AU2018360270A1 - Bicyclic sulfones and sulfoxides and methods of use thereof - Google Patents
Bicyclic sulfones and sulfoxides and methods of use thereof Download PDFInfo
- Publication number
- AU2018360270A1 AU2018360270A1 AU2018360270A AU2018360270A AU2018360270A1 AU 2018360270 A1 AU2018360270 A1 AU 2018360270A1 AU 2018360270 A AU2018360270 A AU 2018360270A AU 2018360270 A AU2018360270 A AU 2018360270A AU 2018360270 A1 AU2018360270 A1 AU 2018360270A1
- Authority
- AU
- Australia
- Prior art keywords
- dihydro
- fluoro
- triazole
- phenyl
- pyrrolo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- -1 Bicyclic sulfones Chemical class 0.000 title claims description 145
- 238000000034 method Methods 0.000 title claims description 131
- 150000003462 sulfoxides Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 219
- 150000003852 triazoles Chemical class 0.000 claims description 506
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 489
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 140
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 108
- 125000000217 alkyl group Chemical group 0.000 claims description 94
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 85
- 208000035475 disorder Diseases 0.000 claims description 71
- 201000010099 disease Diseases 0.000 claims description 66
- 150000003839 salts Chemical class 0.000 claims description 62
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
- 125000001188 haloalkyl group Chemical group 0.000 claims description 55
- 125000003545 alkoxy group Chemical group 0.000 claims description 53
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 50
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 44
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 43
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 39
- 125000000623 heterocyclic group Chemical group 0.000 claims description 38
- 125000001424 substituent group Chemical group 0.000 claims description 38
- 125000001153 fluoro group Chemical group F* 0.000 claims description 37
- 229910052736 halogen Inorganic materials 0.000 claims description 36
- 125000001072 heteroaryl group Chemical group 0.000 claims description 36
- 229910052757 nitrogen Inorganic materials 0.000 claims description 36
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 34
- 238000011282 treatment Methods 0.000 claims description 32
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 30
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- 208000002320 spinal muscular atrophy Diseases 0.000 claims description 30
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- 125000005843 halogen group Chemical group 0.000 claims description 25
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- 229910052717 sulfur Inorganic materials 0.000 claims description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 22
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 22
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 22
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 18
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- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- 239000011593 sulfur Chemical group 0.000 claims description 11
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 9
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- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 8
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- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 125000003627 8 membered carbocyclic group Chemical group 0.000 claims description 4
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
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- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
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- AUQDITHEDVOTCU-UHFFFAOYSA-N cyclopropyl cyanide Chemical compound N#CC1CC1 AUQDITHEDVOTCU-UHFFFAOYSA-N 0.000 claims 5
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- GFBLFDSCAKHHGX-UHFFFAOYSA-N cyclobutanecarbonitrile Chemical compound N#CC1CCC1 GFBLFDSCAKHHGX-UHFFFAOYSA-N 0.000 claims 2
- KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 claims 2
- 125000006002 1,1-difluoroethyl group Chemical group 0.000 claims 1
- MUXDQHYTBGMDRV-UHFFFAOYSA-N 7-fluoro-2-(2-fluorocyclopropyl)sulfonyl-5-(3-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole Chemical compound FC1CC(N2N=C(N=C21)S(=O)(=O)C1C(C1)F)C1=CC(=CC=C1)F MUXDQHYTBGMDRV-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/16—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| US201762579392P | 2017-10-31 | 2017-10-31 | |
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| PCT/EP2018/079772 WO2019086494A1 (en) | 2017-10-31 | 2018-10-30 | Bicyclic sulfones and sulfoxides and methods of use thereof |
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| AU2018360270A1 true AU2018360270A1 (en) | 2020-03-26 |
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| TW (1) | TW201922748A (enExample) |
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| WO2018100070A1 (en) | 2016-12-02 | 2018-06-07 | F. Hoffmann-La Roche Ag | Bicyclic amide compounds and methods of use thereof |
| CN119613408A (zh) | 2017-07-14 | 2025-03-14 | 豪夫迈·罗氏有限公司 | 二环酮化合物及其使用方法 |
| US11072617B2 (en) | 2017-10-31 | 2021-07-27 | Genentech, Inc. | Bicyclic sulfones and sulfoxides and methods of use thereof |
| EP3908586B1 (en) | 2019-01-11 | 2022-12-21 | F. Hoffmann-La Roche AG | Bicyclic pyrrolotriazolr ketone compounds and methods of use thereof |
| TW202214617A (zh) | 2020-06-02 | 2022-04-16 | 法商賽諾菲公司 | 作為ｒｉｐｋ１抑制劑之異㗁唑啶及其用途 |
| JP2024544533A (ja) | 2021-11-11 | 2024-12-03 | ジェンザイム・コーポレーション | Ｒｉｐｋ１阻害剤としてのイソオキサゾリジン及びその使用 |
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- 2018-10-30 TW TW107138469A patent/TW201922748A/zh unknown
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| CO2020003475A2 (es) | 2020-04-24 |
| RU2020115915A (ru) | 2021-12-01 |
| CL2020001062A1 (es) | 2020-08-21 |
| EP3704097C0 (en) | 2023-10-25 |
| PH12020550537A1 (en) | 2021-03-22 |
| IL273847A (en) | 2020-05-31 |
| CN111278809B (zh) | 2024-06-25 |
| US12338241B2 (en) | 2025-06-24 |
| MX2020003451A (es) | 2020-08-03 |
| EP3704097A1 (en) | 2020-09-09 |
| CR20200168A (es) | 2020-07-12 |
| JP2021501183A (ja) | 2021-01-14 |
| AR113811A1 (es) | 2020-06-10 |
| KR20200083515A (ko) | 2020-07-08 |
| RU2020115915A3 (enExample) | 2022-05-06 |
| US20190127382A1 (en) | 2019-05-02 |
| CN111278809A (zh) | 2020-06-12 |
| BR112020008446A2 (pt) | 2020-12-29 |
| US11072617B2 (en) | 2021-07-27 |
| TW201922748A (zh) | 2019-06-16 |
| MA50503A (fr) | 2020-09-09 |
| EP3704097B1 (en) | 2023-10-25 |
| US20230002391A1 (en) | 2023-01-05 |
| CA3078688A1 (en) | 2019-05-09 |
| WO2019086494A1 (en) | 2019-05-09 |
| PE20211247A1 (es) | 2021-07-13 |
| SG11202002877RA (en) | 2020-04-29 |
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| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |