GENERAL INCORPORATED ASSOCIATION PHARMA VALLEY PROJECT SUPPORTING ORGANIZATION (Japan)
CanBas Co., Ltd. (Japan)
Inventor
Asai, Akira
Ogo, Naohisa
Muraoka, Daisuke
Takikawa, Osamu
Kawabe, Takumi
Sato, Takuji
Abstract
A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I), ring A represents an aromatic ring, an aliphatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, an aliphatic ring and a heterocyclic ring; X, R1 and R2 represent a substituent on a ring atom constituting ring A; m represents an integer of 0 to 6; X represents, for example, a halogen atom; and R1 and R2 are the same or different and are selected from, for example, the group consisting of groups of formula (a) or formula (b); and in the following formula (a) and formula (b), Y is selected from the group consisting of O, S, and Se, Z is selected from the group consisting of O, S, and Se, n represents an integer of 1 to 8, r represents an integer of 1 to 8, s represents an integer of 1 to 8, R4 represents, for example, —C(═NH)—HN2, and R6 represents, for example, a substituted or unsubstituted aryl group].
A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I), ring A represents an aromatic ring, an aliphatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, an aliphatic ring and a heterocyclic ring; X, R1 and R2 represent a substituent on a ring atom constituting ring A; m represents an integer of 0 to 6; X represents, for example, a halogen atom; and R1 and R2 are the same or different and are selected from, for example, the group consisting of groups of formula (a) or formula (b); and in the following formula (a) and formula (b), Y is selected from the group consisting of O, S, and Se, Z is selected from the group consisting of O, S, and Se, n represents an integer of 1 to 8, r represents an integer of 1 to 8, s represents an integer of 1 to 8, R4 represents, for example, —C(═NH)—HN2, and R6 represents, for example, a substituted or unsubstituted aryl group].
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61P 35/04 - Antineoplastic agents specific for metastasis
C07C 335/32 - Isothioureas having sulfur atoms of isothiourea groups bound to acyclic carbon atoms
C07D 241/42 - Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
C07D 333/18 - Radicals substituted by singly bound hetero atoms other than halogen by sulfur atoms
C07D 333/54 - Benzo [b] thiophenesHydrogenated benzo [b] thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Presented herein, in certain aspects, are conjugates capable of binding phosphatidylserine (PS) and toll-like receptors (TLRs), and their uses for the treatment of selected diseases and disorders, such as cancer.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 31/165 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
Presented herein, in certain aspects, are conjugates capable of binding phosphatidylserine (PS) and toll-like receptors (TLRs), and their uses for the treatment of selected diseases and disorders, such as cancer.
A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
4.
CONJUGATES BINDING PHOSPHATIDYLSERINE AND TOLL-LIKE RECEPTORS
Presented herein, in certain aspects, are conjugates capable of binding phosphatidylserine (PS) and toll-like receptors (TLRs), and their uses for the treatment of selected diseases and disorders, such as cancer.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
GENERAL INCORPORATED ASSOCIATION PHARMA VALLEY PROJECT SUPPORTING ORGANIZATION (Japan)
CanBas Co., Ltd. (Japan)
Inventor
Asai, Akira
Ogo, Naohisa
Muraoka, Daisuke
Takikawa, Osamu
Kawabe, Takumi
Sato, Takuji
Murakami, Hisashi
Abstract
A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I),
ring A represents an aromatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, and a heterocyclic ring, wherein ring A is selected from the group consisting of a benzene ring, a naphthalene ring, a quinoxaline ring, a thiophene ring, an indole ring, a benzothiophene ring, an imidazole ring, a quinoline ring, a quinazoline ring, and a pyridine ring;
X, R1 and R2 represent a substituent on a ring atom constituting ring A, wherein R1 and R2 are bonded to adjacent ring atoms of ring A;
m represents an integer of 1 or 2;
X is a halogen atom, and when m is 2, each X is the same or different;
R1 and R2 are the same or different;
R1 and R2 independently represent a group represented from the following groups:
A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I),
ring A represents an aromatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, and a heterocyclic ring, wherein ring A is selected from the group consisting of a benzene ring, a naphthalene ring, a quinoxaline ring, a thiophene ring, an indole ring, a benzothiophene ring, an imidazole ring, a quinoline ring, a quinazoline ring, and a pyridine ring;
X, R1 and R2 represent a substituent on a ring atom constituting ring A, wherein R1 and R2 are bonded to adjacent ring atoms of ring A;
m represents an integer of 1 or 2;
X is a halogen atom, and when m is 2, each X is the same or different;
R1 and R2 are the same or different;
R1 and R2 independently represent a group represented from the following groups:
—(CH2)n—Y—R4
A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I),
ring A represents an aromatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, and a heterocyclic ring, wherein ring A is selected from the group consisting of a benzene ring, a naphthalene ring, a quinoxaline ring, a thiophene ring, an indole ring, a benzothiophene ring, an imidazole ring, a quinoline ring, a quinazoline ring, and a pyridine ring;
X, R1 and R2 represent a substituent on a ring atom constituting ring A, wherein R1 and R2 are bonded to adjacent ring atoms of ring A;
