CA2196529A1 - Procedes permettant de traiter et/ou de prevenir la maladie d'alzheimer a l'aide de phenothiazines et/ou de thioxanthenes - Google Patents
Procedes permettant de traiter et/ou de prevenir la maladie d'alzheimer a l'aide de phenothiazines et/ou de thioxanthenesInfo
- Publication number
- CA2196529A1 CA2196529A1 CA002196529A CA2196529A CA2196529A1 CA 2196529 A1 CA2196529 A1 CA 2196529A1 CA 002196529 A CA002196529 A CA 002196529A CA 2196529 A CA2196529 A CA 2196529A CA 2196529 A1 CA2196529 A1 CA 2196529A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- carbon atoms
- lower alkyl
- hydrogen
- alkyl
- 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
- 238000000034 method Methods 0.000 title claims abstract description 50
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 17
- 150000005075 thioxanthenes Chemical class 0.000 title claims description 6
- 150000002990 phenothiazines Chemical class 0.000 title claims description 5
- 238000009825 accumulation Methods 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 64
- -1 monomethylamino, monoethylamino, dimethylamino, diethylamino, pyrrolidino Chemical group 0.000 claims description 37
- 125000004432 carbon atom Chemical group C* 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 150000001875 compounds Chemical class 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000001931 aliphatic group Chemical group 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical group 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 125000004193 piperazinyl group Chemical group 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- ZEWQUBUPAILYHI-UHFFFAOYSA-N trifluoperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 ZEWQUBUPAILYHI-UHFFFAOYSA-N 0.000 claims description 6
- 229960002324 trifluoperazine Drugs 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000005936 piperidyl group Chemical group 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
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- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
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- 125000002252 acyl group Chemical group 0.000 claims description 3
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- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 claims description 3
- 229960001076 chlorpromazine Drugs 0.000 claims description 3
- 125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 3
- XSCGXQMFQXDFCW-UHFFFAOYSA-N triflupromazine Chemical compound C1=C(C(F)(F)F)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 XSCGXQMFQXDFCW-UHFFFAOYSA-N 0.000 claims description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 claims description 2
- GFBKORZTTCHDGY-UWVJOHFNSA-N Thiothixene Chemical compound C12=CC(S(=O)(=O)N(C)C)=CC=C2SC2=CC=CC=C2\C1=C\CCN1CCN(C)CC1 GFBKORZTTCHDGY-UWVJOHFNSA-N 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 125000006267 biphenyl group Chemical group 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 claims description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001302 tertiary amino group Chemical group 0.000 claims description 2
- 150000003254 radicals Chemical class 0.000 claims 2
- RGCVKNLCSQQDEP-UHFFFAOYSA-N Perphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 RGCVKNLCSQQDEP-UHFFFAOYSA-N 0.000 claims 1
- NUKVZKPNSKJGBK-SPIKMXEPSA-N acetophenazine dimaleate Chemical compound [H+].[H+].[H+].[H+].[O-]C(=O)\C=C/C([O-])=O.[O-]C(=O)\C=C/C([O-])=O.C12=CC(C(=O)C)=CC=C2SC2=CC=CC=C2N1CCCN1CCN(CCO)CC1 NUKVZKPNSKJGBK-SPIKMXEPSA-N 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
- 229950000688 phenothiazine Drugs 0.000 abstract description 6
- PQJUJGAVDBINPI-UHFFFAOYSA-N 9H-thioxanthene Chemical compound C1=CC=C2CC3=CC=CC=C3SC2=C1 PQJUJGAVDBINPI-UHFFFAOYSA-N 0.000 abstract description 5
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 abstract description 3
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- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 16
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- LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (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
On décrit des procédés qui permettent de prévenir ou traiter la maladie d'Alzheimer et consistent à administrer à un patient une quantité d'une phénothiazine ou d'un thioxanthène efficace pour prévenir ou diminuer l'accumulation d'épitopes anormalement phosphorylés, à filaments hélicoïdaux appariés, qui sont associés à la maladie d'Alzheimer.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28733994A | 1994-08-08 | 1994-08-08 | |
| US08/287,339 | 1994-08-08 | ||
| US34675794A | 1994-11-30 | 1994-11-30 | |
| US08/346,757 | 1994-11-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2196529A1 true CA2196529A1 (fr) | 1996-02-22 |
Family
ID=26964404
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002196529A Abandoned CA2196529A1 (fr) | 1994-08-08 | 1995-08-07 | Procedes permettant de traiter et/ou de prevenir la maladie d'alzheimer a l'aide de phenothiazines et/ou de thioxanthenes |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0778773A1 (fr) |
