ES2983003T3 - Compuestos heterocíclicos y heteroarílicos para el tratamiento de la enfermedad de Huntington - Google Patents
Compuestos heterocíclicos y heteroarílicos para el tratamiento de la enfermedad de Huntington Download PDFInfo
- Publication number
- ES2983003T3 ES2983003T3 ES19736566T ES19736566T ES2983003T3 ES 2983003 T3 ES2983003 T3 ES 2983003T3 ES 19736566 T ES19736566 T ES 19736566T ES 19736566 T ES19736566 T ES 19736566T ES 2983003 T3 ES2983003 T3 ES 2983003T3
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- Prior art keywords
- phenol
- tetramet
- daz
- azolo
- pyr
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- 208000023105 Huntington disease Diseases 0.000 title claims abstract description 75
- 125000001072 heteroaryl group Chemical group 0.000 title abstract description 46
- 125000000623 heterocyclic group Chemical group 0.000 title description 48
- 238000011282 treatment Methods 0.000 title description 22
- 150000001875 compounds Chemical class 0.000 claims abstract description 619
- 238000000034 method Methods 0.000 claims abstract description 57
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 958
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 278
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 70
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 70
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- 150000003839 salts Chemical class 0.000 claims description 41
- 229910052799 carbon Inorganic materials 0.000 claims description 34
- 239000008194 pharmaceutical composition Substances 0.000 claims description 31
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 22
- 239000012453 solvate Substances 0.000 claims description 21
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 13
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 12
- 125000004122 cyclic group Chemical group 0.000 claims description 11
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 10
- 125000004942 pyridazin-6-yl group Chemical group N1=NC=CC=C1* 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 7
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 6
- HQTOGRJJEXEVDY-UHFFFAOYSA-N 2-(3,5-dimethoxy-4-propoxyphenyl)ethanamine;hydrochloride Chemical compound Cl.CCCOC1=C(OC)C=C(CCN)C=C1OC HQTOGRJJEXEVDY-UHFFFAOYSA-N 0.000 claims description 5
- ZXRCAYWYTOIRQS-UHFFFAOYSA-N hydron;phenol;chloride Chemical compound Cl.OC1=CC=CC=C1 ZXRCAYWYTOIRQS-UHFFFAOYSA-N 0.000 claims description 5
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 5
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 4
- CBHTTYDJRXOHHL-UHFFFAOYSA-N 2h-triazolo[4,5-c]pyridazine Chemical compound N1=NC=CC2=C1N=NN2 CBHTTYDJRXOHHL-UHFFFAOYSA-N 0.000 claims description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 3
- LMKPHJYTFHAGHK-UHFFFAOYSA-N cyclodrine Chemical compound C1CCCC1(O)C(C(=O)OCCN(CC)CC)C1=CC=CC=C1 LMKPHJYTFHAGHK-UHFFFAOYSA-N 0.000 claims description 3
- NKDRVWDDKGMPCZ-UHFFFAOYSA-N 4-fluoro-2-(1H-pyrazol-4-yl)-5-[3-(2,2,6,6-tetramethylpiperidin-4-yl)triazolo[4,5-c]pyridazin-6-yl]phenol Chemical compound FC1=CC(=C(C=C1C1=CC2=C(N=N1)N(N=N2)C1CC(NC(C1)(C)C)(C)C)O)C=1C=NNC=1 NKDRVWDDKGMPCZ-UHFFFAOYSA-N 0.000 claims description 2
- DMSDXTCCTHPVTI-UHFFFAOYSA-N C1CN(CCN1)C1=CNC2=C1N=NC(=C2)C1=CC=C(C=2C=NNC=2)C=C1O Chemical compound C1CN(CCN1)C1=CNC2=C1N=NC(=C2)C1=CC=C(C=2C=NNC=2)C=C1O DMSDXTCCTHPVTI-UHFFFAOYSA-N 0.000 claims description 2
- UDHXJZHVNHGCEC-UHFFFAOYSA-N Chlorophacinone Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)C(=O)C1C(=O)C2=CC=CC=C2C1=O UDHXJZHVNHGCEC-UHFFFAOYSA-N 0.000 claims description 2
- BAVYCCNBKZJTQG-UHFFFAOYSA-N FC1=C(C=CC(=C1F)C=1C=NNC=1)C1=CC2=C(N=N1)N(CC2)C1CC(NC(C1)(C)C)(C)C Chemical compound FC1=C(C=CC(=C1F)C=1C=NNC=1)C1=CC2=C(N=N1)N(CC2)C1CC(NC(C1)(C)C)(C)C BAVYCCNBKZJTQG-UHFFFAOYSA-N 0.000 claims description 2
- DHHGMXVHXODILS-UHFFFAOYSA-N N1N=CC(=C1)C=1C=CC(=C(C=1)O)C1=CC2=C(N=N1)C(=CN2)C=1CC(NC(C=1)(C)C)(C)C Chemical compound N1N=CC(=C1)C=1C=CC(=C(C=1)O)C1=CC2=C(N=N1)C(=CN2)C=1CC(NC(C=1)(C)C)(C)C DHHGMXVHXODILS-UHFFFAOYSA-N 0.000 claims description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N monoethyl amine Natural products CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 2
- LEJIWJCKYUOQDZ-UHFFFAOYSA-N 1h-pyrrole;hydrobromide Chemical compound Br.C=1C=CNC=1 LEJIWJCKYUOQDZ-UHFFFAOYSA-N 0.000 claims 2
- NDQVGHCUUVQCTH-UHFFFAOYSA-N 2-[6-(methylamino)-7-(2,2,6,6-tetramethylpiperidin-4-yl)imidazo[4,5-c]pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol Chemical compound C1(NC(CC(C1)N1C2=C(N=C1NC)C=C(C1=CC=C(C=3C=NNC=3)C=C1O)N=N2)(C)C)(C)C NDQVGHCUUVQCTH-UHFFFAOYSA-N 0.000 claims 1
- HODKQVFXRRLNPJ-UHFFFAOYSA-N 5-(1H-pyrazol-4-yl)-2-[5-(2,2,6,6-tetramethyl-1,3-dihydropyridin-4-yl)pyrrolo[2,3-b]pyrazin-2-yl]phenol Chemical compound N1C(CC(=CC1(C)C)N1C2=NC=C(N=C2C=C1)C1=CC=C(C2=CNN=C2)C=C1O)(C)C HODKQVFXRRLNPJ-UHFFFAOYSA-N 0.000 claims 1
- IETUBBFAMCEKDY-UHFFFAOYSA-N C(C)N1N=CC(=C1)C=1C=CC(=C(C=1)O)C1=CC2=C(N=N1)N(N=N2)C1CC(NC(C1)(C)C)(C)C Chemical compound C(C)N1N=CC(=C1)C=1C=CC(=C(C=1)O)C1=CC2=C(N=N1)N(N=N2)C1CC(NC(C1)(C)C)(C)C IETUBBFAMCEKDY-UHFFFAOYSA-N 0.000 claims 1
- KHTWIGWWVCHDGM-UHFFFAOYSA-N C(C)NC1=NC2=C(N=NC(=C2)C2=C(C=C(C=C2)C=2C=NNC=2)O)N1C1CC(NC(C1)(C)C)(C)C Chemical compound C(C)NC1=NC2=C(N=NC(=C2)C2=C(C=C(C=C2)C=2C=NNC=2)O)N1C1CC(NC(C1)(C)C)(C)C KHTWIGWWVCHDGM-UHFFFAOYSA-N 0.000 claims 1
- SJJFQXDPRPTDDW-UHFFFAOYSA-N CC1(NC(CC(C1)N1N=NC2=C1N=NC(=C2)C1=C(C=C(C=C1)C1=CC=C(C=C1)O)O)(C)C)C Chemical compound CC1(NC(CC(C1)N1N=NC2=C1N=NC(=C2)C1=C(C=C(C=C1)C1=CC=C(C=C1)O)O)(C)C)C SJJFQXDPRPTDDW-UHFFFAOYSA-N 0.000 claims 1
- QTPNFWZMBNTULA-UHFFFAOYSA-N CN1N=C(C=C1)C=1C=CC(=C(C=1)O)C1=CC2=C(N=N1)N(N=N2)C1CC(NC(C1)(C)C)(C)C Chemical compound CN1N=C(C=C1)C=1C=CC(=C(C=1)O)C1=CC2=C(N=N1)N(N=N2)C1CC(NC(C1)(C)C)(C)C QTPNFWZMBNTULA-UHFFFAOYSA-N 0.000 claims 1
- XXVGQLCBMSURJO-UHFFFAOYSA-N COC1=NC2=C(N=NC(=C2)C2=C(C=C(C=C2)C=2C=NNC=2)O)N1C1CC(NC(C1)(C)C)(C)C Chemical compound COC1=NC2=C(N=NC(=C2)C2=C(C=C(C=C2)C=2C=NNC=2)O)N1C1CC(NC(C1)(C)C)(C)C XXVGQLCBMSURJO-UHFFFAOYSA-N 0.000 claims 1
- VEXZGXHMUGYJMC-DYCDLGHISA-N Deuterium chloride Chemical compound [2H]Cl VEXZGXHMUGYJMC-DYCDLGHISA-N 0.000 claims 1
- GDAHALNLMUDALK-UHFFFAOYSA-N FC1=CC(=C(C=C1C1=CC=C(C=C1)O)O)C1=CC2=C(N=N1)N(N=N2)C1CC(NC(C1)(C)C)(C)C Chemical compound FC1=CC(=C(C=C1C1=CC=C(C=C1)O)O)C1=CC2=C(N=N1)N(N=N2)C1CC(NC(C1)(C)C)(C)C GDAHALNLMUDALK-UHFFFAOYSA-N 0.000 claims 1
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- XUIIKFGFIJCVMT-LBPRGKRZSA-N L-thyroxine Chemical compound IC1=CC(C[C@H]([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-LBPRGKRZSA-N 0.000 claims 1
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- 125000002618 bicyclic heterocycle group Chemical group 0.000 abstract description 3
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Classifications
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- 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
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- 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
- C07D491/02—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 two hetero rings
- C07D491/04—Ortho-condensed systems
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- 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
- C07D491/02—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 two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
-
- 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
- C07D491/02—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 two hetero rings
- C07D491/08—Bridged systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
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- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
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| KR20200033249A (ko) | 2017-06-05 | 2020-03-27 | 피티씨 테라퓨틱스, 인크. | 헌팅턴병 치료 화합물 |
| MX2019015578A (es) | 2017-06-28 | 2020-07-28 | Ptc Therapeutics Inc | Metodos para tratar la enfermedad de huntington. |
| MX2019015580A (es) | 2017-06-28 | 2020-07-28 | Ptc Therapeutics Inc | Metodos para tratar la enfermedad de huntington. |
| CN111194215B (zh) | 2017-08-04 | 2024-03-01 | 斯基霍克疗法公司 | 用于调节剪接的方法和组合物 |
| JP7569688B2 (ja) | 2017-12-22 | 2024-10-18 | ハイバーセル,インコーポレイテッド | ホスファチジルイノシトールリン酸キナーゼ阻害剤としてのアミノピリジン誘導体 |
| US12103926B2 (en) | 2018-03-27 | 2024-10-01 | Ptc Therapeutics, Inc. | Compounds for treating huntington's disease |
| AU2019294478B2 (en) | 2018-06-27 | 2023-03-23 | Ptc Therapeutics, Inc. | Heterocyclic and heteroaryl compounds for treating Huntington's disease |
| WO2020005877A1 (en) | 2018-06-27 | 2020-01-02 | Ptc Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
| US11685746B2 (en) | 2018-06-27 | 2023-06-27 | Ptc Therapeutics, Inc. | Heteroaryl compounds for treating Huntington's disease |
| WO2020163405A1 (en) | 2019-02-05 | 2020-08-13 | Skyhawk Therapeutics, Inc. | Methods and compositions for modulating splicing |
| JP7603595B2 (ja) | 2019-02-06 | 2024-12-20 | スカイホーク・セラピューティクス・インコーポレーテッド | スプライシングを調節するための方法および組成物 |
| CN113840602A (zh) * | 2019-03-15 | 2021-12-24 | 斯基霍克疗法公司 | 用于校正异常剪接的组合物和方法 |
| AU2020277027A1 (en) * | 2019-05-13 | 2021-12-09 | Ptc Therapeutics, Inc. | Compounds for treating huntington's disease |
| TW202112767A (zh) | 2019-06-17 | 2021-04-01 | 美商佩特拉製藥公司 | 作為磷脂酸肌醇磷酸激酶抑制劑之胺基吡啶衍生物 |
| US11129829B2 (en) | 2019-06-17 | 2021-09-28 | Skyhawk Therapeutics, Inc. | Methods for modulating splicing |
| MX2022005254A (es) * | 2019-11-01 | 2022-06-29 | Novartis Ag | El uso de un modulador de empalme para un tratamiento que retrasa la progresion de la enfermedad de huntington. |
| EP4110459A1 (en) * | 2020-02-28 | 2023-01-04 | Remix Therapeutics Inc. | Heterocyclic amides and their use for modulating splicing |
| US20230234942A1 (en) * | 2020-04-09 | 2023-07-27 | Ptc Therapeutics, Inc. | Compounds for treating huntington's disease |
| MX2022013856A (es) | 2020-05-13 | 2023-04-05 | Chdi Foundation Inc | Moduladores htt para tratar la enfermedad de huntington. |
| AU2021299515A1 (en) | 2020-07-02 | 2023-02-02 | Remix Therapeutics Inc. | 2-(indazol-5-yl)-6-(piperidin-4-yl)-1,7-naphthyridine derivatives and related compounds as modulators for splicing nucleic acids and for the treatment of proliferative diseases |
| JP2023532331A (ja) | 2020-07-02 | 2023-07-27 | リミックス セラピューティクス インコーポレイテッド | 核酸をスプライシングするため及び増殖性疾患を処置するための修飾因子としての5-[5-(ピペリジン-4-イル)チエノ[3,2-c]ピラゾール-2-イル]インダゾール誘導体及び関連する化合物並びにスプライシングを調節するための化合物及び方法 |
| WO2022060943A1 (en) * | 2020-09-16 | 2022-03-24 | Skyhawk Therapeutics, Inc. | Compositions for modulating splicing |
| WO2022060944A1 (en) * | 2020-09-16 | 2022-03-24 | Skyhawk Therapeutics, Inc. | Compositions for modulating splicing |
| WO2022060951A1 (en) * | 2020-09-16 | 2022-03-24 | Skyhawk Therapeutics, Inc. | Compositions for modulating splicing |
| AU2021380758A1 (en) * | 2020-11-12 | 2023-06-15 | Ptc Therapeutics Inc. | Novel rna transcript |
| SI4243782T1 (sl) * | 2020-11-13 | 2025-11-28 | Ptc Therapeutics, Inc. | Tableta za uporabo v zdravljenju huntingtonove bolezni in postopek njene izdelave |
| EP4308572B1 (en) * | 2021-03-17 | 2025-04-23 | F. Hoffmann-La Roche AG | New thienopyrimidinone derivatives |
| TW202304446A (zh) | 2021-03-29 | 2023-02-01 | 瑞士商諾華公司 | 剪接調節子用於減慢杭丁頓氏舞蹈症進展的治療之用途 |
| CA3227287A1 (en) | 2021-07-30 | 2023-02-02 | Suresh Babu | Heteroaryl compounds for treating huntington's disease |
| US20250101034A1 (en) * | 2021-11-04 | 2025-03-27 | Skyhawk Therapeutics, Inc. | Compositions useful for modulating splicing |
| JP2024540477A (ja) | 2021-11-17 | 2024-10-31 | シーエイチディーアイ ファウンデーション,インコーポレーテッド | ハンチントン病を治療するためのhttモジュレータとしてのn-(2h-インダゾール-5-イル)ピラジン-2-カルボキサミド誘導体及び類似化合物 |
| AU2023270000A1 (en) * | 2022-05-10 | 2024-11-28 | Foghorn Therapeutics Inc. | Pyrazine derivatives and uses thereof |
| EP4539841A2 (en) * | 2022-06-15 | 2025-04-23 | PTC Therapeutics, Inc. | Heterocyclic and heteroaryl compounds for treating huntington's disease |
| TW202432551A (zh) | 2022-10-26 | 2024-08-16 | 日商安斯泰來製藥股份有限公司 | 稠環嗒嗪衍生物 |
| KR20250136883A (ko) | 2023-01-24 | 2025-09-16 | 다이이찌 산쿄 가부시키가이샤 | 치환 벤젠 화합물 |
| WO2024233306A1 (en) * | 2023-05-09 | 2024-11-14 | Ptc Therapeutics, Inc. | Crystalline forms of 2-[3-(2,2,6,6-tetramethylpiperidin-4-yl)-3h-[1,2,3]triazolo[4,5-c]pyridazin-6-yl]-5-(2h-1,2,3-triazol-2-yl)phenol |
| AR132817A1 (es) * | 2023-06-02 | 2025-07-30 | Merck Sharp & Dohme Llc | Heterociclos bicíclicos 5,6 insaturados útiles como inhibidores de la proteína receptora 3 similar a nod |
| WO2024249389A2 (en) * | 2023-06-02 | 2024-12-05 | Merck Sharp & Dohme Llc | 5,6 saturated bicyclic heterocyles useful as inhibitors of nod-like receptor protein 3 |
| WO2025040014A1 (zh) * | 2023-08-18 | 2025-02-27 | 英矽智能科技知识产权有限公司 | 并环化合物及其制备方法和用途 |
Family Cites Families (194)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL297170A (enExample) | 1963-04-04 | 1900-01-01 | ||
| US3558618A (en) | 1968-04-01 | 1971-01-26 | Dow Chemical Co | Novel 4h-pyrazino(1,2-a)pyrimidine-4-ones |
| GB1383409A (en) | 1972-09-09 | 1974-02-12 | Pfizer Ltd | Derivatives of 2-amino- and 4-amino-quinazoline and pharmaceutical compositions containing them |
| US4122274A (en) | 1977-05-25 | 1978-10-24 | Bristol-Myers Company | 3-Tetrazolo-5,6,7,8-substituted-pyrido[1,2-a]pyrimidin-4-ones |
| JPS56150091A (en) | 1980-03-28 | 1981-11-20 | Janssen Pharmaceutica Nv | 3-(1-piperidinylalkyl)-4h-pyrido(1,2-a)pyrimidine- 4-one derivative and its manufacture |
| US4342870A (en) | 1980-03-28 | 1982-08-03 | Janssen Pharmaceutica N.V. | Novel 3-(1-piperidinylalkyl)-4H-pyrido[1,2-a]pyrimidin-4-one derivatives |
| FR2567518B1 (fr) | 1984-07-11 | 1987-11-13 | Sanofi Sa | Nouveaux composes a noyau heterocyclique azote, leur preparation et les medicaments qui en contiennent |
| US5089633A (en) | 1987-04-28 | 1992-02-18 | Georgia Tech Research Corporation | Substituted isocoumarins |
| US5726182A (en) | 1990-05-02 | 1998-03-10 | Abbott Laboratories | Quinolizinone type compounds |
| AU4231293A (en) | 1992-05-13 | 1993-12-13 | E.I. Du Pont De Nemours And Company | Substituted pyrido(1,2-A)pyrimidinone derivatives as fungicides |
| AU6786594A (en) | 1993-05-11 | 1994-12-12 | University Of North Carolina At Chapel Hill, The | Antisense oligonucleotides which combat aberrant splicing and methods of using the same |
