Provided herein is the use of certain pyruvate kinase activators or pharmaceutically acceptable salts or compositions thereof for treating MDS-associated anemia and other conditions.
Described herein are methods of treating pyruvate kinase deficiency (PKD), sickle cell disease or thalassemia with mitapivat or a pharmaceutically acceptable salt thereof, or use of the drug for the treatment of these conditions, in combination with or in the absence of with a secondary drug, such as an inducer or an inhibitor of cytochrome P450. Various doses and dosing regimens of mitapivat in monotherapy and in concomitant medications are described.
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
3.
4-PYRAZOLO[1,5-A]PYRIDIN-2-YL-4,5,6,7-TETRAHYDRO-1 H-IMIDAZO[4,5-C]PYRIDINE DERIVATIVES AS MUTANT PAH PROTEIN STABILIZERS FOR THE TREATMENT OF PHENYLKETONURIA
The disclosure is directed to compounds, such as e.g. 4-pyrazolo[1,5- a]pyridin-2-yl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine derivatives, e.g. : and pharmaceutically acceptable salts thereof, that stabilize phenylalanine hydroxylase (PAH) mutations, pharmaceutical compositions comprising those compounds, and methods of using those compounds in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, orV388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.
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
The disclosure relates to compounds of Formula I, or a pharmaceutically acceptable salt thereof, wherein Ra, Rb, and x are defined herein, and pharmaceutical compositions comprising compounds of Formula I, or a pharmaceutically acceptable salt thereof.
The disclosure relates to compounds of Formula I, or a pharmaceutically acceptable salt thereof, wherein Ra, Rb, and x are defined herein, and pharmaceutical compositions comprising compounds of Formula I, or a pharmaceutically acceptable salt thereof.
The disclosure relates to compounds of Formula I, or a pharmaceutically acceptable salt thereof, wherein Ra, Rb, and x are defined herein, and pharmaceutical compositions comprising compounds of Formula I, or a pharmaceutically acceptable salt thereof.
These compounds and pharmaceutical compositions are useful in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.
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 31/444 - 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 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/501 - PyridazinesHydrogenated pyridazines not condensed and containing further heterocyclic rings
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
5.
4-PYRAZOLO[1,5-A]PYRIDIN-2-YL-4,5,6,7-TETRAHYDRO-1H-IMIDAZO[4,5-C]PYRIDINE DERIVATIVES AS MUTANT PAH PROTEIN STABILIZERS FOR THE TREATMENT OF PHENYLKETONURIA
The disclosure is directed to 4-pyrazolo[1,5-a]pyridin-2-yl-4, 5,6,7- tetrahydro-1H-imidazo[4,5-c]pyridine derivatives of formula (I) and pharmaceutically acceptable salts thereof, that stabilize phenylalanine hydroxylase (PAH) mutations, pharmaceutical compositions comprising those compounds, and methods of using those compounds in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.
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
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations, namely, for the activation of PKR (pyruvate kinase R), for the activation of PKM2 (pyruvate kinase isozyme M2), and for the prevention and treatment of blood disorders, sickle cell disease, pyruvate kinase deficiency (PKD), beta thalassemia and alpha thalassemia, genetically defined diseases affecting red blood cells, hereditary spherocytosis, hereditary elliptocytosis, dyserythropoiesis, hemolytic anemia, and other anemias
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations, namely, for the activation of PKR (pyruvate kinase R), for the activation of PKM2 (pyruvate kinase isozyme M2), and for the prevention and treatment of blood disorders, sickle cell disease, pyruvate kinase deficiency (PKD), beta thalassemia and alpha thalassemia, genetically defined diseases affecting red blood cells, hereditary spherocytosis, hereditary elliptocytosis, dyserythropoiesis, hemolytic anemia, and other anemias
9.
CRYSTALLINE SALTS OR AMORPHOUS FORMS OF 2-((1H-PYRAZOL-3-YL)METHYL)-6-((6-AMINOPYRIDIN-2-YL)METHYL)-4-METHYL-4,6-DIHYDRO -5H-THIAZOLO[5',4':4,5]PYRROLO[2,3-D]PYRIDAZIN-5-ONE
Provided herein are crystalline salts and free base forms as well as amorphous forms of the compound having the formula:(I) Also provided are pharmaceutical compositions comprising such crystalline and amorphous forms, methods for their manufacture, and uses thereof for treating various conditions such as, hemolytic anemia, sickle cell disease and MDS (very low risk MDS, low risk MDS, lower risk MDS and/or intermediate risk MDS).
The disclosure is directed to compounds, and pharmaceutically acceptable salts thereof, that inhibit branched-chain amino acid aminotransferase 2 (BCAT2), pharmaceutical compositions comprising those compounds, and methods of using those compounds for treating branched chain amino acid (BCAA)-catabolism-related diseases. The disclosure is also directed to in vivo models for the study of disorders characterized by defects in the metabolism of BCAAs.
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
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
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 31/444 - 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 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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
A61K 31/536 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with carbocyclic ring systems
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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
Compounds and compositions comprising compounds that modulate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that modulate PKM2 in the treatment of cancer.
C07D 243/08 - Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
C07D 271/12 - Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
C07D 277/64 - Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
C07D 277/68 - Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
C07D 295/192 - Radicals derived from carboxylic acids from aromatic carboxylic acids
C07D 319/18 - Ethylenedioxybenzenes, not substituted on the hetero ring
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/12 - 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 407/12 - 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 two hetero rings linked by a chain containing hetero atoms as chain links
C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 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
12.
METHODS OF TREATMENT WITH AMINOLEVULINIC ACID SYNTHASE 2 (ALAS2) MODULATORS
Described herein is a compound of Formula I or a pharmaceutically acceptable salt thereof: wherein Ring A R1, R2, a, b, and n are as defined herein. Also described is a method of treating a subject having a disorder in need of treatment, comprising inhibiting aminolevulinic acid synthase 2 (ALAS2) in the subject by administering a compound of Formula (I) or a pharmaceutically acceptable salt thereof. Disorders that are of particular interest are blood disorders, such as porphyria and anemia.
Described herein is a compound of Formula I or a pharmaceutically acceptable salt thereof: wherein Ring A R1, R2, a, b, and n are as defined herein. Also described is a method of treating a subject having a disorder in need of treatment, comprising inhibiting aminolevulinic acid synthase 2 (ALAS2) in the subject by administering a compound of Formula (I) or a pharmaceutically acceptable salt thereof. Disorders that are of particular interest are blood disorders, such as porphyria and anemia.
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/535 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
C07C 13/04 - Monocyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with a three-membered ring
C07C 307/10 - Diamides of sulfuric acids having nitrogen atoms of the sulfamide groups bound to carbon atoms of six-membered aromatic rings
C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
C07D 215/14 - Radicals substituted by oxygen atoms
C07D 235/06 - BenzimidazolesHydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
C07D 241/04 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
C07D 271/12 - Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
C07D 295/192 - Radicals derived from carboxylic acids from aromatic carboxylic acids
C07D 307/14 - Radicals substituted by nitrogen atoms not forming part of a nitro radical
C07D 333/24 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 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 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations for the prevention and treatment
of genetically defined diseases, hematologic disorders and
diseases related to aberrant cellular metabolism.
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations for the prevention and treatment
of genetically defined diseases, hematologic disorders and
diseases related to aberrant cellular metabolism.
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations, namely, for the activation of
PKR (pyruvate kinase R), for the activation of PKM2
(pyruvate kinase isozyme M2), and for the prevention and
treatment of blood disorders, pyruvate kinase deficiency
(PKD), genetically defined diseases affecting red blood
cells, hemolytic anemia.
Described herein are mouse models of porphyrias, including mouse models of X- linked protoporphyria and erythropoietic protoporphyria (EPP). Immortalized human CD34+ blood cell lines expressing shRNAs targeting a human Ferrochelatase (FECH) gene or a human Uroporphyrinogen III Synthase (UROS) gene for use as in vitro models of EPP or congenital erythropoietic porphyria (CEP), respectively, are also described.
A01K 67/0278 - Knock-in vertebrates, e.g. humanised vertebrates
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
41 - Education, entertainment, sporting and cultural services
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
45 - Legal and security services; personal services for individuals.
Goods & Services
Education services, namely, providing mentoring, tutoring, classes, seminars and workshops in the field of diagnosis, management and treatment of thalassemia Providing medical and scientific research information in the field of pharmaceuticals and clinical trials Providing an internet-based database of patient medical information where patients can inquire about medical issues and procedures from other patients and can relay information about their medical experiences for support and community; Providing health information; Providing medical information via a website Providing personal support services for patients and families of patients, namely, emotional counseling and emotional support
41 - Education, entertainment, sporting and cultural services
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Promoting public awareness of hematological disorders and their treatment and management Education services, namely, providing mentoring, tutoring, classes, seminars and workshops in the field of diagnosis, management and treatment of hematological disorders Providing an internet-based database of patient medical information where patients can inquire about medical issues and procedures from other patients and can relay information about their medical experiences for support and community; Providing health information; Providing medical information via a website
09 - Scientific and electric apparatus and instruments
Goods & Services
downloadable software in the nature of a mobile application to allow patients and healthcare professionals to access, collect and share information in the management of pyruvate kinase deficiency; downloadable software in the nature of a mobile application to provide information related to the management of pyruvate kinase deficiency
22.
MITAPIVAT THERAPY AND MODULATORS OF CYTOCHROME P450
Described herein are methods of treating pyruvate kinase deficiency (PKD), sickle cell disease or thalassemia with mitapivat or a pharmaceutically acceptable salt thereof, or use of the drug for the treatment of these conditions, in combination with or in the absence of with a secondary drug, such as an inducer or an inhibitor of cytochrome P450. Various doses and dosing regimens of mitapivat in monotherapy and in concomitant medications are described.
Described herein are methods of treating pyruvate kinase deficiency (PKD), sickle cell disease or thalassemia with mitapivat or a pharmaceutically acceptable salt thereof, or use of the drug for the treatment of these conditions, in combination with or in the absence of with a secondary drug, such as an inducer or an inhibitor of cytochrome P450. Various doses and dosing regimens of mitapivat in monotherapy and in concomitant medications are described.
The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R1-R5, R5A, and L are defined herein.
The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R1-R5, R5A, and L are defined herein.
The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R1-R5, R5A, and L are defined herein.
These compounds are useful in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.
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
Disclosed is a pharmaceutical mini-tablet comprising mitapivat or a pharmaceutically acceptable salt thereof, and in a particular embodiment comprising a mitapivat sulfate salt, and one or more inactive ingredients selected from a filler, disintegrant, lubricant, binder, and diluent.
5A, and L are defined herein.
These compounds are useful in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.
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
27.
(4-BENZO[D]OXAZOL-2-YL)-6,7-DIHYDRO-1H-IMIDAZO[4,5-C]PYRIDINE-5(4H)-YL)METHANONE DERIVATIVES AS MUTANT PAH STABILIZERS FOR THE TREATMENT OF PHENYLKETONURIA
The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R1-R5, R5A, and L are defined herein. These compounds are useful in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.
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 31/437 - 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 25/00 - Drugs for disorders of the nervous system
28.
COMPOUNDS AND METHODS USEFUL FOR STABILIZING PHENYLALANINE HYDROXYLASE MUTATIONS
The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R1-R5, R5A, and L are defined herein. These compounds are useful in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.
The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R1-R5, R5A, and L are defined herein. These compounds are useful in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.
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
A61P 25/00 - Drugs for disorders of the nervous system
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
30.
COMPOUNDS AND METHODS USEFUL FOR STABILIZING PHENYLALANINE HYDROXYLASE MUTATIONS
The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R1-R5, R5A, and L are defined herein. These compounds are useful in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.
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 31/437 - 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
31.
COMPOUNDS AND METHODS USEFUL FOR STABILIZING PHENYLALANINE HYDROXYLASE MUTATIONS
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 25/00 - Drugs for disorders of the nervous system
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
32.
COMPOUNDS AND METHODS USEFUL FOR STABILIZING PHENYLALANINE HYDROXYLASE MUTATIONS
The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R1-R5, R5A, and L are defined herein. These compounds are useful in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.
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 31/437 - 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
Compounds and compositions comprising compounds that modulate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that modulate PKM2 in the treatment of cancer.
C07D 243/08 - Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
C07D 271/12 - Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
C07D 277/64 - Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
C07D 277/68 - Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
C07D 295/192 - Radicals derived from carboxylic acids from aromatic carboxylic acids
C07D 319/18 - Ethylenedioxybenzenes, not substituted on the hetero ring
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/12 - 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 407/12 - 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 two hetero rings linked by a chain containing hetero atoms as chain links
C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 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
36.
CRYSTALLINE SALT FORMS OF N-(4-(4-(CYCLOPROPYLMETHYL)PIPERAZINE-1-CARBONYL)PHENYL)QUINOLINE-8-SULFONAMIDE
Provided herein are various crystalline salt forms of compound (I) represented by the following structural formula: Also provided are pharmaceutical compositions comprising the crystalline salt forms, methods for their manufacture, and uses thereof for treating conditions associated with pyruvate kinase such as e.g., pyruvate kinase deficiency.
Provided herein is the use of certain pyruvate kinase activators or pharmaceutically acceptable salts or compositions thereof for treating MDS -associated anemia and other conditions.
Provided herein is the use of certain pyruvate kinase activators or pharmaceutically acceptable salts or compositions thereof for treating MDS -associated anemia and other conditions.
The disclosure is directed to compounds, and pharmaceutically acceptable salts thereof, that inhibit branched-chain amino acid aminotransferase 2 (BCAT2), pharmaceutical compositions comprising those compounds, and methods of using those compounds for treating branched chain amino acid (BCAA)-catabolism-related diseases.
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 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
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
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42.
Pyruvate kinase activators for use in treating blood disorders
Described herein are methods of using compounds of Formula (I) to modulate PKM2 activity in a subject. These compounds are represented by Formula (I):
2 are as defined herein.
Provided herein are amorphous and crystalline hemisulfate salt forms of the formula.
Provided herein are amorphous and crystalline hemisulfate salt forms of the formula.
Provided herein are amorphous and crystalline hemisulfate salt forms of the formula.
Also provided are pharmaceutical compositions comprising the amorphous and crystalline hemisulfate salt forms, methods for their manufacture, and uses thereof for treating conditions associated with pyruvate kinase such as e.g., pyruvate kinase deficiency.
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
THIENO[3,2-B] PYRROLE[3,2-D]PYRIDAZINONE DERIVATIVES AND THEIR USE AS PKM2 DERIVATIVES FOR THE TREATMENT OF CANCER, OBESITY AND DIABETES RELATED DISORDERS
Described herein are compounds that regulate pyruvate kinase activity, pharmaceutical compositions and methods of use thereof. These compounds are represented by Formula (I) wherein R2, L1-L2, U1-U7, m, ring A, and Q are as defined herein.
Described herein are compounds that regulate pyruvate kinase activity, pharmaceutical compositions and methods of use thereof. These compounds are represented by Formula (I) wherein R2, L1-L2, U1-U7, m, ring A, and Q are as defined herein.
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Disclosed is a pharmaceutical mini-tablet comprising mitapivat or a pharmaceutically acceptable salt thereof, and in a particular embodiment comprising a mitapivat sulfate salt, and one or more inactive ingredients selected from a filler, disintegrant, lubricant, binder, and diluent.
Disclosed is a pharmaceutical mini-tablet comprising mitapivat or a pharmaceutically acceptable salt thereof, and in a particular embodiment comprising a mitapivat sulfate salt, and one or more inactive ingredients selected from a filler, disintegrant, lubricant, binder, and diluent.
