A method of treating an alpha-synucleinopathy in a patient in need thereof includes administering to the patient a therapeutically effective amount of a dual TYK2/JAK1 inhibitor, wherein the dual TYK2/JAK1 inhibitor is a compound of Formula I as described herein or a pharmaceutically acceptable salt, solvate, hydrate, or polymorph thereof. Also disclosed is a method of providing neuroprotection to the central or peripheral nervous system of a patient in need of such neuroprotection. The method includes administering to the patient the dual TYK2/JAK1 inhibitor.
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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 9/00 - Medicinal preparations characterised by special physical form
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
2.
METHOD FOR SYNTHESIZING FUROIMIDAZOPYRIDINE COMPOUND, POLYMORPHIC SUBSTANCE AND POLYMORPHIC SUBSTANCE OF SALT
A method for synthesizing a compound 2-[(2R,5S)-5-[2-methylfuro[3,2-b]imidazo[4,5-d]pyridin-1-yl]tetrahydropyran-2-yl]acetonitrile as a selective JAK1/TYK2 kinase inhibitor. The compound is prepared by taking 7-chloro-6-nitrofuro[3,2-b]pyridine as the starting material, and by nucleophilic substitution, palladium on carbon reduction and cyclization reactions. The present synthesis method has mild reaction conditions, high product yield and high purity, and is suitable for industrial production. A crystal form of the compound, crystal forms of the salts thereof and preparation methods thereof. The crystal form of the compound and the crystal forms of the salts thereof have good physical and chemical properties and are suitable for drug development.
C07D 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
Provided are compounds of Formula (I): wherein all of the variables are as defined herein, which inhibit NOD-like receptor protein 3 (NLRP3) inflammasome activity. Disclosed are the processes for their preparation, pharmaceutical compositions and medicaments containing them, and their use in the treatment of disease and disorders mediated by NLRP3.
Provided are compounds of Formula (I): wherein all of the variables are as defined herein, which inhibit NOD-like receptor protein 3 (NLRP3) inflammasome activity. Disclosed are the processes for their preparation, pharmaceutical compositions and medicaments containing them, and their use in the treatment of disease and disorders mediated by NLRP3.
A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
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
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
Provided is a method for synthesizing 1H-furo[3,2-b]imidazo[4,5-d]pyridine compounds. The method comprises the following steps of: reacting compound 1 with compound 2 in a solvent in the presence of a base to obtain compound 3; subjecting the compound 3 to a reduction reaction to obtain compound 4; and subjecting the compound 4 to a ring-closing reaction with compound 5 or compound 5′ to obtain compound 6 or a hydrate thereof, wherein R is methyl or ethyl, the methyl or ethyl is optionally substituted by hydroxyl, and X═O or CH2. The method for synthesizing the 1H-furo[3,2-b]imidazo[4,5-d]pyridine compound has the advantages of high yield, fewer impurities and is easy to control, saves the cost. The method is simple and convenient to operate, and is suitable for industrial scale.
Provided is a method for synthesizing 1H-furo[3,2-b]imidazo[4,5-d]pyridine compounds. The method comprises the following steps of: reacting compound 1 with compound 2 in a solvent in the presence of a base to obtain compound 3; subjecting the compound 3 to a reduction reaction to obtain compound 4; and subjecting the compound 4 to a ring-closing reaction with compound 5 or compound 5′ to obtain compound 6 or a hydrate thereof, wherein R is methyl or ethyl, the methyl or ethyl is optionally substituted by hydroxyl, and X═O or CH2. The method for synthesizing the 1H-furo[3,2-b]imidazo[4,5-d]pyridine compound has the advantages of high yield, fewer impurities and is easy to control, saves the cost. The method is simple and convenient to operate, and is suitable for industrial scale.
C07D 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
C07D 309/14 - Nitrogen atoms not forming part of a nitro radical
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
The present invention provides compounds of Formula (I), wherein all of the variables are as defined herein, which inhibit NOD-like receptor protein 3 (NLRP3) inflammasome activity. The invention further relates to the processes for their preparation, pharmaceutical compositions and medicaments containing them, and their use in the treatment of disease and disorders mediated by NLRP3.
