AU2022387106A1 - Protein tyrosine phosphatase inhibitors and methods of use thereof - Google Patents
Protein tyrosine phosphatase inhibitors and methods of use thereof Download PDFInfo
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- AU2022387106A1 AU2022387106A1 AU2022387106A AU2022387106A AU2022387106A1 AU 2022387106 A1 AU2022387106 A1 AU 2022387106A1 AU 2022387106 A AU2022387106 A AU 2022387106A AU 2022387106 A AU2022387106 A AU 2022387106A AU 2022387106 A1 AU2022387106 A1 AU 2022387106A1
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- methyl
- fluoro
- dihydro
- amino
- hydroxy
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- 238000000034 method Methods 0.000 title description 19
- 239000003806 protein tyrosine phosphatase inhibitor Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 305
- -1 5-[(2R)-4-fluoro-6-hydroxy-2-{[(2-methylpropyl)amino]methyl}-2,3-dihydro-1-benzofuran-5- yl]-1λ6,2,5-thiadiazolidine-1,1,3-trione Chemical compound 0.000 claims description 530
- 239000000203 mixture Substances 0.000 claims description 197
- 229910052757 nitrogen Inorganic materials 0.000 claims description 75
- 125000000623 heterocyclic group Chemical group 0.000 claims description 55
- 125000001424 substituent group Chemical group 0.000 claims description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 36
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 552
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 451
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 444
- 239000011541 reaction mixture Substances 0.000 description 290
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 284
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 256
- 239000000243 solution Substances 0.000 description 237
- 239000000047 product Substances 0.000 description 189
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 172
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 83
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 40
- 125000000753 cycloalkyl group Chemical group 0.000 description 39
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- 239000007864 aqueous solution Substances 0.000 description 38
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- 125000004432 carbon atom Chemical group C* 0.000 description 30
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 29
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 238000002953 preparative HPLC Methods 0.000 description 27
- 239000011369 resultant mixture Substances 0.000 description 26
- 238000003756 stirring Methods 0.000 description 26
- 125000003118 aryl group Chemical group 0.000 description 25
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 25
- 125000005842 heteroatom Chemical group 0.000 description 24
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 23
- 150000003863 ammonium salts Chemical class 0.000 description 23
- 125000000217 alkyl group Chemical group 0.000 description 22
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 21
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- 239000000908 ammonium hydroxide Substances 0.000 description 20
- 235000011181 potassium carbonates Nutrition 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
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- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 17
- 102100033001 Tyrosine-protein phosphatase non-receptor type 1 Human genes 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
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- 102100033141 Tyrosine-protein phosphatase non-receptor type 2 Human genes 0.000 description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
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- 101001135572 Homo sapiens Tyrosine-protein phosphatase non-receptor type 2 Proteins 0.000 description 11
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- 101001087394 Homo sapiens Tyrosine-protein phosphatase non-receptor type 1 Proteins 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
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- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 9
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- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 8
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- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000005305 thiadiazolinyl group Chemical group 0.000 description 1
- 125000005458 thianyl group Chemical group 0.000 description 1
- 125000002053 thietanyl group Chemical group 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000005881 triazolinyl group Chemical group 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- YNBQAYKYNYRCCA-UHFFFAOYSA-N venadaparib Chemical compound C1(CC1)NCC1CN(C1)C(=O)C=1C=C(CC2=NNC(C3=CC=CC=C23)=O)C=CC1F YNBQAYKYNYRCCA-UHFFFAOYSA-N 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 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
- A61K31/41—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
- A61K31/433—Thidiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202163278339P | 2021-11-11 | 2021-11-11 | |
| US63/278,339 | 2021-11-11 | ||
| PCT/US2022/049584 WO2023086498A1 (en) | 2021-11-11 | 2022-11-10 | Protein tyrosine phosphatase inhibitors and methods of use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2022387106A1 true AU2022387106A1 (en) | 2024-05-23 |
Family
ID=84689141
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2022387106A Pending AU2022387106A1 (en) | 2021-11-11 | 2022-11-10 | Protein tyrosine phosphatase inhibitors and methods of use thereof |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20250019374A1 (https=) |
| EP (1) | EP4430038A1 (https=) |
| JP (1) | JP2024543452A (https=) |
| CN (1) | CN118525016A (https=) |
| AU (1) | AU2022387106A1 (https=) |
| CA (1) | CA3236854A1 (https=) |
| MX (1) | MX2024005658A (https=) |
| WO (1) | WO2023086498A1 (https=) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PE20252789A1 (es) | 2023-05-24 | 2025-12-22 | Kumquat Biosciences Inc | Compuestos heterociclicos y usos de estos |
| WO2025026158A1 (zh) * | 2023-07-28 | 2025-02-06 | 杭州中美华东制药有限公司 | 具有ptpn2抑制作用的化合物及其用途 |
| WO2025242216A1 (zh) * | 2024-05-24 | 2025-11-27 | 杭州百新生物医药科技有限公司 | 吲哚啉类化合物及其用途 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA94921C2 (en) * | 2005-12-08 | 2011-06-25 | Новартис Аг | 1-orthofluorophenyl substituted 1, 2, 5-thiazolidinedione derivatives as ptp-as inhibitors |
| UA94724C2 (en) * | 2005-12-08 | 2011-06-10 | Новартис Аг | Thiadiazolidinone derivatives as antidiabetic agents |
| BR112020026086A2 (pt) * | 2018-06-21 | 2021-03-23 | Calico Life Sciences Llc | inibidores da proteína tirosina fosfatase e métodos de uso destes |
| IL286373B2 (en) * | 2019-03-14 | 2026-03-01 | Calico Life Sciences Llc | Protein tyrosine phosphate inhibitor compounds and uses thereof |
| CA3162069A1 (en) * | 2019-12-18 | 2021-06-24 | Elliot P. Farney | Protein tyrosine phosphatase inhibitors and methods of use thereof |
-
2022
- 2022-11-10 WO PCT/US2022/049584 patent/WO2023086498A1/en not_active Ceased
- 2022-11-10 JP JP2024527750A patent/JP2024543452A/ja active Pending
- 2022-11-10 MX MX2024005658A patent/MX2024005658A/es unknown
- 2022-11-10 CA CA3236854A patent/CA3236854A1/en active Pending
- 2022-11-10 AU AU2022387106A patent/AU2022387106A1/en active Pending
- 2022-11-10 US US18/709,214 patent/US20250019374A1/en active Pending
- 2022-11-10 CN CN202280088273.9A patent/CN118525016A/zh active Pending
- 2022-11-10 EP EP22834767.0A patent/EP4430038A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2023086498A1 (en) | 2023-05-19 |
| CN118525016A (zh) | 2024-08-20 |
| EP4430038A1 (en) | 2024-09-18 |
| CA3236854A1 (en) | 2023-05-19 |
| US20250019374A1 (en) | 2025-01-16 |
| JP2024543452A (ja) | 2024-11-21 |
| MX2024005658A (es) | 2024-08-06 |
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