| EP0871628A1 (en) | 1995-06-06 | 1998-10-21 | Abbott Laboratories | Quinolizinone type compounds |
| US5916916A (en) | 1996-10-10 | 1999-06-29 | Eli Lilly And Company | 1-aryloxy-2-arylnaphthyl compounds, intermediates, compositions, and methods |
| US5869500A (en) | 1996-12-13 | 1999-02-09 | Hoffmann-La Roche Inc. | Pyridone compounds useful in treating Alzheimer's disease |
| CA2269561C (en) | 1998-04-22 | 2007-06-05 | Dainippon Ink And Chemicals, Inc. | Naphthalene derivative and liquid crystal composition comprising the same |
| HK1040076A1 (zh) | 1998-09-21 | 2002-05-24 | 希雷生物化学有限公司 | 作为整联蛋白抑制剂的喹嗪酮 |
| US6172216B1 (en) | 1998-10-07 | 2001-01-09 | Isis Pharmaceuticals Inc. | Antisense modulation of BCL-X expression |
| US6214986B1 (en) | 1998-10-07 | 2001-04-10 | Isis Pharmaceuticals, Inc. | Antisense modulation of bcl-x expression |
| US6210892B1 (en) | 1998-10-07 | 2001-04-03 | Isis Pharmaceuticals, Inc. | Alteration of cellular behavior by antisense modulation of mRNA processing |
| CN1414951A (zh) | 1999-10-28 | 2003-04-30 | 基本治疗公司 | 药剂排出泵抑制药 |
| CN1263743C (zh) | 2000-01-24 | 2006-07-12 | 基纳西亚股份有限公司 | 用于治疗的吗啉代基取代的化合物 |
| WO2002038738A2 (en) | 2000-11-09 | 2002-05-16 | Cold Spring Harbor Laboratory | Chimeric molecules to modulate gene expression |
| US6774134B2 (en) | 2000-12-20 | 2004-08-10 | Bristol-Myers Squibb Company | Heterocyclic substituted 2-methyl-benzimidazole antiviral agents |
| AP2003002825A0 (en) | 2000-12-21 | 2003-09-30 | Vertex Pharma | Pyrazole compounds useful as protein kinase inhibitors |
| GB0100624D0 (en) | 2001-01-10 | 2001-02-21 | Vernalis Res Ltd | Chemical compounds VII |
| US20050009843A1 (en) | 2001-04-26 | 2005-01-13 | Kiyoshi Nakayama | Medicine for inhibiting drug elimination pump |
| AU2002364536B2 (en) | 2001-12-07 | 2008-10-23 | Vertex Pharmaceuticals, Inc. | Pyrimidine-based compounds useful as GSK-3 inhibitors |
| GB0205281D0 (en) | 2002-03-06 | 2002-04-17 | Novartis Ag | Organic compounds |
| CA2493458A1 (en) | 2002-07-24 | 2004-01-29 | Ptc Therapeutics, Inc. | Ureido substituted benzoic acid compounds, their use for nonsense suppression and the treatment of diseases caused by such mutations |
| WO2004019002A2 (en) | 2002-08-23 | 2004-03-04 | The Board Of Trustees Of The Leland Stanford Junior University | Fluorescent glycosides and methods for their use |
| DE60326894D1 (de) | 2002-09-30 | 2009-05-07 | Neurosearch As | 1,4-Diazabicycloalkanderivate, deren Herstellung und Verwendung |
| US20070078144A1 (en) | 2003-01-29 | 2007-04-05 | Stockwell Brent R | Agents for treating neurodegenerative diseases |
| AU2004249730A1 (en) | 2003-06-20 | 2004-12-29 | Novartis Vaccines And Diagnostics, Inc. | Pyridino(1,2-A)pyrimidin-4-one compounds as anticancer agents |
| GB0315494D0 (en) | 2003-07-02 | 2003-08-06 | Biofocus Plc | Compounds which bind to the active site of protein kinase enzymes |
| US7511145B2 (en) | 2003-08-01 | 2009-03-31 | Genelabs Technologies, Inc. | Bicyclic heteroaryl derivatives |
| US7160888B2 (en) | 2003-08-22 | 2007-01-09 | Warner Lambert Company Llc | [1,8]naphthyridin-2-ones and related compounds for the treatment of schizophrenia |
| US20050074801A1 (en) | 2003-09-09 | 2005-04-07 | Monia Brett P. | Chimeric oligomeric compounds comprising alternating regions of northern and southern conformational geometry |
| US20050137203A1 (en) | 2003-12-22 | 2005-06-23 | Jianguo Ji | 3-quinuclidinyl amino-substituted biaryl derivatives |
| US7309699B2 (en) | 2003-12-22 | 2007-12-18 | Abbott Laboratories | 3-Quinuclidinyl amino-substituted biaryl derivatives |
| US7655657B2 (en) | 2003-12-22 | 2010-02-02 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
| US20050245531A1 (en) | 2003-12-22 | 2005-11-03 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
| NZ551468A (en) | 2003-12-24 | 2010-05-28 | Biota Scient Management | Polycyclic agents for the treatment of respiratory syncytial virus infections |
| SE0400184D0 (sv) | 2004-01-30 | 2004-01-30 | Fyrkloevern Scandinavia Ab | New therapeutical use |
| TW200536830A (en) | 2004-02-06 | 2005-11-16 | Chugai Pharmaceutical Co Ltd | 1-(2H)-isoquinolone derivative |
| WO2005099710A1 (en) | 2004-04-08 | 2005-10-27 | Neurogen Corporation | Substituted cinnolin-4-ylamines |
| ES2292130T3 (es) | 2004-05-04 | 2008-03-01 | Warner-Lambert Company Llc | Pirido(2,3-d)pirimidin-7-onas pirrolil-sustituidas y derivados de las mismas como agentes terapeuticos. |
| EP1846397A1 (en) | 2005-01-21 | 2007-10-24 | Janssen Pharmaceutica N.V. | Novel heterocyclic benzoy[c]chromene derivatives useful as modulators of the estrogen receptors |
| US7879992B2 (en) | 2005-01-31 | 2011-02-01 | Isis Pharmaceuticals, Inc. | Modification of MyD88 splicing using modified oligonucleotides |
| GB0501999D0 (en) | 2005-02-01 | 2005-03-09 | Sentinel Oncology Ltd | Pharmaceutical compounds |
| JP2006219453A (ja) | 2005-02-14 | 2006-08-24 | Tokyo Univ Of Pharmacy & Life Science | キノリン環を母核とする金属識別型二波長性蛍光分子 |
| US7563601B1 (en) | 2005-06-01 | 2009-07-21 | City Of Hope | Artificial riboswitch for controlling pre-mRNA splicing |
| WO2006138418A2 (en) | 2005-06-14 | 2006-12-28 | President And Fellows Of Harvard College | Improvement of cognitive performance with sirtuin activators |
| EP2233470B1 (en) | 2005-07-04 | 2011-12-07 | High Point Pharmaceuticals, LLC | Histamine H3 receptor antagonists |
| US7473784B2 (en) | 2005-08-01 | 2009-01-06 | Bristol-Myers Squibb Company | Benzothiazole and azabenzothiazole compounds useful as kinase inhibitors |
| WO2007047913A2 (en) | 2005-10-20 | 2007-04-26 | Isis Pharmaceuticals, Inc | Compositions and methods for modulation of lmna expression |
| JP2009515523A (ja) | 2005-11-10 | 2009-04-16 | サンタリス ファーマ アー/エス | Tnfスーパーファミリー受容体に対するスプライス切替オリゴマーならびに疾病治療における該オリゴマーの使用 |
| EP1963323B1 (en) | 2005-12-06 | 2010-07-14 | Neurosearch A/S | Novel diazabicyclic aryl derivatives and their medical use |
| JP2009520700A (ja) | 2005-12-21 | 2009-05-28 | ペインセプター ファーマ コーポレーション | 依存性イオンチャネルを調節するための組成物および方法 |
| EP2161038B1 (en) | 2006-01-26 | 2013-12-25 | Isis Pharmaceuticals, Inc. | Compositions and their uses directed to Huntingtin |
| AU2007211082B2 (en) | 2006-01-27 | 2012-09-27 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and compositions for the use in modulation of microRNAs |
| AR059339A1 (es) | 2006-02-09 | 2008-03-26 | Chugai Pharmaceutical Co Ltd | Derivados de la cumarina para trastornos proliferativos de celulas, composicion farmaceutica y agente terapeutico que los contiene |
| US8110681B2 (en) | 2006-03-17 | 2012-02-07 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Compounds for the treatment of spinal muscular atrophy and other uses |
| AU2007229492B2 (en) | 2006-03-28 | 2011-11-03 | High Point Pharmaceuticals, Llc | Benzothiazoles having histamine H3 receptor activity |
| WO2007130383A2 (en) | 2006-04-28 | 2007-11-15 | Northwestern University | Compositions and treatments using pyridazine compounds and secretases |
| US20080247964A1 (en) | 2006-05-08 | 2008-10-09 | Yuelian Xu | Substituted azaspiro derivatives |
| TW200812588A (en) * | 2006-05-15 | 2008-03-16 | Neurogen Corp | CRF1 receptor ligands comprising heteroaryl fused bicycles |
| US7910578B2 (en) | 2006-05-23 | 2011-03-22 | Neurosearch A/S | 8,10-diaza-bicyclo[4.3.1]decane derivatives and their medical use |
| ES2344760T3 (es) | 2006-07-20 | 2010-09-06 | Amgen Inc. | Compuestos de piridona sustituidos y metodo de uso. |
| US8337941B2 (en) | 2006-07-27 | 2012-12-25 | The Trustees Of Columbia University In The City Of New York | Fluorescent substrates for monoamine transporters as optical false neurotransmitters |
| CN101528728B (zh) | 2006-08-03 | 2014-01-01 | 罗塔药品股份有限公司 | 6-1h-咪唑并-喹唑啉和喹啉衍生物,镇痛剂和抗炎剂 |
| WO2008049864A1 (en) | 2006-10-25 | 2008-05-02 | Neurosearch A/S | Oxadiazole and thiadiazole compounds and their use as nicotinic acetylcholine receptor modulators |
| US8314119B2 (en) | 2006-11-06 | 2012-11-20 | Abbvie Inc. | Azaadamantane derivatives and methods of use |
| EP2269992A1 (en) | 2006-12-22 | 2011-01-05 | Avexa Limited | Bicyclic pyrimidinones for the treatment of viral infections |
| US20080171792A1 (en) | 2006-12-28 | 2008-07-17 | Jobdevairakkam Christopher New | Use of highly concentrated formulations of 4-phenylbutyrate for treatment of certain disorders |
| FR2914188B1 (fr) | 2007-03-28 | 2012-06-22 | Trophos | Nouvelle composition a base d'oxime de cholest-4-en-3-one |
| EP2014656A3 (en) | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | New heteocyclic h3 antagonists |
| WO2009042907A1 (en) | 2007-09-27 | 2009-04-02 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Isoindoline compounds for the treatment of spinal muscular atrophy and other uses |
| DK2193133T3 (en) | 2007-09-27 | 2015-10-05 | Fundacion Ct Nac Investigaciones Oncologicas Carlos Iii | IMIDAZOLOTHIADIAZOLES USED AS PROTEINKINASE INHIBITORS |
| US8153813B2 (en) | 2007-12-20 | 2012-04-10 | Abbott Laboratories | Benzothiazole and benzooxazole derivatives and methods of use |
| US8993580B2 (en) | 2008-03-14 | 2015-03-31 | Intellikine Llc | Benzothiazole kinase inhibitors and methods of use |
| US20090258907A1 (en) | 2008-04-09 | 2009-10-15 | Abbott Laboratories | Compounds useful as inhibitors of rock kinases |
| WO2009131958A2 (en) | 2008-04-21 | 2009-10-29 | Institute For Oneworld Health | Compounds, compositions and methods comprising triazine derivatives |
| WO2009151546A2 (en) | 2008-05-27 | 2009-12-17 | Ptc Therapeutics, Inc. | Methods for treating spinal muscular atrophy |
