AR127277A1 - COMPOSITIONS AND METHODS TO MODULATE THE FORMATION OF INCLUSION AND STRESS GRANULES - Google Patents
COMPOSITIONS AND METHODS TO MODULATE THE FORMATION OF INCLUSION AND STRESS GRANULESInfo
- Publication number
- AR127277A1 AR127277A1 ARP220102714A ARP220102714A AR127277A1 AR 127277 A1 AR127277 A1 AR 127277A1 AR P220102714 A ARP220102714 A AR P220102714A AR P220102714 A ARP220102714 A AR P220102714A AR 127277 A1 AR127277 A1 AR 127277A1
- Authority
- AR
- Argentina
- Prior art keywords
- alkyl
- xre
- haloalkyl
- orb
- optionally substituted
- Prior art date
Links
- 230000015572 biosynthetic process Effects 0.000 title abstract 2
- 239000008187 granular material Substances 0.000 title abstract 2
- 239000000203 mixture Substances 0.000 title abstract 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 10
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 abstract 7
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 5
- 125000005843 halogen group Chemical group 0.000 abstract 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 5
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 abstract 3
- 150000001875 compounds Chemical class 0.000 abstract 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract 2
- 102100039788 GTPase NRas Human genes 0.000 abstract 2
- 101000744505 Homo sapiens GTPase NRas Proteins 0.000 abstract 2
- 125000003118 aryl group Chemical group 0.000 abstract 2
- 125000004429 atom Chemical group 0.000 abstract 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 abstract 2
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 2
- 125000001072 heteroaryl group Chemical group 0.000 abstract 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 2
- 208000023178 Musculoskeletal disease Diseases 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 208000036142 Viral infection Diseases 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 125000005842 heteroatom Chemical group 0.000 abstract 1
- 230000004770 neurodegeneration Effects 0.000 abstract 1
- 208000015122 neurodegenerative disease Diseases 0.000 abstract 1
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 1
- 125000004043 oxo group Chemical group O=* 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- 230000009385 viral infection Effects 0.000 abstract 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—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
- C07D401/02—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
- C07D401/04—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—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 C07D415/00
- C07D417/02—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 C07D415/00 containing two hetero rings
- C07D417/04—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 C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—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 C07D415/00
- C07D417/14—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 C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/18—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
En el presente documento, se describen compuestos, composiciones y métodos para modular la formación de inclusión y gránulos de estrés en células relacionadas al comienzo de enfermedades neurodegenerativas, enfermedades musculoesqueléticas, cáncer, enfermedades oftalmológicas e infecciones virales. Reivindicación 1: Un compuesto de la fórmula (1) o una sal farmacéuticamente aceptable de este, caracterizado porque: X es un compuesto de fórmula (2); Y es C=O o S(O)₂; G es N o CR³; R² es H, alquilo C₁-C₆, C₁-C₆ haloalquilo o halo; R³ es H, alquilo C₁-C₆, C₁-C₆ haloalquilo o halo; donde al menos uno de R² y R³ es un sustituyente que no es H; R⁶ es H o alquilo C₁-C₆ opcionalmente sustituido con 1 a 4 R⁸; R⁷ es alquilo C₁-C₆, cicloalquilo C₃-C₇, -N(R¹⁰)-alquilo C₁-C₆ o -N(R¹⁰)-cicloalquilo C₃-C₇, cada uno de los cuales está opcionalmente sustituido con 1 a 4 R⁸; o R⁶ y R⁷, tomados junto con los átomos a los que están unidos, forman un anillo heterocicloalquilo de 4 a 7 miembros, opcionalmente sustituido con 1 a 5 R⁸, donde dicho anillo heterocicloalquilo no incluye heteroátomos en el anillo distintos del N al que R⁶ está unido y en el grupo Y al que está unido R⁷, o incluye otro átomo de N sustituido con R¹⁰; cada R⁸ es independientemente halo, alquilo C₁-C₆, -ORB, -C(O)ORB o haloalquilo C₁-C₆; cada R⁹ es independientemente alquilo C₁-C₆, alquenilo C₂-C₆, alquinilo C₂-C₆, heteroalquilo C₁-C₆, haloalquilo C₁-C₆, halo, ciano, nitro, azido, -ORB, -C(O)RD, -C(O)NRARC, -C(O)ORB, -NRARC, -NRAC(O)RD, -S(O)ˣRE, -OS(O)ˣRE, -C(O)NRAS(O)ˣRE, -NRAS(O)ˣRE, -S(O)ˣNRA