63 results about "Histone deacetylase activity" patented technology

In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel compounds of general formula (I):and pharmaceutically acceptable derivatives thereof, wherein R1, R2, R3, n, X and Y are as defined herein. The present invention also provides pharmaceutical compositions comprising a compound of formula (I) and a pharmaceutically acceptable carrier. The present invention further provides compounds capable of inhibiting histone deacetylatase activity and methods for treating disorders regulated by histone deacetylase activity (e.g., cancer and protozoal infections) comprising administering a therapeutically effective amount of a compound of formula (I) to a subject in need thereof. The present invention additionally provides methods for modulating the glucose-sensitive subset of genes downstream of Ure2p. The present invention also provides methods for preparing compounds of the invention.

The present invention is directed to certain hydroxamate derivatives that are useful in the treatment of hepatitis C. These compounds are also inhibitors of histone deacetylase and are therefore useful in the treatment of diseases associated with histone deacetylase activity. Pharmaceutical compositions and processes for preparing these compounds are also disclosed.

Isolated compounds of formula I:and stereoisomers, enantiomers, diastereomers, and pharmaceutically acceptable salts thereof are described, as well as processes for production, and methods of use of these compounds and compositions thereof for the treatment of diseases associated with abnormal protein kinase activities and / or abnormal histone deacetylase activities including, for example, inflammatory diseases, autoimmune diseases, cancer, neurological and neurodegenerative diseases, cardiovascular diseases, metabolic disease, allergies and asthma and / or hormone-related diseases.

The present invention relates to compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to heterocyclic compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with enzymes having histone deacetylase (HDAC) activities.

The present invention relates to the medical use of compounds acting as inhibitors of enzymes having histone deacetylase activity in conditions where their combination with compounds known as NSAID's, Non Steroidal Anti Inflammatory Drugs, causes an enhanced beneficial therapeutic effect. These conditions comprise cancer, cancer predisposing conditions, inflammatory and metabolic diseases. Furthermore, the invention includes the manufacture of clinically used medicaments for the therapy of the diseases mentioned herein, administering the compounds separately in the form of two individual drugs or in an administrative form which contains both drugs in a single application unit.

The present invention relates to hydroxamate compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to imidazo[1,2-a]pyridine containing compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with enzymes having histone deacetylase activities (HDAC).

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(O)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 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 B is a monocyclic heterocyclic ring of 5 or 6 ring atoms wherein R1 is linked to a ring carbon adjacent the ring nitrogen shown, and ring B is optionally fused to a second carbocyclic or heterocyclic ring of 5 or 6 ring atoms in which case the bond shown intersected by a wavy line may be from a ring atom in said second ring;

Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers.

The present invention relates to compounds which inhibit histone deacetylase activity and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing these compounds. The present invention also relates to methods of treating and preventing hematological cell proliferative disorders, such as multiple myeloma, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

The invention discloses E-configuration benzamide compounds, and a pharmaceutical preparation application thereof. The structure of the E-configuration benzamide compounds is disclosed as Formula (I); the chemical name is N-(2-amino-4-fluorophenyl)-4-[N-[(E)-3-(3-pyridyl)acryloyl]aminomethyl]benzamide; and in the structural formula, the configuration of the 3-pyridylacryloyl group is E. The E-configuration benzamide compounds disclosed as Formula (I) have subtype selective histone deacetylase inhibition activity, and are mainly used for inhibiting HDAC1, HDAC2 and HDAC3 in Class I HDAC and HDAC10 in Class IIb HDAC. The E-configuration benzamide compounds disclosed as Formula (I) can be used for treating diseases related to histone deacetylase activity abnormity, such as cancers, including lymphomata, entity tumor, blood system tumors and the like.

The present invention relates to hydroxamate compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to imidazo[1,2-a]pyridine containing compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with enzymes having histone deacetylase activities (HDAC).

The present invention relates to hydroxamate compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to acylurea / sulfonylurea containing compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with enzymes having histone deacetylase activities.