| RU2472508C2 (ru) | 2008-06-20 | 2013-01-20 | Роттафарм С.П.А. | Производные 6-1н-имидазохиназолина и хинолина - ингибиторы мао для лечения депрессии |
| EP2138493A1 (en) | 2008-06-26 | 2009-12-30 | Sanofi-Aventis | Substituted pyrimidone derivatives |
| EP2759544A1 (en) | 2008-07-02 | 2014-07-30 | Avexa Limited | Compounds having antiviral properties |
| WO2010019236A1 (en) | 2008-08-13 | 2010-02-18 | Ptc Therapeutics, Inc | Methods for treating spinal muscular atrophy |
| WO2010024903A1 (en) | 2008-08-29 | 2010-03-04 | Yangbo Feng | BENZO[d]OXAZOLES AND BENZO[d]THIAZOLES AS KINASE INHIBITORS |
| AU2009303441A1 (en) | 2008-10-16 | 2010-04-22 | Schering Corporation | Pyrrolidine, piperidine and piperazine derivatives and methods of use thereof |
| GB2465405A (en) | 2008-11-10 | 2010-05-19 | Univ Basel | Triazine, pyrimidine and pyridine analogues and their use in therapy |
| US8283360B2 (en) | 2008-12-19 | 2012-10-09 | Merck Sharp & Dohme Corp. | Bicyclic heterocyclic derivatives and methods of use thereof |
| SG173639A1 (en) | 2009-02-11 | 2011-09-29 | Sunovion Pharmaceuticals Inc | Histamine h3 inverse agonists and antagonists and methods of use thereof |
| FR2945289A1 (fr) | 2009-05-11 | 2010-11-12 | Sanofi Aventis | Derives de 2-cycloamino-5-(pyridin-4-yl)imidazo°2,1-b! °1,3,4!thiadiazole, leur preparation et leur application en therapeutique |
| NZ597511A (en) | 2009-06-19 | 2014-01-31 | Abbvie Inc | Diazahomoadamantane derivatives and methods of use thereof |
| CA2931725C (en) | 2009-09-11 | 2021-10-19 | Ionis Pharmaceuticals, Inc. | Modulation of huntingtin expression |
| WO2011050245A1 (en) | 2009-10-23 | 2011-04-28 | Yangbo Feng | Bicyclic heteroaryls as kinase inhibitors |
| US20150018301A1 (en) | 2009-11-06 | 2015-01-15 | The Johns Hopkins University | LRRK-2-Mediated Neuronal Toxicity |
| US8754220B2 (en) | 2009-11-20 | 2014-06-17 | Merck Sharp & Dohme Corp. | Quinolizidinone carboxamide M1 receptor positive allosteric modulators |
| BR112012017473A2 (pt) | 2010-01-13 | 2019-09-24 | Institut National De La Sante Et De La Rech Medicale Inserm Epst | pirido(1,2-a) pirimidinas, seu uso, bem como composição farmacêutica compreendendo tais compostos |
| US20130059902A1 (en) | 2010-02-08 | 2013-03-07 | Isis Pharmaceuticals, Inc. | Methods and compositions useful in treatment of diseases or conditions related to repeat expansion |
| EP2534262B1 (en) | 2010-02-08 | 2016-12-14 | Ionis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
| DK2534248T3 (en) | 2010-02-08 | 2018-11-19 | Ionis Pharmaceuticals Inc | SELECTIVE REDUCTION OF ALLELVARIANS |
| EP2575866A4 (en) | 2010-05-24 | 2013-10-16 | Presidio Pharmaceuticals Inc | HCV NS5A INHIBITORS |
| AU2011282243B2 (en) | 2010-07-19 | 2016-09-22 | Ionis Pharmaceuticals, Inc. | Modulation of nuclear-retained RNA |
| WO2012019106A2 (en) | 2010-08-06 | 2012-02-09 | Board Of Regents Of The University Of Nebraska | Positive and negative modulators of nmda receptors |
| WO2012075393A2 (en) | 2010-12-02 | 2012-06-07 | President And Fellows Of Harvard College | Activators of proteasomal degradation and uses thereof |
| CN102617548A (zh) | 2011-01-31 | 2012-08-01 | 北京赛林泰医药技术有限公司 | 作为gpr受体激动剂的双环杂芳基化合物及其组合物和应用 |
| WO2012104823A2 (en) | 2011-02-04 | 2012-08-09 | Novartis Ag | Pyridopyrimidinone compounds in the treatment of neurodegenerative diseases |
| EP3467109A1 (en) | 2011-02-08 | 2019-04-10 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| US8703763B2 (en) | 2011-03-02 | 2014-04-22 | Hoffmann-La Roche Inc. | Bridged piperidine derivatives |
| WO2013019938A1 (en) | 2011-08-02 | 2013-02-07 | The Brigham And Women's Hospital, Inc. | Pyridazine derivatives as eaat2 activators |
| US8871756B2 (en) | 2011-08-11 | 2014-10-28 | Hoffmann-La Roche Inc. | Compounds for the treatment and prophylaxis of Respiratory Syncytial Virus disease |
| ES2651514T3 (es) | 2011-08-11 | 2018-01-26 | Ionis Pharmaceuticals, Inc. | Compuestos oligoméricos gapados que comprenden deoxirribonucleósidos modificados en 5 ' -en la brecha y usos de ellos |
| US20130046093A1 (en) | 2011-08-18 | 2013-02-21 | Korea Institute Of Science And Technology | Pharmaceutical compositions for preventing or treating degenerative brain disease and method of screening the same |
| WO2013033223A1 (en) | 2011-08-29 | 2013-03-07 | Isis Pharmaceuticals, Inc. | Methods and compounds useful in conditions related to repeat expansion |
| US9662314B2 (en) | 2011-10-21 | 2017-05-30 | Tufts Medical Center, Inc. | Compounds and methods for the treatment of muscular disease, and related screening methods |
| GB201119538D0 (en) | 2011-11-10 | 2011-12-21 | Viral Ltd | Pharmaceutical compounds |
