Abstract: Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group; R2 is the side chain of a natural or non-natural alpha amino acid; Y is a bond, —C(?O), —S(?O)2—, —C(?O)O—, —C(O)NR3—, —C(?S)—NR3, —C(?NH)NR3 or —S(?O)2NR3— wherein R3 is hydrogen or optionally substituted C1-C6 alkyl; L1 is a divalent radical of formula -(Alk1)m(Q)n(Alk2)p- wherein m, n and p are independently 0 or 1, Q is (i) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, or (ii), in the case where both m and p are 0, a divalent radical of formula —X2-Q1- or -Q1-X2— wherein X2 is —O—, S— or NRA— wherein RA is hydrogen or optionally substituted C1-C3 alkyl, and Q1 is an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic r

Abstract: Compounds of formula (I), inhibit HDAC activity: wherein A, B and D independently represent ?CH— or ?N—; W is —CH?CH— Or —CH2CH2—; R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group; R2 and R3 are selected from the side chains of a natural or non-natural alpha amino acid, provided that neither R2 nor R3 is hydrogen, or R2 and R3, taken together with the carbon to which they are attached, form a 3-6 membered saturated cycloalkyl or heterocyclyl ring; Y is a bond, —C(C?O)—, —S(?O)2—, —C(C?O)O—, —C(C?O)NR?—, —C(?S)—NR?, —C(?NH)NR? or —S(?O)2NR— wherein R? is hydrogen or optionally substituted C1-C6 alkyl; L1 is a divalent radical of formula -(Alk1)m(Q)(Alk2)p— wherein in, n, p, Q, AIk1 and AIk2 are as defined in the claims; X1 represents a bond; —C(?O); or —S(?O)2—; —NR4C(?O)—, —C(C?O)NR4—, —NR4C(?O)NR5—, —NR4S(?O)2—, or —S(?O)2NR4— wherein R4 and R5 are independently hydrogen or optionally substituted C1

Abstract: Covalent conjugates of an ?,?-disubstituted glycine ester and a modulator of the activity of a target intracellular enzyme or receptor, wherein the ester group of the conjugate is hydrolysable by one or more intracellular carboxylesterase enzymes to the corresponding acid and the ?,?-disubstituted glycine ester is conjugated to the modulator at a position remote from the binding interface between the inhibitor and the target enzyme or receptor pass into cells and the active acid hydrolysis product accumulates within the cells.

Abstract: Compounds of formula (I), inhibit HDAC activity: wherein A, B and D independently represent ?CH— or ?N—; W is —CH?CH—Or —CH2CH2—; R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group; R2 and R3 are selected from the side chains of a natural or non-natural alpha amino acid, provided that neither R2 nor R3 is hydrogen, or R2 and R3, taken together with the carbon to which they are attached, form a 3-6 membered saturated cycloalkyl or heterocyclyl ring; Y is a bond, —C(?O)—, —S(?O)2—, —C(?O)O—, —C(?O)NR?—, —C(?S)—NR?, —C(?NH)NR? or —S(?O)2NR— wherein R? is hydrogen or optionally substituted C1-C6 alkyl; L1 is a divalent radical of formula -(Alk1)m(Q)n(Alk2)p- wherein m, n, p, Q.

Abstract: The invention provides a compound which is (a) a phenylamide derivative of formula (I) or a tautomer thereof, or (b) a pharmaceutically acceptable salt, N-oxide, hydrate, prodrug or solvate thereof: wherein R1, R2, R3, R4, R5, R6 and R7 are as defined herein. The compounds are useful in the treatment of diseases mediated by HSP90.

Abstract: The invention provides a compound which is (a) an amino acid derivative of formula (I) or a tautomer thereof, or (b) a pharmaceutically acceptable salt, N-oxide, hydrate or solvate thereof: wherein R1, R2, L1, Het, A, x, y and W are as defined herein. The compounds are useful in the treatment of diseases mediated by HSP90.

Abstract: Compounds of formula (I), inhibit HDAC activity: wherein A, B and D independently represent ?CH— or ?N—; W is —CH?CH— Or —CH2CH2—; R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intra-cellular carboxylesterase enzymes to a carboxylic acid group; R2 and R3 are selected from the side chains of a natural or non-nat-ural alpha amino acid, provided that neither R2 nor R3 is hydrogen, or R2 and R3, taken together with the carbon to which they are attached, form a 3-6 membered saturated cycloalkyl or heterocyclyl ring; Y is a bond, —C(?O)—, —S(?O)2—, —C(?O)O—, —C(?O)NR?—, —C(?5)—NR?, —C(?NH)NR? or —S(?O)2NR — wherein R? is hydrogen or optionally substituted C1—C6 alkyl; L1 is a divalent radical of formula —(Alk1)m,(Q)n(Alk2)p— wherein m, n, p, Q, Alk1 and Alk2 are as defined in the claims; X1 represents a bond; —C(?O); or —S(?O)2—; —NR4C(?O)—, —C(?O)NR4—,— NR4C(?O)NR5—, —NR4S(?O)2—, or —S(?O)2NR4— wherein R4 and R5 are independently hydrogen or optionally substituted C1

Abstract: Compounds of formula (IA) or (IB), are inhibitors of aurora kinase activity: Formula (IA), (IB) wherein -L1Y1-[CH2]z- is a linker radical wherein Y1, L1 and z are as defined in the claims; R6 is C1-C4alkoxy, hydrogen or halo; W represents a bond, —CH2—, —O—, —S—, —S(?O)2—, or —NR5— where R5 is hydrogen or C1-C4 alkyl; Q is ?N—, ?CH— or ?C(X1)— wherein X1 is cyano, cyclopropyl or halo; linker radicals L2 are as defined in the claims; R is a radical of formula (X) or (Y): wherein R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group; R4 is hydrogen; or optionally substituted C1-C6 alkyl, C3-C7 cycloalkyl, aryl, aryl(C1-C6 alkyl)-, heteroaryl, heteroaryl(C1-C6 alkyl)-, —(C?O)R3, —(C?O)OR3, or —(C?O)NR3 wherein R3 is hydrogen or optionally substituted (C1-C6)alkyl, C3-C7 cycloalkyl, aryl, aryl(C1-C6 alkyl)-, heteroaryl, or heteroaryl(C1-C6 alkyl)-; R41 is hydrogen or optionally substituted C1-C6 alkyl; and D

Abstract: Compounds of formula (IA) or (IB) are inhibitors of IkB kinase (IKK) activity, and are useful in the treatment of autoimmune and inflammatory diseases: Formula (A) and (B) wherein R7 is hydrogen or optionally substituted (C1-C6)alkyl; ring A is an optionally substituted aryl or heteroaryl ring of 5-13 ring atoms; Z is (a) a radical of formula R1R2CHNH—Y-L1-X1—(CH2)z— wherein: z is 0 or 1; R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular esterase enzymes to a carboxylic acid group; R2 is the side chain of a natural or non-natural alpha amino acid; Y is a bond, —C(?O)—, —S(?P)2-, —C(?O)O—, —C(?O)NR3-, —C(?S)—NR3, —C(?NH)—NR3 or —S(?O)2NR3— wherein R3 is hydrogen or optionally substituted C1-C6 alkyl; L is a divalent linker radical of formula -(Alk1)m(Q)(Alk2)p- wherein m, n, p, Q, AIk1 and AIk2 are as defined in the claims.