m represents an integer of 1 or 2;
X is a halogen atom, and when m is 2, each X is the same or different;
R1 and R2 are the same or different;
R1 and R2 independently represent a group represented from the following groups:
—(CH2)n—Y—R4
wherein
Y is selected from the group consisting of O, S, SO, SO2, and Se,
n represents an integer of 1 to 8,
R4 represents
A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I),
ring A represents an aromatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, and a heterocyclic ring, wherein ring A is selected from the group consisting of a benzene ring, a naphthalene ring, a quinoxaline ring, a thiophene ring, an indole ring, a benzothiophene ring, an imidazole ring, a quinoline ring, a quinazoline ring, and a pyridine ring;
X, R1 and R2 represent a substituent on a ring atom constituting ring A, wherein R1 and R2 are bonded to adjacent ring atoms of ring A;
m represents an integer of 1 or 2;
X is a halogen atom, and when m is 2, each X is the same or different;
R1 and R2 are the same or different;
R1 and R2 independently represent a group represented from the following groups:
—(CH2)n—Y—R4
wherein
Y is selected from the group consisting of O, S, SO, SO2, and Se,
n represents an integer of 1 to 8,
R4 represents
A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I),
ring A represents an aromatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, and a heterocyclic ring, wherein ring A is selected from the group consisting of a benzene ring, a naphthalene ring, a quinoxaline ring, a thiophene ring, an indole ring, a benzothiophene ring, an imidazole ring, a quinoline ring, a quinazoline ring, and a pyridine ring;
X, R1 and R2 represent a substituent on a ring atom constituting ring A, wherein R1 and R2 are bonded to adjacent ring atoms of ring A;
m represents an integer of 1 or 2;
X is a halogen atom, and when m is 2, each X is the same or different;
R1 and R2 are the same or different;
R1 and R2 independently represent a group represented from the following groups:
—(CH2)n—Y—R4
wherein
Y is selected from the group consisting of O, S, SO, SO2, and Se,
n represents an integer of 1 to 8,
R4 represents
wherein R41, R42 and R47 are the same and are a hydrogen atom
A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I),
ring A represents an aromatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, and a heterocyclic ring, wherein ring A is selected from the group consisting of a benzene ring, a naphthalene ring, a quinoxaline ring, a thiophene ring, an indole ring, a benzothiophene ring, an imidazole ring, a quinoline ring, a quinazoline ring, and a pyridine ring;
X, R1 and R2 represent a substituent on a ring atom constituting ring A, wherein R1 and R2 are bonded to adjacent ring atoms of ring A;
m represents an integer of 1 or 2;
X is a halogen atom, and when m is 2, each X is the same or different;
R1 and R2 are the same or different;
R1 and R2 independently represent a group represented from the following groups:
—(CH2)n—Y—R4
wherein
Y is selected from the group consisting of O, S, SO, SO2, and Se,
n represents an integer of 1 to 8,
R4 represents
wherein R41, R42 and R47 are the same and are a hydrogen atom
C07D 251/08 - Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
C07D 333/24 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
A61K 31/381 - Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
A61K 31/505 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
C07D 239/545 - Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
C07D 209/42 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
A61K 31/4045 - Indole-alkylaminesAmides thereof, e.g. serotonin, melatonin
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 241/42 - Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
C07D 241/42 - Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
C07D 333/18 - Radicals substituted by singly bound hetero atoms other than halogen by sulfur atoms
C07D 333/54 - Benzo [b] thiophenesHydrogenated benzo [b] thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
GENERAL INCORPORATED ASSOCIATION PHARMA VALLEY PROJECT SUPPORTING ORGANIZATION (Japan)
CANBAS CO., LTD. (Japan)
Inventor
Asai, Akira
Ogo, Naohisa
Muraoka, Daisuke
Takigawa, Osamu
Kawabe, Takumi
Sato, Takuji
Abstract
Provided is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof, which is useful as an IDO/TDO inhibitor. The compound represented by formula (I) or a pharmaceutically acceptable salt thereof can, for example, be used as a therapeutic agent for a disease or disorder selected from tumors, infectious diseases, neurodegenerative disorders, cataracts, organ transplant rejection, autoimmune diseases, postoperative cognitive dysfunction, and disorders relating to female reproductive health [in formula (I), ring A represents an aromatic ring, an aliphatic ring, a heterocyclic ring, or a fused ring including two or more rings selected from aromatic rings, aliphatic rings, and heterocyclic rings, X, R1, and R2each represent a substituent of a ring atom forming ring A, m represents an integer of 0-6, X represents, for example, a halogen atom, and R1and R2may be the same or different and are, for example, selected from groups represented by formula (a) or formula (b), and in formula (a) and formula (b), Y is selected from the group consisting of O, S, and Se, Z is selected from the group consisting of O, S, and Se, n represents an integer of 1-8, r represents an integer of 1-8, s represents an integer of 1-8, R422, and R6 represents, for example, a substituted or unsubstituted aryl group].
