The present invention relates to a pharmaceutical composition containing alkynyl compound, a preparation method thereof and its application. The present invention discloses a pharmaceutical composition comprising an active pharmaceutical ingredient and an available pharmaceutical excipient; The active pharmaceutical ingredient is 3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-benzamide, or its pharmaceutical acceptable salt; The available pharmaceutical excipients includes diluents and lubricants. The pharmaceutical composition can effectively improve the bioavailability of the alkynyl compound, has good dissolution and stability, and improve the drug safety.
A solid dispersion having good dissolution and good bioavailability and comprising an embryonic ectoderm development (EED) inhibitor and a preparation method therefor, a solid dispersion composition comprising the solid dispersion and an excipient, an oral preparation comprising the solid dispersion or the solid dispersion composition and a preparation method therefor, and the use of the solid dispersion, the solid dispersion composition or the oral preparation in the treatment and/or prevention of EED-mediated diseases.
Provided are compounds that function as degraders or inhibitors of Bcl-2/Bcl-xl protein. Provided are pharmaceutical compositions comprising them, and to their use in the treatment of diseases mediated by Bcl-2/Bcl-xl, such as cancer.
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 31/45 - Non-condensed piperidines, e.g. piperocaine having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
The present disclosure provides a pharmaceutical composition comprising a Bcl-2/Bcl-xL inhibitor, a chemotherapeutic agent, and a pharmaceutically acceptable carrier. The present disclosure also provides a method of treating cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a Bcl-2/Bcl-xL inhibitor and a therapeutically effective amount of a chemotherapeutic agent. The present disclosure also provides use of a combination of a Bcl-2/Bcl-xL inhibitor and a chemotherapeutic agent in the manufacture of an anti-tumor medicament. In the present disclosure, a significantly enhanced anti-tumor effect can be achieved by administration of a Bcl-2/Bcl-xL inhibitor in combination with a chemotherapeutic agent.
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
A61K 31/4045 - Indole-alkylaminesAmides thereof, e.g. serotonin, melatonin
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
Disclosed is a method for preventing and/or treating a disease or disorder associated with a defect in hemoglobin protein activity or expression or innate immune response, type 1 or type 3 immunity related immune disorder, which comprises administering to a subject in need thereof a therapeutically effective amount of a substance X or a pharmaceutical composition comprising the substance X; the substance X is a compound of Formula I, a pharmaceutically acceptable salt or solvate thereof.
Disclosed is a method for preventing and/or treating a disease or disorder associated with a defect in hemoglobin protein activity or expression or innate immune response, type 1 or type 3 immunity related immune disorder, which comprises administering to a subject in need thereof a therapeutically effective amount of a substance X or a pharmaceutical composition comprising the substance X; the substance X is a compound of Formula I, a pharmaceutically acceptable salt or solvate thereof.
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/541 - Non-condensed thiazines containing further heterocyclic rings
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
Provided herein is a method of treating a disease, disorder or condition associated with succinate dehydrogenase- (SDH-) deficiency with a multi-targeted tyrosine kinase inhibitor (TKI). Also provided herein is a method of treating a disease with the combination of multi-targeted TKI with Bcl-2 inhibitor.
Disclosed in the present invention are a benzo six-membered heterocyclic compound or a pharmaceutically acceptable salt, tautomer, mesomer, racemate, enantiomer, and diastereomer thereof. The degradation effect of the compound of the present invention on GSPT1 proteins and the anti-proliferation inhibitory activity of the compound of the present invention for AML cells are remarkably improved. Therefore, the compound of the present invention can be used for preparing a drug for treating or preventing diseases related to mutation, expression imbalance, and allosteric and dysfunction of GSPT1, IKZF1, IKZF2, IKZF3, CK1α, N-MYC or C-MYC proteins, and can be used for preparing a GSPT1 degradation agent.
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 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
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
Provided herein are the pharmaceutical combination comprising an embryonic ectoderm development (EED) inhibitor and one or more anticancer reagents, and the use of the combination in the treatment of a disease. Provided also is a pharmaceutical composition or a kit comprising the combination.
Disclosed are methods of treating multiple sclerosis. The method comprises: administering an effective amount of a compound represented by Formula I below, a pharmaceutically acceptable salt or solvate thereof to a subject in need thereof.
Disclosed are methods of treating multiple sclerosis. The method comprises: administering an effective amount of a compound represented by Formula I below, a pharmaceutically acceptable salt or solvate thereof to a subject in need thereof.
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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
A pharmaceutical composition and the use thereof. Specifically, disclosed is a pharmaceutical composition, comprising: a substance X, which is a compound as represented by formula (I), a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of the pharmaceutically acceptable salt thereof; and a substance Y, which is doxorubicin, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of the pharmaceutically acceptable salt thereof. The pharmaceutical composition has a synergistic effect against ovarian cancer.
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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
The present disclosure relates to compounds that inhibit KRAS. In particular, the present disclosure relates to compounds that inhibit the activity of KRAS G12D, pharmaceutical compositions comprising the compounds and methods of use therefor.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
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 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
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 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
12.
CRYSTAL FORM OF ALK INHIBITOR OR SALT AND SOLVATE THEREOF, PREPARATION METHOD THEREFOR, AND USE THEREOF
Provided is a crystal form of a compound represented by formula I or a salt thereof, wherein the crystal form is one equivalent of mesylate crystal form A of the compound represented by formula I, crystal form D of the compound represented by formula I, one equivalent of maleate crystal form A of the compound represented by formula I, one equivalent of tartrate crystal form C of the compound represented by formula I, one equivalent of citrate crystal form B of the compound represented by formula I, or one equivalent of succinate crystal form D of the compound represented by formula I. The crystal form has one or more of the following advantages: high crystallinity, good stability, low hygroscopicity, high solubility, and high bioavailability.
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 405/04 - 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 two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
Provided herein is a solid dispersion, which comprises a carrier and an active ingredient. The active ingredient is one or more of the compound shown in formula (I) (APG-115), its pharmaceutically acceptable salt, its crystal form and its hydrate. The solid dispersion can improve the dissolution of the active ingredient APG-115. The dissolution of APG-115 of some solid dispersions can reach more than 90%, and has good stability. It can improve the dissolution and dissolution of drugs in gastrointestinal fluid, so as to improve the oral bioavailability. The solid dispersion shows high plasma exposure in animals, that is, higher drug peak concentration and higher area under blood concentration curve.
