ES2347321T3 - Metanosulfonato de 8-(4-(3-(5-fluoro-1h-indol-3-il)propil)-1-piperazininil)-2-metil-2h-1,4-benzoxazin-3(4h)-dna con alta afinidad por el receptor d2 de la dopamina y el sitio de reabsorcion de la serotonina. - Google Patents
Metanosulfonato de 8-(4-(3-(5-fluoro-1h-indol-3-il)propil)-1-piperazininil)-2-metil-2h-1,4-benzoxazin-3(4h)-dna con alta afinidad por el receptor d2 de la dopamina y el sitio de reabsorcion de la serotonina. Download PDFInfo
- Publication number
- ES2347321T3 ES2347321T3 ES02719880T ES02719880T ES2347321T3 ES 2347321 T3 ES2347321 T3 ES 2347321T3 ES 02719880 T ES02719880 T ES 02719880T ES 02719880 T ES02719880 T ES 02719880T ES 2347321 T3 ES2347321 T3 ES 2347321T3
- Authority
- ES
- Spain
- Prior art keywords
- dopamine
- site
- benzoxazin
- indol
- fluoro
- 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.)
- Expired - Lifetime
Links
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 title description 5
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 title description 3
- 229960003638 dopamine Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims 1
- 208000015114 central nervous system disease Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- 239000012458 free base Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- -1 5-Fluoro-1H-indol-3-yl Chemical group 0.000 description 2
- 102000004980 Dopamine D2 Receptors Human genes 0.000 description 2
- 108090001111 Dopamine D2 Receptors Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000020114 Schizophrenia and other psychotic disease Diseases 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 229940005530 anxiolytics Drugs 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical class C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 230000000697 serotonin reuptake Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 1
- 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 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 208000009132 Catalepsy Diseases 0.000 description 1
- 101150049660 DRD2 gene Proteins 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 208000012886 Vertigo Diseases 0.000 description 1
- 206010047853 Waxy flexibility Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 1
- 229960004046 apomorphine Drugs 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 231100000889 vertigo Toxicity 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
Compuesto de la fórmula **(Ver fórmula)**
Description
Metanosulfonato de
8-{4-[3-(5-fluoro-1H-indol-3-il)propil]-1-piperazinil}-2-metil-2H-1,4-benzoxazin-3(4H)-
DNA con alta afinidad por el receptor D_{2} de la dopamina y el sitio de reabsorción de la serotonina.
DNA con alta afinidad por el receptor D_{2} de la dopamina y el sitio de reabsorción de la serotonina.
La invención se refiere al nuevo derivado de
fenilpiperazina de la fórmula (I):
\vskip1.000000\baselineskip
La solicitud de patente WO 01/14330 A se refiere
a un grupo de nuevas fenilpiperazinas. Los compuestos de ese grupo
muestran alta afinidad tanto por el receptor D_{2} de la dopamina
como por el sitio de recaptación de la serotonina. Esta combinación
es útil para el tratamiento de la esquizofrenia y otros trastornos
psicóticos lo cual permite un tratamiento más completo de todos los
síntomas de la enfermedad (p. ej., síntomas positivos y síntomas
negati-
vos).
vos).
Los compuestos muestran actividad como
antagonistas en los receptores D_{2} de la dopamina pues
potencialmente son antagónicos del comportamiento de escalada
inducido por apomorfina en ratones. Los compuestos también muestran
actividad como inhibidores de la recaptación de la serotonina, pues
potencian el comportamiento inducido por
5-HTP en ratones.
5-HTP en ratones.
Los compuestos son activos en modelos
terapéuticos sensibles a antipsicóticos clínicamente relevantes (p.
ej., la respuesta condicionada de evitación; Van der Heyden &
Bradford, Behav. Brain Res., 1988, 31:61-67) y
antidepresivos o ansiolíticos (p. ej., supresión de la vocalización
inducida por el estrés; Van der Poel et al.,
Psychopharmacology, 1989, 97:147-148).
En contraste con los antagonistas del receptor
D_{2} de la dopamina clínicamente relevante, los compuestos
descritos tienen baja propensión a inducir catalepsia en roedores y
como tales es probable que induzcan menos efectos secundarios
extrapiramidales que los agentes antipsicóticos existentes.
La actividad inhibitoria de la recaptación de la
serotonina inherente en estos compuestos puede ser responsable de
los efectos terapéuticos observados en modelos de comportamiento
sensibles a o antidepresivos o ansiolíticos.
