JP2017502961A5 - - Google Patents
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- JP2017502961A5 JP2017502961A5 JP2016543197A JP2016543197A JP2017502961A5 JP 2017502961 A5 JP2017502961 A5 JP 2017502961A5 JP 2016543197 A JP2016543197 A JP 2016543197A JP 2016543197 A JP2016543197 A JP 2016543197A JP 2017502961 A5 JP2017502961 A5 JP 2017502961A5
- Authority
- JP
- Japan
- Prior art keywords
- azaspiro
- octane
- diol
- alkyl
- compound
- 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.)
- Pending
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- 150000001875 compounds Chemical class 0.000 claims 15
- 125000000217 alkyl group Chemical group 0.000 claims 12
- 102000004547 Glucosylceramidase Human genes 0.000 claims 11
- 108010017544 Glucosylceramidase Proteins 0.000 claims 11
- 125000001424 substituent group Chemical group 0.000 claims 8
- 150000003839 salts Chemical class 0.000 claims 7
- 206010012289 Dementia Diseases 0.000 claims 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 4
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 4
- 201000011240 Frontotemporal dementia Diseases 0.000 claims 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 4
- 125000003545 alkoxy group Chemical group 0.000 claims 4
- 125000000304 alkynyl group Chemical group 0.000 claims 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 4
- 201000010099 disease Diseases 0.000 claims 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 4
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims 3
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims 3
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims 3
- 208000010877 cognitive disease Diseases 0.000 claims 3
- 230000007850 degeneration Effects 0.000 claims 3
- 230000000694 effects Effects 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 208000033808 peripheral neuropathy Diseases 0.000 claims 3
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims 3
- WOKVFVFSTFFEDJ-FSDSQADBSA-N (6R,7R,8R)-6,7-dihydroxy-4-azaspiro[2.5]octane-8-carbonitrile Chemical compound O[C@@H]1CNC2(CC2)[C@@H]([C@H]1O)C#N WOKVFVFSTFFEDJ-FSDSQADBSA-N 0.000 claims 2
- UVWFVBWKBBONDJ-FSDSQADBSA-N (6R,7R,8R)-8-(hydroxymethyl)-4-azaspiro[2.5]octane-6,7-diol Chemical compound OC[C@@H]1[C@H]([C@@H](CNC12CC2)O)O UVWFVBWKBBONDJ-FSDSQADBSA-N 0.000 claims 2
- UREIBDHTHIOCAG-BWZBUEFSSA-N (6R,7R,8R)-8-(methoxymethyl)-4-azaspiro[2.5]octane-6,7-diol Chemical compound COC[C@@H]1[C@H]([C@@H](CNC12CC2)O)O UREIBDHTHIOCAG-BWZBUEFSSA-N 0.000 claims 2
- JOBWNRYDTOZDMC-SRQIZXRXSA-N (6R,7R,8S)-6,7-dihydroxy-4-azaspiro[2.5]octane-8-carboxylic acid Chemical compound O[C@@H]1CNC2(CC2)[C@@H]([C@H]1O)C(=O)O JOBWNRYDTOZDMC-SRQIZXRXSA-N 0.000 claims 2
- JIXJUDKLYVZZEK-VQVTYTSYSA-N (6R,7R,8S)-6,7-dihydroxy-N-methyl-4-azaspiro[2.5]octane-8-carboxamide Chemical compound O[C@@H]1CNC2(CC2)[C@@H]([C@H]1O)C(=O)NC JIXJUDKLYVZZEK-VQVTYTSYSA-N 0.000 claims 2
- GYYKXPIHCCASMM-ATRFCDNQSA-N (6R,7R,8S)-8-(2,2-difluoroethenyl)-4-azaspiro[2.5]octane-6,7-diol Chemical compound FC(=C[C@@H]1[C@H]([C@@H](CNC12CC2)O)O)F GYYKXPIHCCASMM-ATRFCDNQSA-N 0.000 claims 2
- QAWQTKDITYMSEA-ATRFCDNQSA-N (6R,7R,8S)-8-(2,2-difluoroethyl)-4-azaspiro[2.5]octane-6,7-diol Chemical compound FC(C[C@@H]1[C@H]([C@@H](CNC12CC2)O)O)F QAWQTKDITYMSEA-ATRFCDNQSA-N 0.000 claims 2
- MVUMUMOZSPIRQJ-BWZBUEFSSA-N (6R,7R,8S)-8-(2-fluoroethyl)-4-azaspiro[2.5]octane-6,7-diol Chemical compound FCC[C@@H]1[C@H]([C@@H](CNC12CC2)O)O MVUMUMOZSPIRQJ-BWZBUEFSSA-N 0.000 claims 2