Provided herein is a solid dispersion, which comprises a carrier and an active ingredient. The active ingredient is one or more of the compound shown in formula (I) (APG-115), its pharmaceutically acceptable salt, its crystal form and its hydrate. The solid dispersion can improve the dissolution of the active ingredient APG-115. The dissolution of APG-115 of some solid dispersions can reach more than 90%, and has good stability. It can improve the dissolution and dissolution of drugs in gastrointestinal fluid, so as to improve the oral bioavailability. The solid dispersion shows high plasma exposure in animals, that is, higher drug peak concentration and higher area under blood concentration curve.
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
The present disclosure provides compounds having Formula I: and the pharmaceutically acceptable salts and solvates thereof, wherein variables are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I for use to treat a disease, disorder, or condition responsive to Bcl-2 protein inhibition, particularly Bcl-2 WT and/or Bcl-2 G101V.
The present disclosure provides compounds having Formula I: and the pharmaceutically acceptable salts and solvates thereof, wherein variables are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I for use to treat a disease, disorder, or condition responsive to Bcl-2 protein inhibition, particularly Bcl-2 WT and/or Bcl-2 G101V.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
The present disclosure relates to compounds that inhibit KRAS. In particular, the present disclosure relates to compounds that inhibit the activity of KRAS G12D or KRAS G12V, pharmaceutical compositions comprising the compounds and methods of use therefor.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
The present invention relates to methods for treating patients with cancer, including patients with hematological malignancy, wherein the method comprises administering to the patient a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are as defined herein.
The present invention relates to methods for treating patients with cancer, including patients with hematological malignancy, wherein the method comprises administering to the patient a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are as defined herein.
The invention discloses a solid dispersion, a pharmaceutical preparation, a preparation method and an application thereof. The solid dispersion of the invention comprises carriers and active constituents, which is a compound as shown in formula (I) and/or a pharmaceutically acceptable salt thereof; The carrier is “homopolymer and copolymer of N-vinyl lactam” and/or pH-dependent cellulose derivatives. The preparation of the invention comprises the solid dispersion, fillers and disintegrating agents. The solid dispersion of the invention has good dissolution and significantly improves the solubility of effective constituents. The preparation can effectively improve the bioavailability of Bcl-2 inhibitor, has good dissolution and stability, and can improve the safety of a medication.
The invention discloses a solid dispersion, a pharmaceutical preparation, a preparation method and an application thereof. The solid dispersion of the invention comprises carriers and active constituents, which is a compound as shown in formula (I) and/or a pharmaceutically acceptable salt thereof; The carrier is “homopolymer and copolymer of N-vinyl lactam” and/or pH-dependent cellulose derivatives. The preparation of the invention comprises the solid dispersion, fillers and disintegrating agents. The solid dispersion of the invention has good dissolution and significantly improves the solubility of effective constituents. The preparation can effectively improve the bioavailability of Bcl-2 inhibitor, has good dissolution and stability, and can improve the safety of a medication.
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
The present invention relates to one or more combination treatments of cancer patients with a compound of formula (I),
The present invention relates to one or more combination treatments of cancer patients with a compound of formula (I),
and an allosteric inhibitor or an immune checkpoint molecule, wherein R1 and R2 are as described herein.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61P 35/02 - Antineoplastic agents specific for leukemia
19.
COMPOSITIONS AND METHODS FOR TREATING NON-ALCOHOLIC STEATOHEPATITIS
Methods for treating non-alcoholic steatohepatitis using compounds or pharmaceutical compositions that modulate the activity of Bcl-2 family proteins are disclosed. In some methods, the patient to be treated is diagnosed with one or more additional diseases selected from cardiovascular disease, chronic kidney disease, type 2 diabetes mellitus, obesity, and metabolic syndrome, wherein the metabolic syndrome may include, but is not limited to patient presentation of one or more of hypertension, hyperglycaemia, hyper-lipemia, insulin resistance (IR). In some methods, the compound or pharmaceutical composition is administered to the patient in need thereof at a therapeutically effective dose sufficient to elicit one or more effects selected from: reduced liver steatosis, reduced lobular inflammation, reduced hepatocellular ballooning, and reduced liver fibrosis.
A61K 31/575 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
20.
A PHARMACEUTICAL COMPOSITION AND USE THEREOF FOR TREATMENT OF CANCER
Provided herein in the biomedical field are a pharmaceutical composition, use thereof for treating or suppressing a cancer, reducing its severity, lowering its risk or inhibiting its metastasis in an individual, and a method for treating or suppressing a cancer, reducing its severity, lowering its risk or inhibiting its metastasis in an individual. The method comprises administering to the individual a therapeutically effective amount of an ALK inhibitor, and a therapeutically effective amount of one or more other anticancer reagents. It also relates to a kit comprising an ALK inhibitor, and one or more other anticancer reagents.
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/4045 - Indole-alkylaminesAmides thereof, e.g. serotonin, melatonin
A61K 31/502 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
Methods for treating systemic lupus erythematosus using compounds or pharmaceutical compositions that modulate the activity of Bcl-2 family proteins are disclosed. In some methods, the patient to be treated is diagnosed with lupus nephritis. In some methods, the compound or pharmaceutical composition is administered to the patient in need thereof at a therapeutically effective dose sufficient to elicit one or more effects selected from: reduced excretion of protein in the urine of the patient, reduced serum anti-dsDNA autoantibody levels in the patient, reduced skin lesion severity in the patient, reduced lymphadenopathy severity in the patient, reduced glomerulonephritis severity in the patient, reduced vasculitis severity in the patient, reduced lymphocyte cell counts in a peripheral blood mononuclear cell (PMBC) panel taken from the patient, reduced lymphocyte cell counts in the spleen of the patient, and reduced lymphocyte infiltration of the kidneys of the patient.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
Methods for treating immune diseases, specifically methods for the prevention and/or inhibition of autoimmune response or overactive immune response, comprising administering to the subject an effective amount of a compound of formula I, X or XI, or a pharmaceutically acceptable salt or solvate thereof. Methods for the prevention and/or inhibition of autoimmune disease, allergic disease or immune-mediated inflammatory disease, comprising administering to the subject an effective amount of a compound of formula I, X or XI, or a pharmaceutically acceptable salt or solvate thereof.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
23.
TRICYCLIC HETEROCYCLE COMPOUNDS AS IAP ANTAGONISTS
The present disclosure relates to compounds that inhibit IAP (preferably cIAP1, cIAP2 or XIAP) protein, pharmaceutical compositions comprising the same and methods of using the IAP protein inhibitors in the treatment of diseases and conditions wherein inhibition of IAP protein provides a benefit.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
Disclosed herein are a crystalline or amorphous form of a Bcl-2/Bcl-xL inhibitor compound or a salt thereof, and a preparation method and application thereof.
C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
Crystallines form or amorphous forms of bisdiazabicyclic compounds or salts thereof for the treatment and/or prevention of diseases or disorders related to hepatitis virus, and a preparation method and application thereof are provided. The crystalline forms or amorphous forms involved provide important reference value for the development and utilization of drugs in the future.
Disclosed are a crystalline form or an amorphous form of a macrocyclic compound or a salt or solvate thereof, as well as a preparation method therefor and an application thereof. The structure of the macrocyclic compound is represented by formula I.
C07D 471/22 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups in which the condensed systems contains four or more hetero rings
C07D 487/22 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups in which the condensed system contains four or more hetero rings
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
Provided are methods for treating hematologic malignancy, especially AML-MRC, MDS and/or MM. Specifically, provided are methods for treating AML-MRC and MDS with a compound of formula (I) or a pharmaceutically acceptable salt thereof, optionally in combination with at least one additional anti-cancer agent such as 5-azacitidine or cytarabine, and treating MM with a compound of formula (I) or a pharmaceutically acceptable salt thereof, optionally in combination with at least one additional anti-cancer agent such as pomalidomide, thalidomide, lenalidomide, and/or dexamethasone.
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
Provided herein is a microsuspension of an MDM2 inhibitor, comprising microparticles of the MDM2 inhibitor, e.g., a compound of Formula (I), a surfactant, and a tonicity agent. Also provided herein is a method of treating an MDM2-mediated disorder, disease, or condition with the microsuspension.
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
29.
METHODS FOR SYNTHESIZING N-(PHENYLSULFONYL)BENZAMIDE COMPOUNDS AND INTERMEDIATES THEREOF
Disclosed is a method for synthesizing N-(phenylsulfonyl)benzamide compound and intermediate thereof. The method comprises a method for synthesizing a compound 1, comprising conducting a Buchwald-Hartwig coupling reaction as shown below with compound A and compound B in a solvent and in the presence of a base and a palladium catalyst to obtain the compound 1; wherein R is C1-C8 alkyl. The present disclosure synthesizes three intermediate compounds required by the target compound and their preparation methods for the first time. Using the method disclosed in the present disclosure to synthesize the target compound 3 has the advantages of high yield, good purity, easy-to-obtain reaction raw materials, suitable for industrial production.
Disclosed is a method for synthesizing N-(phenylsulfonyl)benzamide compound and intermediate thereof. The method comprises a method for synthesizing a compound 1, comprising conducting a Buchwald-Hartwig coupling reaction as shown below with compound A and compound B in a solvent and in the presence of a base and a palladium catalyst to obtain the compound 1; wherein R is C1-C8 alkyl. The present disclosure synthesizes three intermediate compounds required by the target compound and their preparation methods for the first time. Using the method disclosed in the present disclosure to synthesize the target compound 3 has the advantages of high yield, good purity, easy-to-obtain reaction raw materials, suitable for industrial production.
C07D 295/073 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
C07D 319/12 - 1,4-DioxanesHydrogenated 1,4-dioxanes not condensed with other rings
The present invention provides crystalline forms or amorphous forms of N-(phenylsulfonyl) benzoamide compound or its salts or solvates used as a Bcl-2 inhibitor, and the preparation method and the application thereof.
Provided use of MDM2 inhibitors alone or in combination with additional therapeutic agent in the treatment of conditions and diseases wherein inhibition of MDM2 and MDM2-related proteins provides a benefit.
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61P 35/02 - Antineoplastic agents specific for leukemia
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61P 35/04 - Antineoplastic agents specific for metastasis
The invention discloses the crystal form, preparation method and application of an alkynyl compound, its salt and solvent compound. The invention specifically discloses 3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazine-1-yl)methyl)-3-(trifluoromethyl)phenyl) benzamide crystal form I and 3-((1H-pyrazolo [3,4-b]pyridin-5-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazine-1-yl)methyl)-3-(trifluoromethyl)phenyl) benzamide fumarate crystal form II. The crystal form of the invention has good stability and has important value for drug optimization and development.
A method for treating patients with viral infections, particularly coronavirus infections, wherein the method comprises administering to the patient a therapeutically effective amount of a compound of any one of formulas (I)-(VI) or Compound 1, 2, 3, 4, or 5, or a pharmaceutically acceptable salt thereof.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
Disclosed relates to compounds that inhibit KRAS. In particular, disclosed relates to compounds that inhibit the activity of KRAS G12D,pharmaceutical compositions co-mprising the compounds and methods of use there for.
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
Amorphous form or crystalline form of a 2-indolinolinololylspironone compound or its salt and solvate used as an MDM2 inhibitor, a preparation method and an application thereof. The amorphous form or crystalline form of the invention has good stability and is of great value for drug development, preparation development and production.
Disclosed is a method for preventing and/or treating a disease or disorder associated with a defect in hemoglobin protein activity or expression or innate immune response, type 1 or type 3 immunity related immune disorder, which comprises administering to a subject in need thereof a therapeutically effective amount of a substance X or a pharmaceutical composition comprising the substance X; the substance X is a compound of Formula I, a pharmaceutically acceptable salt or solvate thereof.
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
C07D 471/22 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups in which the condensed systems contains four or more hetero rings
C07D 491/22 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains four or more hetero rings
The present invention relates to the field of medicine, and particularly relates to a pharmaceutical combination comprising a Bcl-2 inhibitor or a Bcl-2/Bcl-xL inhibitor and one or more anticancer agents, and use of the combination for treatment of a disease such as cancer, particularly acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or multiple myeloma (MM) which is resistant or insensitive to a Bcl-2 inhibitor and/or carries a Bcl-2 mutation and/or a TP53 mutation. The present invention also relates to a pharmaceutical composition or kit comprising the combination.
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/502 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
A pharmaceutical composition comprising: a) an effective amount of an Inhibitors of Apoptosis Proteins (IAP) inhibitor, wherein the IAP inhibitor is represented by formula (I): or a pharmaceutically acceptable salt thereof, the definitions of each variable are provided herein; b) an effective amount of a second inhibitor, wherein the second inhibitor is a poly ADP ribose polymerase (PARP) inhibitor or a mitogen-activated protein kinase kinase (MEK) inhibitor; and a pharmaceutically acceptable carrier or diluent.
A pharmaceutical composition comprising: a) an effective amount of an Inhibitors of Apoptosis Proteins (IAP) inhibitor, wherein the IAP inhibitor is represented by formula (I): or a pharmaceutically acceptable salt thereof, the definitions of each variable are provided herein; b) an effective amount of a second inhibitor, wherein the second inhibitor is a poly ADP ribose polymerase (PARP) inhibitor or a mitogen-activated protein kinase kinase (MEK) inhibitor; and a pharmaceutically acceptable carrier or diluent.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
Provided are compounds represented by Formula IA: (IA), and the pharmaceutically acceptable salts and solvates thereof, wherein R, R1a, R1b, L1, L2, L3, X, A, B and C are as defined as set forth in the specification. Also provided compounds of Formula IA for use to treat a condition or disorder responsive to Mcl-1 inhibition such as cancer.
Provided are compounds represented by Formula IA: (IA), and the pharmaceutically acceptable salts and solvates thereof, wherein R, R1a, R1b, L1, L2, L3, X, A, B and C are as defined as set forth in the specification. Also provided compounds of Formula IA for use to treat a condition or disorder responsive to Mcl-1 inhibition such as cancer.
C07D 515/22 - Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups , or in which the condensed system contains four or more hetero rings
C07D 497/22 - Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
Provided herein are the pharmaceutical combination comprising an embryonic ectoderm development (EED) inhibitor and one or more anticancer reagents, and the use of the combination in the treatment of a disease. Privided also is a pharmaceutical composition or a kit comprising the combination.
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/5383 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
3, #, #, # are as defined as set forth in the re) specification. Disclosed is compound of formula I for use to treat a condition or disorder responsive to Mcl-1 inhibition such as cancer.
C07D 497/22 - Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
C07D 515/22 - Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups , or in which the condensed system contains four or more hetero rings
C07D 231/12 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
Described herein are methods of treating a cancer, for example, a hematologic malignancy or a solid tumor, in a patient in need thereof, comprising administering to the patient a Bcl-2 inhibitor in combination with a second anti-cancer agent.
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
A61P 35/02 - Antineoplastic agents specific for leukemia
A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
Provided are biomarkers for predicting the efficacy of MDM2 inhibitor or Bcl-2/Bcl-xL dual inhibitors or Bcl-2 inhibitor or Bcl-xL inhibitor in treating cancer patients. Also provided are compositions, e.g., kits, for evaluating gene levels of the biomarkers and methods of using such gene levels to predict a cancer patient's response to the MDM2 inhibitors or Bcl-2/Bcl-xL dual inhibitors or Bcl-2 inhibitor or Bcl-xL inhibitor. Such information can be used in determining prognosis and treatment options for cancer patients.
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
6, m, and p are defined herein. Compounds of Formula I are BCR-ABL inhibitors. BCR-ABL inhibitors are useful for the treatment of cancer and other diseases.
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
A61P 35/02 - Antineoplastic agents specific for leukemia
C07D 209/94 - [b, c]- or [b, d]-condensed containing carbocyclic rings other than six-membered
C07D 401/04 - 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 directly linked by a ring-member-to-ring- member bond
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 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
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 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/14 - 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 three or more hetero rings
Described herein are methods of treating a hematologic malignancy in a patient in need thereof, comprising administering to the patient a Bcl-2 inhibitor in a step-wise dosing regimen.
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 31/706 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61P 35/02 - Antineoplastic agents specific for leukemia
46.
COMBINATIONS OF BCL-2/BCL-XL INHIBITORS AND RELATED USES
The present disclosure relates to combinations of Compound No. 1 or a pharmaceutically acceptable salt thereof and at least one additional therapeutic agent. The present disclosure also relates to methods of treating or preventing a disease via administering to subjects in need thereof Compound No. 1 or a pharmaceutically acceptable salt thereof and at least one additional therapeutic agent.
The present invention relates to a pharmaceutical composition containing alkynyl compound, a preparation method thereof and its application. The present invention discloses a pharmaceutical composition comprising an active pharmaceutical ingredient and an available pharmaceutical excipient; The active pharmaceutical ingredient is 3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-benzamide, or its pharmaceutical acceptable salt; The available pharmaceutical excipients includes diluents and lubricants. The pharmaceutical composition can effectively improve the bioavailability of the alkynyl compound, has good dissolution and stability, and improve the drug safety.
The present invention provides a preparation method of (5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamine or a salt thereof, which uses 4-fluoro-3-methylphenol as the starting material, and is carried out through the steps of bromination, O-alkylation, cyclization, bromination, azidation or ammonolysis, and reduction. The reaction route of the present invention has simple synthesis process, convenient operation, high yield, and is environmentally friendly. The prepared (5-fluoro-2,3-dihydrobenzofuran-4-yl)methylamine can be used as an intermediate in pharmaceuticals and fine chemicals.
C07D 307/79 - Benzo [b] furansHydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
49.
PHARMACEUTICAL COMPOSITIONS AND PREPARATION METHODS THEREOF
It provides a pharmaceutical composition and a preparation method thereof. In particular, it provides a pharmaceutical composition which comprising compound 1 of the following structural formula or its pharmaceutically acceptable salt thereof as an active ingredient, pH regulators and solubilizers. The pH value of aqueous solution of the pharmaceutical composition is 5.0-8.0. The pharmaceutical compositions enable the formulations having good solubility and good stability of compound 1 or its pharmaceutically acceptable salt thereof.
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
The present disclosure provides compounds having Formula I: and the pharmaceutically acceptable salts and solvates thereof, wherein variables are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I for use to treat a disease, disorder, or condition responsive to Bcl-2 protein inhibition, particiularly Bcl-2 WT and/or Bcl-2 G101V.