| BR112014012815A8 (pt) | 2011-11-28 | 2017-06-20 | Novartis Ag | derivados de trifluormetil-oxadiazol e uso dos mesmos no tratamento de doença |
| CA2861609C (en) | 2011-12-30 | 2021-02-16 | Ptc Therapeutics, Inc. | Compounds for treating spinal muscular atrophy |
| CA2862084C (en) | 2012-01-26 | 2021-05-11 | Ptc Therapeutics, Inc. | 1h-isochromen-1-one derivatives and compositions thereof for treating spinal muscular atrophy |
| PL2812004T3 (pl) | 2012-02-10 | 2019-01-31 | Ptc Therapeutics, Inc. | Związki do leczenia rdzeniowego zaniku mięśni |
| EA029155B1 (ru) | 2012-03-01 | 2018-02-28 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Соединения для лечения спинальной мышечной атрофии |
| MX358514B (es) | 2012-03-23 | 2018-08-24 | Ptc Therapeutics Inc | Compuestos para tratar la atrofia muscular espinal. |
| IN2014KN02601A (enExample) * | 2012-04-24 | 2015-05-08 | Vertex Pharma | |
| EP2872493B1 (en) | 2012-07-13 | 2018-11-14 | Indiana University Research and Technology Corporation | 5,6,7-trimethoxy 4-phenyl quinolin-2-one derivatives for treatment of spinal muscular atrophy |
| US8729263B2 (en) | 2012-08-13 | 2014-05-20 | Novartis Ag | 1,4-disubstituted pyridazine analogs there of and methods for treating SMN-deficiency-related conditions |
| US20150275208A1 (en) | 2012-10-12 | 2015-10-01 | Isis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
| EP4144845B1 (en) | 2012-10-12 | 2024-04-24 | Ionis Pharmaceuticals, Inc. | Antisense compounds and uses thereof |
| US9227976B2 (en) * | 2012-10-25 | 2016-01-05 | Usher Iii Initiative, Inc. | Pyrazolopyridazines and methods for treating retinal-degenerative diseases and hearing loss associated with usher syndrome |
| PL2911671T3 (pl) | 2012-10-25 | 2018-11-30 | Usher Iii Initiative, Inc. | Pirazolopirydazyny oraz sposoby leczenia zwyrodnieniowych chorób siatkówki i utraty słuchu związanych z zespołem ushera |
| JP6255711B2 (ja) | 2012-11-01 | 2018-01-10 | 株式会社リコー | エレクトロクロミック化合物、エレクトロクロミック組成物及び表示素子 |
| US9040712B2 (en) | 2013-01-23 | 2015-05-26 | Novartis Ag | Thiadiazole analogs thereof and methods for treating SMN-deficiency-related-conditions |
| US10260069B2 (en) | 2013-02-04 | 2019-04-16 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
| AU2014224975B2 (en) | 2013-03-05 | 2017-09-14 | Merck Patent Gmbh | Triazolo(4,5-d)pyrimidine derivatives for the treatment of diseases such as cancer |
| JP2016518421A (ja) | 2013-05-14 | 2016-06-23 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 呼吸器合胞体ウイルス感染症の処置および予防のためのアザ−オキソ−インドール |
| KR102314290B1 (ko) | 2013-06-25 | 2021-10-21 | 에프. 호프만-라 로슈 아게 | 척수성 근위축증을 치료하기 위한 화합물 |
| MX383686B (es) | 2013-07-31 | 2025-03-14 | Novartis Ag | Derivados de piridazina 1,4-disustituida, y su uso para el tratamiento de afecciones relacionadas con la deficiencia de smn. |
| RU2016109324A (ru) | 2013-08-19 | 2017-09-26 | Ф. Хоффманн-Ля Рош Аг | Способ скрининга |
| WO2015095449A1 (en) | 2013-12-19 | 2015-06-25 | Ptc Therapeutics, Inc. | Methods for modulating the amount rna transcripts |
| WO2015095446A1 (en) | 2013-12-19 | 2015-06-25 | Ptc Therapeutics, Inc. | Methods for modulating the amount of rna transcripts |
| US10195202B2 (en) | 2013-12-19 | 2019-02-05 | Ptc Therapeutics, Inc. | Methods for modulating the amount of RNA transcripts |
| WO2015099196A1 (en) | 2013-12-26 | 2015-07-02 | Takeda Pharmaceutical Company Limited | 4-(piperrazin-1-yl)-pyrrolidin-2-one compounds as monoacylglycerol lipase (magl) inhibitors |
| CN106068325B (zh) | 2014-01-16 | 2021-07-09 | 波涛生命科学有限公司 | 手性设计 |
| JP6473457B2 (ja) | 2014-01-17 | 2019-02-20 | ノバルティス アーゲー | Shp2の活性を阻害するための1−(トリアジン−3−イル/ピリダジン−3−イル)−ピペリジン/ピペラジン誘導体およびその組成物 |
| AR099134A1 (es) | 2014-01-24 | 2016-06-29 | Hoffmann La Roche | Procedimiento para la preparación de n-[(3-aminooxetán-3-il)metil]-2-(1,1-dioxo-3,5-dihidro-1,4-benzotiazepín-4-il)-6-metil-quinazolín-4-amina |
| ES2850999T3 (es) | 2014-03-14 | 2021-09-02 | Raqualia Pharma Inc | Derivados de azaespiro como antagonistas de TRPM8 |
| CA2942975C (en) | 2014-03-19 | 2023-08-29 | Amydis Diagnostics, Inc. | Substituted acrylamide and substituted ethenesulfonamide derivatives and pharmaceutical compositions thereof useful as amyloid targeting agents |
| PE20170128A1 (es) | 2014-05-15 | 2017-03-16 | Ptc Therapeutics Inc | Compuestos para tratar atrofia muscular espinal |
| GB201410693D0 (en) | 2014-06-16 | 2014-07-30 | Univ Southampton | Splicing modulation |
| US20170121197A1 (en) | 2014-06-17 | 2017-05-04 | Novozymes A/S | Biological Phosphorus Removal from Wastewater |
| KR102565544B1 (ko) | 2014-06-25 | 2023-08-10 | 에프. 호프만-라 로슈 아게 | 척수성 근위축증을 치료하기 위한 이미다조[1,2-a]피라진-1일-벤즈아마이드 화합물 |
| CN107207526A (zh) | 2014-12-02 | 2017-09-26 | 拜耳作物科学股份公司 | 作为害虫防治剂的双环化合物 |
| KR102636633B1 (ko) | 2014-12-24 | 2024-02-13 | 유니큐어 아이피 비.브이. | 헌팅턴 유전자 억제를 유도하는 RNAi |
