CA3067871A1 - Anti-cancer/anti-fibrosis compounds - Google Patents
Anti-cancer/anti-fibrosis compounds Download PDFInfo
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- CA3067871A1 CA3067871A1 CA3067871A CA3067871A CA3067871A1 CA 3067871 A1 CA3067871 A1 CA 3067871A1 CA 3067871 A CA3067871 A CA 3067871A CA 3067871 A CA3067871 A CA 3067871A CA 3067871 A1 CA3067871 A1 CA 3067871A1
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- Prior art keywords
- compound
- substituted
- salt
- hydrate
- solvate
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 236
- 230000001093 anti-cancer Effects 0.000 title description 2
- 230000002300 anti-fibrosis Effects 0.000 title description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 62
- 201000010099 disease Diseases 0.000 claims abstract description 61
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 56
- 239000003814 drug Substances 0.000 claims abstract description 38
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 30
- 201000011510 cancer Diseases 0.000 claims abstract description 26
- 206010016654 Fibrosis Diseases 0.000 claims abstract description 14
- 230000004761 fibrosis Effects 0.000 claims abstract description 14
- -1 amino substituted pyridine Chemical class 0.000 claims description 76
- 150000003839 salts Chemical class 0.000 claims description 73
- 125000000217 alkyl group Chemical group 0.000 claims description 54
- 239000012453 solvate Substances 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 46
- 241001465754 Metazoa Species 0.000 claims description 39
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 229910052757 nitrogen Inorganic materials 0.000 claims description 29
- 150000002367 halogens Chemical class 0.000 claims description 27
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- 102100024456 Cyclin-dependent kinase 8 Human genes 0.000 claims description 25
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
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- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 claims description 3
- PMMURAAUARKVCB-UHFFFAOYSA-N alpha-D-ara-dHexp Natural products OCC1OC(O)CC(O)C1O PMMURAAUARKVCB-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
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- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 3
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 66
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- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 53
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 36
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- 125000001424 substituent group Chemical group 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 19
- 239000002253 acid Substances 0.000 description 19
- 230000015572 biosynthetic process Effects 0.000 description 19
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 18
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- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 17
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 16
- 241000699670 Mus sp. Species 0.000 description 16
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- 125000005605 benzo group Chemical group 0.000 description 16
- 150000003254 radicals Chemical class 0.000 description 16
- 150000007942 carboxylates Chemical class 0.000 description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 14
- 231100000673 dose–response relationship Toxicity 0.000 description 14
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 13
- 125000004404 heteroalkyl group Chemical group 0.000 description 13
- 239000002775 capsule Substances 0.000 description 12
- 125000005842 heteroatom Chemical group 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 11
- 239000013543 active substance Substances 0.000 description 11
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 11
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- 125000004432 carbon atom Chemical group C* 0.000 description 10
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- 235000019341 magnesium sulphate Nutrition 0.000 description 10
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- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 8
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 8
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- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 8
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- LMHJWYGPCJEMAE-UHFFFAOYSA-M sodium 5-bromo-1-chlorobenzo[h]isoquinoline-8-carboxylate Chemical compound BrC1=C2C=CN=C(C2=C2C(=C1)C=C(C=C2)C(=O)[O-])Cl.[Na+] LMHJWYGPCJEMAE-UHFFFAOYSA-M 0.000 description 4
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- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- 238000012447 xenograft mouse model Methods 0.000 description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762539237P | 2017-07-31 | 2017-07-31 | |
| US62/539,237 | 2017-07-31 | ||
| PCT/US2018/044663 WO2019028059A1 (en) | 2017-07-31 | 2018-07-31 | ANTICANCER COMPOUNDS / ANTI-FIBROSIS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3067871A1 true CA3067871A1 (en) | 2019-02-07 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3067871A Pending CA3067871A1 (en) | 2017-07-31 | 2018-07-31 | Anti-cancer/anti-fibrosis compounds |
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| EP (1) | EP3661512A4 (enExample) |
| JP (1) | JP7277390B2 (enExample) |
| CN (1) | CN111447931B (enExample) |
| CA (1) | CA3067871A1 (enExample) |
| WO (1) | WO2019028059A1 (enExample) |
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| WO2019028059A1 (en) * | 2017-07-31 | 2019-02-07 | The Regents Of The University Of California | ANTICANCER COMPOUNDS / ANTI-FIBROSIS |
| EP4003339A4 (en) * | 2019-07-30 | 2023-02-22 | Sanford Burnham Prebys Medical Discovery Institute | DOPAMINE RECEPTOR D1 AGONISTS AND METHODS OF USE |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5648021A (en) * | 1994-01-17 | 1997-07-15 | Hoechst Aktiengesellschaft | Phenanthrene derivatives and their use in liquid-crystalline mixtures |
| DE19524230A1 (de) * | 1995-07-04 | 1997-01-09 | Hoechst Ag | Fluorierte Phenanthren-Derivate und ihre Verwendung in flüssigkristallinen Mischungen |
| KR19990029052A (ko) * | 1995-07-17 | 1999-04-15 | 악커만 요아힘, 되르 클라우스 | 강유전성 액정 혼합물 |
| EP1904449A4 (en) * | 2005-07-08 | 2010-07-28 | Merck Sharp & Dohme | CHECKPOINT KINASE INHIBITORS |
| ES2528316T3 (es) * | 2006-09-01 | 2015-02-06 | Senhwa Biosciences, Inc. | Moduladores de la serina-treonina proteína quinasa y de PARP |
| US7910600B2 (en) * | 2007-08-31 | 2011-03-22 | Cylene Pharmaceuticals, Inc. | Therapeutic kinase modulators |
| RU2011146544A (ru) * | 2009-04-17 | 2013-05-27 | Силин Фармасьютикалз, Инк. | Способы лечения болезней, связанных с активностью протеинкиназы ck2 |
| BR112012005970A2 (pt) * | 2009-09-16 | 2015-09-08 | Cylene Pharmaceuticals Inc | moduladores tricíclicos de proteína quinase |
| US10432142B2 (en) * | 2017-07-21 | 2019-10-01 | Oracle International Corporation | Voltage controlled oscillator with tunable inductor and capacitor |
| WO2019028059A1 (en) * | 2017-07-31 | 2019-02-07 | The Regents Of The University Of California | ANTICANCER COMPOUNDS / ANTI-FIBROSIS |
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2018
- 2018-07-31 WO PCT/US2018/044663 patent/WO2019028059A1/en not_active Ceased
- 2018-07-31 CA CA3067871A patent/CA3067871A1/en active Pending
- 2018-07-31 EP EP18840434.7A patent/EP3661512A4/en not_active Withdrawn
- 2018-07-31 US US16/634,063 patent/US11932606B2/en active Active
- 2018-07-31 JP JP2019572809A patent/JP7277390B2/ja active Active
- 2018-07-31 CN CN201880049675.1A patent/CN111447931B/zh active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP3661512A1 (en) | 2020-06-10 |
| JP2020529396A (ja) | 2020-10-08 |
| WO2019028059A1 (en) | 2019-02-07 |
| US20230192621A1 (en) | 2023-06-22 |
| JP7277390B2 (ja) | 2023-05-18 |
| CN111447931A (zh) | 2020-07-24 |
| US11932606B2 (en) | 2024-03-19 |
| CN111447931B (zh) | 2024-01-26 |
| EP3661512A4 (en) | 2020-12-30 |
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