WO2024040045A3 - 2-diarylmethyl-4-aminotetrahydropyran sulfonimidamides as anticancer, antiinflammatory, antifibrotic and neuroprotective agents - Google Patents
2-diarylmethyl-4-aminotetrahydropyran sulfonimidamides as anticancer, antiinflammatory, antifibrotic and neuroprotective agents Download PDFInfo
- Publication number
- WO2024040045A3 WO2024040045A3 PCT/US2023/072200 US2023072200W WO2024040045A3 WO 2024040045 A3 WO2024040045 A3 WO 2024040045A3 US 2023072200 W US2023072200 W US 2023072200W WO 2024040045 A3 WO2024040045 A3 WO 2024040045A3
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pp2a
- compounds
- diarylmethyl
- aminotetrahydropyran
- sulfonimidamides
- Prior art date
Links
- 230000001093 anti-cancer Effects 0.000 title 1
- 230000003510 anti-fibrotic effect Effects 0.000 title 1
- 230000003110 anti-inflammatory effect Effects 0.000 title 1
- 239000004090 neuroprotective agent Substances 0.000 title 1
- 101000741929 Caenorhabditis elegans Serine/threonine-protein phosphatase 2A catalytic subunit Proteins 0.000 abstract 3
- 206010028980 Neoplasm Diseases 0.000 abstract 3
- 150000001875 compounds Chemical class 0.000 abstract 3
- 201000011510 cancer Diseases 0.000 abstract 2
- 101001059929 Caenorhabditis elegans Forkhead box protein O Proteins 0.000 abstract 1
- 108700012912 MYCN Proteins 0.000 abstract 1
- 101150022024 MYCN gene Proteins 0.000 abstract 1
- 102000055056 N-Myc Proto-Oncogene Human genes 0.000 abstract 1
- 108700026495 N-Myc Proto-Oncogene Proteins 0.000 abstract 1
- 108091000080 Phosphotransferase Proteins 0.000 abstract 1
- 102000040945 Transcription factor Human genes 0.000 abstract 1
- 108091023040 Transcription factor Proteins 0.000 abstract 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 abstract 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 abstract 1
- 230000003213 activating effect Effects 0.000 abstract 1
- 230000001028 anti-proliverative effect Effects 0.000 abstract 1
- 230000001413 cellular effect Effects 0.000 abstract 1
- 238000002512 chemotherapy Methods 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 231100000590 oncogenic Toxicity 0.000 abstract 1
- 230000002246 oncogenic effect Effects 0.000 abstract 1
- 102000020233 phosphotransferase Human genes 0.000 abstract 1
- 230000035945 sensitivity Effects 0.000 abstract 1
- 230000011664 signaling Effects 0.000 abstract 1
- 238000009097 single-agent therapy Methods 0.000 abstract 1
- 230000035897 transcription Effects 0.000 abstract 1
- 238000013518 transcription Methods 0.000 abstract 1
- 230000005945 translocation Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/14—Nitrogen atoms not forming part of a nitro radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A genus of 2-diarylmethyl-4-aminotetrahydropyran derivatives is disclosed, which includes the following genus: The compounds activate cellular PP2A, suppress oncogenic kinase signaling and negatively regulate MYC and MYCN in cancer. The compounds also restrain transcription by activating PP2A-Integrator-RNAPII, and this activity also contributes the tumor suppressor property of PP2A in transcriptionally addicted cancers The compounds also induce FOXO transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a monotherapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202263398077P | 2022-08-15 | 2022-08-15 | |
| US63/398,077 | 2022-08-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2024040045A2 WO2024040045A2 (en) | 2024-02-22 |
| WO2024040045A3 true WO2024040045A3 (en) | 2024-04-11 |
Family
ID=89942366
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2023/072200 WO2024040045A2 (en) | 2022-08-15 | 2023-08-15 | 2-diarylmethyl-4-aminotetrahydropyran sulfonimidamides as anticancer, antiinflammatory, antifibrotic and neuroprotective agents |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2024040045A2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024182363A1 (en) * | 2023-02-27 | 2024-09-06 | Atux Iskay Llc | N,n'-sulfonimidamides as anticancer, antiinflammatory, antifibrotic and neuroprotective agents |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060122263A1 (en) * | 2003-03-28 | 2006-06-08 | Dutta Aloke K | Tri-substituted 2-benzhydryl-5-benzlamino-tetrahydro-pyran-4-ol and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-ol analogues, and novel 3,6-disubstituted pyran derivatives |
| WO2017044575A1 (en) * | 2015-09-09 | 2017-03-16 | Icahn School Of Medicine At Mount Sinai | Constrained benzhydryl sulfonamides as anticancer and neuroprotective agents |
| WO2021170913A1 (en) * | 2020-02-28 | 2021-09-02 | Rappta Therapeutics Oy | Tricyclic modulators of pp2a |
| WO2021188949A1 (en) * | 2020-03-20 | 2021-09-23 | Atux Iskay Llc | 3-diarylmethylenes and uses thereof |
-
2023
- 2023-08-15 WO PCT/US2023/072200 patent/WO2024040045A2/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060122263A1 (en) * | 2003-03-28 | 2006-06-08 | Dutta Aloke K | Tri-substituted 2-benzhydryl-5-benzlamino-tetrahydro-pyran-4-ol and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-ol analogues, and novel 3,6-disubstituted pyran derivatives |
| WO2017044575A1 (en) * | 2015-09-09 | 2017-03-16 | Icahn School Of Medicine At Mount Sinai | Constrained benzhydryl sulfonamides as anticancer and neuroprotective agents |
| WO2021170913A1 (en) * | 2020-02-28 | 2021-09-02 | Rappta Therapeutics Oy | Tricyclic modulators of pp2a |
| WO2021188949A1 (en) * | 2020-03-20 | 2021-09-23 | Atux Iskay Llc | 3-diarylmethylenes and uses thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2024040045A2 (en) | 2024-02-22 |
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