Abstract

One aspect of the disclosure relates to a cargo delivery system comprising an autophagy targeting ligand and a target-binding ligand. In one aspect of the disclosure, by comprising an autophagy targeting ligand, cargo, which is a target-binding ligand that specifically binds to a target, is delivered to the p62 protein and autophagy is activated, so that depending on the type of target-binding ligand used, a target to be degraded can be selectively and directly removed. Accordingly, the cargo delivery system according to an aspect of the disclosure may be used in pharmaceutical compositions or food compositions for preventing, alimerating, and treating various diseases.

IPC Classes  ?

• A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound

Abstract

The present specification relates to a compound as a UBR box domain ligand. The present specification provides a small molecule compound that binds to the UBR box domain. Further, the present specification provides a composition for inhibiting UBR box domain substrate binding, including a ligand compound that binds to a UBR box domain, a pharmaceutical composition for treating UBR-related disease, and a use thereof.

IPC Classes  ?

• C07C 311/49 - Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups having nitrogen atoms of sulfonamide groups further bound to another hetero atom to nitrogen atoms
• C07D 295/135 - 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 singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• C07D 209/34 - Oxygen atoms in position 2
• C07D 209/08 - IndolesHydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• C07D 209/42 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• C07D 231/18 - One oxygen or sulfur atom
• C07D 209/44 - Iso-indolesHydrogenated iso-indoles
• C07D 209/30 - IndolesHydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
• C07D 231/56 - BenzopyrazolesHydrogenated benzopyrazoles
• C07D 211/54 - Sulfur atoms
• C07D 277/36 - Sulfur atoms
• C07D 307/68 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• C07D 207/12 - Oxygen or sulfur atoms
• C07D 471/04 - Ortho-condensed systems
• C07C 243/38 - Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to carbon atoms of six-membered aromatic rings
• C07C 243/36 - Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
• C07C 311/39 - Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
• C07C 317/28 - SulfonesSulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
• C07C 317/36 - SulfonesSulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring with the nitrogen atoms of the amino groups bound to hydrogen atoms or to carbon atoms

Abstract

The present specification relates to a compound as a UBR box domain ligand. The present specification provides a small molecule compound that binds to the UBR box domain. Further, the present specification provides a composition for inhibiting UBR box domain substrate binding, including a ligand compound that binds to a UBR box domain, a pharmaceutical composition for treating UBR-related disease, and a use thereof.

IPC Classes  ?

• C07C 237/42 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
• C07C 235/16 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring

Abstract

Described herein novel compounds as androgen-receptor inhibitors for the treatment of prostate cancer and use thereof.

IPC Classes  ?

• C07D 233/86 - Oxygen and sulfur atoms, e.g. thiohydantoin
• 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
• A61K 31/4166 - 1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61P 35/00 - Antineoplastic agents

Abstract

The present description pertains to a novel compound as a ligand binding to a UBR box domain that is involved in an intracellular protein degradation pathway, and a use thereof.

IPC Classes  ?

• C07C 235/42 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
• C07C 275/64 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups singly-bound to oxygen atoms
• A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system

Abstract

The present disclosure relates to a bifunctional compound using a UBR box domain-binding ligand. The UBR box domain is a domain commonly present in the UBR (Ubiquitin protein ligase E3 component n-recognin) protein of the N-end rule pathway. In this regard, the UBR box domain is known as a domain to which a substrate binds. The UBR box domain binds to the N-terminal residue of a substrate, playing an essential role in forming multi-ubiquitin chains in the substrate, and it is known that the substrate is degraded through this process. Employing the UBR box domain ligand that takes advantage of the UBR box domain function, the bifunctional compound can be used to induce a desired target protein (or peptide) to be more effectively degraded.

IPC Classes  ?

• C07D 295/04 - 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
• C07D 209/34 - Oxygen atoms in position 2
• C07D 209/08 - IndolesHydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• C07D 207/04 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
• C07D 211/14 - 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 radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• C07D 231/14 - 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 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 to ring carbon atoms
• C07D 277/36 - Sulfur atoms
• C07D 471/04 - Ortho-condensed systems
• C07C 317/28 - SulfonesSulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
• C07C 311/49 - Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups having nitrogen atoms of sulfonamide groups further bound to another hetero atom to nitrogen atoms

Abstract

The present specification relates to a compound represented by chemical formula 1, a salt, a stereoisomer, a solvent or a hydrate thereof, an antibacterial composition, a composition for inhibiting bacterial infections, a composition for preventing, alleviating or treating bacterial infectious diseases, and a composition for preventing, alleviating or treating inflammation caused by a bacterial infection. The composition containing, as an active ingredient, a compound represented by chemical formula 1 or a salt, a stereoisomer, a solvent or a hydrate thereof, according to one aspect of the present invention, specifically binds to p62 protein so as to activate p62, thereby increasing the activity of autophagy, which is inhibited by a bacterial infection, and thus has antibacterial activity against various bacteria, can inhibit bacterial infectivity and has the excellent effect of enabling prevention, alleviation or treatment of bacterial infectious diseases and inflammation caused by an infection. Therefore, the composition can be effectively used in therapeutic agents, food, food additives, feed additives, disinfectants, cosmetics and the like.

IPC Classes  ?

• C07D 207/08 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
• A61K 31/40 - 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
• A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
• A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• A61P 31/04 - Antibacterial agents
• A23L 33/10 - Modifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives
• A61K 8/49 - Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
• A61K 8/41 - Amines
• A61K 8/42 - Amides
• A61Q 17/00 - Barrier preparationsPreparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings

Abstract

Provided herein is a novel conjugate compound that can induce p62 oligomerization and targeted autophagosome and finally perform targeted degradation of RAS through lysosomal degradation. The conjugate compound according to the present disclosure can inhibit tumor growth in a mouse xenograft model, which is the first in vivo experiment accounting for tumor suppression through a targeted degradation system. Thus, the present disclosure provides possibilities and new approaches to treating cancers resulting from RAS mutations.

IPC Classes  ?

• 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 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• A61K 31/4433 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
• A61P 35/00 - Antineoplastic agents
• A23L 33/10 - Modifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives

Abstract

Novel p62 ligand compounds, or a stereoisomer, a solvate, a hydrate, or a prodrug thereof are disclosed. The novel compounds, stereoisomer, solvate, hydrate, or prodrug activates selective autophagy in cells to selectively remove proteins, organelles, and coagulations in the body, and thus can be advantageously used as a pharmaceutical composition for preventing, ameliorating, or treating various proteinopathies. Compositions such as pharmaceutical composition or food compositions containing the novel p62 ligand compounds, stereoisomer, solvate, hydrate, or prodrug thereof as well as uses thereof are disclosed.

IPC Classes  ?

• C07D 213/64 - One oxygen atom attached in position 2 or 6
• C07D 213/69 - Two or more oxygen atoms
• C07D 239/34 - One oxygen atom
• C07D 213/74 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• C07D 207/335 - Radicals substituted by nitrogen atoms not forming part of a nitro radical
• C07D 333/32 - Oxygen atoms
• C07D 307/58 - One oxygen atom, e.g. butenolide
• C07D 307/52 - Radicals substituted by nitrogen atoms not forming part of a nitro radical
• C07D 213/65 - One oxygen atom attached in position 3 or 5

Abstract

The present specification discloses a novel benzyloxy pyridine derivative compound represented by Chemical Formula 1, a salt thereof, a stereoisomer thereof, a hydrate thereof, or a solvate thereof, and novel uses thereof. The uses comprise the uses in the preparation of a composition for activating autophagy, a composition for activating p62 protein, a composition for inducing oligomerization of p62 protein, or a composition for ameliorating, preventing or treating a disease caused by misfolded protein.

IPC Classes  ?

• C07D 213/69 - Two or more oxygen atoms

Abstract

The present invention relates to a novel p62 ligand compound, a stereoisomer, hydrate, solvate or prodrug thereof, and a pharmaceutical or food composition for preventing or treating proteinopathies comprising the same as an active ingredient. The p62 ligand compound according to the present invention can be usefully used as a pharmaceutical composition for the prevention, amelioration or treatment of various proteinopathies by activating autophagy in cells and thus selectively eliminating in vivo proteins, organelles and aggregates.

IPC Classes  ?

• C07C 217/58 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
• A23L 33/10 - Modifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives
• A61K 31/05 - Phenols
• A61K 31/12 - Ketones
• A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
• A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
• A61K 31/277 - NitrilesIsonitriles having a ring, e.g. verapamil
• A61K 31/336 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having three-membered rings, e.g. oxirane, fumagillin
• A61K 31/355 - Tocopherols, e.g. vitamin E
• A61K 31/4015 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• A61K 31/421 - 1,3-Oxazoles, e.g. pemoline, trimethadione
• A61K 31/428 - Thiazoles condensed with carbocyclic rings
• A61K 31/4535 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
• A61K 31/4709 - Non-condensed quinolines 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 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/50 - PyridazinesHydrogenated pyridazines
• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• 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 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61K 31/5415 - 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 sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• 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 31/565 - 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 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
• A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• 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
• C07C 43/23 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
• C07C 47/575 - Compounds having —CHO groups bound to carbon atoms of six-membered aromatic rings containing ether groups, groups, groups, or groups
• C07C 235/06 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• C07C 237/06 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• C07C 275/24 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
• C07C 279/12 - Derivatives of guanidine, i.e. compounds containing the group the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by nitrogen atoms not being part of nitro or nitroso groups
• C07D 303/18 - Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals

Abstract

The present specification relates to a compound as a UBR-box domain ligand. The present specification provides a low-molecular weight compound that binds to a UBR-box domain. In addition, the present specification provides a composition for inhibiting binding of a UBR-box domain substrate, a pharmaceutical composition for treating UBR-related diseases, and use thereof, the composition comprising a ligand compound that binds to the a UBR-box domain.

