Heterocyclic compounds and methods of use
AssigneeTargeGen, Inc.
InventorsWolfgang Wrasidlo, Elena Dneprovskaia
Life of this patent
Estimating the term…
Abstract
Heterocyclic compounds derived from benzotriazine, triazines, triazoles and oxadiazoles are disclosed. The methods of synthesis and of use of such heterocyclic compounds are also provided.
Claims90
A compound having the structure (A) or an N-oxide, N,N′-dioxide, N,N′,N″-trioxide, or a pharmaceutically acceptable salt thereof:
- wherein:
- Y is absent or is a moiety selected from a group consisting of:
- R1 is a substituent selected from a group consisting of an aryl, a substituted aryl, a heterocycle, a heteroaryl, a substituted heterocycle, and a substituted heteroaryl;
- R2 is a substituent selected from a group consisting of hydrogen, hydroxyl, C1-C6 alkyl, C1-C6 alkylamino, halogen, C1-C6 alkoxy, —NO2, —NH2, and —C≡N;
- and
- R3 is a substituent selected from a group consisting of an aryl, a substituted aryl, a heterocycle, a heteroaryl, a substituted heterocycle, and a substituted heteroaryl.
A compound having the structure (B) or an N-oxide, N,N′-dioxide, N,N′,N″-trioxide, or a pharmaceutically acceptable salt thereof:
- wherein:
- each of Z1, Z2 and Z3 is independently selected from a group consisting of N, CH, N═CH, O, S and N—R4, wherein R4 is hydrogen or lower alkyl, with the further proviso that at least one of Z1, Z2 and Z3 is not CH;
- X is absent or is NH;
- and
- Y is absent or is selected from a group consisting of the following moieties:
- R1 is an unsubstituted or a substituted C3-C12 heteroaryl having 1-3 heteroatoms;
- R2 is selected from a group consisting of of hydrogen, halogen, C1-C18 alkyl, —OH, —NO2, —CN, C1-C18 alkoxy, —NHSO2R5, —SO2NHR5, —NHCOR5, —NH2, —NR5R6, —S(O)R5, —S(O)2R5, —CO2R5, —CONR5R6, wherein R5 and R6 are independently selected from a group consisting of hydrogen, a C1-C18 alkyl, and a substituted C1-C12 alkyl;
- and
- R3 is selected from a group consisting of hydrogen, a C1-C18 alkyl, a substituted C1-C12 alkyl, a C1-C12 cycloalkyl, a substituted C1-C12 cycloalkyl, a substituted C3-C10 cycloalkyl having 0-3 heteroatoms, an C6-C12 aryl, a substituted C6-C12 aryl, a heterocycle, a substituted heterocycle, a C3-C12 heteroaryl having 1-3 heteroatoms, a substituted C3-C12 heteroaryl having 1-3 heteroatoms, a C7-C24 aralkyl, a substituted C7-C24 aralkyl, a C7-C24 alkylaryl, and a substituted C7-C24 alkaryl.
A compound comprising a derivative of benzotriazine, the compound including a benzotriazine moiety having at least a first substituent attached to the benzene ring of benzotriazine and a second substitutent attached to the triazine ring of the benzotriazine, wherein:
- (a) the first substitutent includes a substituted phenyl, substituted pyridyl or substituted pyrimidyl group;
- and
- (b) the second substitutent is selected from a secondary amino group, a substituted amide group, and a substituted sulfonylamino group.
A compound comprising a benzene derived moiety bridged to a heterocyclic moiety, wherein:
- (a) the benzene-derived moiety includes a molecule of benzene having a substitutent selected from:
- a pyridyl group connected to the benzene molecule via an oxygen link, and a sulfonyl group;
- and
- (b) the heterocyclic moiety is selected from triazine, triazole, oxadiazole, pyridazine, pyrimidine, pyridine, oxazole, pyrazol, pyrrole, imidazole, thiadiazole.
A method for treating a disorder comprising administering to a subject in need thereof an effective amount of a compound, wherein the compound is set forth in Structures (A), (B) or a combination thereof.
A method for treating a disorder, comprising administering to a subject in need thereof an effective amount of a compound having the structure (A):
- wherein:
- Y is absent or is a moiety selected from a group consisting of:
- R1 is a substituent selected from a group consisting of an aryl, a substituted aryl, a heterocycle, a heteroaryl, a substituted heterocycle, and a substituted heteroaryl;
- R2 is a substituent selected from a group consisting of hydrogen, hydroxyl, C1-C6 alkyl, C1-C6 alkylamino, halogen, C1-C6 alkoxy, —NO2, —NH2, and —C≡N;
- and
- R3 is a substituent selected from a group consisting of an aryl, a substituted aryl, a heterocycle, a heteroaryl, a substituted heterocycle, and a substituted heteroaryl.
