CA3043612A1 - Magl inhibitors - Google Patents
Magl inhibitors Download PDFInfo
- Publication number
- CA3043612A1 CA3043612A1 CA3043612A CA3043612A CA3043612A1 CA 3043612 A1 CA3043612 A1 CA 3043612A1 CA 3043612 A CA3043612 A CA 3043612A CA 3043612 A CA3043612 A CA 3043612A CA 3043612 A1 CA3043612 A1 CA 3043612A1
- Authority
- CA
- Canada
- Prior art keywords
- pharmaceutically acceptable
- compound
- solvate
- acceptable salt
- formula
- 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
- 239000003112 inhibitor Substances 0.000 title description 6
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- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
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- 238000000034 method Methods 0.000 claims description 97
- 229910052736 halogen Inorganic materials 0.000 claims description 72
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 59
- 239000001257 hydrogen Substances 0.000 claims description 59
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 49
- 229910052805 deuterium Inorganic materials 0.000 claims description 49
- 201000010099 disease Diseases 0.000 claims description 36
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- 125000001072 heteroaryl group Chemical group 0.000 description 27
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- 125000003118 aryl group Chemical group 0.000 description 26
- 239000000126 substance Substances 0.000 description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 24
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 19
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- 125000000592 heterocycloalkyl group Chemical group 0.000 description 17
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- 239000002904 solvent Substances 0.000 description 16
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- 125000004446 heteroarylalkyl group Chemical group 0.000 description 15
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- 125000004450 alkenylene group Chemical group 0.000 description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 125000003709 fluoroalkyl group Chemical group 0.000 description 11
- 239000000651 prodrug Substances 0.000 description 11
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 229910052799 carbon Inorganic materials 0.000 description 10
- 125000004122 cyclic group Chemical group 0.000 description 10
- 239000003937 drug carrier Substances 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
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- 239000010410 layer Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
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- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
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- RIXVESSVKLKKFV-UHFFFAOYSA-N piperazine-1,4-dicarboxylic acid Chemical compound OC(=O)N1CCN(C(O)=O)CC1 RIXVESSVKLKKFV-UHFFFAOYSA-N 0.000 description 6
- RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
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- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| SI2800565T1 (sl) | 2012-01-06 | 2020-10-30 | Lundbeck La Jolla Research Center, Inc. | Karbamatne spojine in metode izdelave in uporabe le-teh |
| JP2018515460A (ja) | 2015-05-11 | 2018-06-14 | アビデ セラピューティクス，インク． | 炎症または神経障害性疼痛を処置する方法 |
| US10899737B2 (en) | 2016-09-19 | 2021-01-26 | Lundbeck La Jolla Research Center, Inc. | Piperazine carbamates and methods of making and using same |
| JOP20190106A1 (ar) * | 2016-11-16 | 2019-05-09 | Lundbeck La Jolla Research Center Inc | مثبطات أحادي أسيل جليسرول ليباز (magl) |
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| KR102508739B1 (ko) | 2016-11-16 | 2023-03-09 | 하. 룬드벡 아크티에셀스카브 | Magl 억제제의 결정형 |
| PE20200664A1 (es) | 2017-08-29 | 2020-06-11 | Lundbeck La Jolla Research Center Inc | Compuestos espirociclicos y sus metodos de preparacion y uso |
| CN111448199A (zh) * | 2017-11-02 | 2020-07-24 | 艾库里斯有限及两合公司 | 具有抗乙型肝炎病毒(hbv)活性的新的高活性的氨基-噻唑取代的吲哚-2-甲酰胺 |
| TW201946906A (zh) | 2018-05-15 | 2019-12-16 | 美商阿拜德生物製藥公司 | Magl抑制劑 |
| US11702393B2 (en) * | 2020-04-21 | 2023-07-18 | H. Lundbeck A/S | Synthesis of a monoacylglycerol lipase inhibitor |
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| JP7777891B2 (ja) | 2021-12-29 | 2025-12-01 | サイ セラピューティクス インコーポレイテッド | モノアシルグリセロールリパーゼ（ｍａｇｌ）の阻害 |
| KR20250005229A (ko) | 2022-05-04 | 2025-01-09 | 하. 룬드벡 아크티에셀스카브 | 모노아실글리세롤 리파제 억제제로서 1,1,1,3,3,3-헥사플루오로프로판-2-일 (s)-1-(피리다진-3-일카르바모일)-6 아자스피로[2.5]옥탄-6-카르복실레이트의 결정질 형태 |
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| DE69211015T2 (de) | 1991-11-27 | 1997-01-09 | Du Pont | Herbizide acylierte amino-(phenyl-oder-pyridinyl-oder thienyl-)phenyl derivate |
| AU1384795A (en) | 1993-12-22 | 1995-07-10 | Shell Internationale Research Maatschappij B.V. | Process for preparing carbamates |
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| WO1998000408A1 (en) | 1996-07-02 | 1998-01-08 | Novartis Ag | N-phenylimino heterocyclic derivatives and their use as herbicides |
| RU2167150C2 (ru) | 1998-03-25 | 2001-05-20 | Фокин Александр Васильевич | Полифторалкил-n-арилкарбаматы, обладающие антимикробной активностью |
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| DE10348022A1 (de) | 2003-10-15 | 2005-05-25 | Imtm Gmbh | Neue Dipeptidylpeptidase IV-Inhibitoren zur funktionellen Beeinflussung unterschiedlicher Zellen und zur Behandlung immunologischer, entzündlicher, neuronaler und anderer Erkrankungen |
| FR2864080B1 (fr) | 2003-12-23 | 2006-02-03 | Sanofi Synthelabo | Derives de 1-piperazine-et-1-homopiperazine-carboxylates, leur preparation et leur application en therapeutique |
| AU2003300702A1 (en) | 2003-12-31 | 2005-07-21 | Council Of Scientific And Industrial Research | Process for preparing carbamates |
| KR20070026382A (ko) | 2004-02-18 | 2007-03-08 | 아스트라제네카 아베 | 아세틸린성 피페라진 화합물 및 대사성 글루타메이트수용체 길항제로서 이들의 용도 |
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| CN108912066B (zh) | 2012-01-06 | 2022-06-24 | 安吉奥斯医药品有限公司 | 治疗活性化合物及其使用方法 |
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| EP3271352B1 (en) | 2015-03-18 | 2021-05-12 | H. Lundbeck A/S | Piperazine carbamates and methods of making and using same |
| JP2018515460A (ja) * | 2015-05-11 | 2018-06-14 | アビデ セラピューティクス，インク． | 炎症または神経障害性疼痛を処置する方法 |
| US10463753B2 (en) * | 2016-02-19 | 2019-11-05 | Lundbeck La Jolla Research Center, Inc. | Radiolabeled monoacylglycerol lipase occupancy probe |
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| CR20190243A (es) | 2019-06-26 |
| ES2908632T3 (es) | 2022-05-03 |
| CO2019005038A2 (es) | 2019-05-31 |
| TN2019000150A1 (en) | 2020-10-05 |
| RU2019116514A (ru) | 2020-12-17 |
| EP3541822A1 (en) | 2019-09-25 |
| US9981930B1 (en) | 2018-05-29 |
| IL266550A (en) | 2019-07-31 |
| AR110088A1 (es) | 2019-02-20 |
| MX2019005771A (es) | 2019-12-05 |
| ECSP19035377A (es) | 2019-05-31 |
| NI201900050A (es) | 2019-10-30 |
| BR112019009991A2 (pt) | 2019-08-27 |
| JP2020502047A (ja) | 2020-01-23 |
| CN110248947A (zh) | 2019-09-17 |
| CN110248947B (zh) | 2022-04-01 |
| AU2017361250A1 (en) | 2019-05-30 |
| JP6987859B2 (ja) | 2022-01-05 |
| MA46860A (fr) | 2019-09-25 |
| EP3541822B1 (en) | 2022-01-19 |
| CL2019001335A1 (es) | 2019-10-04 |
| DOP2019000121A (es) | 2019-09-30 |
| WO2018093946A1 (en) | 2018-05-24 |
| KR20190077087A (ko) | 2019-07-02 |
| US20180134675A1 (en) | 2018-05-17 |
| EA201991074A1 (ru) | 2019-12-30 |
| JOP20190105A1 (ar) | 2019-05-09 |
| EP3541822A4 (en) | 2020-04-29 |
| PH12019501102A1 (en) | 2019-08-19 |
| TW201831458A (zh) | 2018-09-01 |
| PE20191146A1 (es) | 2019-09-02 |
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