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Pharmaceutical preparations for the prevention and treatment of genetically defined diseases, hematologic disorders and diseases related to aberrant cellular metabolism
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Pharmaceutical preparations for the prevention and treatment of genetically defined diseases, hematologic disorders and diseases related to aberrant cellular metabolism Providing pre-clinical, clinical and scientific research information in the field of pharmaceuticals including genetically defined diseases, hematologic disorders and diseases related to aberrant cellular metabolism
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Pharmaceutical preparations for the prevention and treatment of genetically defined diseases, hematologic disorders and diseases related to aberrant cellular metabolism Providing pre-clinical, clinical and scientific research information in the field of pharmaceuticals including genetically defined diseases, hematologic disorders and diseases related to aberrant cellular metabolism
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Pharmaceutical preparations for the prevention and treatment of genetically defined diseases, hematologic disorders and diseases related to aberrant cellular metabolism Providing pre-clinical, clinical and scientific research information in the field of pharmaceuticals including genetically defined diseases, hematologic disorders and diseases related to aberrant cellular metabolism
68.
MENIN INHIBITORS AND METHODS OF USE FOR TREATING CANCER
The present disclosure provides compounds represented by Formula (I): or a pharmaceutically acceptable salt thereof, wherein Ra, Rb, Rc, Rd, L1, R2 B, Q and E are as defined as set forth in the specification. The present disclosure also provides compounds of Formula (I) for use to treat cancer or any other disease, condition, or disorder that is responsive to inhibition of menin. :
C07D 211/34 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 401/06 - 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 carbon chain containing only aliphatic carbon atoms
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 35/02 - Antineoplastic agents specific for leukemia
A61K 31/4523 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
69.
MENIN INHIBITORS AND METHODS OF USE FOR TREATING CANCER
The present disclosure provides compounds represented by Formula (I), or a pharmaceutically acceptable salt thereof, wherein Ra, Rb, Rc, Rd, V, Q, T, n, p, q, r and s are as defined as set forth in the specification. The present disclosure also provides compounds of Formula (I) for use to treat cancer or any other disease, condition, or disorder that is responsive to inhibition of menin.
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 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
A61P 35/02 - Antineoplastic agents specific for leukemia
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
05 - Pharmaceutical, veterinary and sanitary products
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Pharmaceutical preparations, namely, for the activation of
PKR (pyruvate kinase R), for the activation of PKM2
(pyruvate kinase isozyme M2), and for the prevention and
treatment of blood disorders, sickle cell disease, pyruvate
kinase deficiency (PKD), beta thalassemia and/or alpha
thalassemia, genetically defined diseases affecting red
blood cells, hereditary spherocytosis, hereditary
elliptocytosis, dyserythropoiesis, hemolytic anemia, and
other anemias.
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73.
METHODS OF TREATING AUTOIMMUNE OR INFLAMMATORY DISEASES OR DISORDERS
A61K 31/535 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
C07D 215/14 - Radicals substituted by oxygen atoms
C07D 235/06 - BenzimidazolesHydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
C07D 271/12 - Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
C07D 295/192 - Radicals derived from carboxylic acids from aromatic carboxylic acids
C07D 333/24 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 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 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07C 307/10 - Diamides of sulfuric acids having nitrogen atoms of the sulfamide groups bound to carbon atoms of six-membered aromatic rings
C07D 241/04 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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(1) Pharmaceutical preparations, namely, for the activation of PKR (pyruvate kinase R), for the activation of PKM2 (pyruvate kinase isozyme M2), and for the prevention and treatment of blood disorders, pyruvate kinase deficiency (PKD), genetically defined diseases affecting red blood cells, hemolytic anemia.