| KR (1) | KR970704445A (fr) |
| AU (1) | AU708682B2 (fr) |
| CA (1) | CA2196529A1 (fr) |
| WO (1) | WO1996004915A1 (fr) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9506197D0 (en) | 1995-03-27 | 1995-05-17 | Hoffmann La Roche | Inhibition of tau-tau association. |
| AU7260398A (en) * | 1997-04-28 | 1998-11-24 | University Of British Columbia, The | Method and composition for modulating amyloidosis |
| GB9713484D0 (en) * | 1997-06-27 | 1997-09-03 | Smithkline Beecham Plc | Neuroprotective vanilloid compounds |
| DE19842416A1 (de) * | 1998-09-16 | 2000-04-13 | Max Planck Gesellschaft | Sekundäre Amine zur Prävention und Therapie von Erkrankungen, die durch Oxidationsprozesse verursacht oder verstärkt werden |
| GB0017060D0 (en) * | 2000-07-11 | 2000-08-30 | Hunter Fleming Ltd | Production, stabilisation and use of reduced forms of pharmaceutical compounds |
| GB0100119D0 (en) | 2001-01-03 | 2001-02-14 | Univ Aberdeen | Materials and methods relating to protein aggregation in neurodegenerative disease |
| GB0101049D0 (en) | 2001-01-15 | 2001-02-28 | Univ Aberdeen | Materials and methods relating to protein aggregation in neurodegenerative disease |
| GB0106953D0 (en) | 2001-03-20 | 2001-05-09 | Univ Aberdeen | Neufofibrillary labels |
| GB0117326D0 (en) | 2001-07-16 | 2001-09-05 | Univ Aberdeen | Napthoquinone-type inhibitors of protein aggregation |
| EP1470818B1 (fr) * | 2003-04-25 | 2006-07-26 | Neuro3D | Utilisation de dérivés de phénothiazine pipérazine pour la préparation d'un médicament ayant des effets neuroprotecteurs et/ou neurotrophiques sur le SNC et/ou SNP |
| US7414076B2 (en) | 2003-06-23 | 2008-08-19 | Neurochem (International) Limited | Methods and compositions for treating amyloid-related diseases |
| US7244764B2 (en) | 2003-06-23 | 2007-07-17 | Neurochem (International) Limited | Methods and compositions for treating amyloid-related diseases |
| US7790881B2 (en) | 2004-09-23 | 2010-09-07 | Wista Laboratories Ltd. | Methods of chemical synthesis and purification of diaminophenothiazinium compounds including methylthioninium chloride (MTC) |
| BRPI0519243A2 (pt) | 2004-12-22 | 2009-01-06 | Neurochem Int Ltd | mÉtodos e composiÇÕes para tratar doenÇas relacionadas a amilàide |
| MY153198A (en) | 2006-03-29 | 2015-01-29 | Wista Lab Ltd | Inhibitors of protein aggregation |
| PL2853293T3 (pl) | 2006-03-29 | 2018-05-30 | Wista Laboratories Ltd. | Związki tioniny i ich zastosowanie |
| ES2349322T7 (es) | 2006-03-29 | 2019-10-17 | Wista Lab Ltd | Sales de 3,7-diamino-10H-fenotiazina y su utilización |
| EP3851447B1 (fr) | 2006-10-12 | 2023-09-06 | Bellus Health Inc. | Procédés, composés, compositions et véhicules pour l'administration d'acide 3-amino-1-propanesulfonique |
| GB0701970D0 (en) * | 2007-02-01 | 2007-03-14 | Wilson Stuart | Treatment of protein aggregation diseases |
| ES2331282B1 (es) * | 2008-06-25 | 2010-10-21 | Consejo Superior De Investigaciones Cientificas (Csic) (45%) | Hidrazidas de sistemas heterociclicos y su uso en el tratamiento de enfermedades neurodegenerativas. |
| DE102010062810B4 (de) * | 2010-09-07 | 2014-03-13 | Immungenetics Ag | 2-(R2-Thio)-10-[3-(4-R1-piperazin-1-yl)propyl]-10H-phenothiazine zur Behandlung neurodegenerativer Erkrankungen ausgewählt aus beta-Amyloidopathien und alpha-Synucleinopathien |
| AU2011358840B2 (en) | 2011-02-11 | 2017-05-04 | TauRx Therapeutics Management Ltd | Phenothiazine diaminium salts and their use |
| WO2012166862A1 (fr) | 2011-06-01 | 2012-12-06 | Wisconsin Alumni Research Foundation | Compositions et méthodes pour le traitement de la maladie d'alzheimer |
| EP4241774A1 (fr) * | 2020-11-04 | 2023-09-13 | Gliacelltech Inc. | Composition pour la prévention ou le traitement de maladies neuro-inflammatoires, comprenant de la chlorpromazine |
| US20240025868A1 (en) * | 2020-11-13 | 2024-01-25 | Icahn School Of Medicine At Mount Sinai | Phenothiazine compounds for the treatment of alzheimer's disease and other age-related and neurological diseases |
| CN118510519A (zh) * | 2022-01-04 | 2024-08-16 | 免疫基因股份公司 | 用于在治疗或预防阿尔茨海默痴呆中使用的特定剂量的吩噻嗪化合物 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2837518A (en) * | 1958-06-03 | Phenthiazine compounds | ||
| US2902484A (en) * | 1954-04-27 | 1959-09-01 | Rhone Poulenc Sa | Phenthiazine derivatives and processes for their preparation |
| NL108827C (fr) * | 1956-04-09 |
-
1995
- 1995-08-07 CA CA002196529A patent/CA2196529A1/fr not_active Abandoned
- 1995-08-07 EP EP95929441A patent/EP0778773A1/fr not_active Withdrawn
- 1995-08-07 AU AU32793/95A patent/AU708682B2/en not_active Ceased
- 1995-08-07 WO PCT/US1995/010110 patent/WO1996004915A1/fr not_active Ceased
-
1997
- 1997-02-10 KR KR1019970700943A patent/KR970704445A/ko not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO1996004915A1 (fr) | 1996-02-22 |
| AU3279395A (en) | 1996-03-07 |
| EP0778773A1 (fr) | 1997-06-18 |
| KR970704445A (ko) | 1997-09-06 |
| AU708682B2 (en) | 1999-08-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |