ES2890226T3 - Compuestos de benzodiazolio como inhibidores del ENaC - Google Patents
Compuestos de benzodiazolio como inhibidores del ENaC Download PDFInfo
- Publication number
- ES2890226T3 ES2890226T3 ES17807900T ES17807900T ES2890226T3 ES 2890226 T3 ES2890226 T3 ES 2890226T3 ES 17807900 T ES17807900 T ES 17807900T ES 17807900 T ES17807900 T ES 17807900T ES 2890226 T3 ES2890226 T3 ES 2890226T3
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- Prior art keywords
- methyl
- ethyl
- amino
- pyrrolo
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- Prior art date
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- 239000003112 inhibitor Substances 0.000 title description 3
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical class C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 349
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 181
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 65
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 61
- 125000005843 halogen group Chemical group 0.000 claims abstract description 49
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 49
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 47
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 46
- 125000001424 substituent group Chemical group 0.000 claims abstract description 29
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 125000003118 aryl group Chemical group 0.000 claims abstract description 22
- 150000001450 anions Chemical class 0.000 claims abstract description 17
- 125000001475 halogen functional group Chemical group 0.000 claims abstract description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 14
- 125000004452 carbocyclyl group Chemical group 0.000 claims abstract description 13
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 10
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 9
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 9
- 125000004450 alkenylene group Chemical group 0.000 claims abstract description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 9
- 125000004419 alkynylene group Chemical group 0.000 claims abstract description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 6
- 230000000155 isotopic effect Effects 0.000 claims abstract description 5
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- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 3
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- 238000006243 chemical reaction Methods 0.000 claims description 166
- -1 3-{[(tert-butoxy)carbonyl]amino}propyl Chemical group 0.000 claims description 101
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 98
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- 238000011282 treatment Methods 0.000 claims description 23
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
- 230000007062 hydrolysis Effects 0.000 claims description 17
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- 238000002360 preparation method Methods 0.000 claims description 16
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- 239000013543 active substance Substances 0.000 claims description 14
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 14
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
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- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 8
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- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 7
- 150000001768 cations Chemical class 0.000 claims description 7
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- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 claims description 6
- LMOINURANNBYCM-UHFFFAOYSA-N metaproterenol Chemical compound CC(C)NCC(O)C1=CC(O)=CC(O)=C1 LMOINURANNBYCM-UHFFFAOYSA-N 0.000 claims description 6
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- 125000000134 2-(methylsulfanyl)ethyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])[*] 0.000 claims description 3
- ZKLPARSLTMPFCP-OAQYLSRUSA-N 2-[2-[4-[(R)-(4-chlorophenyl)-phenylmethyl]-1-piperazinyl]ethoxy]acetic acid Chemical compound C1CN(CCOCC(=O)O)CCN1[C@@H](C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-OAQYLSRUSA-N 0.000 claims description 3
