IL299512A - Pyridine-1,5-diones exhibitng mnk inhibition and their method of use - Google Patents
Pyridine-1,5-diones exhibitng mnk inhibition and their method of useInfo
- Publication number
- IL299512A IL299512A IL299512A IL29951222A IL299512A IL 299512 A IL299512 A IL 299512A IL 299512 A IL299512 A IL 299512A IL 29951222 A IL29951222 A IL 29951222A IL 299512 A IL299512 A IL 299512A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- alkyl
- cycloalkyl
- heterocyclyl
- group
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 103
- -1 -NHS(O)2CH3 Chemical group 0.000 claims description 93
- 125000001424 substituent group Chemical group 0.000 claims description 65
- 229910052799 carbon Inorganic materials 0.000 claims description 43
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 36
- 125000000623 heterocyclic group Chemical group 0.000 claims description 34
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 229940002612 prodrug Drugs 0.000 claims description 33
- 239000000651 prodrug Substances 0.000 claims description 33
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 208000004296 neuralgia Diseases 0.000 claims description 21
- 208000021722 neuropathic pain Diseases 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 16
- 208000002193 Pain Diseases 0.000 claims description 15
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 claims description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 2
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 3
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- 125000000524 functional group Chemical group 0.000 description 39
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- 125000004432 carbon atom Chemical group C* 0.000 description 32
- 239000003112 inhibitor Substances 0.000 description 25
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 17
- 238000006467 substitution reaction Methods 0.000 description 17
- HKTBYUWLRDZAJK-UHFFFAOYSA-N 6-[(6-aminopyrimidin-4-yl)amino]-8-methylspiro[2H-imidazo[1,5-a]pyridine-3,1'-cyclohexane]-1,5-dione Chemical class NC1=CC(=NC=N1)NC1=CC(=C2N(C1=O)C1(NC2=O)CCCCC1)C HKTBYUWLRDZAJK-UHFFFAOYSA-N 0.000 description 16
- 125000005842 heteroatom Chemical group 0.000 description 16
- 150000003254 radicals Chemical class 0.000 description 16
- 238000011282 treatment Methods 0.000 description 15
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 14
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- 125000004429 atom Chemical group 0.000 description 10
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- 125000003368 amide group Chemical group 0.000 description 9
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- 125000004433 nitrogen atom Chemical group N* 0.000 description 9
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- 230000000694 effects Effects 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 7
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical group NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 7
- 150000003335 secondary amines Chemical class 0.000 description 7
- 229910052717 sulfur Chemical group 0.000 description 7
- 150000003512 tertiary amines Chemical class 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
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- 125000003277 amino group Chemical group 0.000 description 6
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- 150000002148 esters Chemical class 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 125000003710 aryl alkyl group Chemical group 0.000 description 5
- 150000005840 aryl radicals Chemical class 0.000 description 5
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- 239000001301 oxygen Chemical group 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000011593 sulfur Chemical group 0.000 description 5
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 5
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/20—Spiro-condensed systems
-
- 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
- C07D491/12—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 three hetero rings
- C07D491/14—Ortho-condensed systems
- C07D491/147—Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
-
- 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
- C07D491/12—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 three hetero rings
- C07D491/20—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epidemiology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Steroid Compounds (AREA)
- Cosmetics (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063046325P | 2020-06-30 | 2020-06-30 | |
| PCT/US2021/039982 WO2022006331A2 (en) | 2020-06-30 | 2021-06-30 | Pyridine-1,5-diones exhibitng mnk inhibition and their method of use |
Publications (1)
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|---|---|
| IL299512A true IL299512A (en) | 2023-02-01 |
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| IL299512A IL299512A (en) | 2020-06-30 | 2021-06-30 | Pyridine-1,5-diones exhibitng mnk inhibition and their method of use |
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|---|---|
| US (1) | US20230286983A1 (https=) |
| EP (1) | EP4171565A4 (https=) |
| JP (1) | JP2023533616A (https=) |
| KR (1) | KR20230041715A (https=) |
| CN (1) | CN116194112A (https=) |
| AU (1) | AU2021300363A1 (https=) |
| BR (1) | BR112022026275A2 (https=) |
| CA (1) | CA3183551A1 (https=) |
| IL (1) | IL299512A (https=) |
| MX (1) | MX2022016516A (https=) |
| WO (1) | WO2022006331A2 (https=) |
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| EP4646266A1 (en) * | 2023-01-04 | 2025-11-12 | 4E Therapeutics, Inc. | Solid state forms of mnk inhibitors |
| WO2026006417A1 (en) * | 2024-06-26 | 2026-01-02 | 4E Therapeutics, Inc. | Formulations of mnk inhibitors |
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| CN103874496A (zh) * | 2011-08-22 | 2014-06-18 | 默沙东公司 | 作为bace抑制剂的2-螺-取代的亚氨基噻嗪类及其单和二氧化物、组合物及其用途 |
| GB201205669D0 (en) * | 2012-03-30 | 2012-05-16 | Agency Science Tech & Res | Bicyclic heterocyclic derivatives as mnk2 and mnk2 modulators and uses thereof |
| TWI713455B (zh) * | 2014-06-25 | 2020-12-21 | 美商伊凡克特治療公司 | ＭｎＫ抑制劑及其相關方法 |
| WO2017068064A1 (en) * | 2015-10-22 | 2017-04-27 | Selvita S.A. | Pyridone derivatives and their use as kinase inhibitors |
| BR112018008711A2 (pt) * | 2015-10-29 | 2018-10-30 | Effector Therapeutics Inc | compostos de pirrolo-, pirazolo-, imidazo-pirimidina e piridina que inibem mnk1 e mnk2 |
| GB201520500D0 (en) * | 2015-11-20 | 2016-01-06 | Medical Res Council Technology | Compounds |
| WO2017165908A1 (en) * | 2016-03-31 | 2017-10-05 | South Australian Health And Medical Research Institute Limited | Method of inhibiting high fat diet-related conditions |
| CA3064000A1 (en) * | 2017-05-24 | 2018-11-29 | Effector Therapeutics, Inc. | Methods and compositions for cellular immunotherapy |
| CN113286592A (zh) * | 2018-10-24 | 2021-08-20 | 效应治疗股份有限公司 | Mnk抑制剂的结晶形式 |
| CN111484494B (zh) * | 2019-01-29 | 2022-09-13 | 诺沃斯达药业(上海)有限公司 | 抑制mnk1和mnk2的多环化合物 |
| EP3972593B1 (en) * | 2019-05-23 | 2025-07-02 | Board of Regents, The University of Texas System | Inhibitor of mnk for the treatment of neuropathic pain |
| CN110256432A (zh) * | 2019-06-27 | 2019-09-20 | 诺沃斯达药业有限公司 | 抑制mnk1和mnk2的多环化合物 |
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| WO2022006331A3 (en) | 2022-02-10 |
| EP4171565A2 (en) | 2023-05-03 |
| EP4171565A4 (en) | 2024-11-27 |
| CN116194112A (zh) | 2023-05-30 |
| US20230286983A1 (en) | 2023-09-14 |
| MX2022016516A (es) | 2023-03-28 |
| KR20230041715A (ko) | 2023-03-24 |
| WO2022006331A9 (en) | 2022-03-03 |
| JP2023533616A (ja) | 2023-08-03 |
| WO2022006331A8 (en) | 2023-03-16 |
| WO2022006331A2 (en) | 2022-01-06 |
| AU2021300363A1 (en) | 2023-02-09 |
| BR112022026275A2 (pt) | 2023-03-14 |
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