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 405/12 - 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 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
C07D 407/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
Provides compounds represented by Formula(I): wherein R 3, R 8c, R 8d, A, A 1, A 2, A 3, A 4, E, E 1, L, Q, Z, and (II) are as defined in the specification, and the pharmaceutically acceptable salts and solvates thereof. Compounds of Formula I are KRAS inhibitors and are thus useful to treat cancer and other diseases.
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/527 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim spiro-condensed
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Medicines for dental purposes; chemical preparations for
medical purposes; antibiotics; injectable medicinal
solutions; tablets [medicines]; bulk drugs; biochemical
medicines; antiseptics; collyrium; suppositories; medicated
plasters; diagnostic preparations for medical purposes;
diagnostic biomarker reagents for medical purposes;
medicated sweets; candy for medical purposes; dietetic foods
adapted for medical purposes; dietetic beverages adapted for
medical purposes; dietetic substances adapted for medical
use; oil solution [medicines]; mineral food supplements;
nutritional supplements; medicines for human purposes;
bacterial poisons; pharmaceutical preparations;
chemico-pharmaceutical preparations; drugs for medical
purposes; biological preparations for medical purposes;
chemical preparations for pharmaceutical purposes;
radioactive substances for medical purposes; gases for
medical purposes; chemical conductors for electrocardiograph
electrodes; semen for artificial insemination;
disinfectants; solutions for contact lenses; media for
bacteriological cultures; depuratives; veterinary
preparations; pesticides; sanitary napkins; cotton for
medical purposes; dental abrasives; diapers for pets.
53.
METHOD AND COMPOSITION FOR PREDICTING EFFICACY OF BCL2/BCL-XL INHIBITORS ON CANCER
Provided are biomarkers for predicting the efficacy of BCL-2/BCL-XL dual or selective inhibitors in treating cancer patients. The biomarkers comprise a complex comprising BCL-2 or BCL-XL. Also provided are methods and compositions, e.g., kits, for evaluating levels of the biomarkers and methods of using such levels to predict a cancer patient's response to the BCL-2/BCL-XL dual inhibitors or BCL-XL or BCL-2 inhibitors. Such information can be used in determining prognosis and treatment options for cancer patients.
Disclosed are methods of treating multiple sclerosis. The method comprises: administering an effective amount of a compound represented by Formula (I) below, a pharmaceutically acceptable salt or solvate thereof to a subject in need thereof.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
Provided herein is a solid dispersion of a compound as shown in formula (I) and/or a pharmaceutically acceptable salt thereof, a pharmaceutical preparation, a preparation method and an application thereof. The solid dispersion comprises carriers and the compound of formula (I). The carriers are "homopolymer and copolymer of N-vinyl lactam" and/or pH-dependent cellulose derivatives. The preparation comprises the solid dispersion, fillers and disintegrating agents. The solid dispersion has good dissolution and stability, and can significantly improve the solubility and the bioavailability of the compound of formula (I).
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
Provided herein is a formulation combination containing a freeze-dried formulation and a reconstituted solvent composition, preparation method and application thereof. A formulation combination comprising: a free-dried formulation containing compound (1) as an inhibitor of Bcl-2/Bcl-xL or its pharmaceutically acceptable salt and appropriate excipients, and a reconstitution solvent is also provided. The formulation combination is suitable for clinical injection and administration with the advantages of good stability and reconstitution effect.
Provided are one or more combination treatments of cancer patients with a compound of formula (I), as described herein, and an allosteric inhibitor or an immune checkpoint molecule.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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 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
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Chemical preparations for medical purposes, for use in the treatment of cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; drugs sold in bulk, for use in the treatment of cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; biochemical medicines for use in the treatment of cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; diagnostic preparations for medical purposes; diagnostic biomarker reagents for medical purposes; medicines for human purposes for use in the treatment of cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; pharmaceutical preparations for the treatment of cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; chemico-pharmaceutical preparations for the treatment of cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; drugs for medical purposes in the nature of prescription apoptosis targeted compounds, next-generation kinase inhibitors and senolytic drugs; biological preparations for medical purposes, namely, biological preparations for the treatment of cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; chemical preparations for pharmaceutical purposes, namely, for use in the treatment of cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; radioactive substances for medical purposes; gases for medical purposes, namely, nitric oxide for medical purposes; chemical conductors for electrocardiograph electrodes; semen for artificial insemination; disinfectants; solutions for contact lenses; media for bacteriological cultures; medicated sweets; dietetic preparations adapted for medical use; depuratives for the body; diagnostic preparations for veterinary purposes; pesticides; sanitary napkins; cotton for medical purposes; dental abrasives; diapers for pets
59.
Pharmaceutical composition of MDM2 inhibitor and use thereof for preventing and/or treating disease
Provided herein are pharmaceutical compositions comprising an MDM2 inhibitor and one or more anti-cancer agents for preventing and/or treating diseases, such as cancer. Methods for preventing and/or treating diseases, such as cancer, comprising administering to the patient in need thereof with the pharmaceutical compositions are also provided.
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
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 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
Provided herein is a combination product comprising a Bcl-2/Bcl-xL inhibitor and a chemotherapeutic agent, in particular a Bcl-2/Bcl-xL inhibitor of formula (I-A) and homoharringtonine or an active derivative thereof, in free or pharmaceutically acceptable salt or solvate form. Provided herein is also the use of the aforementioned combination for the preparation of a medicament for the prevention and/or treatment of cancer, in particular of hematological malignancies, and to a method for the prevention and/or treatment of cancer, in particular of hematological malignancies, using the aforementioned combination.
Provided herein is a combination product comprising a Bcl-2/Bcl-xL inhibitor and a chemotherapeutic agent, in particular a Bcl-2/Bcl-xL inhibitor of formula (I-A) and homoharringtonine or an active derivative thereof, in free or pharmaceutically acceptable salt or solvate form. Provided herein is also the use of the aforementioned combination for the preparation of a medicament for the prevention and/or treatment of cancer, in particular of hematological malignancies, and to a method for the prevention and/or treatment of cancer, in particular of hematological malignancies, using the aforementioned combination.
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61P 35/02 - Antineoplastic agents specific for leukemia
The invention discloses a novel pharmaceutical combination and a use thereof. The pharmaceutical combination comprises a compound of formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof; and a compound of formula (II), a pharmaceutically acceptable salt thereof or a solvate thereof. The pharmaceutical combination can be used to treat cancer.
A61K 31/403 - 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 condensed with carbocyclic rings, e.g. carbazole
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61P 35/02 - Antineoplastic agents specific for leukemia
62.
A COMPOSITION COMPRISING HETEROCYCLIC COMPOUNDS, PREPARATION METHOD AND APPLICATION THEREOF
Provided herein is a solid dispersion, which comprises a carrier and an active ingredient. The active ingredient is one or more of the compound shown in formula (I) (APG-115), its pharmaceutically acceptable salt, its crystal form and its hydrate. The solid dispersion can improve the dissolution of the active ingredient APG-115. The dissolution of APG-115 of some solid dispersions can reach more than 90%, and has good stability. It can improve the dissolution and dissolution of drugs in gastrointestinal fluid, so as to improve the oral bioavailability. The solid dispersion shows high plasma exposure in animals, that is, higher drug peak concentration and higher area under blood concentration curve.
Disclosed herein are a process for preparing alkynyl-containing compound and intermediate thereof. In particular, the present invention discloses a process for preparing a compound of formula 6 as shown in below and a pharmaceutical composition comprising a compound of formula 6 for treating cancer,
Provided herein in the biomedical field are a pharmaceutical composition, use thereof for treating or suppressing a cancer, reducing its severity, lowering its risk or inhibiting its metastasis in an individual, and a method for treating or suppressing a cancer, reducing its severity, lowering its risk or inhibiting its metastasis in an individual. The method comprises administering to the individual a therapeutically effective amount of an ALK inhibitor, and a therapeutically effective amount of one or more other anticancer reagents. It also relates to a kit comprising an ALK inhibitor, and one or more other anticancer reagents.
Disclosed are processes for preparing alkylnyl-containing compounds of Formula (I) as shown below, intermediates and related compounds thereof. Pharmaceutical compositions comprising the compounds and methods of treating cancer thereof are also disclosed.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
Methods for treating non-alcoholic steatohepatitis using compounds or pharmaceutical compositions that modulate the activity of Bcl-2 family proteins are disclosed. In some methods, the patient to be treated is diagnosed with one or more additional diseases selected from cardiovascular disease, chronic kidney disease, type 2 diabetes mellitus, obesity, and metabolic syndrome, wherein the metabolic syndrome may include, but is not limited to patient presentation of one or more of hypertension, hyperglycaemia, hyperlipemia, insulin resistance (IR). In some methods, the compound or pharmaceutical composition is administered to the patient in need thereof at a therapeutically effective dose sufficient to elicit one or more effects selected from: reduced liver steatosis, reduced lobular inflammation, reduced hepatocellular ballooning, and reduced liver fibrosis.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
67.
COMPOSITIONS AND METHODS FOR TREATING SYSTEMIC LUPUS ERYTHEMATOSUS
Methods for treating systemic lupus erythematosus using compounds or pharmaceutical compositions that modulate the activity of Bcl-2 family proteins are disclosed. In some methods, the patient to be treated is diagnosed with lupus nephritis. In some methods, the compound or pharmaceutical composition is administered to the patient in need thereof at a therapeutically effective dose sufficient to elicit one or more effects selected from: reduced excretion of protein in the urine of the patient, reduced serum anti-dsDNA autoantibody levels in the patient, reduced skin lesion severity in the patient, reduced lymphadenopathy severity in the patient, reduced glomerulonephritis severity in the patient, reduced vasculitis severity in the patient, reduced lymphocyte cell counts in a peripheral blood mononuclear cell (PMBC) panel taken from the patient, reduced lymphocyte cell counts in the spleen of the patient, and reduced lymphocyte infiltration of the kidneys of the patient.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
Improved methods for treating hepatitis B (HB) in patients with (5S,5′S,8S,8′S,10aR,10a′R)-3,3′-(1,3-phenylenedisulfonyl)bis(N-benzhydryl-5-((S)-2-(methylamino)propanamido)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide) (Compound (I)) are disclosed herein. Dosing regimens of Compound (I) for the treatment of HBV infection are provided.
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
A61K 31/708 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
A61K 9/00 - Medicinal preparations characterised by special physical form
Provided herein is a combination product comprising a Bcl-2 inhibitor and an MDM-2 inhibitor, the combination product providing a use in the prevention and/or treatment of diseases (e.g., cancer).
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
70.
COMPOSITIONS AND METHODS FOR TREATING LUNG DISEASES
Provided are methods of treating or preventing lung diseases (e.g., idiopathic pulmonary fibrosis (IPF) or radiation-induced pulmonary fibrosis (RIPF)) using Compound No. 1, Compound No. 2, or a pharmaceutically acceptable salt thereof, pharmaceutical compositions and pharmaceutical kits suitable for the treatment of prevention.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
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
A61P 11/00 - Drugs for disorders of the respiratory system
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
(1) Chemical preparations for medical purposes for treating cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; antibiotics; Injectable medicines for treating cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; medicine in tablet form for treating cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, agerelated diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; drugs sold in bulk for treating cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; biochemical medicines for use in the treatment of cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; antiseptics; collyrium; hemorrhoidal suppositories, laxative suppositories, and vaginal suppositories for the prevention and treatment of infections; medicated plasters; diagnostic preparations for medical purposes namely for use in cancer treatments; diagnostic biomarker reagents for medical purposes; Oil solutions for or use in the treatment of cancer and tumors; mineral food supplements; nutritional supplements for use in the treatment of cancer and tumors; Medicines for human purposes for use in the treatment of cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; bacterial poisons; Pharmaceutical preparations for the treatment of cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; Chemico-pharmaceutical preparations for the treatment of cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; Drugs for medical purposes in the nature of prescription apoptosis targeted compounds, next-generation kinase inhibitors and senolytic drugs; Biological preparations for medical purposes, namely, biological preparations for the treatment of cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; Chemical preparations for pharmaceutical purposes, namely, for use in the treatment of cancer, tumors, blood-related diseases, infectious diseases, osteoarthritis, age-related diseases, fibrotic diseases, Crohn's disease, and cardiovascular disease; radioactive substances for medical purposes for use in the treatment of cancer and tumors; Gases for medical purposes, namely, nitric oxide for medical purposes; chemical conductors for electrocardiograph electrodes; solutions for contact lenses; media for bacteriological cultures; Depuratives for use in the treatment of cancer and tumors; veterinary preparations for use in the treatment of cancer and tumors; pesticides; sanitary napkins; dental abrasives
72.