Los compuestos se pueden usar para el
tratamiento de afecciones o enfermedades del sistema nervioso
central producidas por perturbaciones en los sistemas o
dopaminérgicos o serotonérgicos, por ejemplo: agresión, trastornos
de la ansiedad, autismo, vértigo, depresión, perturbaciones de la
percepción o la memoria, enfermedad de Parkinson y, en particular,
la esquizofrenia y otros trastornos psicóticos.
Se ha encontrado ahora que el mesilato de la
fórmula anterior tiene propiedades particularmente favorables en
comparación con la base libre (es decir, el compuesto nº 89 del
documento EP 99202710.2).
Este compuesto de mesilato es mucho mejor
soluble en agua que la base libre, dando como resultado una buena
biodisponibilidad.
El compuesto tiene un centro de quiralidad;
tanto la mezcla racémica como los enantiómeros individuales
pertenecen a la invención.
El compuesto se puede hacer en formas apropiadas
para la administración por medio de procedimientos apropiados
usando sustancias auxiliares tales como materiales vehículos
líquidos y sólidos.
La base libre de los compuestos se puede
preparar como se describe en el documento EP 99202710.2.
La base libre se puede convertir en el mesilato
según procedimientos conocidos per se para la formación de
la sal.
La invención se ilustra por medio del siguiente
ejemplo.
Ejemplo
2,0 g (4,7 mmol) de la base libre obtenible como
se describe en el documento EP 99202710.2 (compuesto nº 89) se
suspenden en 40 ml de metanol. La suspensión se calienta hasta 60ºC,
y se añade una solución de 0,45 g (4,7 mmol) de ácido
metanosulfónico en 10 ml de metanol en alrededor de dos minutos. Se
obtiene una solución clara. Después de agitar durante 5 minutos a
60ºC comienza la cristalización. La solución se enfría lentamente
en 60 minutos hasta 20ºC, y se agita a esa temperatura durante 30
minutos. Se lleva a cabo enfriamiento adicional hasta 0ºC en 60
minutos y agitación durante 90 minutos. El material sólido se aísla
por medio de filtración, se lava con 5 ml de metanol y se seca
durante una noche a 50ºC bajo presión reducida. Rendimiento 2,17 g
(88%) de mesilato de color blanco.
Claims (3)
1. Compuesto de la fórmula
2. Composición farmacéutica para tratar
trastornos del SNC, caracterizada porque contiene el
compuesto de la reivindicación 1 como un ingrediente activo.
3. Uso del compuesto de la reivindicación 1 para
la preparación de un medicamento para el tratamiento de trastornos
del SNC.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01200610 | 2001-02-21 | ||
| EP01200610 | 2001-02-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2347321T3 true ES2347321T3 (es) | 2010-10-28 |
Family
ID=8179909
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02719880T Expired - Lifetime ES2347321T3 (es) | 2001-02-21 | 2002-02-19 | Metanosulfonato de 8-(4-(3-(5-fluoro-1h-indol-3-il)propil)-1-piperazininil)-2-metil-2h-1,4-benzoxazin-3(4h)-dna con alta afinidad por el receptor d2 de la dopamina y el sitio de reabsorcion de la serotonina. |
Country Status (24)
| Country | Link |
|---|---|
| US (2) | US6958396B2 (es) |
| EP (1) | EP1366044B1 (es) |
| JP (1) | JP4216072B2 (es) |
| KR (1) | KR100859107B1 (es) |
| CN (1) | CN1284780C (es) |
| AR (1) | AR032712A1 (es) |
| AT (1) | ATE472545T1 (es) |
| AU (1) | AU2002250983B2 (es) |
| BR (1) | BR0206162A (es) |
| CA (1) | CA2430707C (es) |
| CZ (1) | CZ20032171A3 (es) |
| DE (1) | DE60236848D1 (es) |
| DZ (1) | DZ3490A1 (es) |
| ES (1) | ES2347321T3 (es) |
| HU (1) | HUP0303330A3 (es) |
| IL (1) | IL155720A0 (es) |
| MX (1) | MXPA03007430A (es) |
| NO (1) | NO325298B1 (es) |
| NZ (1) | NZ526018A (es) |
| PL (1) | PL201176B1 (es) |
| RU (1) | RU2281945C2 (es) |
| SK (1) | SK10412003A3 (es) |
| WO (1) | WO2002066473A1 (es) |
| ZA (1) | ZA200304267B (es) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL148218A0 (en) * | 1999-08-23 | 2002-09-12 | Solvay Pharm Bv | New phenylpiperazines |
| AR032712A1 (es) * | 2001-02-21 | 2003-11-19 | Solvay Pharm Bv | Un mesilato de derivados de fenilpiperazina y composiciones farmaceuticas que lo contienen |
| KR20070091646A (ko) * | 2004-12-07 | 2007-09-11 | 솔베이 파마슈티칼스 비. 브이 | 도파민-ｄ2 수용체 및 세로토닌 재흡수 위치에 대한친화도를 함께 갖는 페닐피페라진 |
| US7371769B2 (en) | 2004-12-07 | 2008-05-13 | Solvay Pharmaceuticals B.V. | Tetrahydropyridin-4-yl indoles with a combination of affinity for dopamine-D2 receptors and serotonin reuptake sites |
| US8101619B2 (en) | 2004-12-08 | 2012-01-24 | Solvay Pharmaceuticals B.V. | Phenylpiperazine derivatives with a combination of partial dopamine-D2 receptor agonism and serotonin reuptake inhibition |
| AR055424A1 (es) * | 2005-09-12 | 2007-08-22 | Wyeth Corp | Formulacion de liberacion sostenida y usos de la misma |
| GT200600416A (es) | 2005-09-12 | 2007-09-20 | Sales salicilato y gentisato de un compuesto de piperazina | |
| GT200600414A (es) * | 2005-09-12 | 2007-09-20 | Sal de glucuranato de compuesto de piperazine | |
| US9066903B2 (en) | 2006-02-28 | 2015-06-30 | The United States Of America As Represented By The Department Of Veterans Affairs | Pharmacological treatment of Parkinson's disease |
Family Cites Families (104)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1075156A (en) | 1963-08-27 | 1967-07-12 | Luso Farmaco Inst | Substituted piperazines |
| SE381564B (sv) * | 1973-03-19 | 1975-12-15 | Stiftelsen Teknisk Hjelp At Ha | Eldriven rullstol |
| US4018440A (en) * | 1975-03-31 | 1977-04-19 | Deutsch Fritz A | Invalid walker with wheel control mechanism |
| US4076270A (en) * | 1976-01-19 | 1978-02-28 | General Motors Corporation | Foldable cambering vehicle |
| US4088199A (en) * | 1976-02-23 | 1978-05-09 | Wolfgang Trautwein | Stabilized three-wheeled vehicle |
| BE841212A (nl) * | 1976-04-28 | 1976-08-16 | Sportvoertuig | |
| US4062558A (en) * | 1976-07-19 | 1977-12-13 | David Wasserman | Unicycle |
| US4094372A (en) * | 1977-02-28 | 1978-06-13 | Notter Michael A | Motorized skateboard with uni-directional rear mounting |
| US4111445A (en) * | 1977-06-09 | 1978-09-05 | Kenneth Haibeck | Device for supporting a paraplegic in an upright position |
| US4109741A (en) * | 1977-07-29 | 1978-08-29 | Gabriel Charles L | Motorized unicycle wheel |
| DE2807517C3 (de) * | 1978-02-22 | 1980-12-04 | Habegger, Willy, Huenibach Bei Thun (Schweiz) | Fahr- und Schreitwerk für Fahrzeuge, insbesondere fahrbare Krane, Bagger u.dgl |
| US4222449A (en) * | 1978-06-08 | 1980-09-16 | Feliz Jack M | Step-climbing wheel chair |
| US4293052A (en) * | 1978-07-17 | 1981-10-06 | Daswick Alexander C | Lightweight two-wheeled vehicle |
| US4264082A (en) * | 1979-03-26 | 1981-04-28 | Fouchey Jr Charles J | Stair climbing cart |
| DE2915387A1 (de) * | 1979-04-14 | 1980-10-16 | Heinz Eichholz | Elektrofahrzeug |
| US4325565A (en) * | 1980-03-03 | 1982-04-20 | General Motors Corporation | Cambering vehicle |
| US4373600A (en) * | 1980-07-18 | 1983-02-15 | Veda, Inc. | Three wheel drive vehicle |
| US4363493A (en) * | 1980-08-29 | 1982-12-14 | Veneklasen Paul S | Uni-wheel skate |
| US4740001A (en) * | 1981-09-14 | 1988-04-26 | Torleumke Keith R | Sprag wheel |
| US4375840A (en) * | 1981-09-23 | 1983-03-08 | Campbell Jack L | Mobile support |
| US4566707A (en) * | 1981-11-05 | 1986-01-28 | Nitzberg Leonard R | Wheel chair |
| US4570078A (en) * | 1982-05-27 | 1986-02-11 | Honda Giken Kogyo Kabushiki Kaisha | Switch assembly for a motor vehicle |