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 413/02 - 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
A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
A61P 25/00 - Drugs for disorders of the nervous system
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
A61P 37/00 - Drugs for immunological or allergic disorders
Methods relate to treat a central nervous system (CNS) disorder using a compound of Formulae (I)-(III), or a salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative. or prodrug thereof. Methods of treating a CNS disorder using a composition comprising such compounds are also provided herein. The present disclosure also provides a compound of Formula (A), or a salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug 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
A61P 25/00 - Drugs for disorders of the nervous system
7.
NOVEL MACROCYCLIC HETEROARYL DERIVATIVES AS KINASE INHIBITORS
Macrocyclic heteroaryl derivatives as kinase inhibitors, particularly brain penetrant TYK2 inhibitors useful for treating a central nervous system (CNS) disorder. Methods of treating a CNS disorder using a composition comprising such compounds are also provided herein.
C07D 498/22 - Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
Provided 4-pyrazolyl-N-heteroarylpyrimidin-2-amine compounds as potent TYK2/JAK1/JAK2 inhibitors with low systemic exposures when applied topically. Thus, these compounds, and compositions are useful as topical treatment of dermatological disorders related to JAK1/JAK2/TYK2 such as atopic dermatitis, psoriasis, hives, alopecia areata, vitiligo, hidradenitis suppurativa, hand eczema, necrobiosis lipoidica, non-sclerotic cutaneous chronic graft-versus-host disease, hand dermatitis, or Lichen Planus.
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
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
The present invention provides compounds of Formula (I) : wherein all of the variables are as defined herein, which inhibit NOD-like receptor protein 3 (NLRP3) inflammasome activity. The invention further relates to the processes for their preparation, pharmaceutical compositions and medicaments containing them, and their use in the treatment of disease and disorders mediated by NLRP3.
C07D 233/90 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07C 43/20 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
C07C 221/00 - Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
C07C 223/02 - Compounds containing amino and —CHO groups bound to the same carbon skeleton having amino groups bound to acyclic carbon atoms of the carbon skeleton
C07C 231/02 - Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
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
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
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
A61P 19/06 - Antigout agents, e.g. antihyperuricemic or uricosuric agents
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
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
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contractionDrugs for heart failure
Provided are compounds of Formula (I): wherein all of the variables are as defined herein, which inhibit NOD-like receptor protein 3 (NLRP3) inflammasome activity. Disclosed are the processes for their preparation, pharmaceutical compositions and medicaments containing them, and their use in the treatment of disease and disorders mediated by NLRP3.
22. The method for synthesizing the 1H-furo[3,2-b]imidazo[4,5-d]pyridine compound of the present invention has a high yield and few impurities, and is easy to control, low cost, simple and convenient to operate, and suitable for industrial scale.
C07D 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
Methods relate to treat a central nervous system (CNS) disorder using a compound of Formulae (I) - (III), or a salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof. Methods of treating a CNS disorder using a composition comprising such compounds are also provided herein. The present disclosure also provides a compound of Formula (A), or a salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic 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 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61P 25/00 - Drugs for disorders of the nervous system
13.
Synthesis method of furoimidazopyridine compound, crystal form of furoimidazopyridine compound, and crystal form of salt thereof
Provided is a method for synthesizing a compound 2-[(2R,5S)-5-[2-[(R)-1-hydroxyethyl]furo[3,2-b]imidazo[4,5-d]pyridin-1-yl]tetrahydropyran-2-yl]acetonitrile as a selective JAK1/TYK2 kinase inhibitor. The compound is prepared by nucleophilic substitution, palladium on carbon reduction, and cyclization reaction using 7-chloro-6-nitrofuro[3,2-b]pyridine as a starting material. The synthesis method has mild reaction conditions, high product yield, and high purity, and is suitable for industrial production. Further provided are a crystal form of the compound, crystal forma of its salts, and their preparation methods. The crystal form of the compound and the crystal forms of its salts have good physical and chemical properties and are suitable for drug development.
C07D 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
patents