IPC Classes  ?

• C07C 233/64 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
• C07C 233/33 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
• A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• A61P 35/00 - Antineoplastic agents
• A61P 13/00 - Drugs for disorders of the urinary system

Abstract

This specification relates to a compound as a UBR box domain ligand. The present specification provides a small molecule compound that binds to a UBR box domain. In addition, the present specification provides a composition for inhibiting UBR box domain substrate binding, comprising a ligand compound binding to a UBR box domain; a pharmaceutical composition for treating UBR-related diseases; and uses thereof.

IPC Classes  ?

• C07C 311/49 - Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups having nitrogen atoms of sulfonamide groups further bound to another hetero atom to nitrogen atoms
• C07D 209/30 - IndolesHydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
• A61K 31/18 - Sulfonamides
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• A61P 13/02 - Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
• A61P 1/18 - Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes

Abstract

The present invention relates to a novel AUTOTAC chimeric compound in which a new p62 ligand and a target-binding ligand are connected by a linker, a stereoisomer, hydrate, solvate or prodrug thereof, and a pharmaceutical or food composition for the prevention or treatment of diseases by degrading the target protein including the same as an active ingredient. They can target specific proteins to adjust their concentrations, and can also deliver drugs and other small molecule compounds to lysosomes. The AUTOTAC chimeric compound according to the present invention can be usefully used as a pharmaceutical composition for the prevention, amelioration or treatment of various diseases by selectively eliminating specific proteins.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A23L 33/10 - Modifying nutritive qualities of foodsDietetic productsPreparation or treatment thereof using additives
• A61K 31/05 - Phenols
• A61K 31/12 - Ketones
• A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
• A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
• A61K 31/277 - NitrilesIsonitriles having a ring, e.g. verapamil
• A61K 31/336 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having three-membered rings, e.g. oxirane, fumagillin
• A61K 31/355 - Tocopherols, e.g. vitamin E
• A61K 31/4015 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• A61K 31/421 - 1,3-Oxazoles, e.g. pemoline, trimethadione
• A61K 31/428 - Thiazoles condensed with carbocyclic rings
• A61K 31/4535 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
• A61K 31/4709 - Non-condensed quinolines 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 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/50 - PyridazinesHydrogenated pyridazines
• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• 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 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61K 31/5415 - 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 sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• 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 31/565 - 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 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
• A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• 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
• C07C 43/23 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
• C07C 47/575 - Compounds having —CHO groups bound to carbon atoms of six-membered aromatic rings containing ether groups, groups, groups, or groups
• C07C 217/58 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
• C07C 235/06 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• C07C 237/06 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• C07C 275/24 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
• C07C 279/12 - Derivatives of guanidine, i.e. compounds containing the group the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by nitrogen atoms not being part of nitro or nitroso groups
• C07D 303/18 - Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals

Abstract

The present invention relates to a novel p62 ligand compound, a stereoisomer, hydrate, solvate or prodrug thereof, and a pharmaceutical or food composition for preventing or treating misfolded protein diseases comprising the same as an active ingredient. The p62 ligand compound according to the present invention can be usefully used as a pharmaceutical composition for the prevention, amelioration or treatment of various proteinopathies by activating selective autophagy in cells and thus selectively eliminating in vivo proteins, organelles and aggregates.

IPC Classes  ?

• C07C 217/58 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
• C07C 279/12 - Derivatives of guanidine, i.e. compounds containing the group the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by nitrogen atoms not being part of nitro or nitroso groups
• C07C 275/24 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
• C07C 235/06 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• C07C 237/06 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• 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

Abstract

The present invention pertains to a pharmaceutical or food composition for preventing or treating proteopathies, the pharmaceutical or food composition containing a novel p62 ligand compound represented by chemical formula 1, or a stereoisomer, a solvate, a hydrate, or a prodrug thereof as an active ingredient. A p62 ligand compound according to the present invention activates selective autophagy in cells to selectively remove proteins, organelles, and coagulations in the body, and thus can be advantageously used as a pharmaceutical composition for preventing, ameliorating, or treating various proteinopathies.

IPC Classes  ?

• C07D 213/30 - Oxygen atoms
• C07D 239/34 - One oxygen atom
• C07D 213/38 - Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
• C07D 307/52 - Radicals substituted by nitrogen atoms not forming part of a nitro radical
• C07D 333/20 - Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
• A61K 31/4412 - Non-condensed pyridinesHydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
• A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• A61K 31/341 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics