Oxton, United Kingdom

Time filter

Source Type

Patent
Chroma Therapeutics | Date: 2016-06-15

The present invention provides a compound which is: tert-butyl N-[2-{4-[6-amino-5-(2,4-difluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenyl}ethyl)-L-alaninate or a salt, hydrate or solvate thereof. The present invention also provides a pharmaceutical composition comprising the compound together with one or more pharmaceutically acceptable carriers and/or excipients. The compound and composition are useful for inhibiting the activity of a p38 MAP kinase enzyme. As such they may be used in the treatment of a autoimmune or inflammatory disease, or a cell proliferative disease. In addition, the invention provides an acid produced by hydrolysis of the ester group of the compound of the invention. The acid is N-[2-{4-[6-amino-5-(2,4-difluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenyl}ethyl)-L-alanine.


Patent
Chroma Therapeutics | Date: 2013-06-26

The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt, N-oxide, hydrate or solvate thereof: wherein: ring A, R^(1), R^(2), n, X, V, W, Z, ring B, [Linker] and R areas defined herein. The compounds are useful as inhibitors of CSF-1R kinase. The compounds can thus be used in medicine.


Patent
Chroma Therapeutics | Date: 2013-10-15

The present invention provides a compound which is: tert-butyl N-[2-{4-[6-amino-5-(2,4-difluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenyl}ethyl)-L-alaninate or a salt, hydrate or solvate thereof. The present invention also provides a pharmaceutical composition comprising the compound together with one or more pharmaceutically acceptable carriers and/or excipients. The compound and composition are useful for inhibiting the activity of a p38 MAP kinase enzyme. As such they may be used in the treatment of a autoimmune or inflammatory disease, or a cell proliferative disease. In addition, the invention provides an acid produced by hydrolysis of the ester group of the compound of the invention. The acid is N-[2-{4-[6-amino-5-(2,4-difluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenyl}ethyl)-L-alanine.


Patent
Chroma Therapeutics | Date: 2014-02-07

Compounds of formula (I), inhibit HDAC activity: wherein A, B and D independently represent CH or N; W is CHCH Or CH_(2)CH_(2); R_(1 )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; R_(2 )and R_(3 )are selected from the side chains of a natural or non-natural alpha amino acid, provided that neither R_(2 )nor R_(3 )is hydrogen, or R_(2 )and R_(3), 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(CO), S(O)_(2), C(CO)O, C(CO)NR, C(S)NR, C(NH)NR or S(O)_(2)NR wherein R is hydrogen or optionally substituted C_(1)-C_(6 )alkyl; L^(1 )is a divalent radical of formula -(Alk^(1))_(m)(Q)(Alk^(2))_(p) wherein in, n, p, Q, AIk^(1 )and AIk^(2 )are as defined in the claims; X^(1 )represents a bond; C(O); or S(O)_(2); NR_(4)C(O), C(CO)NR_(4), NR_(4)C(O)NR_(5), NR_(4)S(O)_(2), or S(O)_(2)NR_(4) wherein R_(4 )and R_(5 )are independently hydrogen or optionally substituted C_(1)-C_(6 )alkyl; and z is 0 or 1.


Patent
Chroma Therapeutics | Date: 2014-10-07

Covalent conjugation of an alpha amino acid ester to 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, leads to accumulation of the carboxylic acid hydrolysis product in the cell and enables improved or more prolonged enzyme or receptor modulation relative to the unconjugated modulator.


Patent
Chroma Therapeutics | Date: 2011-03-30

Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers:R 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; R 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)NR_(3)-, -C(=S)-NR_(3), -C(=NH)NR_(3) or -S(=O)_(2)NR_(3)- wherein R_(3) is hydrogen or optionally substituted C_(1)-C_(6) alkyl; L is a divalent radical of formula -(Alk^(1))_(m)(Q)_(n)(Alk^(2))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 -X^(2)-Q^(1)- or -Q^(1)-X^(2)- wherein X^(2) is -O-, S- or NR^(A)- wherein R^(A) is hydrogen or optionally substituted C_(1)-C_(3) alkyl, and Q^(1) is an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5 - 13 ring members, Alk and Alk independently represent optionally substituted divalent C_(3)-C_(7), cycloalkyl radicals, or optionally substituted straight or branched, C_(1)-C_(6) alkylene, C_(2)-C_(6) alkenylene ,or C_(2)-C_(6) alkynylene radicals which may optionally contain or terminate in an ether (-O-), thioether (-S-) or amino (-NR^(A)-) link wherein R^(A) is hydrogen or optionally substituted C_(1)-C_(3) alkyl; X represents a bond; -C(=O); or - S(=O)_(2)-; -NR_(4)C(=O)-, -C(=O)NR_(4)-,-NR_(4)C(=O)NR_(5)-, -NR_(4)S(=O)_(2)-, or -S(=O)_(2)NR_(4)- wherein R_(4) and R_(5) are independently hydrogen or optionally substituted C_(1)-C_(6) alkyl; z is 0 or 1; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals R_(1)R_(2)NH-Y-L^(1)-X^(1)-[CH_(2)]_(z)- and HONHCO-[LINKER]- are attached different ring atoms; and -[Linker]- represents a divalent radical of formula -(CH_(2))_(x)- L^(3)-Ar^(1)-L^(4)- wherein x is 0 or 1; L^(3) is Z or L^(2) or Z-L^(2) wherein Z is a bond, -NR_(3)-, -NR_(3)C(=O)-, -C(=O)NR_(3)-,-NR_(4)C(=O)-NR_(3)-, -C(=S)-NR_(3), -C(=N)-NR_(3) -NR_(3)S(=O)_(2)-, or -S(=O)_(2)NR_(3)- wherein R_(3) is hydrogen or C_(1)-C_(6) alkyl; - C(=O); or -S(=O)_(2)-; and L^(2) is a bond or an optionally substituted divalent C_(1)-C_(3) alkylene radical; Ar^(1) is a divalent phenyl radical or a divalent mono-, or bi-cyclic heteroaryl radical having 5 to 13 ring members; and L^(4) is a bond or optionally substituted -CH_(2)- or -CH=CH-.


Patent
Chroma Therapeutics | Date: 2014-02-13

Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein R_(1 )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; R_(2 )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)NR_(3), C(S)NR_(3), C(NH)NR_(3 )or S(O)_(2)NR_(3) wherein R_(3 )is hydrogen or optionally substituted C_(1)-C_(6 )alkyl; L^(1 )is a divalent radical of formula -(Alk^(1))_(m)(Q)_(n)(Alk^(2))_(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 X^(2)-Q^(1)- or -Q^(1)-X^(2) wherein X^(2 )is O, S or NR^(A) wherein R^(A )is hydrogen or optionally substituted C_(1)-C_(3 )alkyl, and Q^(1 )is an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, Alk^(1 )and Alk^(2 )independently represent optionally substituted divalent C_(3)-C_(7 )cycloalkyl radicals, or optionally substituted straight or branched, C_(1)-C_(6 )alkylene, C_(2)-C_(6 )alkenylene, or C_(2)-C_(6 )alkynylene radicals which may optionally contain or terminate in an ether (O), thioether (S) or amino (NR^(A)) link wherein R^(A )is hydrogen or optionally substituted C_(1)-C_(3 )alkyl; X^(1 )represents a bond; C(O); or S(O)_(2); NR_(4)C(O), C(O)NR_(4), NR_(4)C(O)NR_(5), NR_(4)S(O)_(2), or S(O)_(2)NR_(4) wherein R_(4 )and R_(5 )are independently hydrogen or optionally substituted C_(1)-C_(6 )alkyl; z is 0 or 1; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals R_(1)R_(2)NHY-L^(1)-X^(1)-[CH_(2)]_(Z) and HONHCO-[LINKER]- are attached different ring atoms; and -[Linker]- represents a divalent linker radical linking a ring atom in A with the hydroxamic acid group CONIIOII, the length of the linker radical, from the terminal atom linked to the ring atom of A to the terminal atom linked to the hydroxamic acid group, is equivalent to that of an unbranched saturated hydrocarbon chain of from 3-10 carbon atoms.


Patent
Chroma Therapeutics | Date: 2013-11-27

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.


Patent
Chroma Therapeutics | Date: 2016-03-17

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 R^(1), R^(2), R^(3), R^(4), R^(5), R^(6 )and R^(7 )are as defined herein. The compounds are useful in the treatment of diseases mediated by HSP90.


Patent
Chroma Therapeutics | Date: 2011-03-16

Cyclopentyl (2S)-cyclohexyl[({6-[3-(hydroxyamino)-3-oxopropyl]pyridin-3 yl}methyl)amino]acetate inhibits HDAC activity.

Loading Chroma Therapeutics collaborators
Loading Chroma Therapeutics collaborators