Compounds and compositions comprising compounds that modulate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that modulate PKM2 in the treatment of cancer.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/12 - 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 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 407/12 - 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 two hetero rings linked by a chain containing hetero atoms as chain links
C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 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
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
C07D 243/08 - Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
C07D 271/12 - Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
C07D 277/64 - Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
C07D 277/68 - Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
C07D 319/18 - Ethylenedioxybenzenes, not substituted on the hetero ring
C07D 295/192 - Radicals derived from carboxylic acids from aromatic carboxylic acids
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Pharmaceutical preparations, namely, for the activation of PKR (pyruvate kinase R), for the activation of PKM2 (pyruvate kinase isozyme M2), and for the prevention and treatment of blood disorders, sickle cell disease, pyruvate kinase deficiency (PKD), beta thalassemia and alpha thalassemia, genetically defined diseases affecting red blood cells, hereditary spherocytosis, hereditary elliptocytosis, dyserythropoiesis, hemolytic anemia, and other anemias
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Pharmaceutical preparations, namely, for the activation of PKR (pyruvate kinase R), for the activation of PKM2 (pyruvate kinase isozyme M2), and for the prevention and treatment of blood disorders, pyruvate kinase deficiency (PKD), genetically defined diseases affecting red blood cells, hemolytic anemia
05 - Pharmaceutical, veterinary and sanitary products
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Pharmaceutical preparations, namely, for the activation of PKR (pyruvate kinase R), for the activation of PKM2 (pyruvate kinase isozyme M2), and for the prevention and treatment of blood disorders, pyruvate kinase deficiency (PKD), genetically defined diseases affecting red blood cells, hemolytic anemia
05 - Pharmaceutical, veterinary and sanitary products
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Pharmaceutical preparations, namely, for the activation of PKR (pyruvate kinase R), for the activation of PKM2 (pyruvate kinase isozyme M2), and for the prevention and treatment of blood disorders, pyruvate kinase deficiency (PKD), genetically defined diseases affecting red blood cells, hemolytic anemia
05 - Pharmaceutical, veterinary and sanitary products
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Pharmaceutical preparations, namely, for the activation of PKR (pyruvate kinase R), for the activation of PKM2 (pyruvate kinase isozyme M2), and for the prevention and treatment of blood disorders, pyruvate kinase deficiency (PKD), genetically defined diseases affecting red blood cells, hemolytic anemia
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations, namely, for the activation of PKR (pyruvate kinase R), for the activation of PKM2 (pyruvate kinase isozyme M2), and for the prevention and treatment of blood disorders, pyruvate kinase deficiency (PKD), genetically defined diseases affecting red blood cells, hemolytic anemia
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations, namely, for the activation of PKR (pyruvate kinase R), for the activation of PKM2 (pyruvate kinase isozyme M2), and for the prevention and treatment of blood disorders, pyruvate kinase deficiency (PKD), genetically defined diseases affecting red blood cells, hemolytic anemia
05 - Pharmaceutical, veterinary and sanitary products
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Pharmaceutical preparations, namely, for the activation of PKR (pyruvate kinase R), for the activation of PKM2 (pyruvate kinase isozyme M2), and for the prevention and treatment of blood disorders, pyruvate kinase deficiency (PKD), genetically defined diseases affecting red blood cells, hemolytic anemia
05 - Pharmaceutical, veterinary and sanitary products
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Pharmaceutical preparations, namely, for the activation of PKR (pyruvate kinase R), for the activation of PKM2 (pyruvate kinase isozyme M2), and for the prevention and treatment of blood disorders, sickle cell disease, pyruvate kinase deficiency (PKD), beta thalassemia and alpha thalassemia, genetically defined diseases affecting red blood cells, hereditary spherocytosis, hereditary elliptocytosis, dyserythropoiesis, hemolytic anemia, and other anemias
Provided are deuterated analogs of a compound and methods of using such deuterated analogs for treating a brain tumor in a patient in need thereof; the treatment comprising administering to the patient a deuterated compound described herein. The deuterated compound may be administered in combination with radiation therapy and/or an additional therapeutic agent.
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
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
87.
Pyruvate kinase activators for use in treating blood disorders
The present disclosure provides compounds represented by Formula (la): and the pharmaceutically acceptable salts thereof, wherein R1a, R1b, R1c, R2, R3, L, M and G are as defined as set forth in the specification. The present disclosure also provides compounds of Formula la for use to treat a condition or disorder responsive to menin inhibition such as cancer.
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 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
The present application relates to a method for preparing a substantially and diastereomerically pure crystalline ethanol solvate of Compound IIa and its use for synthesizing Ivosidenib.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
91.
METHODS OF TREATMENT WITH AMINOLEVULINIC ACID SYNTHASE 2 (ALAS2) MODULATORS
Described herein is a compound of Formula I or a pharmaceutically acceptable salt thereof: wherein Ring A R1, R2a, b,a, b, and n are as defined herein. Also described is a method of treating a subject having a disorder in need of treatment, comprising inhibiting aminolevulinic acid synthase 2 (ALAS2) in the subject by administering a compound of Formula (I) or a pharmaceutically acceptable salt thereof. Disorders that are of particular interest are blood disorders, such as porphyria and anemia.
C07D 257/06 - Five-membered rings with nitrogen atoms directly attached to the ring carbon atom
C07D 263/48 - Nitrogen atoms not forming part of a nitro radical
C07D 271/07 - 1,2,4-OxadiazolesHydrogenated 1,2,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
C07D 271/113 - 1,3,4-OxadiazolesHydrogenated 1,3,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
C07D 277/50 - Nitrogen atoms bound to hetero atoms
C07D 277/56 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
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
92.
HETEROBICYCLIC INHIBITORS OF MAT2A AND METHODS OF USE FOR TREATING CANCER
The present disclosure provides for compounds according to Formula I, Formula II, and their pharmaceutically acceptable salts, tautomers, and/or isotopologues as described in the disclosure. The compounds are inhibitors of methionine adenosyltransferase isoform 2A (MAT2A). Also provided are pharmaceutical compositions and methods of using the compounds for treating cancers, including some cancers in which the gene encoding methylthioadenosine phosphorylase (MTAP) is deleted.
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 31/4375 - 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 six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 31/522 - Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
93.
CRYSTALLINE SALT FORMS OF N-(4-(4-(CYCLOPROPYLMETHYL)PIPERAZINE-1-CARBONYL)PHENYL)QUINOLINE-8-SULFONAMIDE
Provided herein are various crystalline salt forms of compound (I) represented by the following structural formula: Also provided are pharmaceutical compositions comprising the crystalline salt forms, methods for their manufacture, and uses thereof for treating conditions associated with pyruvate kinase such as e.g., pyruvate kinase deficiency.
Provided herein are various crystalline salt forms of compound (I) represented by the following structural formula: Also provided are pharmaceutical compositions comprising the crystalline salt forms, methods for their manufacture, and uses thereof for treating conditions associated with pyruvate kinase such as e.g., pyruvate kinase deficiency.
Provided herein are amorphous and crystalline hemisulfate salt forms of the formula (I). Also provided are pharmaceutical compositions comprising the amorphous and crystalline hemisulfate salt forms, methods for their manufacture, and uses thereof for treating conditions associated with pyruvate kinase such as e.g., pyruvate kinase deficiency.
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
96.
THIENO[3,2-B] PYRROLE[3,2-D]PYRIDAZINONE DERIVATIVES AND THEIR USE AS PKM2 DERIVATIVES FOR THE TREATMENT OF CANCER, OBESITY AND DIABETES RELATED DISORDERS
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 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
The compound of Formula (I), or pharmaceutically acceptable salts thereof, is useful in, among other things, the treatment of MTAP-deficient lung cancer, such as NSCLC, or MTAP-deficient pancreatic cancer, such as PDAC, or MTAP-deficient esophageal cancer and provides a therapeutic advantage when used in combination with other agents as herein described compared to treatment with each agent when administered alone.
A61K 31/555 - Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
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
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The present disclosure provides for compounds according to Formula I and their pharmaceutically acceptable salts, tautomers, and/or isotopologues as described in the disclosure. The compounds are inhibitors of methionine adenosyltransferase isoform 2A (MAT2A). Also provided are pharmaceutical compositions and methods of using the compounds for treating cancers, including some cancers in which the gene encoding methylthioadenosine phosphorylase (MTAP) is deleted.