- MBUVEWMHONZEQD-UHFFFAOYSA-N Azeptin Chemical compound C1CN(C)CCCC1N1C(=O)C2=CC=CC=C2C(CC=2C=CC(Cl)=CC=2)=N1 MBUVEWMHONZEQD-UHFFFAOYSA-N 0.000 claims description 3
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 claims description 3
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 3
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 claims description 3
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 claims description 3
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- GXDALQBWZGODGZ-UHFFFAOYSA-N astemizole Chemical compound C1=CC(OC)=CC=C1CCN1CCC(NC=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CC1 GXDALQBWZGODGZ-UHFFFAOYSA-N 0.000 claims description 3
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- VVDCRJGWILREQH-UHFFFAOYSA-N tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(B2OC(C)(C)C(C)(C)O2)=C1 VVDCRJGWILREQH-UHFFFAOYSA-N 0.000 description 1
- IOKGWQZQCNXXLD-UHFFFAOYSA-N tert-butyl n-(3-bromopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCBr IOKGWQZQCNXXLD-UHFFFAOYSA-N 0.000 description 1
- ORVXNBKOWDNMGB-UHFFFAOYSA-N tert-butyl n-(3-iodopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCI ORVXNBKOWDNMGB-UHFFFAOYSA-N 0.000 description 1
- YBOWCGQWAVIWQT-LURJTMIESA-N tert-butyl n-[(3s)-3,4-diamino-4-oxobutyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC[C@H](N)C(N)=O YBOWCGQWAVIWQT-LURJTMIESA-N 0.000 description 1
- CUPBLDPRUBNAIE-UHFFFAOYSA-N tert-butyl n-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOCCOCCOCCN CUPBLDPRUBNAIE-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- ULYLMHUHFUQKOE-UHFFFAOYSA-N trimethyl(prop-2-ynyl)silane Chemical compound C[Si](C)(C)CC#C ULYLMHUHFUQKOE-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- 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
-
- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
-
- 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
- A61P11/12—Mucolytics
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
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| GBGB1619694.1A GB201619694D0 (en) | 2016-11-22 | 2016-11-22 | Compounds |
| PCT/GB2017/053499 WO2018096325A1 (en) | 2016-11-22 | 2017-11-22 | Benzodiazolium compounds as enac inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2890226T3 true ES2890226T3 (es) | 2022-01-18 |
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|---|---|---|---|
| ES17807900T Active ES2890226T3 (es) | 2016-11-22 | 2017-11-22 | Compuestos de benzodiazolio como inhibidores del ENaC |
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| CN (1) | CN110214141B (enExample) |
| AU (1) | AU2017364308B2 (enExample) |
| CA (1) | CA3043132A1 (enExample) |
| DK (1) | DK3544981T3 (enExample) |
| EA (1) | EA039607B1 (enExample) |
| ES (1) | ES2890226T3 (enExample) |
| GB (1) | GB201619694D0 (enExample) |
| HU (1) | HUE055692T2 (enExample) |
| IL (1) | IL266745B (enExample) |
| MA (1) | MA46878A (enExample) |
| MX (1) | MX389496B (enExample) |
| PL (1) | PL3544981T3 (enExample) |
| PT (1) | PT3544981T (enExample) |
| TW (1) | TWI756305B (enExample) |
| WO (1) | WO2018096325A1 (enExample) |
| ZA (1) | ZA201902710B (enExample) |
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| GB201610854D0 (en) | 2016-06-21 | 2016-08-03 | Entpr Therapeutics Ltd | Compounds |
| GB201619694D0 (en) | 2016-11-22 | 2017-01-04 | Entpr Therapeutics Ltd | Compounds |
| GB201717051D0 (en) | 2017-10-17 | 2017-11-29 | Enterprise Therapeutics Ltd | Compounds |
| GB201801355D0 (en) | 2018-01-26 | 2018-03-14 | Enterprise Therapeutics Ltd | Compounds |
| GB201808093D0 (en) | 2018-05-18 | 2018-07-04 | Enterprise Therapeutics Ltd | Compounds |
| CN114269721B (zh) | 2019-06-12 | 2024-12-20 | Tmem16A有限公司 | 用于治疗呼吸系统疾病的化合物 |
| GB201908453D0 (en) | 2019-06-12 | 2019-07-24 | Enterprise Therapeutics Ltd | Compounds for treating respiratory disease |
| GB201910608D0 (en) * | 2019-07-24 | 2019-09-04 | Enterprise Therapeutics Ltd | Compounds |
| AR124316A1 (es) | 2020-12-11 | 2023-03-15 | Tmem16A Ltd | Compuestos para tratar una enfermedad respiratoria |
