PE20231987A1 - Inhibidores de molecula pequena de la funcion de slc6a19 de mamifero - Google Patents
Inhibidores de molecula pequena de la funcion de slc6a19 de mamiferoInfo
- Publication number
- PE20231987A1 PE20231987A1 PE2023002500A PE2023002500A PE20231987A1 PE 20231987 A1 PE20231987 A1 PE 20231987A1 PE 2023002500 A PE2023002500 A PE 2023002500A PE 2023002500 A PE2023002500 A PE 2023002500A PE 20231987 A1 PE20231987 A1 PE 20231987A1
- Authority
- PE
- Peru
- Prior art keywords
- alkyl
- slc6a19
- absent
- cycloalkyl
- mammal
- Prior art date
Links
- 102000005025 SLC6A19 Human genes 0.000 title abstract 2
- 108060007758 SLC6A19 Proteins 0.000 title abstract 2
- 241000124008 Mammalia Species 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 150000003384 small molecules Chemical class 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 abstract 4
- 150000001875 compounds Chemical class 0.000 abstract 3
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 2
- -1 1-cyclopropyl-3-[(3-phenyl-1,2-oxazol-5-yl)methyl]-1-[(3R)-1-(pyridazin-3-yl)piperidin-3-yl]urea Chemical compound 0.000 abstract 1
- DJVYMPDONIEPDV-QGZVFWFLSA-N CC(C(Cl)=C1)=CC(CNC(N(C2CC2)[C@H](CCC2)CN2C2=CC=CN=N2)=O)=C1F Chemical compound CC(C(Cl)=C1)=CC(CNC(N(C2CC2)[C@H](CCC2)CN2C2=CC=CN=N2)=O)=C1F DJVYMPDONIEPDV-QGZVFWFLSA-N 0.000 abstract 1
- 102100033495 Glycine dehydrogenase (decarboxylating), mitochondrial Human genes 0.000 abstract 1
- 208000035544 Nonketotic hyperglycinaemia Diseases 0.000 abstract 1
- 108010069013 Phenylalanine Hydroxylase Proteins 0.000 abstract 1
- 102100038223 Phenylalanine-4-hydroxylase Human genes 0.000 abstract 1
- 201000011252 Phenylketonuria Diseases 0.000 abstract 1
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 abstract 1
- 125000000304 alkynyl group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- 230000009395 genetic defect Effects 0.000 abstract 1
- 201000011205 glycine encephalopathy Diseases 0.000 abstract 1
- 150000004820 halides Chemical class 0.000 abstract 1
- 125000001188 haloalkyl group Chemical group 0.000 abstract 1
- 125000001072 heteroaryl group Chemical group 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract 1
- 201000011296 tyrosinemia Diseases 0.000 abstract 1
Classifications
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—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
- C07D211/36—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 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
- C07D211/56—Nitrogen atoms
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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- C07D211/06—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
- C07D211/36—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 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
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- 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
- C07D401/06—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
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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Abstract
Esta referido a un compuesto de Formula I, en donde n es 0, 1, o 2; L1 esta ausente o es alquilo, hidroxialquilo, cicloalquilo, heteroaril-CH2-; L2 esta ausente o es -CH2-; L3 esta ausente o es -C(O)-; X1 y X2 son H, alquilo, haloalquilo, cicloalquilo, alquil-cicloalquilo, heterociclilo; Y1 es arilo, heteroarilo; Y2 es alquilo, alquenilo, alquinilo, alcoxi, entre otros; Y3, Y4, Y5 son H, OH, haluro, alquilo, entre otros. Entre los compuestos preferidos tenemos los siguientes: 3-[(4-cloro-2-fluoro-5-metilfenil)metil]-1-ciclopropil-1-[(3R)-1-(piridazin3-il)piperidin-3-il]urea; 1-ciclopropil-3-[(3-fenil-1,2-oxazol-5- il)metil]-1-[(3R)-1-(piridazin-3- il)piperidin-3-il]urea; entre otros. Estos compuestos modulan el transporte de SLC6A19 y se emplean para tratar o prevenir una enfermedad o trastorno asociado con un defecto genetico en la fenilalanina hidroxilasa como fenilcetonuria, hiperfenilalaninemia, tirosinemia, hiperglicinemia no cetosica, entre otras.
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US202163159271P | 2021-03-10 | 2021-03-10 | |
US202163226551P | 2021-07-28 | 2021-07-28 | |
US202163234487P | 2021-08-18 | 2021-08-18 | |
US202163292815P | 2021-12-22 | 2021-12-22 | |
US202263308790P | 2022-02-10 | 2022-02-10 | |
PCT/US2022/019513 WO2022192370A1 (en) | 2021-03-10 | 2022-03-09 | Small molecule inhibitors of mammalian slc6a19 function |
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WO2024058926A1 (en) * | 2022-09-14 | 2024-03-21 | Jnana Therapeutics Inc. | Dosing regimen for treating pku with a piperidine inhibitor of slc6a19 function |
WO2024112830A1 (en) * | 2022-11-22 | 2024-05-30 | Maze Therapeutics, Inc. | Inhibitors of solute carrier family 6a member 19 (slc6a19) and methods of use thereof |
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WO2019046303A1 (en) * | 2017-08-28 | 2019-03-07 | The Trustees Of Columbia University In The City Of New York | METHOD FOR PREDICTING PATIENT RESPONSE TO SLC MODULATOR PROCESSING |
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CL2023002581A1 (es) | 2024-02-16 |
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MX2023010467A (es) | 2023-11-22 |
US20240208923A1 (en) | 2024-06-27 |
WO2022192370A1 (en) | 2022-09-15 |
DOP2023000178A (es) | 2023-12-29 |
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