| AU554344B2 (en) * | 1982-06-09 | 1986-08-14 | Jeco Co. Ltd. | Magnetically damped angle change detector |
| JPS6025302U (ja) * | 1983-07-22 | 1985-02-21 | アツプリカ葛西株式会社 | 電動式子供用乗物 |
| US4510956A (en) * | 1983-08-15 | 1985-04-16 | Lorraine King | Walking aid, particularly for handicapped persons |
| FR2576863A1 (fr) * | 1985-01-31 | 1986-08-08 | Brunet Pierre | Dispositif de deplacement motorise, par exemple pour monter et descendre des escaliers |
| GB8515992D0 (en) * | 1985-06-25 | 1985-07-31 | Hester R | Wheelchair |
| US4657272A (en) * | 1985-09-11 | 1987-04-14 | Davenport James M | Wheeled vehicle |
| US4624469A (en) * | 1985-12-19 | 1986-11-25 | Bourne Jr Maurice W | Three-wheeled vehicle with controlled wheel and body lean |
| US4867188A (en) * | 1986-01-28 | 1989-09-19 | Michael Reid | Orthopaedic trolley |
| US4716980A (en) * | 1986-02-14 | 1988-01-05 | The Prime Mover Company | Control system for rider vehicles |
| US4786069A (en) * | 1986-06-30 | 1988-11-22 | Tang Chun Yi | Unicycle |
| US4770410A (en) * | 1986-07-03 | 1988-09-13 | Brown Guies L | Walker |
| GB8618044D0 (en) * | 1986-07-24 | 1986-09-03 | Sheeter E | Vehicle |
| WO1988000899A1 (en) * | 1986-07-28 | 1988-02-11 | Arthur George Yarrington | Heli-hover amphibious surface effect vehicle |
| US4802542A (en) * | 1986-08-25 | 1989-02-07 | Falcon Rehabilitation Products, Inc. | Powered walker |
| US4809804A (en) * | 1986-08-25 | 1989-03-07 | Falcon Rehabilitation Products, Inc. | Combination wheelchair and walker apparatus |
| US4685693A (en) * | 1986-09-16 | 1987-08-11 | Vadjunec Carl F | Upright wheelchair |
| JPS63150176A (ja) * | 1986-12-15 | 1988-06-22 | 工業技術院長 | 動的歩行ロボツトの歩行制御方法 |
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-
2002
- 2002-02-18 AR ARP020100548A patent/AR032712A1/es not_active Application Discontinuation
- 2002-02-19 RU RU2003114440/04A patent/RU2281945C2/ru not_active IP Right Cessation
- 2002-02-19 MX MXPA03007430A patent/MXPA03007430A/es active IP Right Grant
- 2002-02-19 SK SK1041-2003A patent/SK10412003A3/sk unknown
- 2002-02-19 CZ CZ20032171A patent/CZ20032171A3/cs unknown
- 2002-02-19 ES ES02719880T patent/ES2347321T3/es not_active Expired - Lifetime
- 2002-02-19 BR BR0206162-7A patent/BR0206162A/pt not_active Application Discontinuation
- 2002-02-19 CN CNB028029682A patent/CN1284780C/zh not_active Expired - Fee Related
- 2002-02-19 DZ DZ023490A patent/DZ3490A1/fr active
- 2002-02-19 IL IL15572002A patent/IL155720A0/xx not_active IP Right Cessation
- 2002-02-19 WO PCT/EP2002/001795 patent/WO2002066473A1/en not_active Ceased
- 2002-02-19 US US10/432,225 patent/US6958396B2/en not_active Expired - Fee Related
- 2002-02-19 KR KR1020037010907A patent/KR100859107B1/ko not_active Expired - Fee Related
- 2002-02-19 AU AU2002250983A patent/AU2002250983B2/en not_active Ceased
- 2002-02-19 CA CA2430707A patent/CA2430707C/en not_active Expired - Fee Related
- 2002-02-19 NZ NZ526018A patent/NZ526018A/en unknown
- 2002-02-19 EP EP02719880A patent/EP1366044B1/en not_active Expired - Lifetime
- 2002-02-19 PL PL362288A patent/PL201176B1/pl not_active IP Right Cessation
- 2002-02-19 JP JP2002565987A patent/JP4216072B2/ja not_active Expired - Fee Related
- 2002-02-19 DE DE60236848T patent/DE60236848D1/de not_active Expired - Lifetime
- 2002-02-19 AT AT02719880T patent/ATE472545T1/de not_active IP Right Cessation
- 2002-02-19 HU HU0303330A patent/HUP0303330A3/hu unknown
-
2003
- 2003-05-30 ZA ZA200304267A patent/ZA200304267B/en unknown
- 2003-06-24 NO NO20032914A patent/NO325298B1/no not_active IP Right Cessation
-
2005
- 2005-05-23 US US11/134,455 patent/US8106044B2/en not_active Expired - Fee Related
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