PE20231380A1 - MACROCYCLE CONTAINING A 1,3,4-OXADIAZOLE RING FOR USE AS MODULATORS OF THE REGULATOR OF TRANSMEMBRANE CONDUCTANCE IN CYSTIC FIBROSIS - Google Patents
MACROCYCLE CONTAINING A 1,3,4-OXADIAZOLE RING FOR USE AS MODULATORS OF THE REGULATOR OF TRANSMEMBRANE CONDUCTANCE IN CYSTIC FIBROSISInfo
- Publication number
- PE20231380A1 PE20231380A1 PE2023001653A PE2023001653A PE20231380A1 PE 20231380 A1 PE20231380 A1 PE 20231380A1 PE 2023001653 A PE2023001653 A PE 2023001653A PE 2023001653 A PE2023001653 A PE 2023001653A PE 20231380 A1 PE20231380 A1 PE 20231380A1
- Authority
- PE
- Peru
- Prior art keywords
- modulators
- alkyl
- cystic fibrosis
- hydroxy
- transmembrane conductance
- Prior art date
Links
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical group C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 title abstract 2
- 201000003883 Cystic fibrosis Diseases 0.000 title abstract 2
- 150000002678 macrocyclic compounds Chemical class 0.000 title 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
- 102000012605 Cystic Fibrosis Transmembrane Conductance Regulator Human genes 0.000 abstract 2
- 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- 229910052736 halogen Inorganic materials 0.000 abstract 2
- 150000002367 halogens Chemical class 0.000 abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract 2
- 239000001257 hydrogen Substances 0.000 abstract 2
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 abstract 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract 1
- -1 -ORX2 and -N(RX2)2 Chemical group 0.000 abstract 1
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 abstract 1
- 125000000041 C6-C10 aryl group Chemical group 0.000 abstract 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—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
- A61K31/403—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 carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—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
- A61K31/439—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 the ring forming part of a bridged ring system, e.g. quinuclidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—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
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/529—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim forming part of bridged ring systems
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—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 three hetero rings
- C07D498/18—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains four or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Abstract
Referido a un compuesto de Formula I, y derivados deuterados y sales farmaceuticamente aceptables de estos, en donde: X se selecciona de -N(RX1)- ; RX1 se selecciona de H, alquilo C1-C6, sustituido opcionalmente con 1-3 grupos que se seleccionan independientemente de hidroxi, oxo, -ORX2 y -N(RX2)2, y cicloalquilo C3-C8; cada RX2 se selecciona independientemente de H y alquilo C1-C6; cada Y se selecciona independientemente de -C(RY)2-, -O-, -CO-, entre otros; cada R1 se selecciona independientemente de halogeno, fluoroalquilo C1-C6, alquilo C1-C6 (sustituido opcionalmente con un grupo que se selecciona de hidroxi, entre otros; n se selecciona de 4, 5, 6, 7 y 8; y m se selecciona de 0, 1, 2 y 3; el anillo C se selecciona de arilo C6 - C10 y heteroarilo de 5 a 10 miembros; R Z1 se selecciona de hidrogeno, -CN; R Z2 se selecciona de hidrogeno, halogeno, hidroxi, NH 2 , NH(CO)(alquilo C 1 -C 6 ) ; cada R Z3 se selecciona independientemente de hidroxi, alcoxi C 1 -C 6 , alquilo C 1 -C 6 y arilo C 6 -C 10. Estos compuestos son macrociclicos con anillo de 1,3,4-oxadiazol, y son moduladores del regulador de la conductancia transmembrana de la fibrosis quistica (CFTR). Tambien se refiere a composiciones farmaceuticas que contienen al menos uno de dichos moduladores, procesos de fabricacion de tales moduladores y metodos de tratamiento de la fibrosis quistica que usan tales moduladores.Referring to a compound of Formula I, and deuterated derivatives and pharmaceutically acceptable salts thereof, wherein: X is selected from -N(RX1)-; RX1 is selected from H, C1-C6 alkyl, optionally substituted with 1-3 groups independently selected from hydroxy, oxo, -ORX2 and -N(RX2)2, and C3-C8 cycloalkyl; each RX2 is independently selected from H and C1-C6 alkyl; each Y is selected independently of -C(RY)2-, -O-, -CO-, among others; each R1 is independently selected from halogen, C1-C6 fluoroalkyl, C1-C6 alkyl (optionally substituted with a group selected from hydroxy, among others; n is selected from 4, 5, 6, 7 and 8; and m is selected from 0, 1, 2 and 3; ring C is selected from C6-C10 aryl and 5 to 10 membered heteroaryl; R Z1 is selected from hydrogen, -CN; R Z2 is selected from hydrogen, halogen, hydroxy, NH 2, NH(CO)(C 1 -C 6 alkyl); each R Z3 is independently selected from hydroxy, C 1 -C 6 alkoxy, C 1 -C 6 alkyl and C 6 -C 10 aryl. These compounds are macrocyclic with ring 1,3,4-oxadiazole, and are modulators of the cystic fibrosis transmembrane conductance regulator (CFTR). It also refers to pharmaceutical compositions containing at least one of said modulators, manufacturing processes of such modulators and methods of treatment of cystic fibrosis using such modulators.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063115552P | 2020-11-18 | 2020-11-18 | |
| PCT/US2021/072475 WO2022109573A1 (en) | 2020-11-18 | 2021-11-17 | Macrocycles containing a 1,3,4-oxadiazole ring for use as modulators of cystic fibrosis transmembrane conductance regulator |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20231380A1 true PE20231380A1 (en) | 2023-09-07 |
Family
ID=79602287
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2023001653A PE20231380A1 (en) | 2020-11-18 | 2021-11-17 | MACROCYCLE CONTAINING A 1,3,4-OXADIAZOLE RING FOR USE AS MODULATORS OF THE REGULATOR OF TRANSMEMBRANE CONDUCTANCE IN CYSTIC FIBROSIS |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP4247817A1 (en) |
| JP (1) | JP2023549547A (en) |
| KR (1) | KR20230123522A (en) |
| CN (1) | CN116670140A (en) |
| AR (1) | AR124090A1 (en) |
| AU (1) | AU2021383176A1 (en) |
| CA (1) | CA3201793A1 (en) |
| CL (1) | CL2023001398A1 (en) |
| CO (1) | CO2023007896A2 (en) |
| CR (1) | CR20230260A (en) |
| DO (1) | DOP2023000099A (en) |
| EC (1) | ECSP23045439A (en) |
| IL (1) | IL302873A (en) |
| MX (1) | MX2023005721A (en) |
| PE (1) | PE20231380A1 (en) |
| WO (1) | WO2022109573A1 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023150237A1 (en) * | 2022-02-03 | 2023-08-10 | Vertex Pharmaceuticals Incorporated | Methods of treatment for cystic fibrosis |
| WO2023154291A1 (en) * | 2022-02-08 | 2023-08-17 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| WO2023224931A1 (en) * | 2022-05-16 | 2023-11-23 | Vertex Pharmaceuticals Incorporated | Methods of treatment for cystic fibrosis |
| WO2023224924A1 (en) | 2022-05-16 | 2023-11-23 | Vertex Pharmaceuticals Incorporated | Solid forms of a macrocyclic compounds as cftr modulators and their preparation |
| WO2024054851A1 (en) * | 2022-09-07 | 2024-03-14 | Sionna Therapeutics | Macrocyclic compounds, compositions and methods of using thereof |
| WO2024056779A1 (en) | 2022-09-15 | 2024-03-21 | Idorsia Pharmaceuticals Ltd | Crystalline form of (3s,7s,10r,13r)-13-benzyl-20-fluoro-7-isobutyl-n-(2-(3-methoxy-1,2,4-oxadiazol-5-yl)ethyl)-6,9-dimethyl-1,5,8,11-tetraoxo-10-(2,2,2-trifluoroethyl)-1,2,3,4,5,6,7,8,9,10,11,12,13,14-tetradecahydro-[1]oxa[4,7,10,14]tetraazacycloheptadecino[16,17-f]quinoline-3-carboxamide |
| WO2024056791A1 (en) * | 2022-09-15 | 2024-03-21 | Idorsia Pharmaceuticals Ltd | Combination of macrocyclic cftr modulators with cftr correctors and / or cftr potentiators |
| WO2024056798A1 (en) | 2022-09-15 | 2024-03-21 | Idorsia Pharmaceuticals Ltd | Macrocyclic cftr modulators |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013038386A1 (en) * | 2011-09-16 | 2013-03-21 | Novartis Ag | Heterocyclic compounds for the treatment of cystic fibrosis |
| MD3752510T2 (en) * | 2018-02-15 | 2023-06-30 | Vertex Pharma | Macrocycles as modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions thereof, their use in the treatment of cycstic fibrosis, and process for making them |
-
2021
- 2021-11-17 AU AU2021383176A patent/AU2021383176A1/en active Pending
- 2021-11-17 CR CR20230260A patent/CR20230260A/en unknown
- 2021-11-17 EP EP21843853.9A patent/EP4247817A1/en active Pending
- 2021-11-17 JP JP2023529022A patent/JP2023549547A/en active Pending
- 2021-11-17 WO PCT/US2021/072475 patent/WO2022109573A1/en active Application Filing
- 2021-11-17 PE PE2023001653A patent/PE20231380A1/en unknown
- 2021-11-17 KR KR1020237020002A patent/KR20230123522A/en unknown
- 2021-11-17 CN CN202180090910.1A patent/CN116670140A/en active Pending
- 2021-11-17 IL IL302873A patent/IL302873A/en unknown
- 2021-11-17 MX MX2023005721A patent/MX2023005721A/en unknown
- 2021-11-17 CA CA3201793A patent/CA3201793A1/en active Pending
- 2021-11-18 AR ARP210103184A patent/AR124090A1/en unknown
-
2023
- 2023-05-16 CL CL2023001398A patent/CL2023001398A1/en unknown
- 2023-05-17 DO DO2023000099A patent/DOP2023000099A/en unknown
- 2023-06-16 EC ECSENADI202345439A patent/ECSP23045439A/en unknown
- 2023-06-16 CO CONC2023/0007896A patent/CO2023007896A2/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA3201793A1 (en) | 2022-05-27 |
| CN116670140A (en) | 2023-08-29 |
| CL2023001398A1 (en) | 2023-11-24 |
| AU2021383176A1 (en) | 2023-06-22 |
| AR124090A1 (en) | 2023-02-15 |
| CO2023007896A2 (en) | 2023-09-18 |
| ECSP23045439A (en) | 2023-08-31 |
| IL302873A (en) | 2023-07-01 |
| CR20230260A (en) | 2023-10-05 |
| JP2023549547A (en) | 2023-11-27 |
| KR20230123522A (en) | 2023-08-23 |
| WO2022109573A1 (en) | 2022-05-27 |
| DOP2023000099A (en) | 2023-08-15 |
| EP4247817A1 (en) | 2023-09-27 |
| MX2023005721A (en) | 2023-07-25 |
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