A method for treating a disorder, comprising administering to a subject in need thereof an effective amount of a compound having the structure (B):
- wherein:
- each of Z1, Z2 and Z3 is independently selected from a group consisting of N, CH, N═CH, O, S and N—R4, wherein R4 is hydrogen or lower alkyl, with the further proviso that at least one of Z1, Z2 and Z3 is not CH;
- X is absent or is NH;
- and
- Y is absent or is selected from a group consisting of the following moieties:
- R1 is an unsubstituted or a substituted C3-C12 heteroaryl having 1-3 heteroatoms;
- R2 is selected from a group consisting of of hydrogen, halogen, C1-C18 alkyl, —OH, —NO2, —CN, C1-C18 alkoxy, —NHSO2R5, —SO2NHR5, —NHCOR5, —NH2, —NR5R6, —S(O)R5, —S(O)2R5, —CO2R5, —CONR5R6, wherein R5 and R6 are independently selected from a group consisting of hydrogen, a C1-C18 alkyl, and a substituted C1-C12 alkyl;
- and
- R3 is selected from a group consisting of hydrogen, a C1-C18 alkyl, a substituted C1-C12 alkyl, a C1-C12 cycloalkyl, a substituted C1-C12 cycloalkyl, a substituted C3-C10 cycloalkyl having 0-3 heteroatoms, an C6-C12 aryl, a substituted C6-C12 aryl, a heterocycle, a substituted heterocycle, a C3-C12 heteroaryl having 1-3 heteroatoms, a substituted C3-C12 heteroaryl having 1-3 heteroatoms, a C7-C24 aralkyl, a substituted C7-C24 aralkyl, a C7-C24 alkylaryl, and a substituted C7-C24 alkaryl.
A pharmaceutical composition comprising a compound set forth in structures (A), (B) or any combination thereof, in a pharmaceutically acceptable carrier.
An article of manufacture comprising packaging material and a pharmaceutical composition contained within the packaging material, wherein the packaging material comprises a label which indicates that the pharmaceutical composition can be used for treatment of disorders and wherein said pharmaceutical composition comprises a compound set forth in structures (A), (B) or any combination thereof.
An article of manufacture comprising packaging material and a pharmaceutical composition contained within said packaging material, wherein said packaging material comprises a label which indicates that said pharmaceutical composition can be used for treatment of cancer and wherein said pharmaceutical composition comprises a compound set forth in structures (A), (B) or any combination thereof.
A method of treating a disorder, comprising the administration of a therapeutically effective amount of at least one compound set forth in structures (A), (B) or any combination thereof, or pharmaceutically acceptable salts, hydrates, solvates, crystal forms and individual diastereomers thereof, to a subject in need of such treatment.
A method of treating a disorder comprising the administration of a therapeutically effective amount of at least one compound as set forth in structures (A), (B) or any combination thereof, or pharmaceutically acceptable salts, hydrates, solvates, crystal forms and individual diastereomers thereof, in combination with a chemotherapeutic agent, immunomodulatory agent, therapeutic antibody or a protein kinase inhibitor, to a subject in need of such treatment.
A method of treating a subject having cancer comprising administering to the subject a therapeutically effective amount of a compound as set forth in structures (A), (B) or any combination thereof, thereby treating the subject.
A process for making a pharmaceutical composition comprising combining a combination of a compound set forth in structures (A), (B) or any combination thereof or its pharmaceutically acceptable salts, hydrates, solvates, crystal forms salts and individual diastereomers thereof, and a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising a compound as set forth in Structure (A1) in a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising a compound as set forth in Structure (A2) in a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising a compound as set forth in Structure (A3) in a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising a compound as set forth in Structure (A4) in a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising a compound as set forth in Structure (B) in a pharmaceutically acceptable carrier.
A method for treating cancer or a tumor in a subject, comprising administering to a subject in need thereof an effective amount of a therapeutic antibody, chemotherapeutic agent or immunotoxic agents, in combination with a compound set forth in Structures (A), (B) or any combination thereof, thereby treating the cancer or tumor in the subject.
A pharmaceutical composition comprising a therapeutic agent and at least one compound as set forth in Structures (A1), (A2), (A3), (A4) or any combination thereof, in a concentration effective to treat cancer in a subject.
Dependencies are inferred from the claim text.