| CN118852442A (zh) | 2023-04-26 | 2024-10-29 | 上海麦科思生物医药有限公司 | 抗ptk7抗体及其用途 |
| GB202406247D0 (en) | 2024-05-03 | 2024-06-19 | Enterprise Therapeutics Ltd | Compounds and pharmaceutical compositions |
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| US6858615B2 (en) | 2002-02-19 | 2005-02-22 | Parion Sciences, Inc. | Phenyl guanidine sodium channel blockers |
| US6903105B2 (en) | 2003-02-19 | 2005-06-07 | Parion Sciences, Inc. | Sodium channel blockers |
| EP1670474A4 (en) | 2003-08-18 | 2008-08-06 | Parion Sciences Inc | BLOCKERS OF THE PYRAZINOYL-GUANIDINE SODIUM CHANNEL |
| CA2534568A1 (en) | 2003-08-18 | 2005-03-24 | Parion Sciences, Inc. | Aliphatic pyrazinoylguanidine sodium channel blockers |
| CA2534682C (en) | 2003-08-18 | 2013-02-26 | Parion Sciences, Inc. | Capped pyrazinoylguanidine sodium channel blockers |
| US20050090505A1 (en) | 2003-08-18 | 2005-04-28 | Johnson Michael R. | Methods of reducing risk of infection from pathogens |
| US7745442B2 (en) | 2003-08-20 | 2010-06-29 | Parion Sciences, Inc. | Methods of reducing risk of infection from pathogens |
| WO2005042497A2 (en) * | 2003-10-28 | 2005-05-12 | Vertex Pharmaceuticals, Incorporated | Benzimidazoles useful as modulators of ion channels |
| US7399766B2 (en) | 2004-08-18 | 2008-07-15 | Parion Sciences, Inc. | Soluble amide & ester pyrazinoylguanidine sodium channel blockers |
| AU2006223070B2 (en) * | 2005-03-14 | 2012-02-09 | High Point Pharmaceuticals, Llc | Benzazole derivatives, compositions, and methods of use as B-secretase inhibitors |
| US7807834B2 (en) | 2005-08-03 | 2010-10-05 | Parion Sciences, Inc. | Capped pyrazinoylguanidine sodium channel blockers |
| GB0526244D0 (en) | 2005-12-22 | 2006-02-01 | Novartis Ag | Organic compounds |
| GB0526240D0 (en) | 2005-12-22 | 2006-02-01 | Novartis Ag | Organic compounds |
| WO2008124491A1 (en) | 2007-04-03 | 2008-10-16 | Parion Sciences, Inc. | Pyrazinoylguanidine compounds for use taste modulators |
| ES2361595T3 (es) | 2007-05-07 | 2011-06-20 | Novartis Ag | Compuestos orgánicos. |
| WO2009019506A1 (en) | 2007-08-03 | 2009-02-12 | Astrazeneca Ab | Heterocyclyc sulfonamides having edg-1 antagonistic activity |
| KR101578235B1 (ko) | 2007-12-10 | 2015-12-16 | 노파르티스 아게 | 유기 화합물 |
| TWI432198B (zh) | 2008-02-26 | 2014-04-01 | Parion Sciences Inc | 多芳香族鈉通道阻斷劑 |
| CN102015662A (zh) | 2008-05-13 | 2011-04-13 | 诺瓦提斯公司 | 3,5-二氨基-6-氯-吡嗪-2-甲酸衍生物和它们作为上皮钠通道阻断剂用于治疗气道疾病的用途 |
| AU2009256645A1 (en) | 2008-06-10 | 2009-12-17 | Novartis Ag | Pyrazine derivatives as epithelial sodium channel blockers |
| WO2011028740A1 (en) | 2009-09-03 | 2011-03-10 | Glaxo Group Limited | ENaC BLOCKERS |
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| US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
| TW201204353A (en) * | 2010-06-08 | 2012-02-01 | Vertex Pharma | Formulations of (R)-1-(2,2-difluorobenzo[D][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide |
| US8372845B2 (en) | 2010-09-17 | 2013-02-12 | Novartis Ag | Pyrazine derivatives as enac blockers |
| AR086745A1 (es) | 2011-06-27 | 2014-01-22 | Parion Sciences Inc | 3,5-diamino-6-cloro-n-(n-(4-(4-(2-(hexil(2,3,4,5,6-pentahidroxihexil)amino)etoxi)fenil)butil)carbamimidoil)pirazina-2-carboxamida |
| KR102006612B1 (ko) | 2011-11-02 | 2019-08-02 | 베링거 인겔하임 인터내셔날 게엠베하 | 헤테로사이클릭 화합물, 상기 화합물을 포함하는 약제, 이의 용도, 및 이의 제조 방법 |
| US8859559B2 (en) | 2011-12-20 | 2014-10-14 | Boehringer Ingelheim International Gmbh | Substituted pyrazines and their use in the treatment of disease |
| LT2855435T (lt) | 2012-05-29 | 2018-09-10 | Parion Sciences, Inc. | Amino amidai, panašūs į dendrimerus, su natrio kanalų blokavimo aktyvumu, skirti gydyti sausų akių sindromą ir kitas gleivinių ligas |
| EP2897940B1 (en) | 2012-09-24 | 2019-05-01 | Boehringer Ingelheim International GmbH | Heterocyclic compounds, medicaments containing said compounds, use thereof and processes for the preparation thereof |
| WO2014099673A1 (en) | 2012-12-17 | 2014-06-26 | Parion Sciences, Inc. | 3,5-diamino-6-chloro-n-(n-(4-phenylbutyl)carbamimidoyl) pyrazine-2- carboxamide compounds |