Abstract: Compounds of formula (I) are PLK inhibitors, useful for the treatment of cell proliferative diseases: wherein R1 is hydrogen, or an optionally substituted (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl group; R2 is hydrogen, or an optionally substituted (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl group; R3 is hydrogen, —CN, hydroxyl, halogen, optionally substituted (C1C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl, —NR5R6 or C1-C4 alkoxy, wherein R5 and R6 are independently hydrogen or optionally substituted (C1-C6)alkyl; ring A is an optionally substituted mono- or bi-cyclic carbocyclic or heterocyclic ring or a ring system having up to 12 ring atoms; T is a radical of formula R-L1-Y1— wherein L1 and Y1 are as defined in the claims and R is an carbon-linked, alpha alpha disubstituted amino acid or amino acid ester residue.

Abstract: Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers: wherein Y1 is a bond, —(C?O)—, —S(O2)—, —C(?O)O—, —OC(?O)—, —(C?O)NR3—, —NR3(C?O)—, —S(O2)NR3—, —NR3S(O2)—, or —NR3(C?O)NR5—, wherein R3 and R5 are independently hydrogen or optionally substituted (C1-C6)alkyl, L1 is a divalent radical of formula -(Alk1)m(Q)n(Alk2)p wherein m, n, p, Alk1, Alk2 and Q are as defined in the claims; z is 0 or 1; A represents an optionally substituted mono-, bi— or tri-cyclic carbocyclic or heterocyclic ring system; -[Linker]- represents a divalent linker radical; R is a radical of formula (X) or (Y): wherein R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group; R4 is hydrogen; or optionally substituted C1-C6 alkyl, C3-C7cycloalkyl, aryl, aryl(C1-C6 alkyl)-, heteroaryl, heteroaryl(C1-C6 alkyl)-, —(C?O)R3, —(C?O)OR3, or —(C?O)NR3 wherein R

Abstract: Compounds of formula: (I), and salts, N-oxides, hydrates and solvates thereof are histone deacetylase inhibitors and are useful in the treatment of cell proliferative diseases, including cancers: (I) wherein Q, V and W independently represent —N? or —C?; B is a divalent radical selected from: (IIA), (IIB), (IIC), (IID), and (IIE). Wherein the bond marked * is linked to the ring containing Q, V and W through -[Linker1]- and the bond marked ** is linked to A through -[Linker2]-; A is an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system; and -[Linker1]- and -[Linker2]- independently represent a bond, or a divalent linker radical.

Abstract: Compounds of formula (IA) or (IB) are IKK inhibitors useful in the treatment of autoimmune and inflammatory diseases: wherein R7 is hydrogen or optionally substituted (C1-C6)alkyl; A is an optionally substituted aryl or heteroaryl of 5-13 ring atoms; Z is a radical of formula R1C(R2)(R3)NH—Y-L1-X1-(CH2)z— wherein R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular esterase enzymes to a carboxylic acid group; and R2 and R3 independently represent the side chain of a natural or non-natural alpha amino acid but neither of R2 and R3 is hydrogen, or R2 and R3 taken together with the carbon atom to which they are attached form a C3-C7 cycloalkyl ring, and z, Y, L1 and X1 are as defined in the claims.

Abstract: Cyclopentyl(2S,4E)-2-amino-5-{3-[4-carbamoyl-5(carbamoylamino)-2-thienyl]phenyl}pent-4-enoate; Cyclopentyl 5-{3-[4-carbamoyl-5-(carbamoylamino)-2-thienyl]phenyl}-L-norvalinate; Cyclopentyl(2S,4E)-2-amino-5-{3-[4-carbamoyl-5-(carbamoylamino)-2-thienyl]-5-methylphenyl}pent-4-enoate; Cyclopentyl(25,4E)-2-amino-5-{5-[4-carbamoyl-5-(carbamoylamino)-2-thienyl]-2-methylphenyl}pent-4-enoate; Cyclopentyl O-{3-[4-carbamoyl-5-(carbamoylamino)-2-thienyl]phenyl}-L-homoserinate; Cyclopentyl O-{3-[4-carbamoyl-5-(carbamoylamino)-2-thienyl]phenyl}-L-homoserinate; Cyclopentyl N-{3-[4-carbamoyl-5-(carbamoylamino)-2-thienyl]benzyl}-L-alaninate; and tert-Butyl N-{3-[4-carbamoyl-5-(carbamoylamino)-2-thienyl]benzyl}-L-alaninate are hydrolysed to the corresponding carboxylic acids by intracellular carboxylesterases, and are useful for the inhibition of IKK? activity.

Abstract: Compounds of formula (I) are p38 MAP kinase inhibitors useful for the treatment of autoimmune and inflammatory diseases: wherein: G is —N? or —CH?; D is an optionally substituted divalent mono- or bi-cyclic aryl or heteroaryl radical having 5-13 ring members; R6 is hydrogen or optionally substituted CrC3 alkyl; P represents hydrogen and U represents a radical of formula (IA); or U represents hydrogen and P represents a radical of formula (IA); wherein A represents an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members; z is O or 1; —X1-L1-Y— is a linker radical or bond; R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular esterase enzymes to a carboxylic acid group; and R2 and R3 are as defined in the claims.

Abstract: Covalent conjugates of an ?,?-disubstituted glycine ester and a modulator of the activity of a target intracellular enzyme or receptor, wherein the ester group of the conjugate is hydrolysable by one or more intracellular carboxylesterase enzymes to the corresponding acid and the ?,?-disubstituted glycine ester is conjugated to the modulator at a position remote from the binding interface between the inhibitor and the target enzyme or receptor pass into cells and the active acid hydrolysis product accumulates within the cells.

Abstract: Compounds of formula (I), and salts, N-oxides, hydrates and solvates thereof are histone deacetylase inhibitors and are useful in the treatment of cell proliferative diseases, including cancers: wherein Q, V and W independently represent —N? or —C?; B is a divalent radical selected from (B1), (B2), (B3), (B4), (B5) and (B6).

Abstract: Compounds of formula (I) are inhibitors of p38 MAP kinase, and are therefore of utility in the treatment of, inter alia, inflammatory conditions including rheumatoid arthritis and COPD: formula (I) wherein: G is —N? or —CH?; D is an optionally substituted divalent mono- or bi-cyclic aryl or heteroaryl radical having 5-13 ring members; R6 is hydrogen or optionally substituted C1-C3 alkyl; P represents hydrogen and U represents a radical of formula (IA); or U represents hydrogen and P represents a radical of formula -A-(CH2)z—X1-L1-Y—NH—CHR1R2 wherein A represents an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members; z, Y, L1, and X1 are as defined in the specification; R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular esterase enzymes to a carboxylic acid group; and R2 is the side chain of a natural or non-natural alpha amino acid.

Abstract: Compound of formula (I) are inhibitors of Polo-like kinases (PLKs), and are useful in treatment of cell proliferative diseases: wherein R1 and R2 are hydrogen, or an optionally substituted (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl group; R3 and R3? are independently selected from hydrogen, —CN, hydroxyl, halogen, optionally substituted (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl, —NR5R6 or C1-C4 alkoxy, wherein R5 and R6 are independently hydrogen or optionally substituted (C1-C6)alkyl; ring A is an optionally substituted mono- or bi-cyclic carbocyclic or heterocyclic ring or a ring system having up to 12 ring atoms; T is a radical of formula R-L1-Y1— wherein R is an alpha amino acid or alpha amino acid ester motif, linked to ring A by linker R-L1-Y1— as defined in the claims.

Abstract: Compounds of formula: (I), and salts, N-oxides, hydrates and solvates thereof are histone deacetylase inhibitors and are useful in the treatment of cell proliferative diseases, including cancers: (I) wherein Q, V and W independently represent —N? or —C?; B is a divalent radical selected from: (IIA), (IIB), (IIC), (IID), and (IIE). Wherein the bond marked * is linked to the ring containing Q, V and W through -[Linker1]- and the bond marked ** is linked to A through -[Linker2]-; A is an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system; and -[Linker1]- and -[Linker2]- independently represent a bond, or a divalent linker radical.