- PJBIJTLFOHTQLS-FSDSQADBSA-N (6R,7R,8S)-8-(chloromethyl)-4-azaspiro[2.5]octane-6,7-diol Chemical compound ClC[C@@H]1[C@H]([C@@H](CNC12CC2)O)O PJBIJTLFOHTQLS-FSDSQADBSA-N 0.000 claims 2
- HNWFXDPDLGNHIM-SRQIZXRXSA-N (6R,7R,8S)-8-(difluoromethyl)-4-azaspiro[2.5]octane-6,7-diol Chemical compound FC([C@@H]1[C@H]([C@@H](CNC12CC2)O)O)F HNWFXDPDLGNHIM-SRQIZXRXSA-N 0.000 claims 2
- OMLFGBKTKHVSQF-HIDXBHDTSA-N (6R,7R,8S)-8-[(E)-2-fluoroethenyl]-4-azaspiro[2.5]octane-6,7-diol Chemical compound F/C=C/[C@@H]1[C@H]([C@@H](CNC12CC2)O)O OMLFGBKTKHVSQF-HIDXBHDTSA-N 0.000 claims 2
- OMLFGBKTKHVSQF-BWZBUEFSSA-N (6R,7R,8S)-8-[(Z)-2-fluoroethenyl]-4-azaspiro[2.5]octane-6,7-diol Chemical compound FC=C/[C@@H]1[C@H]([C@@H](CNC12CC2)O)O OMLFGBKTKHVSQF-BWZBUEFSSA-N 0.000 claims 2
- JNIYJHDOBMNALK-BWZBUEFSSA-N (6R,7R,8S)-8-ethenyl-4-azaspiro[2.5]octane-6,7-diol Chemical compound C(=C)[C@@H]1[C@H]([C@@H](CNC12CC2)O)O JNIYJHDOBMNALK-BWZBUEFSSA-N 0.000 claims 2
- LYPUWEGFMHAGTQ-BWZBUEFSSA-N (6R,7R,8S)-8-ethyl-4-azaspiro[2.5]octane-6,7-diol Chemical compound C(C)[C@@H]1[C@H]([C@@H](CNC12CC2)O)O LYPUWEGFMHAGTQ-BWZBUEFSSA-N 0.000 claims 2
- WZAZBGHAPRDLFW-BWZBUEFSSA-N (6R,7R,8S)-8-ethynyl-4-azaspiro[2.5]octane-6,7-diol Chemical compound C(#C)[C@@H]1[C@H]([C@@H](CNC12CC2)O)O WZAZBGHAPRDLFW-BWZBUEFSSA-N 0.000 claims 2
- SNBKQXWAMBQGSA-FSDSQADBSA-N (6R,7R,8S)-8-methyl-4-azaspiro[2.5]octane-6,7-diol Chemical compound C[C@@H]1[C@H]([C@@H](CNC12CC2)O)O SNBKQXWAMBQGSA-FSDSQADBSA-N 0.000 claims 2
- CFLYIQUIFBLZQN-IWSPIJDZSA-N (6R,7R,8S)-8-prop-1-ynyl-4-azaspiro[2.5]octane-6,7-diol Chemical compound C(#CC)[C@@H]1[C@H]([C@@H](CNC12CC2)O)O CFLYIQUIFBLZQN-IWSPIJDZSA-N 0.000 claims 2
- FDKSMHXBSQZVST-IWSPIJDZSA-N (6R,7R,8S)-8-propyl-4-azaspiro[2.5]octane-6,7-diol Chemical compound C(CC)[C@@H]1[C@H]([C@@H](CNC12CC2)O)O FDKSMHXBSQZVST-IWSPIJDZSA-N 0.000 claims 2
- OZMBWHOGRHGGHS-VGMNWLOBSA-N (6R,7R,8S)-N-cyclopropyl-6,7-dihydroxy-4-azaspiro[2.5]octane-8-carboxamide Chemical compound C1(CC1)NC(=O)[C@@H]1[C@H]([C@@H](CNC12CC2)O)O OZMBWHOGRHGGHS-VGMNWLOBSA-N 0.000 claims 2
- TYUVSEJCCYQRRS-DSYKOEDSSA-N (6R,7S,8S)-8-methoxy-4-azaspiro[2.5]octane-6,7-diol Chemical compound CO[C@@H]1[C@H]([C@@H](CNC12CC2)O)O TYUVSEJCCYQRRS-DSYKOEDSSA-N 0.000 claims 2
- MFUFEXHORIKDTD-FSDSQADBSA-N (6r,7r,8s)-8-(fluoromethyl)-4-azaspiro[2.5]octane-6,7-diol Chemical compound FC[C@@H]1[C@@H](O)[C@H](O)CNC11CC1 MFUFEXHORIKDTD-FSDSQADBSA-N 0.000 claims 2
- 102000004190 Enzymes Human genes 0.000 claims 2
- 108090000790 Enzymes Proteins 0.000 claims 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims 2
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims 2
- 208000036757 Postencephalitic parkinsonism Diseases 0.000 claims 2
- 208000027061 mild cognitive impairment Diseases 0.000 claims 2
- 230000004770 neurodegeneration Effects 0.000 claims 2
- 201000001119 neuropathy Diseases 0.000 claims 2
- 230000007823 neuropathy Effects 0.000 claims 2
- 208000000170 postencephalitic Parkinson disease Diseases 0.000 claims 2
- NCVMRSPXAUZSMD-NQMVMOMDSA-N (6R,7R,8S)-8-(4,4-difluorobut-1-ynyl)-4-azaspiro[2.5]octane-6,7-diol Chemical compound FC(CC#C[C@@H]1[C@H]([C@@H](CNC12CC2)O)O)F NCVMRSPXAUZSMD-NQMVMOMDSA-N 0.000 claims 1
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims 1
- -1 2,2-difluorovinyl Chemical group 0.000 claims 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims 1
- 208000023697 ABri amyloidosis Diseases 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 208000004434 Calcinosis Diseases 0.000 claims 1
- 208000033647 Classic progressive supranuclear palsy syndrome Diseases 0.000 claims 1
- 208000028698 Cognitive impairment Diseases 0.000 claims 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims 1
- 201000010374 Down Syndrome Diseases 0.000 claims 1
- 208000010412 Glaucoma Diseases 0.000 claims 1
- 206010018341 Gliosis Diseases 0.000 claims 1
- 208000023105 Huntington disease Diseases 0.000 claims 1
- 201000000162 ITM2B-related cerebral amyloid angiopathy 1 Diseases 0.000 claims 1
- 208000009829 Lewy Body Disease Diseases 0.000 claims 1
- 201000002832 Lewy body dementia Diseases 0.000 claims 1
- 208000015439 Lysosomal storage disease Diseases 0.000 claims 1
- 208000001089 Multiple system atrophy Diseases 0.000 claims 1
- 206010068871 Myotonic dystrophy Diseases 0.000 claims 1
- 206010029240 Neuritis Diseases 0.000 claims 1
- 208000014060 Niemann-Pick disease Diseases 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- 208000027089 Parkinsonian disease Diseases 0.000 claims 1
- 206010034010 Parkinsonism Diseases 0.000 claims 1
- 208000024777 Prion disease Diseases 0.000 claims 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 claims 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 claims 1
- 102000019355 Synuclein Human genes 0.000 claims 1
- 108050006783 Synuclein Proteins 0.000 claims 1
- 206010044688 Trisomy 21 Diseases 0.000 claims 1
- 208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 claims 1
- 238000009825 accumulation Methods 0.000 claims 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims 1
- 210000004227 basal ganglia Anatomy 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 230000002308 calcification Effects 0.000 claims 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims 1
- 210000000349 chromosome Anatomy 0.000 claims 1
- 230000001054 cortical effect Effects 0.000 claims 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 1
- 230000007387 gliosis Effects 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
- 206010022437 insomnia Diseases 0.000 claims 1
- 229910052742 iron Inorganic materials 0.000 claims 1
- 231100000518 lethal Toxicity 0.000 claims 1
- 230000001665 lethal effect Effects 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 208000015122 neurodegenerative disease Diseases 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000651 prodrug Substances 0.000 claims 1
- 229940002612 prodrug Drugs 0.000 claims 1
- 208000032207 progressive 1 supranuclear palsy Diseases 0.000 claims 1
- 230000000750 progressive effect Effects 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 201000000980 schizophrenia Diseases 0.000 claims 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 1
- 229920002554 vinyl polymer Polymers 0.000 claims 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361920160P | 2013-12-23 | 2013-12-23 | |
| US61/920,160 | 2013-12-23 | ||
| US201462005196P | 2014-05-30 | 2014-05-30 | |
| US62/005,196 | 2014-05-30 | ||
| PCT/CA2014/051252 WO2015095963A1 (en) | 2013-12-23 | 2014-12-22 | Glucocerebrosidase modulators and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2017502961A JP2017502961A (ja) | 2017-01-26 |
| JP2017502961A5 true JP2017502961A5 (enExample) | 2018-02-08 |
Family
ID=53477250
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016543197A Pending JP2017502961A (ja) | 2013-12-23 | 2014-12-22 | グルコセレブロシダーゼモジュレーターおよびその使用 |
Country Status (4)
| Country | Link |
|---|---|
| US (2) | US9796680B2 (enExample) |
| EP (1) | EP3087056A4 (enExample) |
| JP (1) | JP2017502961A (enExample) |
| WO (1) | WO2015095963A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105631432B (zh) * | 2016-01-04 | 2020-12-08 | 京东方科技集团股份有限公司 | 指纹探测电路及驱动方法和显示装置 |
| CA3043709A1 (en) * | 2016-11-14 | 2018-05-17 | Berg Llc | Methods for treating parkinson's disease |
| EA202091032A1 (ru) * | 2017-10-26 | 2020-07-17 | Шайр Хьюман Дженетик Терапиз, Инк. | Составы, содержащие глюкоцереброзидазу и изофагомин |
| CN108530375B (zh) * | 2018-05-29 | 2020-04-21 | 南京药石科技股份有限公司 | 4-氧杂-7-氮杂螺[2.5]辛烷或其盐的中间体及制备方法 |
| US20220184185A1 (en) | 2018-07-25 | 2022-06-16 | Modernatx, Inc. | Mrna based enzyme replacement therapy combined with a pharmacological chaperone for the treatment of lysosomal storage disorders |
| EP3959196A4 (en) * | 2019-04-25 | 2023-04-12 | Takeda Pharmaceutical Company Limited | ISOFAGOMIN SALTS, METHODS OF USE AND FORMULATIONS |
| WO2020223136A1 (en) * | 2019-05-02 | 2020-11-05 | Merck Sharp & Dohme Corp. | Spiropiperidine allosteric modulators of nicotinic acetylcholine receptors |
| BR112023022567A2 (pt) * | 2021-04-30 | 2024-02-06 | Vanqua Bio Inc | Moduladores de molécula pequena de atividade de glicocerebrosidase e usos dos mesmos |
| EP4329881A4 (en) * | 2021-04-30 | 2025-06-11 | Vanqua Bio, Inc. | Small molecule modulators of glucocerebrosidase activity and uses thereof |
| PE20242105A1 (es) * | 2021-10-13 | 2024-10-28 | Vanqua Bio Inc | Moduladores de micromoleculas de la actividad de la glucocerebrosidasa y usos de estos |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1901907A (zh) | 2003-11-12 | 2007-01-24 | 阿米库斯治疗学公司 | 用于治疗戈谢病的葡糖并咪唑和多羟基环己烯基胺衍生物 |
| WO2006065686A2 (en) * | 2004-12-13 | 2006-06-22 | Galileo Pharmaceuticals, Inc. | Spiro derivatives as lipoxygenase inhibitors |
| EP2040548B1 (en) | 2006-06-23 | 2012-05-02 | Amicus Therapeutics, Inc. | Method for the treatment of neurological disorders by enhancing the activity of beta -glucocerebrosidase |
| WO2010118282A1 (en) | 2009-04-09 | 2010-10-14 | Amicus Therapeutics, Inc. | Methods for preventing and/or treating degenerative disorders of the central nervous system |
| MX337933B (es) | 2009-10-19 | 2016-03-29 | Amicus Therapeutics Inc | Nuevas composiciones para prevenir y/o tratar trastornos de almacenamiento lisosomal. |
| KR101769396B1 (ko) * | 2009-10-19 | 2017-08-18 | 아미쿠스 세라퓨틱스, 인코포레이티드 | 중추신경계의 퇴행성 질환을 예방 및/또는 치료하는 신규 조성물 |
| EP2632260A4 (en) * | 2010-10-29 | 2015-06-17 | Merck Sharp & Dohme | LEUCINREICH REPEAT KINASE ENZYME ACTIVITY |
| WO2013075227A1 (en) * | 2011-11-25 | 2013-05-30 | The Hospital For Sick Children | β-GLUCOCEREBROSIDASE CHAPERONES |
| MX354127B (es) | 2012-03-27 | 2018-02-14 | Amicus Therapeutics Inc | Compuestos novedosos para prevenir y/o tratar tesaurismosis lisosomicas y/o trastornos degenerativos del sistema nervioso central. |
-
2014
- 2014-12-22 JP JP2016543197A patent/JP2017502961A/ja active Pending
- 2014-12-22 US US15/107,269 patent/US9796680B2/en not_active Expired - Fee Related
- 2014-12-22 EP EP14875019.3A patent/EP3087056A4/en not_active Withdrawn
- 2014-12-22 WO PCT/CA2014/051252 patent/WO2015095963A1/en not_active Ceased
-
2017
- 2017-09-21 US US15/711,301 patent/US10081601B2/en active Active
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