| US9593084B2 (en) | 2012-12-17 | 2017-03-14 | Parion Sciences, Inc. | Chloro-pyrazine carboxamide derivatives with epithelial sodium channel blocking activity |
| ES2674665T3 (es) | 2012-12-17 | 2018-07-03 | Parion Sciences, Inc. | Compuestos de 3,5-diamino-6-cloro-N-(N-(4-fenilbutilo)carbamimidoilo)-pirazina-2-carboxamida |
| WO2014177469A1 (en) | 2013-04-30 | 2014-11-06 | Boehringer Ingelheim International Gmbh,M | Diaminopyrazine compounds, medicaments containing said compounds, use thereof and processes for the preparation thereof |
| AU2014284268A1 (en) | 2013-07-02 | 2016-01-07 | The California Institute For Biomedical Research | Compounds for treatment of cystic fibrosis |
| JP6449870B2 (ja) | 2013-07-08 | 2019-01-09 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 肺および気道の疾患を処置するための上皮性ナトリウムチャネルの阻害剤としてのアミロライド型化合物 |
| EP3022196B1 (en) | 2013-07-15 | 2017-09-06 | Boehringer Ingelheim International GmbH | Novel benzimidazolium compounds |
| JP6461133B2 (ja) | 2013-07-15 | 2019-01-30 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規４置換及び５置換ベンゾイミダゾリウム化合物 |
| JP6461948B2 (ja) | 2013-07-15 | 2019-01-30 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規５−置換ベンゾイミダゾリウム化合物 |
| WO2015018754A1 (en) | 2013-08-08 | 2015-02-12 | Boehringer Ingelheim International Gmbh | Novel pyrazine amide compounds |
| US20180002312A1 (en) | 2015-01-12 | 2018-01-04 | Boehringer Ingelheim International Gmbh | Tetra- and pentasubstituted benzimidazolium compounds useful in the treatment of respiratory diseases |
| WO2016113167A1 (en) * | 2015-01-12 | 2016-07-21 | Boehringer Ingelheim International Gmbh | Substituted benzimidazolium compounds useful in the treatment of respiratory diseases |
| WO2016113170A1 (en) | 2015-01-12 | 2016-07-21 | Boehringer Ingelheim International Gmbh | Substituted benzimidazolium compounds useful in the treatment of respiratory diseases |
| EP3245200B1 (en) | 2015-01-12 | 2021-03-10 | Boehringer Ingelheim International GmbH | 2-(pyrazin-2-ylcarbonylaminomethyl)benzimidazolium compounds as epithelial sodium channel inhibitors |
| EP3298022B1 (en) | 2015-08-20 | 2019-06-05 | Boehringer Ingelheim International GmbH | Novel annelated phenoxyacetamides |
| EP3337483B1 (en) | 2015-08-20 | 2019-10-09 | Boehringer Ingelheim International GmbH | Novel annelated benzamides |
| GB201610854D0 (en) * | 2016-06-21 | 2016-08-03 | Entpr Therapeutics Ltd | Compounds |
| GB201619694D0 (en) * | 2016-11-22 | 2017-01-04 | Entpr Therapeutics Ltd | Compounds |
-
2016
- 2016-11-22 GB GBGB1619694.1A patent/GB201619694D0/en not_active Ceased
-
2017
- 2017-11-22 JP JP2019527365A patent/JP6980014B2/ja active Active
- 2017-11-22 MX MX2019005934A patent/MX389496B/es unknown
- 2017-11-22 EA EA201991253A patent/EA039607B1/ru unknown
- 2017-11-22 EP EP17807900.0A patent/EP3544981B1/en active Active
- 2017-11-22 DK DK17807900.0T patent/DK3544981T3/da active
- 2017-11-22 CA CA3043132A patent/CA3043132A1/en active Pending
- 2017-11-22 ES ES17807900T patent/ES2890226T3/es active Active
- 2017-11-22 PT PT178079000T patent/PT3544981T/pt unknown
- 2017-11-22 WO PCT/GB2017/053499 patent/WO2018096325A1/en not_active Ceased
- 2017-11-22 MA MA046878A patent/MA46878A/fr unknown
- 2017-11-22 CN CN201780084165.3A patent/CN110214141B/zh active Active
- 2017-11-22 TW TW106140573A patent/TWI756305B/zh active
- 2017-11-22 AU AU2017364308A patent/AU2017364308B2/en active Active
- 2017-11-22 US US16/462,794 patent/US10941149B2/en active Active
- 2017-11-22 HU HUE17807900A patent/HUE055692T2/hu unknown
- 2017-11-22 PL PL17807900T patent/PL3544981T3/pl unknown
- 2017-11-22 KR KR1020197016141A patent/KR102517273B1/ko active Active
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2019
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- 2019-05-20 IL IL266745A patent/IL266745B/en unknown
-
2020
- 2020-11-24 US US17/103,559 patent/US11739094B2/en active Active
-
2023
- 2023-06-30 US US18/345,840 patent/US12371436B2/en active Active
-
2025
- 2025-06-11 US US19/235,076 patent/US20250304590A1/en active Pending
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