, 2H), 2.89 (m, 2H), 1.60 (d, J=7.0, 3H). LC-MS (Method B): R _T = 3.70 min, m/z = 411.3 [M-H]-. Example 21: N-[(1R)-1-(1-Naphthyl)ethyl]-2-[3-oxo-3-(2-prop-2- enoylhydrazino)propyl]benzamide Step A: 2-(3-Hydrazino-3-oxo-propyl)-N-[(1R)-1-(1-naphthyl)ethyl]ben zamide Hydrazine hydrate (2.00 mL, 20.6 mmol, 50% purity) was added to a solution of methyl 3-[2-[[(1R)-1-(1-naphthyl)ethyl]carbamoyl]phenyl]propanoate (900 mg, 2.50 mmol) (Example 20, Step A) in ethanol (80 mL) and heated to 90 °C overnight under nitrogen. The reaction mixture was recharged with hydrazine hydrate (2.00 mL, 20.6 mmol, 50% purity) and stirred overnight at 90 °C. The reaction mixture was concentrated under reduced pressure, then azeotroped with first DCM (10 mL), then 1:1 DCM in diethyl ether (10 mL x 2). Purification by trituration with diethyl ether gave 2-(3-hydrazino-3-oxo- propyl)-N-[(1R)-1-(1-naphthyl)ethyl]benzamide (980 mg, 98%) as a white solid. ¹ H NMR (500 MHz, DMSO-d6) δ = 8.99 (d, J=7.9, 1H), 8.92 (s, 1H), 8.24 (d, J=8.4, 1H), 7.96 (d, J=7.9, 1H), 7.84 (d, J=8.1, 1H), 7.67-7.58 (m, 2H), 7.57-7.49 (m, 2H), 7.37-7.28 (m, 2H), 7.28-7.20 (m, 2H), 5.93 (quin, J=7.1, 1H), 4.18 (br s, 2H), 2.96-2.85 (m, 2H), 2.38-2.34 (m, 2H), 1.59 (d, J=6.9, 3H). LC-MS (Method B): RT = 3.13 min, m/z = 360.7 [M-H]-. Step B: N-[(1R)-1-(1-Naphthyl)ethyl]-2-[3-oxo-3-(2-prop-2- enoylhydrazino)propyl]benzamide Acryloyl chloride (49 μL, 600 μmol) was added to a solution of 2-(3-hydrazino-3-oxo- propyl)-N-[(1R)-1-(1-naphthyl)ethyl]benzamide (197 mg, 545 μmol) in DCM (20 mL) at - 78 °C and the reaction mixture allowed to stir for 15 mins. Water (75 mL) and DCM (75 mL) were added, and the phases separated. The organic phase was dried (Na2SO4) and the solvent removed in vacuo. Purification by FCC (eluting with 0-50% MeOH in ethyl acetate) gave N-[(1R)-1-(1-naphthyl)ethyl]-2-[3-oxo-3-(2-prop-2- enoylhydrazino)propyl]benzamide (62 mg, 25%) as a white crystalline solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 10.09 (d, J=1.5, 1H), 9.97 (d, J=1.5, 1H), 8.97 (d, J=8.0,1H), 8.24 (d, J=8.5, 1H), 7.96 (d, J=8.0, 1H), 7.84 (d, J=8.0, 1H), 7.65-7.60 (m, 2H), 7.56-7.51 (m, 2H), 7.38-7.31 (m, 3H), 7.26 (m, 1H), 6.30 (dd, J=17.0, 10.0, 1H), 6.19 (dd, J=17.0, 2.0, 1H), 5.93 (quin, J=7.0,1H), 5.71 (dd, J=10.0, 2.0, 1H), 2.94 (m, 2H), 1.59 (d, J=7.0, 3H). LC-MS (Method B): R _T = 2.80 min, m/z = 414.3 [M-H]-. Example 22: Methyl (E)-4-[2-[3-[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]propanoyl] hydrazino]-4-oxo-but-2-enoate Oxalyl chloride (123 μL, 1.41 mmol) was added to a solution of (E)-4-methoxy-4-oxo- but-2-enoic acid (172 mg, 1.32 mmol) and DMF (5 drops) in DCM (20 mL) and the reaction mixture allowed to stir at RT for 15 mins. The reaction mixture was cooled to - 78 °C and DIPEA (453 μL, 2.65 mmol) added followed by a solution of N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]-2-(3-hydrazino-3-oxo-propyl)benzamide (328 mg, 883 μmol) – prepared in a similar manner to 2-(3-hydrazino-3-oxo-propyl)-N-[(1R)-1-(1- naphthyl)ethyl]benzamide (Example 22) – in DCM (5 mL). The reaction mixture was allowed to gradually warm to RT and stirred for 1 hour. Water (75 mL) and DCM (75 mL) were added and the phases separated. The aqueous phase was extracted with DCM (75 mL) and the combined organic phases dried (Na ₂ SO ₄ ). The solvent was removed in vacuo and purification by FCC (eluting with 50-100% ethyl acetate in petroleum ether) gave methyl (E)-4-[2-[3-[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]propanoyl]hydrazino]- 4-oxo-but-2-enoate (55 mg, 12%) as a white crystalline solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 10.55 (s, 1H), 10.19 (s, 1H), 8.70 (d, J=8.5, 1H), 7.38-7.25 (m, 4H), 7.07 (d, J=15.5, 1H), 7.02 (s, 1H), 6.90 (m, 2H), 6.68 (d, J=15.5, 1H), 5.09 (quin, J=7.0, 1H), 3.76 (s, 3H), 3.75 (s, 3H), 3.73 (s, 3H), 2.92 (t, J=7.5, 2H), 1.42 (d, J=7.0, 3H).2H obscured by solvent. LC-MS (Method B): RT = 1.91 min, m/z = 482.4 [M-H]-. Further Examples The following examples were prepared in a similar manner to (E)-4-[2-[3-[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]propanoyl]hydrazino]- 4-oxo-but-2-enoate (Example 22) using the required carboxylic acid.