o -L-Z; L es un enlace, -O-, -NRA- o -(CH₂)₁₋₃-; Z es un cicloalquilo C₃-C₇, heterocicloalquilo, un arilo o un heteroarilo, donde cada Z está opcionalmente sustituido por 1 a 5 R¹¹; cada R¹⁰ es independientemente H, alquilo C₁-C₆ o haloalquilo C₁-C₆; cada R¹¹ es independientemente alquilo C₁-C₆, alquenilo C₂-C₆, alquinilo C₂-C₆, heteroalquilo C₁-C₆, haloalquilo C₁-C₆, halo, ciano, nitro, azido, oxo, cicloalquilo, -ORB, -C(O)RD, -C(O)NRARC, -C(O)ORB, -NRARC, -NRAC(O)RD, -S(O)ˣRE, -OS(O)ˣRE, -C(O)NRAS(O)ˣRE, -NRAS(O)ˣRE o -S(O)ˣNRA; cada RA, RB, RC, RD o RE es independientemente H, alquilo C₁-C₆, heteroalquilo C₁-C₆, haloalquilo C₁-C₆, cicloalquilo, heterocicloalquilo, arilo o heteroarilo, cada uno de los cuales está opcionalmente sustituido con 1 a 4 R⁸; o RA y RC, junto con los átomos a los que está unido cada uno, forman un anillo heterocicloalquilo opcionalmente sustituido con 1 a 4 R⁸; y x es 0, 1 o 2.Disclosed herein are compounds, compositions, and methods for modulating inclusion and stress granule formation in cells related to the onset of neurodegenerative diseases, musculoskeletal diseases, cancer, ophthalmic diseases, and viral infections. Claim 1: A compound of formula (1) or a pharmaceutically acceptable salt thereof, characterized in that: X is a compound of formula (2); And it is C=O or S(O)₂; G is N or CR³; R² is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl or halo; R³ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl or halo; where at least one of R² and R³ is a substituent other than H; R⁶ is H or C₁-C₆ alkyl optionally substituted with 1 to 4 R⁸; R⁷ is C₁-C₆ alkyl, C₃-C₇ cycloalkyl, -N(R¹⁰)-C₁-C₆ alkyl or -N(R¹⁰)-C₃-C₇ cycloalkyl, each of which is optionally substituted with 1 to 4 R⁸; or R⁶ and R⁷, taken together with the atoms to which they are attached, form a 4- to 7-membered heterocycloalkyl ring, optionally substituted with 1 to 5 R⁸, wherein said heterocycloalkyl ring does not include ring heteroatoms other than the N to which R⁶ is attached and in the group Y to which R⁷ is attached, or includes another N atom substituted with R¹⁰; each R⁸ is independently halo, C₁-C₆ alkyl, -ORB, -C(O)ORB or C₁-C₆ haloalkyl; each R⁹ is independently C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ heteroalkyl, C₁-C₆ haloalkyl, halo, cyano, nitro, azido, -ORB, -C(O)RD, -C( O)NRARC, -C(O)ORB, -NRARC, -NRAC(O)RD, -S(O)ˣRE, -OS(O)ˣRE, -C(O)NRAS(O)ˣRE, -NRAS(O) )ˣRE, -S(O)ˣNRA or -L-Z; L is a bond, -O-, -NRA- or -(CH₂)₁₋₃-; Z is a C₃-C₇ cycloalkyl, heterocycloalkyl, an aryl or a heteroaryl, where each Z is optionally substituted by 1 to 5 R¹¹; each R¹⁰ is independently H, C₁-C₆ alkyl or C₁-C₆ haloalkyl; each R¹¹ is independently C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₁-C₆ heteroalkyl, C₁-C₆ haloalkyl, halo, cyano, nitro, azido, oxo, cycloalkyl, -ORB, -C(O)RD , -C(O)NRARC, -C(O)ORB, -NRARC, -NRAC(O)RD, -S(O)ˣRE, -OS(O)ˣRE, -C(O)NRAS(O)ˣRE, -NRAS(O)ˣRE or -S(O)ˣNRA; each RA, RB, RC, RD or RE is independently H, C₁-C₆ alkyl, C₁-C₆ heteroalkyl, C₁-C₆ haloalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each of which is optionally substituted with 1 to 4 R⁸ ; or RA and RC, together with the atoms to which each is attached, form a heterocycloalkyl ring optionally substituted with 1 to 4 R⁸; and x is 0, 1 or 2.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202163252844P | 2021-10-06 | 2021-10-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR127277A1 true AR127277A1 (en) | 2024-01-03 |
Family
ID=85803751
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP220102714A AR127277A1 (en) | 2021-10-06 | 2022-10-06 | COMPOSITIONS AND METHODS TO MODULATE THE FORMATION OF INCLUSION AND STRESS GRANULES |
Country Status (3)
| Country | Link |
|---|---|
| AR (1) | AR127277A1 (en) |
| TW (1) | TW202330472A (en) |
| WO (1) | WO2023060173A1 (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1697308B1 (en) * | 2003-12-19 | 2014-03-19 | Merck Sharp & Dohme Corp. | Phenylamide and pyridylamide beta-secretase inhibitors for the treatment of alzheimer's disease |
| WO2020117877A1 (en) * | 2018-12-04 | 2020-06-11 | Aquinnah Pharmaceuticals, Inc. | Compounds, compositions and methods of use |
-
2022
- 2022-10-06 AR ARP220102714A patent/AR127277A1/en unknown
- 2022-10-06 WO PCT/US2022/077670 patent/WO2023060173A1/en active Application Filing
- 2022-10-06 TW TW111138014A patent/TW202330472A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TW202330472A (en) | 2023-08-01 |
| WO2023060173A1 (en) | 2023-04-13 |
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