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 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 B is a monocyclic heterocyclic ring of 5 or 6 ring atoms wherein R1 is linked to a ring carbon adjacent the ring nitrogen shown, and ring B is optionally fused to a second carbocyclic or heterocyclic ring of 5 or 6 ring atoms in which case the bond shown intersected by a wavy line may be from a ring atom in said second ring.

The invention relates to the field of medicinal chemistry, and specifically relates to lactam histone deacetylase inhibitors, preparation methods thereof, medicine compositions containing the histone deacetylase inhibitors, and applications of the inhibitors in preventing and / or treating diseases related to uncontrolled histone deacetylase activity.

Isolated compounds of formula I:and stereoisomers, enantiomers, diastereomers, and pharmaceutically acceptable salts thereof are described, as well as processes for production, and methods of use of these compounds and compositions thereof for the treatment of diseases associated with abnormal protein kinase activities and / or abnormal histone deacetylase activities including, for example, inflammatory diseases, autoimmune diseases, cancer, neurological and neurodegenerative diseases, cardiovascular diseases, metabolic disease, allergies and asthma and / or hormone-related diseases.

The present invention relates to compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to heterocyclic compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with enzymes having histone deacetylase (HDAC) activities.

The present invention relates to hydroxamate compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to biaryl containing compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with enzymes having histone deacetylase activities. Formula (I), where Z is a single bond or C1-C4 hydrocarbon, A is an aromatic ring, B is an aromatic ring.

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; L is a divalent radical of formula -(Alk1)m(O)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 hetero-cyclic radical having 5-13 ring members, AIk1 and AIk2 independently represent optionally substituted divalent C3-C7 cycloalkyl radicals, or optionally substituted straight or branched, C1-C6 alkylene, C2-C6 alkenylene, or C2-C6 alkynylene radicals which may optionally contain or terminate in an ether (—O—), thioether (—S—) or amino (—NRA-) link wherein RA is hydrogen or optionally substituted C1-C3 alkyl; X 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-C6 alkyl; z is 0 or 1; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals R1R2NH—Y-L1-X1—[CH2]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 CONHOH, 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.

The invention relates to isatin histone deacetylase inhibitors as well as a preparation method and applications thereof. The series of compounds have a structure as shown in the general formula I in the specification. Activity screening experiments shows that the histone deacetylase inhibitors have excellent in-vitro and in-vivo activity and can be used for preparing medicines for treating diseases with abnormal expression of histone deacetylase activity. The invention also relates to a medicine composition containing the compounds with a structure as shown in the formula I, as well as an application of the composition in medicine preparation.

The invention discloses a salicylamide ester type derivative and a preparation method thereof. The salicylamide ester type derivative has a general formula 1. The salicylamide ester type derivative can be disassociated into a salicylamide type compound with anti-tumor activity and a short-chain fatty acid type compound such as valproic acid, butyric acid and the like with effect of suppressing histone deacetylase activity; thus, the salicylamide ester type derivative disclosed by the invention can be used as an antineoplastic medicament with a double action mechanism.

Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers:

The invention belongs to the technical field of pharmaceutical chemistry, and particularly relates to a phenylglycine histone deacetylase inhibitor as well as a preparation method and applications thereof. The invention provides a superactive histone deacetylase inhibitor, which relates to a compound with a structure shown in the general formula (I), and also relates to various optical isomers thereof, a pharmaceutically acceptable salt, a solvate and a prodrug. The invention also relates to a pharmaceutical composition containing the compound with a structure shown in the formula (I), and pharmaceutical applications thereof. According to the invention, diseases with abnormal histone deacetylase activity expression can be effectively treated.

The present invention includes methods of treatment and compositions for treating diseases related to the activity of a histone deacetylase in a subject by administering to the subject an effective amount of a modified FK228 compound comprising an amino acid conjugate which constitutes an amino thiol, a hydroxy thiol, a dithiol, or a hydroxamic acid, instead of a hydroxy-mercapto-heptenoic acid moiety in FK228.

The invention belongs to the field of medical chemistry, and particularly relates to a class of lactam-based histone deacetylase inhibitors and a preparation method thereof, a pharmaceutical composition containing the histone deacetylase inhibitor, and applications of the inhibitors in drugs for preventing and / or treating diseases related to histone deacetylase activity out-of-control.