Example 25: N-[(1R)-1-(1-Naphthyl)ethyl]-2-[3-oxo-3-(4-prop-2-enoylpiper azin-1- yl)propyl] benzamide Step A: tert-Butyl 4-[3-[2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoyl]piperazine-1-carbo xylate HBTU (540 mg, 1.42 mmol) was added to a solution of 3-[2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoic acid (450 mg, 1.30 mmol) (Example 20, Step B), tert-butyl piperazine-1-carboxylate (241 mg, 1.30 mmol) and DIPEA (664 μL, 3.89 mmol) in DCM (20 mL) and the reaction mixture allowed to stir at RT for 2 hours. Water (75 mL) and DCM (75 mL) were added and the phases separated. The organic phase was dried over sodium sulfate and the solvent removed in vacuo. Purification by FCC (eluting with 0-20% MeOH in ethyl acetate) gave tert-butyl 4-[3-[2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoyl]piperazine-1-carbo xylate (665 mg, 99%) as a colourless oil. LC-MS (Method B): RT = 3.84 min, m/z = 514.4 [M-H]-. Step B: N-[(1R)-1-(1-Naphthyl)ethyl]-2-(3-oxo-3-piperazin-1-yl-propy l)benzamide hydrochloride salt Hydrogen chloride solution, 4N in 1,4-dioxane (5 mL) was added to a solution of tert- butyl 4-[3-[2-[[(1R)-1-(1-naphthyl)ethyl]carbamoyl]phenyl]propanoy l]piperazine-1- carboxylate (665 mg, 1.29 mmol) in DCM (25 mL) and the reaction mixture allowed to stir at RT for 2 hours. Water (75 mL) and diethyl ether (75 mL) were added and the phases separated. The aqueous phase was basified using a saturated aqueous solution of potassium carbonate then extracted with DCM (100 mL). The organic phase was dried over sodium sulfate and the solvent removed in vacuo. DCM (5 mL) was added followed by hydrogen chloride solution, 4N in 1,4-dioxane (2 mL) and the solvent removed to give N-[(1R)-1-(1-naphthyl)ethyl]-2-(3-oxo-3-piperazin-1-yl- propyl)benzamide hydrochloride salt (377 mg, 65%) as a white crystalline solid. LC-MS (Method B): RT = 3.03 min, m/z = 414.4 [M-H]-. Step C: N-[(1R)-1-(1-Naphthyl)ethyl]-2-[3-oxo-3-(4-prop-2-enoylpiper azin-1- yl)propyl]benzamide Acryloyl chloride (17.0 μL, 208 μmol) was added to a solution of N-[(1R)-1-(1- naphthyl)ethyl]-2-(3-oxo-3-piperazin-1-yl-propyl)benzamide hydrochloride salt (85 mg, 189 μmol) and DIPEA (97 μL, 567 μmol) in DCM (20 mL) and the reaction mixture allowed to stir for 30 mins. Water (75 mL) and DCM (75 mL) were added, and the phases separated. The organic phase was dried over sodium sulfate and the solvent removed in vacuo. Purification by FCC (eluting with 0-20% MeOH in ethyl acetate) gave N-[(1R)-1-(1-naphthyl)ethyl]-2-[3-oxo-3-(4-prop-2-enoylpiper azin-1- yl)propyl]benzamide (55 mg, 59%) as a white solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 9.02 (m, 1H), 8.25 (br d, J=8.0, 1H), 7.96 (d, J=8.0, 1H), 7.84 (d, J=8.0, 1H), 7.64-7.59 (m, 2H), 7.56-7.49 (m, 2H), 7.37-7.25 (m, 4H), 6.72 (m, 1H), 6.11 (m, 1H), 5.93 (quin, J=7.0, 1H), 5.70 (m, 1H), 3.49-3.34 (m, 5H), 3.24 (m, 2H), 2.93-2.36 (m, 2H), 2.58 (m, 2H), 1.59 (d, J=7.0, 3H). LC-MS (Method B): RT = 3.15 min, m/z = 468.4 [M-H]-. Example 26: Methyl (E)-4-[4-[3-[2-[[(1R)-1-(1-naphthyl)ethyl]carbamoyl]phenyl] propanoyl]piperazin-1-yl]-4-oxo-but-2-enoate Oxalyl chloride (29 μL, 336 μmol) was added to a solution of (E)-4-methoxy-4-oxo-but-2- enoic acid (41 mg, 315 μmol) and DMF (5 drops) in DCM (20 mL) and the reaction mixture allowed to stir at RT for 10 mins. A solution of N-[(1R)-1-(1-naphthyl)ethyl]-2-(3- oxo-3-piperazin-1-yl-propyl)benzamide hydrochloride salt (95 mg, 210 μmol) (Example 25, Step B) in DCM (5 mL) was added and the reaction mixture allowed to stir for 1 hour. Water (75 mL) and DCM (75 mL) was added, and the phases separated. The aqueous phase was extracted with DCM (50 mL). The combined organic phases were dried over sodium sulfate and the solvent removed in vacuo. Purification by FCC (eluting with 0- 10% MeOH in ethyl acetate gave methyl (E)-4-[4-[3-[2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl] propanoyl]piperazin-1-yl]-4-oxo-but-2-enoate (52 mg, 45%) as a pale yellow solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 9.03 (dd, J=12.5, 8.0, 1H), 8.25 (d, J=8.5, 1H), 7.95 (m, 1H), 7.84 (d, J=8.0, 1H), 7.64-7.58 (m, 2H), 7.56-7.45 (m, 3H), 7.38-7.26 (m, 4H), 6.58 (dd, J=15.5, 7.0, 1H), 5.93 (quin, J=7.0, 1H), 3.75 (d, J=4.0, 3H), 3.48 (m, 3H), 3.43-3.36 (m, 2H), 3.30-3.20 (m, 3H), 2.93-2.83 (m, 2H), 2.60-2.55 (m, 2H), 1.58 (d, J=7.0, 3H). LC-MS (Method B): R _T = 3.28 min, m/z = 526.4 [M-H]-. Example 27: Methyl (E)-4-[3-[3-[2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoylamino] azetidin-1-yl]-4-oxo-but-2-enoate Step A: tert-Butyl 3-[3-[2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoylamino]azetidine-1-c arboxylate HBTU (489 mg, 1.29 mmol) was added to a solution of 3-[2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoic acid (407 mg, 1.17 mmol) (Example 20, Step B), 3-amino-1-N-Boc-azetidine (202 mg, 1.17 mmol) and DIPEA (601 μL, 3.51 mmol) in DCM (20 mL) and the reaction mixture allowed to stir at RT for 2 hours. Water (75 mL) and DCM (75 mL) were added and the phases separated. The organic phase was dried over sodium sulfate and the solvent removed in vacuo. Purification by FCC (eluting with 0-20% MeOH in ethyl acetate) gave tert-butyl 3-[3-[2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoylamino]azetidine-1-c arboxylate (476 mg, 81%) as a colourless oil. LC-MS (Method B): RT = 3.81 min, m/z = 500.5 [M-H]-. Step B: 2-[3-(Azetidin-3-ylamino)-3-oxo-propyl]-N-[(1R)-1-(1-naphthy l)ethyl]benzamide Trifluoroacetic acid (2 mL, 27.01 mmol) was added to a solution of tert-butyl 3-[3-[2- [[(1R)-1-(1-naphthyl)ethyl]carbamoyl]phenyl]propanoylamino]a zetidine-1-carboxylate (476 mg, 949 μmol) in DCM (2 mL) and the reaction mixture allowed to stir at RT for 2 hours. The reaction mixture was loaded directly onto a 5g SCX cartridge that was pre- equilibrated with MeOH and eluted with MeOH followed by 1N NH3 in MeOH. The fractions containing amine were combined and the solvent removed in vacuo which gave 2-[3-(azetidin-3-ylamino)-3-oxo-propyl]-N-[(1R)-1-(1-naphthy l)ethyl]benzamide (297 mg, 78%) as a colourless oil. LC-MS (Method B): R - T = 4.02 min, m/z = 400.3 [M-H] Step C: Methyl (E)-4-[3-[3-[2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoylamino]azetidin-1-yl ]-4-oxo-but-2-enoate Oxalyl chloride (37 μL, 426 μmol) was added to a solution of (E)-4-methoxy-4-oxo-but-2- enoic acid (52 mg, 400 μmol) and DMF (5 drops) in DCM (20 mL) and the reaction mixture allowed to stir at RT for 10 mins. The reaction mixture was cooled to -78 °C and a solution of 2-[3-(azetidin-3-ylamino)-3-oxo-propyl]-N-[(1R)-1-(1- naphthyl)ethyl]benzamide (107 mg, 267 μmol) in DCM (5 mL) and DMF (2 mL) was added dropwise. Mixture was stirred for 15 mins, then water (75 mL) and DCM (75 mL) was added, and the phases separated. The aqueous phase was extracted with DCM (50 mL). The combined organic phases were dried over sodium sulfate and the solvent removed in vacuo. Purification by FCC (eluting with 0-50% MeOH in ethyl acetate) gave methyl (E)-4-[3-[3-[2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoylamino]azetidin-1-yl ]-4-oxo-but-2-enoate (72 mg, 50%) as a white solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 8.99 (d, J=8.0, 1H), 8.45 (d, J=7.0, 1H), 8.24 (d, J=8.0, 1H), 7.96 (d, J=8.0, 1H), 7.84 (br d, J=8.0, 1H), 7.64-7.58 (m, 2H), 7.56-7.50 (m, 2H), 7.37-7.32 (m, 2H), 7.27-7.24 (m, 2H), 6.98 (dd, J=15.5, 2.0, 1H), 6.60 (dd, J=15.5, 1.5, 1H), 5.92 (quin, J=7.0, 1H), 4.56 (m, 1H), 4.47 (m, 1H), 4.19 (dd, J=9.5, 9.0, 1H), 4.02 (dt, J=9.0, 4.5, 1H), 3.77 (m, 1H), 3.74 (s, 3H), 2.90 (t, J=8.0, 2H), 2.42 (t, J=8.0, 2H), 1.59 (t, J=7.0, 3H). LC-MS (Method B): RT = 3.29 min, m/z = 512.4 [M-H]-. Further Examples The following example was prepared in a similar manner to methyl (E)-4-[3-[3-[2-[[(1R)- 1-(1-naphthyl)ethyl]carbamoyl]phenyl]propanoylamino] azetidin-1-yl]-4-oxo-but-2-enoate (Example 27). The required intermediate was prepared in a similar manner to 3-[2- [[(1R)-1-(1-naphthyl)ethyl]carbamoyl]phenyl]propanoic acid (Example 20, Step B), using methyl 3-[4-[4-(cyclopropylmethyl)piperazin-1-yl]-2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl] propanoate (Example 12, Step B). Example 29: Methyl (E)-4-[[2-[[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]methylamino]-2-oxo-et hyl]amino]-4-oxo-but-2- enoate Step A: Methyl 2-[(tert-butoxycarbonylamino)methyl]benzoate Di-tert-butyl dicarbonate (1.16 g, 5.31 mmol) was added to a solution of 2- carbomethoxybenzylamine hydrochloride (1.07 g, 5.31 mmol), DIPEA (1.81 mL, 10.61 mmol) in DCM (20 mL) and the reaction mixture allowed to stir at RT overnight. Water (75 mL) and DCM (75 mL) were added, and the phases separated. The organic phase was dried (Na ₂ SO ₄ ) and the solvent removed in vacuo. Purification by FCC (eluting with 0-60% ethyl acetate in petroleum ether) gave methyl 2-[(tert- butoxycarbonylamino)methyl]benzoate (1.27 g, 90%) as a colourless oil. ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.97 (br d, J=7.5, 1H), 7.53-7.48 (m, 2H), 7.34 (br t, J=8.0, 1H), 5.59 (br s, 1H), 4.51 (br d, J=6.5, 2H), 3.91 (s, 3H), 1.42 (s, 9H) Step B: 2-[(tert-Butoxycarbonylamino)methyl]benzoic acid lithium salt Lithium hydroxide monohydrate (412 mg, 9.83 mmol) was added to a solution of methyl 2-[(tert-butoxycarbonylamino)methyl]benzoate (2.37 g, 8.93 mmol) in THF (30 mL) and water (30 mL) and the reaction mixture allowed to stir at RT overnight. The solvent was removed in vacuo which gave 2-[(tert-butoxycarbonylamino)methyl]benzoic acid lithium salt (2.11 g, 91%) as a white crystalline solid. LC-MS (Method B): R _T = 0.46 min, m/z = 250.3 [M-H]-. Step C: tert-Butyl N-[[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]methyl]carbamate Used General Procedure 1 with (1R)-1-(3,4-dimethoxyphenyl)ethanamine hydrochloride salt (1.12 g, 5.15 mmol) and 2-[(tert-butoxycarbonylamino)methyl]benzoic acid lithium salt (1.33 g, 5.15 mmol) in DMF (20 mL) at RT overnight. Water (120 mL) and ethyl acetate (120 mL) was added, and the phases separated. The organic phase was washed with brine (100 mL) and the solvent removed in vacuo. Purification by FCC (eluting with 10-100% ethyl acetate in petroleum ether) gave tert-butyl N-[[2-[[(1R)-1- (3,4-dimethoxyphenyl)ethyl]carbamoyl]phenyl]methyl]carbamate (1.77 g, 83%) as an off- white solid. LC-MS (Method B): RT = 3.63 min, m/z = 413.4 [M-Boc]-. Step D: 2-(Aminomethyl)-N-[(1R)-1-(3,4-dimethoxyphenyl)ethyl]benzami de hydrochloride salt Hydrogen chloride solution (4M in 1,4-dioxane, 10 mL) was added to a solution of tert- butyl N-[[2-[[(1R)-1-(3,4-dimethoxyphenyl)ethyl]carbamoyl]phenyl]m ethyl]carbamate (1.77 g, 4.27 mmol) in DCM (10 mL) and the reaction mixture allowed to stir for 2 hours. The solvent was removed in vacuo. Trituration with diethyl ether gave 2-(aminomethyl)- N-[(1R)-1-(3,4-dimethoxyphenyl)ethyl]benzamide hydrochloride salt (1.21 g, 81%) as a white solid. LC-MS (Method B): RT = 3.12 min, m/z = 313.3 [M-H]-. Step E: tert-Butyl N-[2-[[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]methylamino]-2-oxo-et hyl]carbamate Used General Procedure 1 with 2-(tert-butoxycarbonylamino)acetic acid (412 mg, 2.35 mmol) and 2-(aminomethyl)-N-[(1R)-1-(3,4-dimethoxyphenyl)ethyl]benzami de hydrochloride salt (910 mg, 2.35 mmol) in DMF (20 mL) at RT for 2 hours. Water (100 mL) and ethyl acetate (100 mL) were added and the phases separated. The organic phase was washed with brine (100 mL), dried (Na ₂ SO ₄ ) and the solvent removed in vacuo. Purification by FCC (eluting with 20-100% ethyl acetate in petroleum ether followed by 0-10% MeOH in ethyl acetate) gave tert-butyl N-[2-[[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]methylamino]-2-oxo-et hyl]carbamate (1.10 g, 99%) as a white solid. LC-MS (Method B): R _T = 3.20 min, m/z = 470.4 [M-H]-. Step F: 2-[[(2-Aminoacetyl)amino]methyl]-N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]benzamide hydrochloride salt Hydrogen chloride solution (4M in 1,4-dioxane, 15 mL) was added to a solution of tert- butyl N-[2-[[2-[[(1R)-1-(3,4-dimethoxyphenyl)ethyl]carbamoyl]pheny l]methylamino]-2- oxo-ethyl]carbamate (1.10 g, 2.33 mmol) in DCM (20 mL) and the reaction mixture was allowed to stir at RT for 1 hour. Diethyl ether (100 mL) was added and the resulting solid filtered and dried under vacuum affording 2-[[(2-aminoacetyl)amino]methyl]-N-[(1R)-1- (3,4-dimethoxyphenyl)ethyl]benzamide hydrochloride salt (800 mg, 76%) as a white crystalline solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 8.85-8.81 (m, 2H), 8.18 (br s, 3H), 7.44-7.42 (m, 2H), 7.38-7.33 (m, 2H), 7.04 (br s, 1H), 6.93-6.89 (m, 2H), 5.09 (quin, J=7.0, 1H), 4.46-4.38 (m, 2H), 3.76 (s, 3H), 3.74 (s, 3H), 3.62 (q, J=6.0, 2H), 1.44 (d, J=7.0, 3H). LC-MS (Method B): RT = 2.54 min, m/z = 370.3 [M-H]-. Step G: Methyl (E)-4-[[2-[[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]methylamino]-2-oxo-et hyl]amino]-4-oxo-but-2- enoate Oxalyl chloride (42 μL, 478 μmol) was added to a solution of (E)-4-methoxy-4-oxobut-2- enoic acid (58 mg, 448 μmol) in DCM (5 mL) and DMF (5 drops). The reaction mixture was allowed to stir for 10 mins then a solution of 2-[[(2-aminoacetyl)amino]methyl]-N- [(1R)-1-(3,4-dimethoxyphenyl)ethyl]benzamide (111 mg, 299 μmol) and DIPEA (153 μL, 897 μmol) in DCM (2 mL) was added and the reaction mixture allowed to stir at RT for 45 mins. Water (75 mL) and DCM (75 mL) were added, and the phases separated. The organic phase was dried (Na ₂ SO ₄ ) and the solvent removed in vacuo. Purification by FCC (eluting with 50-100% ethyl acetate in petroleum ether followed by 0-30% MeOH in ethyl acetate) gave methyl (E)-4-[[2-[[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]methylamino]-2-oxo-et hyl]amino]-4-oxo-but-2- enoate (54 mg, 36%) as a white solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 8.89 (t, J=6.0, 1H), 8.81 (d, J=8.0, 1H), 8.39 (t, J=6.0, 1H), 7.43-7.38 (m, 2H), 7.33-7.30 (m, 2H), 7.10 (d, J=15.5, 1H), 7.02 (br s, 1H), 6.92-6.88 (m, 2H), 6.62 (d, J=15.5, 1H), 5.09 (quin, J=7.0, 1H), 4.41-4.32 (m, 2H), 3.88 (d, J=6.0, 2H), 3.76 (s, 3H), 3.74-3.73 (m, 6H), 1.42 (d, J=7.0, 3H). LC-MS (Method B): R _T = 2.83 min, m/z = 482.4 [M-H]-. Further Examples The following examples were prepared in a similar manner to methyl (E)-4-[[2-[[2-[[(1R)- 1-(3,4-dimethoxyphenyl)ethyl]carbamoyl]phenyl]methylamino]-2 -oxo-ethyl]amino]-4-oxo- but-2-enoate (Example 29) using the required substrate in Step A and the required carboxylic acids in Steps E and G.

Example 34: N-[(1R)-1-(3,4-Dimethoxyphenyl)ethyl]-2-[[[2-(prop-2- enoylamino)acetyl]amino]methyl]benzamide

Acryloyl chloride (26 μL, 320 μmol) was added to a solution of 2-[[(2- aminoacetyl)amino]methyl]-N-[(1R)-1-(3,4-dimethoxyphenyl)eth yl]benzamide hydrochloride (87 mg, 213 μmol) (Example 29, Step F) and DIPEA (109 μL, 640 μmol) in DCM (5 mL) and the reaction mixture was allowed to stir for 45 mins. Water (75 mL) and DCM (75 mL) were added, and the phases separated. The organic phase was dried (Na ₂ SO ₄ ) and the solvent removed in vacuo. Purification by FCC (eluting with 50-100% ethyl acetate in petroleum ether followed by 0-30% MeOH in ethyl acetate) gave N- [(1R)-1-(3,4-dimethoxyphenyl)ethyl]-2-[[[2-(prop-2- enoylamino)acetyl]amino]methyl]benzamide (57 mg, 60%) as a white solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 8.81 (d, J=8.0, 1H), 8.42 (t, J=5.5, 1H), 8.33 (t, J=6.0, 1H), 7.42-7.38 (m, 2H), 7.33-7.30 (m, 2H), 7.03 (br s, 1H), 6.92-6.89 (m, 2H), 6.31 (dd, J=17.0, 10.0, 1H), 6.11 (dd, J=17.0, 2.0, 1H), 5.62 (dd, J=10.0, 2.0, 1H), 5.09 (quin, J=7.0, 1H), 4.36 (d, J=6.0, 2H), 3.83 (d, J=5.5, 2H), 3.76 (s, 3H), 3.73 (s, 3H), 1.43 (d, J=7.0, 3H). LC-MS (Method B): R _T = 2.66 min, m/z = 424.4 [M-H]-. Example 35: (E)-N'-[2-[[2-[[(1R)-1-(3,4- Dimethoxyphenyl)ethyl]carbamoyl]phenyl]methylamino]-2-oxo-et hyl]-N-methyl-but-2- enediamide Used General Procedure 1 with 2-[[(2-aminoacetyl)amino]methyl]-N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]benzamide hydrochloride salt (60 mg, 147 μmol) (Example 29, Step F) and (E)-4-(methylamino)-4-oxo-but-2-enoic acid (38 mg, 294 μmol) in DMF (5 mL) for 3 hours at RT. The reaction mixture was quenched with water (5 mL) then sat. aq. K ₂ CO ₃ (8 mL) to afford a saturated solution which was stirred for 30 mins. The resulting solid was filtered and dried under vacuum filtration to afford a beige solid which was purified by FCC (eluting with 0-100% MeOH in ethyl acetate) to afford (E)-N'-[2-[[2- [[(1R)-1-(3,4-dimethoxyphenyl)ethyl]carbamoyl]phenyl]methyla mino]-2-oxo-ethyl]-N- methyl-but-2-enediamide as a white solid (5 mg, 7%). ¹ H NMR (500 MHz, DMSO-d ₆ ) δ = 8.81 (br d, J=8.2, 1H), 8.73 (t, J=6.0, 1H), 8.38-8.30 (m, 2H), 7.43-7.37 (m, 2H), 7.31 (br t, J=6.5, 2H), 7.02 (s, 1H), 6.92-6.87 (m, 3H), 6.84-6.79 (m, 1H), 5.09 (quin, J=7.4, 1H), 4.36 (br d, J=5.6, 2H), 3.85 (d, J=6.0, 2H), 3.77 (d, J=3.8, 1H), 3.75 (s, 2H), 3.73 (s, 3H), 2.69 (d, J=4.6, 3H), 1.42 (d, J=7.0, 3H). LC-MS (Method B): RT = 2.48 min, m/z = 481.5 [M-H]-. Further Examples The following examples were prepared in a similar manner to (E)-N'-[2-[[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]methylamino]-2-oxo-et hyl]-N-methyl-but-2- enediamide (Example 35) using the required carboxylic acid. The required intermediates were in turn prepared in a similar manner to 2-[[(2-aminoacetyl)amino]methyl]-N-[(1R)-1- (3,4-dimethoxyphenyl)ethyl]benzamide hydrochloride salt (Example 29, Step F), using (1R)-1-[3-methoxy-5-(1-methylpyrazol-4-yl)phenyl]ethanamine (Example 17, Step C) in Step C. Example 39: (E)-4-[2-[3-[2-[[(1R)-1-(3,4- Dimethoxyphenyl)ethyl]carbamoyl]phenyl]propanoyl] hydrazino]-4-oxo-but-2-enoic acid Lithium hydroxide monohydrate (2 mg, 52 μmol) was added to a solution of methyl (E)- 4-[2-[3-[2-[[(1R)-1-(3,4-dimethoxyphenyl)ethyl]carbamoyl]phe nyl]propanoyl]hydrazino]-4- oxo-but-2-enoate (24 mg, 50 μmol) (Example 23) in THF (0.5 mL), water (0.25 mL) and MeOH (0.25 mL) and stirred overnight at RT. The reaction mixture was recharged with lithium hydroxide monohydrate (2 mg, 52 μmol) and stirred for a further overnight. The reaction mixture was diluted with water (5 mL) and concentrated under reduced pressure to remove organic solvent. The resulting aqueous solution was extracted with ethyl acetate (2 x 5 mL). The aqueous was acidified with 2M HCl aq. and extracted with ethyl acetate (5 mL) then DCM (5 mL). The combined organics were dried (MgSO ₄ ) and concentrated under reduced pressure to afford (E)-4-[2-[3-[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]propanoyl]hydrazino]- 4-oxo-but-2-enoic acid as a white solid (6.5 mg, 27%). ¹ H NMR (500 MHz, DMSO-d ₆ ) δ = 8.78-8.64 (m, 1H), 7.42-7.22 (m, 4H), 7.02 (s, 1H), 6.91 (s, 2H), 6.77-6.64 (m, 1H), 6.63-6.54 (m, 1H), 5.15- 5.00 (m, 1H), 3.76 (S, 3H), 3.73 (m, 3H), 2.95-2.87 (m, 2H), 1.45-1.39 (m, 3H). NH and COOH signals not observed.2H obscured by solvent. LC-MS (Method A): RT = 2.86 min, m/z = 468.5 [M-H]-. Further Examples The following examples were prepared in a similar manner to (E)-4-[2-[3-[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]propanoyl]hydrazino]- 4-oxo-but-2-enoic acid (Example 39) from methyl (E)-4-[[2-[[2-[[(1R)-1-(3,4- dimethoxyphenyl)ethyl]carbamoyl]phenyl]methylamino]-2-oxo-et hyl]amino]-4-oxo-but-2- enoate (Example 29). Example 41: 2-[3-(But-2-ynoylamino)propyl]-N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]benzamide Step A: 2-[3-[tert-Butyl(dimethyl)silyl]oxypropyl]benzoic acid 3-(2-Bromophenyl)propoxy-tert-butyl-dimethyl-silane (6.23 g, 18.9 mmol) was dissolved in THF (100 mL) and cooled to -78 °C under nitrogen. Once cooled n-butyllithium solution in hexanes (1.9 M, 9.96 mL) was added to afford a very pale-yellow colour. The reaction was stirred for 10 mins before being quenched with CO ₂ to afford a clear solution. The mixture was stirred for 10 mins before being quenched with sat NH ₄ Cl (100 mL), extracted with diethyl ether (100 mL), dried (MgSO ₄ ) and solvent evaporated to afford 2-[3-[tert-butyl(dimethyl)silyl]oxypropyl]benzoic acid (5.25 g, 90%) as a slightly yellow liquid. ¹ H NMR (500 MHz, CDCl ₃ ) δ = 7.97-7.90 (m, 1H), 7.49-7.32 (m, 1H), 7.26- 7.21 (m, 2H), 3.67-3.57 (m, 2H), 3.07-2.95 (m, 2H), 1.86-1.76 (m, 2H), 0.85 (s, 9H), 0.02--0.04 (m, 6H). Step B: 2-[3-[tert-Butyl(dimethyl)silyl]oxypropyl]-N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]benzamide Used General Procedure 1 with (1R)-1-(3,4-dimethoxyphenyl)ethanamine hydrochloride salt (1.35 g, 6.20 mmol) and 2-[3-[tert-butyl(dimethyl)silyl]oxypropyl]benzoic acid (2.01 g, 6.82 mmol) in DMF (25 mL) at RT for 1 hour. The reaction was quenched with water (100 mL), petroleum ether was added and on shaking a solid was observed. The solid was filtered to afford 2-[3-[tert-butyl(dimethyl)silyl]oxypropyl]-N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]benzamide (2.24 g, 79%) as a beige solid. LC-MS (Method B): RT = 4.92 min, m/z = 456.4 [M-H]-. Step C: N-[(1R)-1-(3,4-Dimethoxyphenyl)ethyl]-2-(3-hydroxypropyl)ben zamide 2-[3-[tert-Butyl(dimethyl)silyl]oxypropyl]-N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]benzamide (2.24 g, 4.89 mmol) was added to 4 N HCl in dioxane (5 mL) and stirred for 30 mins. The reaction was carefully quenched with 2 N NaOH (20 mL) and water (50 mL), extracted with diethyl ether (2 x 75 mL), dried (MgSO ₄ ) and solvent evaporated to afford a yellow gum. Purification by trituration with a mix of DCM and diethyl ether afforded N-[(1R)-1-(3,4-dimethoxyphenyl)ethyl]-2-(3- hydroxypropyl)benzamide (920 mg, 55%) as a white solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ = 7.41-7.34 (m, 1H), 7.31 (d, J=7.3, 1H), 7.29-7.25 (m, 1H), 7.23-7.18 (m, 1H), 6.96-6.90 (m, 2H), 6.86 (d, J=7.9, 1H), 6.12 (br d, J=7.9, 1H), 5.29 (quin, J=7.1, 1H), 3.90 (s, 3H), 3.89-3.87 (s, 3H), 3.68-3.60 (m, 1H), 3.48 (q, J=6.0, 2H), 2.90-2.80 (m, 2H), 1.96-1.85 (m, 2H), 1.60 (d, J=6.7, 3H). Step D: 2-(3-Aminopropyl)-N-[(1R)-1-(3,4-dimethoxyphenyl)ethyl]benza mide N-[(1R)-1-(3,4-Dimethoxyphenyl)ethyl]-2-(3-hydroxypropyl)ben zamide (920 mg, 2.68 mmol), di-tert-butyl-iminodicarboxylate (698 mg, 3.21 mmol), triphenylphosphine (843 mg, 3.21 mmol) were added to THF (20 mL) to this was slowly added diisopropyl azodicarboxylate (3.21 mmol, 631 μL) to afford an orange solution which was stirred overnight. The reaction was evaporated, and the gum was dissolved in 4 N HCl in dioxane (30 mL) and stirred for 1 hour to afford a cloudy solution. The reaction was diluted with water (50 mL), extracted with diethyl ether (75 mL), the aqueous was then taken and basified with solid NaOH, then extracted with diethyl ether (2 x 75 mL), dried (MgSO ₄ ) and solvent evaporated to afford a gum. The gum was passed down a SCX column (eluting with 1 N NH ₃ in MeOH) to afford 2-(3-aminopropyl)-N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]benzamide (440 mg, 48%) as a white solid. ¹ H NMR (500 MHz, CDCl3) δ = 7.39-7.35 (m, 1H), 7.35-7.30 (m, 1H), 7.27 (s, 1H), 7.25-7.17 (m, 2H), 6.98 (br d, J=7.6, 1H), 6.95-6.92 (m, 1H), 6.90-6.79 (m, 1H), 5.30 (quin, J=7.1, 1H), 3.89 (s, 3H), 3.88-3.86 (m, 3H), 2.82 (t, J=7.5, 2H), 2.63 (br s, 2H), 1.82-1.71 (m, 2H), 1.59 (d, J=6.7, 3H). LC-MS (Method B): RT = 4.33 min, m/z = 341.4 (M-H)-. Step E: 2-[3-(But-2-ynoylamino)propyl]-N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]benzamide Used General Procedure 1 with 2-(3-aminopropyl)-N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]benzamide (105 mg, 307 μmol) and but-2-ynoic acid (28.6 μL, 368 μmol) in DCM (10 mL) at RT for 1 hour. The reaction was quenched with 1 N HCl (50 mL), extracted with DCM (50 mL), dried (MgSO ₄ ) and solvent evaporated to afford a white solid. This was purified by FCC (eluting with 50% ethyl acetate in diethyl ether) to afford 2-[3-(but-2-ynoylamino)propyl]-N-[(1R)-1-(3,4-dimethoxypheny l)ethyl]benzamide (48 mg, 38%) as a white solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ = 7.38-7.33 (m, 1H), 7.33- 7.29 (m, 1H), 7.26-7.17 (m, 2H), 6.98-6.92 (m, 2H), 6.91-6.84 (m, 2H), 6.06 (br d, J=7.6, 1H), 5.29 (quin, J=7.1, 1H), 3.91 (s, 3H), 3.90-3.87 (m, 3H), 3.27-3.14 (m, 2H), 2.83-2.71 (m, 2H), 1.93 (s, 3H), 1.92-1.79 (m, 2H), 1.62 (d, J=6.7, 3H). LC-MS (Method B): R _T = 3.16 min, m/z = 407.4 (M-H)-. Further Examples The following examples were prepared in a similar manner to 2-[3-(but-2- ynoylamino)propyl]-N-[(1R)-1-(3,4-dimethoxyphenyl)ethyl]benz amide (Example 41) using the required carboxylic acid in Step E. ^a Required intermediate prepared using (1R)-1-[3-methoxy-5-(1-methylpyrazol-4- yl)phenyl]ethanamine (Example 17, Step C) in Step B. Example 45: N-[(1R)-1-(3,4-Dimethoxyphenyl)ethyl]-2-[3-(prop-2- enoylamino)propyl]benzamide 2-(3-Aminopropyl)-N-[(1R)-1-(3,4-dimethoxyphenyl)ethyl]benza mide (100 mg, 292 μmol) (Example 41, Step D) was added to DCM (10 mL) to this was added triethylamine (61.1 μL, 438 μmol) and then prop-2-enoyl chloride (28.6 μL, 350 μmol) and the mixture was stirred for 1 hour. The reaction was quenched with 1 N HCl (50 mL), extracted with DCM (50 mL), dried (MgSO ₄ ) and solvent evaporated to afford a white solid. This was triturated with 60% diethyl ether in petroleum ether to afford N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]-2-[3-(prop-2-enoylamino)propyl]benzam ide (75 mg, 65%) as a white solid. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ = 8.69 (br d, J=8.2, 1H), 8.05 (br s, 1H), 7.38-7.32 (m, 1H), 7.31-7.22 (m, 3H), 7.02 (s, 1H), 6.90 (s, 2H), 6.19 (dd, J=10.2, 16.9, 1H), 6.10-6.03 (d, J=16.9, 1H), 5.60-5.53 (d, J=10.2, 1H), 5.08 (br t, J=7.5, 1H), 3.76 (s, 3H), 3.75-3.72 (s, 3H), 3.13-2.97 (m, 2H), 2.65 (br t, J=7.5, 2H), 1.67 (quin, J=7.2, 2H), 1.41 (d, J=6.7, 3H). LC-MS (Method B): RT = 3.01 min, m/z = 395.4 (M-H)-. Example 46: 2-[3-(But-2-ynoylamino)propyl]-N-[(1R)-1-(3,4-dimethoxypheny l)ethyl]-5- (4-ethylpiperazin-1-yl)benzamide Step A: tert-Butyl 4-[3-[[(1R)-1-(3,4-dimethoxyphenyl)ethyl]carbamoyl]-4-(3- hydroxypropyl)phenyl]piperazine-1-carboxylate tert-Butyl 4-[3-[[(1R)-1-(3,4-dimethoxyphenyl)ethyl]carbamoyl]-4-(3-met hoxy-3-oxo- propyl)phenyl]piperazine-1-carboxylate (2.46 g, 4.43 mmol) – prepared in a similar manner to methyl 3-[4-(4-methylpiperazin-1-yl)-2-[[(1R)-1-(1- naphthyl)ethyl]carbamoyl]phenyl]propanoate (Example 1, Step E) – was dissolved in THF (30 mL) to this was added lithium borohydride solution (2 M, 4.87 mL) and the reaction was stirred 3 hours. The reaction was carefully quenched with 1 N HCl (50 mL), extracted with diethyl ether (2 x 70 mL), dried (MgSO ₄ ) and solvent evaporated to afford a yellow gum. This was purified by FCC (eluting with 50-100% ethyl acetate in diethyl ether) to afford tert-butyl 4-[3-[[(1R)-1-(3,4-dimethoxyphenyl)ethyl]carbamoyl]-4-(3- hydroxypropyl)phenyl]piperazine-1-carboxylate (1.88 g, 80%) as a white solid. LC- MS (Method B): RT = 3.64 min, m/z = 526.5 (M-H)-. Step B: N-[(1R)-1-(3,4-Dimethoxyphenyl)ethyl]-2-(3-hydroxypropyl)-5- piperazin-1-yl- benzamide tert-Butyl 4-[3-[[(1R)-1-(3,4-dimethoxyphenyl)ethyl]carbamoyl]-4-(3- hydroxypropyl)phenyl] piperazine-1-carboxylate (1.88 g, 3.56 mmol) was added to DCM (5 mL), to this was added 4 N HCl in dioxane (20 mL) and the reaction was stirred for 1 hour. The reaction was quenched with water (50 mL), extracted with diethyl ether (2 x 50 mL), the aqueous was basified with solid NaOH to afford a solid which was filtered and dried to afford N-[(1R)-1-(3,4-dimethoxyphenyl)ethyl]-2-(3-hydroxypropyl)-5- piperazin-1- yl-benzamide (1.10 g, 72%) as a white solid which was used directly in Step D. Step C: N-[(1R)-1-(3,4-Dimethoxyphenyl)ethyl]-5-(4-ethylpiperazin-1- yl)-2-(3- hydroxypropyl)benzamide N-[(1R)-1-(3,4-Dimethoxyphenyl)ethyl]-2-(3-hydroxypropyl)-5- piperazin-1-yl-benzamide (1.1 g, 2.57 mmol), K ₂ CO ₃ (533 mg, 3.86 mmol) and iodoethane (248 μL, 3.09 mmol) were added to DMF (20 mL) and stirred for 3 hours at RT. The mixture was diluted with water (70 mL), extracted with DCM (2 x 70 mL), dried (MgSO ₄ ) and solvent evaporated to afford a yellow gum. This was purified by FCC (eluting with 20% MeOH in ethyl acetate then 10% 7 N NH ₃ in MeOH in ethyl acetate) to afford N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]-5-(4-ethylpiperazin-1-yl)-2-(3-hydrox ypropyl)benzamide (840 mg, 72%) as a white solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ = 7.26 (s, 2H), 7.13 (d, J=8.5, 1H), 6.96-6.89 (m, 2H), 6.88-6.80 (m, 2H), 6.19-6.09 (m, 1H), 5.27 (quin, J=7.1, 1H), 3.90 (s, 3H), 3.89-3.87 (m, 3H), 3.46 (br t, J=5.2, 2H), 3.23-3.13 (m, 4H), 2.78-2.69 (m, 2H), 2.64-2.55 (m, 4H), 2.47 (q, J=7.3, 2H), 1.88-1.80 (m, 2H), 1.59 (d, J=6.7, 3H), 1.13 (t, J=7.2, 3H). Step D: 2-(3-Aminopropyl)-N-[(1R)-1-(3,4-dimethoxyphenyl)ethyl]-5-(4 -ethylpiperazin-1- yl)benzamide N-[(1R)-1-(3,4-Dimethoxyphenyl)ethyl]-5-(4-ethylpiperazin-1- yl)-2-(3- hydroxypropyl)benzamide (838 mg, 1.84 mmol), di-tert-butyl-iminodicarboxylate (480 