| TWI727939B (zh) | 2015-01-16 | 2021-05-21 | 美商通用醫院公司 | 改善mRNA剪接之化合物 |
| JP6884102B2 (ja) | 2015-02-09 | 2021-06-09 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | がんの治療のための化合物 |
| GB201502567D0 (en) | 2015-02-16 | 2015-04-01 | Sentinel Oncology Ltd | Pharmaceutical compounds |
| CN112608300B (zh) | 2015-03-11 | 2024-04-26 | Fmc公司 | 杂环取代的二环唑杀有害生物剂 |
| GB201506933D0 (en) | 2015-04-23 | 2015-06-10 | Sentinel Oncology Ltd | Pharmaceutical compounds |
| CN107635999B (zh) | 2015-05-20 | 2020-09-25 | 豪夫迈·罗氏有限公司 | 用于治疗脊髓性肌萎缩的化合物 |
| US10668171B2 (en) | 2015-05-30 | 2020-06-02 | Ptc Therapeutics, Inc. | Methods for modulating RNA splicing |
| MA43072A (fr) | 2015-07-22 | 2018-05-30 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
| WO2017023987A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-pyrrolo[3,2-c]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridines and therapeutic uses thereof |
| US9920032B2 (en) | 2015-10-02 | 2018-03-20 | Incyte Corporation | Heterocyclic compounds useful as pim kinase inhibitors |
| WO2017080967A1 (en) | 2015-11-12 | 2017-05-18 | F. Hoffmann-La Roche Ag | Compositions for treating spinal muscular atrophy |
| EP3374362A1 (en) | 2015-11-12 | 2018-09-19 | H. Hoffnabb-La Roche Ag | Compounds for treating amyotrophic lateral sclerosis |
| US10383867B2 (en) | 2015-11-28 | 2019-08-20 | Russell Dahl | Quinoline derivatives and their use for treating endoplasmic reticulum stress-related diseases and disorders |
| KR102488323B1 (ko) * | 2015-12-10 | 2023-01-12 | 피티씨 테라퓨틱스, 인크. | 헌팅턴병 치료 또는 개선을 위한 조성물 |
| JP6872550B2 (ja) | 2015-12-10 | 2021-05-19 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 架橋されたピペリジン誘導体 |
| US10526345B2 (en) | 2016-04-08 | 2020-01-07 | Mankind Pharma Ltd. | Compounds as GPR119 agonists |
| AR108325A1 (es) | 2016-04-27 | 2018-08-08 | Samumed Llc | Isoquinolin-3-il carboxamidas y preparación y uso de las mismas |
| MA45270A (fr) | 2016-05-04 | 2017-11-09 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
| CN109475531B (zh) | 2016-05-31 | 2021-08-17 | 得克萨斯州立大学董事会 | Ptpn11的杂环抑制剂 |
| WO2018022473A1 (en) | 2016-07-25 | 2018-02-01 | Wave Life Sciences Ltd. | Phasing |
| TW202500565A (zh) * | 2016-10-24 | 2025-01-01 | 美商傳達治療有限公司 | Shp2磷酸酶抑制劑及其使用方法 |
| US11857599B2 (en) | 2017-04-03 | 2024-01-02 | Acceleron Pharma Inc. | Compositions and methods for treating spinal muscular atrophy |
| EP3630770B1 (en) * | 2017-05-26 | 2024-08-28 | Relay Therapeutics, Inc. | Pyrazolo[3,4-b]pyrazine derivatives as shp2 phosphatase inhibitors |
| KR20200033249A (ko) | 2017-06-05 | 2020-03-27 | 피티씨 테라퓨틱스, 인크. | 헌팅턴병 치료 화합물 |
| MX2019015578A (es) | 2017-06-28 | 2020-07-28 | Ptc Therapeutics Inc | Metodos para tratar la enfermedad de huntington. |
| MX2019015580A (es) | 2017-06-28 | 2020-07-28 | Ptc Therapeutics Inc | Metodos para tratar la enfermedad de huntington. |
| CN111194215B (zh) | 2017-08-04 | 2024-03-01 | 斯基霍克疗法公司 | 用于调节剪接的方法和组合物 |
| US20200392161A1 (en) | 2018-02-21 | 2020-12-17 | Relay Therapeutics, Inc. | Shp2 phosphatase inhibitors and methods of use thereof |
| SG11202009245TA (en) * | 2018-03-21 | 2020-10-29 | Relay Therapeutics Inc | Shp2 phosphatase inhibitors and methods of use thereof |
| US12138263B2 (en) * | 2018-03-21 | 2024-11-12 | Relay Therapeutics, Inc. | Pyrazolo[3,4-b]pyrazine SHP2 phosphatase inhibitors and methods of use thereof |
| US12103926B2 (en) | 2018-03-27 | 2024-10-01 | Ptc Therapeutics, Inc. | Compounds for treating huntington's disease |
| US11685746B2 (en) | 2018-06-27 | 2023-06-27 | Ptc Therapeutics, Inc. | Heteroaryl compounds for treating Huntington's disease |
| AU2019294478B2 (en) | 2018-06-27 | 2023-03-23 | Ptc Therapeutics, Inc. | Heterocyclic and heteroaryl compounds for treating Huntington's disease |
| WO2020005877A1 (en) | 2018-06-27 | 2020-01-02 | Ptc Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
| CN113840602A (zh) | 2019-03-15 | 2021-12-24 | 斯基霍克疗法公司 | 用于校正异常剪接的组合物和方法 |
| AU2020277027A1 (en) | 2019-05-13 | 2021-12-09 | Ptc Therapeutics, Inc. | Compounds for treating huntington's disease |
| WO2021007378A1 (en) | 2019-07-11 | 2021-01-14 | Ptc Therapeutics, Inc. | Compounds for use in treating huntington's disease |
| MX2022005254A (es) | 2019-11-01 | 2022-06-29 | Novartis Ag | El uso de un modulador de empalme para un tratamiento que retrasa la progresion de la enfermedad de huntington. |
| US20230234942A1 (en) | 2020-04-09 | 2023-07-27 | Ptc Therapeutics, Inc. | Compounds for treating huntington's disease |
| AU2021380758A1 (en) | 2020-11-12 | 2023-06-15 | Ptc Therapeutics Inc. | Novel rna transcript |
| CA3227287A1 (en) | 2021-07-30 | 2023-02-02 | Suresh Babu | Heteroaryl compounds for treating huntington's disease |
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