JP2010510254A5 - - Google Patents
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- Publication number
- JP2010510254A5 JP2010510254A5 JP2009537460A JP2009537460A JP2010510254A5 JP 2010510254 A5 JP2010510254 A5 JP 2010510254A5 JP 2009537460 A JP2009537460 A JP 2009537460A JP 2009537460 A JP2009537460 A JP 2009537460A JP 2010510254 A5 JP2010510254 A5 JP 2010510254A5
- Authority
- JP
- Japan
- Prior art keywords
- secretase inhibitor
- inositol
- scyllo
- inhibitor
- effective amount
- 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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- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims description 43
- 229940121773 Secretase inhibitor Drugs 0.000 claims description 38
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims description 25
- 229960000367 inositol Drugs 0.000 claims description 24
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 14
- CDAISMWEOUEBRE-CDRYSYESSA-N scyllo-inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O CDAISMWEOUEBRE-CDRYSYESSA-N 0.000 claims description 12
- 230000003941 amyloidogenesis Effects 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 238000004220 aggregation Methods 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 7
- 230000012846 protein folding Effects 0.000 claims description 7
- 238000009825 accumulation Methods 0.000 claims description 6
- 239000002439 beta secretase inhibitor Substances 0.000 claims description 6
- 230000004770 neurodegeneration Effects 0.000 claims description 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
- 230000002688 persistence Effects 0.000 claims description 6
- 230000004845 protein aggregation Effects 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 230000007082 Aβ accumulation Effects 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 230000002776 aggregation Effects 0.000 claims description 3
- 239000003540 gamma secretase inhibitor Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 230000002195 synergetic effect Effects 0.000 claims description 3
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 claims description 2
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 2
- 208000023105 Huntington disease Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 230000009286 beneficial effect Effects 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 206010015037 epilepsy Diseases 0.000 claims description 2
- 238000012423 maintenance Methods 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 239000000651 prodrug Substances 0.000 claims description 2
- 229940002612 prodrug Drugs 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims description 2
- 208000024891 symptom Diseases 0.000 claims description 2
- 230000003977 synaptic function Effects 0.000 claims description 2
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims 3
- 230000015572 biosynthetic process Effects 0.000 claims 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims 3
- 208000037259 Amyloid Plaque Diseases 0.000 claims 2
- 229940125373 Gamma-Secretase Inhibitor Drugs 0.000 claims 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 2
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 claims 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims 2
- 239000000816 peptidomimetic Substances 0.000 claims 2
- 238000002560 therapeutic procedure Methods 0.000 claims 2
- QJYNZEYHSMRWBK-NIKIMHBISA-N 1,2,3,4,6-pentakis-O-galloyl-beta-D-glucose Chemical compound OC1=C(O)C(O)=CC(C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(O)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(O)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(O)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(O)C(O)=C(O)C=2)=C1 QJYNZEYHSMRWBK-NIKIMHBISA-N 0.000 claims 1
- NORCOJNIMIQRNC-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline-2-sulfonamide Chemical compound C1=CC=C2NC(S(=O)(=O)N)CCC2=C1 NORCOJNIMIQRNC-UHFFFAOYSA-N 0.000 claims 1
- ZZHJOZAJYVNDAS-UHFFFAOYSA-N 1,3-thiazole-2,4-dicarboxamide Chemical compound NC(=O)C1=CSC(C(N)=O)=N1 ZZHJOZAJYVNDAS-UHFFFAOYSA-N 0.000 claims 1
- LFWHFZJPXXOYNR-RQZCQDPDSA-N 2-[(3e)-6-fluoro-2-methyl-3-[(4-methylsulfanylphenyl)methylidene]inden-1-yl]acetic acid Chemical compound C1=CC(SC)=CC=C1\C=C/1C2=CC=C(F)C=C2C(CC(O)=O)=C\1C LFWHFZJPXXOYNR-RQZCQDPDSA-N 0.000 claims 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 1
- 229940126077 BACE inhibitor Drugs 0.000 claims 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical class OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims 1
- 230000035508 accumulation Effects 0.000 claims 1
- DXZDEAJXVCLRLE-UHFFFAOYSA-N azepin-2-one Chemical compound O=C1C=CC=CC=N1 DXZDEAJXVCLRLE-UHFFFAOYSA-N 0.000 claims 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims 1
- 229960000590 celecoxib Drugs 0.000 claims 1
- 229940109262 curcumin Drugs 0.000 claims 1
- 235000012754 curcumin Nutrition 0.000 claims 1
- 239000004148 curcumin Substances 0.000 claims 1
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 229960001680 ibuprofen Drugs 0.000 claims 1
- 229960000905 indomethacin Drugs 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 229940124530 sulfonamide Drugs 0.000 claims 1
- 150000003456 sulfonamides Chemical class 0.000 claims 1
- 230000004083 survival effect Effects 0.000 claims 1
- 230000002459 sustained effect Effects 0.000 claims 1
- MURCDOXDAHPNRQ-PJRHAEEISA-N tert-butyl n-[(2s,3r,5s)-6-[[(2s)-1-[[(2s)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-benzyl-3-hydroxy-6-oxo-1-phenylhexan-2-yl]carbamate Chemical group C([C@@H]([C@H](O)C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)CC=1C=CC=CC=1)NC(=O)OC(C)(C)C)C1=CC=CC=C1 MURCDOXDAHPNRQ-PJRHAEEISA-N 0.000 claims 1
- 238000000034 method Methods 0.000 description 9
- 125000000217 alkyl group Chemical group 0.000 description 6
- -1 cycloalkynyl Chemical group 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- CTQJAETYIVEEFX-UHFFFAOYSA-N [N-]=[N+]=NN(N)N=[N+]=[N-] Chemical compound [N-]=[N+]=NN(N)N=[N+]=[N-] CTQJAETYIVEEFX-UHFFFAOYSA-N 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000003302 alkenyloxy group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 230000006933 amyloid-beta aggregation Effects 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- CDAISMWEOUEBRE-NIPYSYMMSA-N epi-inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](O)[C@H]1O CDAISMWEOUEBRE-NIPYSYMMSA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 125000001261 isocyanato group Chemical group *N=C=O 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 125000005000 thioaryl group Chemical group 0.000 description 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86088406P | 2006-11-24 | 2006-11-24 | |
| PCT/CA2007/002118 WO2008061373A1 (en) | 2006-11-24 | 2007-11-22 | Combination treatments for alzheimer's disease and similar diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010510254A JP2010510254A (ja) | 2010-04-02 |
| JP2010510254A5 true JP2010510254A5 (enExample) | 2012-01-12 |
Family
ID=39429352
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009537460A Pending JP2010510254A (ja) | 2006-11-24 | 2007-11-22 | アルツハイマー病および関連の神経変性疾患のための併用処置 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20100292157A1 (enExample) |
| EP (1) | EP2091566A4 (enExample) |
| JP (1) | JP2010510254A (enExample) |
| CA (1) | CA2670405A1 (enExample) |
| WO (1) | WO2008061373A1 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7521481B2 (en) | 2003-02-27 | 2009-04-21 | Mclaurin Joanne | Methods of preventing, treating and diagnosing disorders of protein aggregation |
| WO2008124931A1 (en) * | 2007-04-12 | 2008-10-23 | Joanne Mclaurin | Use of cyclohexanehexol derivatives in the treatment of amyotrophic lateral sclerosis |
| AT506535B1 (de) * | 2008-02-22 | 2010-04-15 | Affiris Forschungs & Entwicklungs Gmbh | Vaccine enthaltend alpha-synuclein-mimotope auf basis von peptiden |
| US9925282B2 (en) | 2009-01-29 | 2018-03-27 | The General Hospital Corporation | Cromolyn derivatives and related methods of imaging and treatment |
| US10058530B2 (en) | 2012-10-25 | 2018-08-28 | The General Hospital Corporation | Combination therapies for the treatment of Alzheimer's disease and related disorders |
| US9855276B2 (en) | 2012-10-25 | 2018-01-02 | The General Hospital Corporation | Combination therapies for the treatment of Alzheimer's disease and related disorders |
| US10525005B2 (en) | 2013-05-23 | 2020-01-07 | The General Hospital Corporation | Cromolyn compositions and methods thereof |
| AU2014340182B2 (en) | 2013-10-22 | 2019-05-23 | The General Hospital Corporation | Cromolyn derivatives and related methods of imaging and treatment |
| GB201416832D0 (en) * | 2014-09-24 | 2014-11-05 | Glaxosmithkline Plc | Methods of treatment |
| LT3209655T (lt) | 2014-10-24 | 2021-01-11 | Landos Biopharma, Inc. | Medicininiai preparatai į lantionino sintezę c panašaus baltymo 2 pagrindu |
| WO2017095250A1 (en) * | 2015-11-30 | 2017-06-08 | Centro De Neurociências E Biologia Celular | Peptide inhibitors of bace1 for the treatment of neurological disorders |
| EP3506894B1 (en) | 2016-08-31 | 2023-08-23 | The General Hospital Corporation | Macrophages/microglia in neuro-inflammation associated with neurodegenerative diseases |
| WO2019017995A1 (en) | 2017-07-20 | 2019-01-24 | Aztherapies, Inc. | FORMULATIONS OF CROMOLYNE SODIUM POWDER AND IBUPROFEN |
| WO2019108418A1 (en) | 2017-11-30 | 2019-06-06 | Landos Biopharma, Inc. | Therapies with lanthionine c-like protein 2 ligands and cells prepared therewith |
| JP2021529771A (ja) | 2018-07-02 | 2021-11-04 | ザ ジェネラル ホスピタル コーポレイション | クロモリンナトリウムおよびα−ラクトースの粉末製剤 |
| US12383528B2 (en) | 2018-12-10 | 2025-08-12 | The General Hospital Corporation | Cromolyn esters and uses thereof |
| CN113748109B (zh) | 2019-12-20 | 2023-07-21 | 朗多生物制药股份有限公司 | 羊毛硫氨酸c样蛋白2配体、用所述配体制备的细胞以及使用所述配体的疗法 |
| JP2023520580A (ja) | 2020-04-06 | 2023-05-17 | ザ ジェネラル ホスピタル コーポレイション | コロナウイルス誘発炎症状態の処置方法 |
| WO2022146914A1 (en) | 2020-12-28 | 2022-07-07 | The General Hospital Corporation | Cromolyn derivatives and uses thereof |
| JP2025530190A (ja) * | 2022-09-07 | 2025-09-11 | エアジェン ファーマ リミテッド | アルツハイマー病治療のための免疫療法薬とｓｃｙｌｌｏ－イノシトールとの組み合わせ |
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| WO2007119108A2 (en) * | 2005-10-13 | 2007-10-25 | Waratah Pharmaceuticals Inc. | Inositol derivatives and their uses in the treatment of diseases characterized by abnormal protein folding or aggregation or amyloid formation, deposition, accumulation or persistence |
| CA2579188A1 (en) * | 2006-02-17 | 2007-08-17 | Joanne Mclaurin | Treatment of amyloid-related diseases |
| EP1996175A4 (en) * | 2006-03-09 | 2009-06-10 | Waratah Pharmaceuticals Inc | CYCLOHEXAN POLYALKOHOL FORMULATION FOR THE TREATMENT OF PROTEIN AGGREGATION DISORDERS |
| WO2008034244A1 (en) * | 2006-09-21 | 2008-03-27 | Waratah Pharmaceuticals Inc. | The combination of a cyclohexanehexol and a nsaid for the treatment of neurodegenerative diseases |
-
2007
- 2007-11-22 WO PCT/CA2007/002118 patent/WO2008061373A1/en not_active Ceased
- 2007-11-22 EP EP07845583A patent/EP2091566A4/en not_active Withdrawn
- 2007-11-22 US US12/445,164 patent/US20100292157A1/en not_active Abandoned
- 2007-11-22 JP JP2009537460A patent/JP2010510254A/ja active Pending
- 2007-11-22 CA CA002670405A patent/CA2670405A1/en not_active Abandoned
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