mg, 2.21 mmol), triphenylphosphine (579 mg, 2.21 mmol) were added to THF (20 mL) to this was slowly added diisopropyl azodicarboxylate (434 μL, 2.21 mmol) to afford an orange solution which was stirred overnight. The reaction was evaporated and then treated with 4 N HCl in dioxane (20 mL), stirred for 1 hour. This was quenched with water (50 mL) and extracted with diethyl ether (50 mL). The aqueous was then basified with solid NaOH extracted with DCM (70 mL), dried (MgSO ₄ ) and solvent evaporated to afford a yellow gum. This was purified by FCC (eluting with 30% MeOH in ethyl acetate then 15% 7 N NH3 in MeOH in ethyl acetate) to afford 2-(3-aminopropyl)-N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]-5-(4-ethylpiperazin-1-yl)benzamide (160 mg, 18%) as a yellow gum. LC-MS (Method B): RT = 5.54 min, m/z = 453.5 (M-H)-. Step E: 2-[3-(But-2-ynoylamino)propyl]-N-[(1R)-1-(3,4-dimethoxypheny l)ethyl]-5-(4- ethylpiperazin-1-yl)benzamide Used General Procedure 1 with 2-(3-aminopropyl)-N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]-5-(4-ethylpiperazin-1-yl)benzamide (140 mg, 308 μmol) and but- 2-ynoic acid (28.6 μL, 370 μmol) in DCM (10 mL) at RT for 1 hour. The mixture was diluted with water (40 mL), extracted with DCM (40 mL), dried (MgSO ₄ ) and solvent evaporated to afford an orange gum. Purification by FCC (eluting with 20% MeOH in ethyl acetate) afforded 2-[3-(but-2-ynoylamino)propyl]-N-[(1R)-1-(3,4- dimethoxyphenyl)ethyl]-5-(4-ethylpiperazin-1-yl)benzamide (89 mg, 53%) as an off white foam. ¹ H NMR (500 MHz, CDCl ₃ ) δ = 7.15-7.05 (m, 1H), 6.98-6.89 (m, 3H), 6.89-6.81 (m, 3H), 6.06 (br d, J=7.9, 1H), 5.27 (quin, J=6.9, 1H), 3.90 (s, 3H), 3.89 (s, 3H), 3.25- 3.08 (m, 6H), 2.70-2.57 (m, 6H), 2.49 (br d, J=7.3, 2H), 1.93 (s, 3H), 1.86-1.71 (m, 2H), 1.65-1.56 (m, 3H), 1.13 (t, J=7.2, 3H). LC-MS (Method B): RT = 3.10 min, m/z = 519.6 (M-H)-. Biological Data Compounds of the invention were tested in a papain-like protease inhibition assay to investigate the mechanism of action of the compounds. Results are reported as the concentration of test article required to inhibit enzyme activity by 50% (IC50). Compounds exhibited IC50 values consistent with potent, specific inhibition of the tested papain-like protease. Inhibition of papain-like protease enzyme function was performed at 37 °C in buffer at pH 7.5 (50 mM HEPES, 0.1 mg/ml BSA, 5 mM DTT; or 20 mM Tris-HCL, 0.1 mg/ml BSA, 2 mM GSH), containing 60 nM papain-like protease, 50 µM Z-Arg-Leu-Arg-Gly- Gly-AMC (Z-RLRGG-AMC), and a range of concentrations of compound. Enzyme, buffer, and inhibitor compound were incubated for 10 minutes or 30 minutes at 37°C before the addition of Z-RLRGG-AMC. Fluorescence was measured (excitation 355 nm, emission 460 nm, gain 800) using a BMG LABTECH FLUOstar Omega microplate reader every minute for 30 minutes. IC50s were determined from the average increase in OD per minute versus the Log10 concentration of compound using GraphPad Prism. Table 1 Key to table: The following letters in Table 1 above represent the IC50 values in µM: A ≤ 2, B ≤ 20, C ≤ 50 and D > 50. Cytotoxicity of compounds of the invention was evaluated in human Hep G2 cells (ATCC HB-8065) seeded at a density of 2 × 10 ⁴ cells per well and incubated for 24 hours at 37 °C, 5% CO2. Cells were exposed to 100 µM solution of test article. After 24-hour exposure, the viability of the cells was determined using CellTiter-Glo® (Promega, WI, USA) according to the manufacturer's instructions. Results in Table 2 below are reported as percentage cell viability at tested concentration. Table 2 Anti-viral potency of compounds of the invention was assessed in 96-well plates using VERO E6 cells. To generate EC50 and EC90 values for each compound, cells were treated in minimal medium at a range of compound concentrations. The plates were then incubated at 37 °C with 5% CO2 for 2 hours. The minimal media containing the experimental compounds and the control media was then removed. Wells were then treated with 50 μL minimal media containing SARS-CoV-2 (MOI of 0.005), 100 μL 2× semi-solid media and then 50 μL minimal media containing experimental compounds and control media, as appropriate. After 48 hours, 4% paraformaldehyde was added to each well and the plate incubated for 1 hour at room temperature. The medium was removed, cells were stained with crystal violet. Cells were washed three times with water and cytopathic viral activity was determined by measuring absorbance of each well at 590 nm using a Varioskan LUX microplate reader (Thermo Fisher Scientific). At all concentrations, treatment of cells was performed alongside 2 µM of CP-100356 – a known efflux pump inhibitor. Table 3

Key to table: The following letters in Table 1 above represent the EC50 values in µM: A ≤ 5, B ≤ 10, C ≤ 20.