Crystalline or Amorphous form of Bcl-2/Bcl-xL inhibitor compound or its salts
Disclosed herein are a crystalline or amorphous form of a Bcl-2/Bcl-xL inhibitor compound or a salt thereof, and a preparation method and application thereof.
C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
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
Crystallines form or amorphous forms of bisdiazabicyclic compounds or salts thereof for the treatment and/or prevention of diseases or disorders related to hepatitis virus, and a preparation method and application thereof are provided. The crystalline forms or amorphous forms involved provide important reference value for the development and utilization of drugs in the future.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
The present invention relates to a process for preparing a sulfonamide compound which is an inhibitor of Bcl-2/Bcl-xL, including the compound (3R)-1-(3-(4-(4-(4-(3-(2-(4-chlorophenyl)-1-isopropyl-4-methylsulfonyl-5-methyl-1H-pyrrol-3-yl)-5-fluorophenyl)piperazine-1-yl)-phenylaminosulfonyl)-2-trifluoromethanesulfonyl-anilino)-4-phenylthio-butyl)-piperidine-4-carboxylic acid 3-phosphonopropyl ester. The present invention also relates to an intermediate for preparing the sulfonamide compound and a preparation process thereof.
C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
C07D 211/62 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
188 alkyl. The present disclosure synthesizes three intermediate compounds required by the target compound and their preparation methods for the first time. Using the method disclosed in the present disclosure to synthesize the target compound 3 has the advantages of high yield, good purity, easy-to-obtain reaction raw materials, suitable for industrial production.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
Disclosed are crystals of an alkynyl-containing compound, a salt and a solvate thereof, a preparation method, and applications. Specifically disclosed are crystal I of 3-(1H-pyrazole[3,4-b]pyridine-5-substituted)ethynyl)-4-methyl-N-(4-((4-methylpiperazine-1-substituted)methyl)-3-(trifluoromethyl)phenyl)benzamide and crystal II of 3-((1H-pyrazole[3,4-b]pyridine-5-substituted)ethynyl)-4-methyl-N-(4-((4-methylpiperazine-1-substituted)methyl)-3-(trifluoromethyl)phenyl)benzamide fumarate. The crystals of the present invention have excellent stability and provide a significant value with respect to the optimization and development of a medicament.
Provided herein is a microsuspension of an MDM2 inhibitor, comprising microparticles of the MDM2 inhibitor, e.g., a compound of Formula (I), a surfactant, and a tonicity agent. Also provided herein is a method of treating an MDM2-mediated disorder, disease, or condition with the microsuspension.
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
Provided herein is a combination product comprising a Bcl-2 inhibitor, an anti-CD20 antibody and/or bendamustine or a combination product comprising a Bcl-2 inhibitor and CHOP, the combination product provides a use of the combination product for prevention and/or treatment of a disease (e.g., cancer, rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis).
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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
79.
HPLC ANALYSIS METHOD FOR N- (PHENYLSULFONYL) BENZAMIDE COMPOUND
Provided is an HPLC analysis method of N-(phenylsulfonyl)benzamide compound; the N-(phenylsulfonyl)benzamide compound is substance X; the substance X is a compound as represented by formula I-A and/or I-B. The HPLC analysis method comprises the following steps: eluting substance X with a mobile phase comprising an alkane solvent, an alcohol solvent, a halogenated hydrocarbon solvent and an ether solvent, in parts by volume, the alkane solvent is 600-800 parts, the alcohol solvent is 50-350 parts, the halogenated hydrocarbon solvents is 30-100 parts, and the ether solvents is 50-200 parts. The analysis method can separate isomers and precisely determine the purity of the isomers.
Provided is a preparation method of (5-fluoro-2, 3-dihydrobenzofuran-4-yl) methylamine or a salt thereof, which uses 4-fluoro-3-methylphenol as the starting material, and is carried out through the steps of bromination, O-alkylation, cyclization, bromination, azidation or ammonolysis, and reduction. The reaction route has simple synthesis process, convenient operation, high yield, and is environmentally friendly. The prepared (5-fluoro-2, 3-dihydrobenzofuran-4-yl) methylamine can be used as an intermediate in pharmaceuticals and fine chemicals.
A method for treating patients with viral infections, particularly coronavirus infections, wherein the method comprises administering to the patient a therapeutically effective amount of a compound of any one of formulas (I)-(VI) or Compound 1, 2, 3, 4, or 5, or a pharmaceutically acceptable salt thereof.
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/662 - Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
C07D 403/10 - 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 carbon chain containing aromatic rings
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
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
1, W, and (aa) are as defined as set forth in the specification. Provided are also compounds of Formula (I-A) for use to treat a condition or disorder responsive to Mcl-1 inhibition such as cancer.
A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
83.
Method for treating cancer by combination of FAK/ALK/ROS1 inhibitor and EGFR inhibitor
The present invention pertains to the biomedical field, and particularly relates to a method for treating or suppressing a cancer, reducing its severity, lowering its risk or inhibiting its metastasis in an individual. The method comprises administering to the individual a therapeutically effective amount of one or more of a FAK inhibitor, an ALK inhibitor and a ROS1 inhibitor, and a therapeutically effective amount of an EGFR inhibitor. The invention also relates to a pharmaceutical composition or kit comprising one or more of a FAK inhibitor, an ALK inhibitor and a ROS1 inhibitor, and an EGFR inhibitor.
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
84.
Pharmaceutical composition and preparation method thereof
The present invention relates to a pharmaceutical composition comprising a sulfonamide as an inhibitor of Bcl-2/Bcl-xL, especially compound (3R)-1-(3-(4-(4-(4-(3-(2-(4-chlorophenyl)-1-isopropyl-4-methylsulfonyl-5-methyl-1H-pyrrol-3-yl)-5-fluorophenyl)piperazin-1-yl)-phenylaminosulfonyl)-2-trifluoromethyl sulfonyl-anilino)-4-phenylthio-butyl)-piperidine-4-carboxylic acid 3-phosphonopropyl ester or a pharmaceutically acceptable salt thereof and suitable excipients, preferably a pharmaceutical composition in the form of a lyophilized powder. The invention also relates to a method for preparing the pharmaceutical composition.
Provided use of MDM2 inhibitors alone or in combination with additional therapeutic agent in the treatment of conditions and diseases wherein inhibition of MDM2 and MDM2-related proteins provides a benefit.
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
The present disclosure relates to combinations of Compound No. 1 or a pharmaceutically acceptable salt thereof and at least one additional therapeutic agent. The present disclosure also relates to methods of treating or preventing a disease via administering to subjects in need thereof Compound No. 1 or a pharmaceutically acceptable salt thereof and at least one additional therapeutic agent.
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
Provided are biomarkers for predicting the efficacy of MDM2 inhibitors in treating cancer patients. Also provided are compositions, e.g., kits, for evaluating the biomarkers and methods of using the biomarkers to predict a cancer patient's response to the MDM2 inhibitors. Such information can be used in determining prognosis and treatment options for cancer patients.
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
88.
TREATMENT METHODS AND BIOMARKERS FOR MDM2 INHIBITORS
Provided are biomarkers for predicting the efficacy of MDM2 inhibitors in treating cancer patients. Also provided are compositions, e.g., kits, for evaluating the biomarkers and methods of using the biomarkers to predict a cancer patient's response to the MDM2 inhibitors. Such information can be used in determining prognosis and treatment options for cancer patients.
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
Crystalline forms or amorphous forms of N- (phenylsulfonyl) benzoamide compound or its salts or solvates used as a Bcl-2 inhibitor, and the preparation method and the application thereof.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
Disclosed herein are a process (I) for preparing alkynyl-containing compound and intermediate thereof. In particular, the present invention discloses a process for preparing a compound of formula 6 as shown in below and a pharmaceutical composition comprising a compound of formula 6 for treating cancer,
Disclosed is a method for preparing 2-indolinospirone compound and intermediate thereof, specifically disclosed is a method for preparing a compound of formula 5. The method is relatively simple and has high stereoselectivity and yield.
The present disclosure provides compounds represented by Formula I:
2, L, Q, Z, and
are as defined in the specification, and the pharmaceutically acceptable salts and solvates thereof. Compounds of Formula I are KRAS inhibitors and are thus useful to treat cancer and other diseases.
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
93.
AMORPHOUS FORM OR CRYSTALLINE FORM OF 2-INDOLINOLINOLOLYLSPIRONONE COMPOUNDS OR THEIR SALTS, SOLVENT COMPLEXES
Amorphous form or crystalline form of a 2-indolinolinololylspironone compound or its salt and solvate used as an MDM2 inhibitor, a preparation method and an application thereof. The amorphous form or crystalline form of the invention has good stability and is of great value for drug development, preparation development and production.
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
The present invention relates to a method for preparing sulfonamides which are inhibitors of Bcl-2/Bcl-xL, comprising the compound (3R)-1-(3-(4-(4-(4-(3-(2-(4-chlorophenyl)-1-isopropyl-4-methylsulfonyl-5-methyl-1H-pyrrol-3-yl)-5-fluorophenyl)piperazin-1-yl)-phenylaminosulfonyl)-2-trifluoro methylsulfonyl-anilino)-4-phenylthio-butyl)-4-hydroxyl-piperidine, and the present invention also relates to intermediates for the preparation of the sulfonamides, a new final product and its therapeutic use, and pharmaceutical use.
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
Provided are compounds represented by Formula I, wherein R3, A, A1, A2, A3, E, E1, E2, L, Q, Z, and (aa) are as defined in the specification, and the pharmaceutically acceptable salts and solvates thereof. Compounds of Formula (I) are KRAS inhibitors and are thus useful to treat cancer and other diseases.
C07D 487/22 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups in which the condensed system contains four or more hetero rings
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
96.
MDM2 inhibitor and a platinum compound for cancer treatment
Provided herein is a method of treating, preventing, or alleviating one or more symptoms of a disorder, disease, or condition mediated by an MDM2 with an MDM2 inhibitor, e.g., a compound of Formula (I), and a platinum compound. Also provided herein is a method of inhibiting the growth of a cell with an MDM2 inhibitor and a platinum compound.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/555 - Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
97.
PHARMACEUTICAL COMPOSITION OF ALKYNYL-CONTAINING COMPOUND, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
The present invention relates to a pharmaceutical composition of alkynyl-containing compound, a preparation method and an application thereof. Disclosed is a pharmaceutical composition, which comprises a pharmaceutically active ingredient and a pharmaceutically usable excipient. The pharmaceutically active ingredient is 3-((1H-pyrazole[3,4-b]pyridine-5-substituted)ethinyl)-4-methyl-N-(4-((4-methylpiperazine-1-substituted)methyl)-3-(trifluoromethyl)phenyl)benzamide or a pharmaceutically acceptable salt thereof; and the pharmaceutically usable excipient comprises a diluent and a lubricant. The pharmaceutical composition is capable of effectively improving the bioavailability of alkynyl-containing compounds, and has good dissolution rate and stability, thereby improving the medication safety.
A pharmaceutical composition comprising: a) an effective amount of an Inhibitors of Apoptosis Proteins (IAP) inhibitor, wherein the IAP inhibitor is represented by formula (I): or a pharmaceutically acceptable salt thereof, the definitions of each variable are provided herein; b) an effective amount of a second inhibitor, wherein the second inhibitor is a poly ADP ribose polymerase (PARP) inhibitor or a mitogen-activated protein kinase kinase (MEK) inhibitor; and a pharmaceutically acceptable carrier or diluent.
Described herein are methods of treating a hematologic malignancy in a patient in need thereof, comprising administering to the patient a Bcl-2 inhibitor in a step-wise dosing regimen.
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 31/00 - Medicinal preparations containing organic active ingredients
Described herein are methods of treating a cancer, for example, a hematologic malignancy or a solid tumor, in a patient in need thereof, comprising administering to the patient a Bcl-2 inhibitor in combination with a second anti-cancer agent.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/407 - 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 condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