C07C 335/32 - Isothioureas having sulfur atoms of isothiourea groups bound to acyclic carbon atoms
A61K 31/165 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
A61K 31/381 - Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
A61K 31/505 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim
A61K 31/565 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. oestrane, oestradiol
A61P 15/08 - Drugs for genital or sexual disordersContraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07D 241/42 - Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
C07D 251/08 - Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
C07D 333/18 - Radicals substituted by singly bound hetero atoms other than halogen by sulfur atoms
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
8.
PEPTIDES AND PEPTIDOMIMETICS IN COMBINATION WITH T CELL ACTIVATING AND/OR CHECKPOINT INHIBITING AGENTS FOR CANCER TREATMENT
This invention provides compounds including peptides and peptidomimetics that can be used to treat cell proliferative disorders, such as those associated with benign and malignant tumor cells, and combinations of T cell activating agents and/or an immune checkpoint inhibitors with and without peptides and peptidimimetics. The invention compounds and combinations can be used to inhibit cell growth, such as treat a tumor or cancer.
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
9.
PEPTIDES AND PEPTIDOMIMETICS IN COMBINATION WITH T CELL ACTIVATING AND/OR CHECKPOINT INHIBITING AGENTS FOR CANCER TREATMENT
This invention provides compounds including peptides and peptidomimetics that can be used to treat cell proliferative disorders, such as those associated with benign and malignant tumor cells, and combinations of T cell activating agents and/or an immune checkpoint inhibitors with and without peptides and peptidimimetics. The invention compounds and combinations can be used to inhibit cell growth, such as treat a tumor or cancer.
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
10.
Peptides and peptidomimetics in combination with t cell activating and/or checkpoint inhibiting agents for cancer treatment
This invention provides compounds including peptides and peptidomimetics that can be used to treat cell proliferative disorders, such as those associated with benign and malignant tumor cells, and combinations of T cell activating agents and/or an immune checkpoint inhibitors with and without peptides and peptidimimetics. The invention compounds and combinations can be used to inhibit cell growth, such as treat a tumor or cancer.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 39/00 - Medicinal preparations containing antigens or antibodies
11.
NRF2-BASED CANCER TREATMENT AND DETECTION METHODS AND USES
Disclosed herein, inter alia, are methods and uses for treating a cancer in a subject. In various embodiments, a method or use includes measuring expression of nuclear factor erythroid-2 related factor 2 (NRF2), or an NRF2 target gene, in a candidate subject having cancer, or a cancer sample from the candidate subject, and determining the amount of NRF2 in the sample or in the subject having cancer, then comparing the amount of NRF2 determined, or NRF2 target gene determined, to a baseline or reference amount of NRF2 or NRF2 target gene. If the amount of NRF2 or NRF2 target gene in the sample or in the subject having cancer is less than the baseline or reference amount of NRF2 or NRF2 target gene, the subject having the cancer may be or is treated with a peptide or peptidomimetic sequence set forth herein, such as P1, P2, P3, P4, P5, P6 (SEQ ID NO:1) or P6, P5, P4, P3, P2, P1 (SEQ ID NO:2), e.g., CBP501.
This invention provides compounds including peptides and peptidomimetics that can be used to treat cell proliferative disorders, such as those associated with benign and malignant tumor cells. While the invention is not limited to any particular mechanism, the compounds of the invention appear to function at least in part by inhibiting G2 cell cycle checkpoint. Thus, invention compounds can be used to inhibit cell growth alone or be used in combination with a nucleic acid damaging treatment to inhibit cell growth.
This invention provides compounds including peptides and peptidomimetics that can be used to treat cell proliferative disorders, such as those associated with benign and malignant tumor cells. While the invention is not limited to any particular mechanism, the compounds of the invention appear to function at least in part by inhibiting G2 cell cycle checkpoint. Thus, invention compounds can be used to inhibit cell growth alone or be used in combination with a nucleic acid damaging treatment to inhibit cell growth.
This invention provides compounds including peptides and peptidomimetics that can be used to treat cell proliferative disorders, such as those associated with benign and malignant tumor cells. While the invention is not limited to any particular mechanism, the compounds of the invention appear to function at least in part by inhibiting G2 cell cycle checkpoint. Thus, invention compounds can be used to inhibit cell growth alone or be used in combination with a nucleic acid damaging treatment to inhibit cell growth.
Novel substituted azole diones are provided that kill cells, suppress cell proliferation, suppress cell growth, abrogate the cell cycle G2 checkpoint and/or cause adaptation to G2 cell cycle arrest. Methods of making and using the invention compounds are provided. The invention provides substituted azole diones to treat cell proliferation disorders. The invention includes the use of substituted azole diones to selectively kill or suppress cancer cells without additional anti-cancer treatment. The invention includes the use of cell cycle G2-checkpoint-abrogating substituted azole diones to selectively sensitize cancer cells to DNA damaging reagents, treatments and/or other types of anti-cancer reagents.
Novel substituted azole diones are provided that kill cells, suppress cell proliferation, suppress cell growth, abrogate the cell cycle G2 checkpoint and/or cause adaptation to G2 cell cycle arrest. Methods of making and using the invention compounds are provided. The invention provides substituted azole diones to treat cell proliferation disorders. The invention includes the use of substituted azole diones to selectively kill or suppress cancer cells without additional anti-cancer treatment. The invention includes the use of cell cycle G2-checkpoint-abrogating substituted azole diones to selectively sensitize cancer cells to DNA damaging reagents, treatments and/or other types of anti-cancer reagents.
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
C07D 207/452 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. maleimide with hydrocarbon radicals, substituted by hetero atoms, directly attached to the ring nitrogen atom
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
Novel substituted azole diones are provided that kill cells, suppress cell proliferation, suppress cell growth, abrogate the cell cycle G2 checkpoint and/or cause adaptation to G2 cell cycle arrest. Methods of making and using the invention compounds are provided. The invention provides substituted azole diones to treat cell proliferation disorders. The invention includes the use of substituted azole diones to selectively kill or suppress cancer cells without additional anti-cancer treatment. The invention includes the use of cell cycle G2-checkpoint-abrogating substituted azole diones to selectively sensitize cancer cells to DNA damaging reagents, treatments and/or other types of anti-cancer reagents.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 207/452 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. maleimide with hydrocarbon radicals, substituted by hetero atoms, directly attached to the ring nitrogen atom
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
Novel substituted azole diones are provided that kill cells, suppress cell proliferation, suppress cell growth, abrogate the cell cycle G2 checkpoint and/or cause adaptation to G2 cell cycle arrest. Methods of making and using the invention compounds are provided. The invention provides substituted azole diones to treat cell proliferation disorders. The invention includes the use of substituted azole diones to selectively kill or suppress cancer cells without additional anti-cancer treatment. The invention includes the use of cell cycle G2-checkpoint-abrogating substituted azole diones to selectively sensitize cancer cells to DNA damaging reagents, treatments and/or other types of anti-cancer reagents.
A61K 31/4015 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61K 31/422 - Oxazoles not condensed and containing further heterocyclic rings
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
Novel substituted azole diones are provided that kill cells, suppress cell proliferation, suppress cell growth, abrogate the cell cycle G2 checkpoint and/or cause adaptation to G2 cell cycle arrest. Methods of making and using the invention compounds are provided. The invention provides substituted azole diones to treat cell proliferation disorders. The invention includes the use of substituted azole diones to selectively kill or suppress cancer cells without additional anti-cancer treatment. The invention includes the use of cell cycle G2-checkpoint-abrogating substituted azole diones to selectively sensitize cancer cells to DNA damaging reagents, treatments and/or other types of anti-cancer reagents. Disclosed are compounds of Formulas (II) and (VI):
A61K 31/4015 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
Novel substituted azole diones are provided that kill cells, suppress cell proliferation, suppress cell growth, abrogate the cell cycle G2 checkpoint and/or cause adaptation to G2 cell cycle arrest. Methods of making and using the invention compounds are provided. The invention provides substituted azole diones to treat cell proliferation disorders. The invention includes the use of substituted azole diones to selectively kill or suppress cancer cells without additional anti-cancer treatment. The invention includes the use of cell cycle G2-checkpoint-abrogating substituted azole diones to selectively sensitize cancer cells to DNA damaging reagents, treatments and/or other types of anti-cancer reagents.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 239/02 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
C07D 215/46 - Nitrogen atoms attached in position 4 with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
patents
