ES2562470T3 - Agente terapéutico o agente profiláctico para la fibromialgia - Google Patents

Agente terapéutico o agente profiláctico para la fibromialgia Download PDF

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ES2562470T3
ES2562470T3 ES11765736.1T ES11765736T ES2562470T3 ES 2562470 T3 ES2562470 T3 ES 2562470T3 ES 11765736 T ES11765736 T ES 11765736T ES 2562470 T3 ES2562470 T3 ES 2562470T3
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atom
agent
formula
hydrogen atom
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Chihiro Yoshida
Kaoru Nakao
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Toray Industries Inc
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Toray Industries Inc
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    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/421—1,3-Oxazoles, e.g. pemoline, trimethadione
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/24—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Pain & Pain Management (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Agente para utilizar en el tratamiento o la profilaxis de la fibromialgia, comprendiendo dicho agente como un ingrediente eficaz un derivado de ciclohexano representado por la fórmula (I):**Fórmula** en el que A es un sustituyente representado por la fórmula (II):**Fórmula** R1 y R2 son cada uno, de manera independiente, un átomo de hidrógeno, un átomo de cloro, un grupo haloalquilo C1-C3, un grupo alquilo C1-C4 o un grupo alcoxi C1-C4; R3 es un átomo de hidrógeno o un átomo de cloro; R4 es un átomo de flúor, un grupo hidroximetilo o un grupo hidroxilo; R5 y R6 son cada uno, de manera independiente, un átomo de hidrógeno, un átomo de flúor, un grupo haloalquilo C1-C3, un grupo carboxilo, un grupo metoxicarbonilo, un grupo etoxicarbonilo, un grupo alcoxi C1-C4, un grupo hidroxilo o un grupo alquilcarboniloxi C2-C5, u, opcionalmente, forman juntos un grupo oxo; R7 y R8 son cada uno, de manera independiente, un átomo de hidrógeno o un átomo de flúor; Z es un átomo de nitrógeno o un grupo metino, o una sal farmacéuticamente aceptable del mismo.

Description

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[Tabla 3]
Compuesto
DE50 (mg/kg) Vehículo
1
3,78 A
2
1,80 A
3
1,40 A
4
1,95 A
5
7,97 B
9
9,92 B
10
0,54 B
11
1,37 B
12
1,77 B
13
5,36 B
14
1,44 B
15
6,07 B
16
1,19 B
41*
3,02 A
43*
7,32 B
46*
9,65 B
48
5,27 B
49
2,69 B
51
4,69 B
53
3,77 A
54
3,73 B
55
0,41 B
58
1,58 A
* Estos compuestos no forman parte de la presente invención. Vehículo A es DMSO:Tween80:agua destilada = 1:1:8; vehículo B es HP-β-CD al 27%
Los compuestos enumerados en la tabla 3 inhibieron la respuesta de retorcimiento en el modelo de ratón con retorcimiento por ácido acético, lo que indica que el compuesto (I) tiene un efecto analgésico sobre el dolor 5 nociceptivo.
(Efectos sobre el modelo de ratón con ligadura parcial del nervio ciático)
Como ejemplo de referencia, se utilizó el modelo de ratón con ligadura parcial del nervio ciático (modelo Seltzer), 10 mediante el cual se puede evaluar el dolor neuropático, para evaluar el efecto analgésico del compuesto (I).
Se prepararon modelos de ratón con ligadura parcial del nervio ciático según el procedimiento de Seltzer (Malmberg y otros, Pain, 1998, volumen 76, pág. 215-222). Se anestesiaron ratones ICR macho de 5 semanas de vida con pentobarbital sódico (70 mg/kg, i.p.), y, a continuación, se expuso el nervio ciático en la región femoral de la
15 extremidad posterior derecha de cada ratón, y el nervio ciático se ligó fuertemente por triplicado con sutura de seda de 8-0 (NATSUME SEISAKUSHO) bajo el microscopio, de manera que sólo la mitad del grosor del nervio quedaba atrapado en la ligadura, cuyos ratones se utilizaron como grupo de ligadura. Los ratones cuyos nervios ciáticos fueron expuestos, pero no ligados, se utilizaron como grupo de cirugía simulada.
20 La evaluación del dolor neuropático (en lo sucesivo como "prueba de von Frey") se llevó a cabo de la siguiente manera. Se acondicionaron los ratones, como mínimo, durante 1 hora en una jaula de acrílico para la medición (NATSUME SEISAKUSHO) colocada en una red de alambres. A continuación, utilizando un filamento (North Coast Medical, Inc. CA, EE.UU.) que ejerció una presión de 0,16 g, se sometieron los ratones a estímulos táctiles
23
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Claims (1)

  1. imagen1
ES11765736.1T 2010-03-31 2011-03-31 Agente terapéutico o agente profiláctico para la fibromialgia Active ES2562470T3 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP2010083721 2010-03-31
JP2010083721 2010-03-31
PCT/JP2011/058218 WO2011125836A1 (ja) 2010-03-31 2011-03-31 線維筋痛症の治療剤又は予防剤

Publications (1)

Publication Number Publication Date
ES2562470T3 true ES2562470T3 (es) 2016-03-04

Family

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ES11765736.1T Active ES2562470T3 (es) 2010-03-31 2011-03-31 Agente terapéutico o agente profiláctico para la fibromialgia

Country Status (13)

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US (1) US8957094B2 (es)
EP (1) EP2554541B1 (es)
JP (1) JP5751168B2 (es)
KR (1) KR101738471B1 (es)
CN (1) CN102822148B (es)
AU (1) AU2011237072B2 (es)
BR (1) BR112012022947B1 (es)
CA (1) CA2793709C (es)
ES (1) ES2562470T3 (es)
MX (1) MX2012010767A (es)
PL (1) PL2554541T3 (es)
RU (1) RU2560168C2 (es)
WO (1) WO2011125836A1 (es)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2560220T3 (es) * 2010-04-28 2016-02-17 Toray Industries, Inc. Agente terapéutico y agente preventivo para la enfermedad de Alzheimer
CA2805371C (en) 2010-07-30 2017-10-31 Toray Industries, Inc. Therapeutic agent or prophylactic agent for neuropathic pain
JPWO2014088106A1 (ja) * 2012-12-06 2017-01-05 株式会社ＰＲＩＳＭ Ｐｈａｒｍａ 線維筋痛症の予防または治療薬
BR112016016674A2 (pt) 2014-01-29 2017-08-08 Toray Industries Agente terapêutico ou profilático para uso no tratamento de esclerose múltipla
KR20180072665A (ko) * 2015-07-28 2018-06-29 베타 캐트 파마슈티칼스, 인코포레이티드 안트라센-9,10-디온 디옥심 화합물 전구약물 및 이의 용도
US11039755B2 (en) 2015-12-03 2021-06-22 Robert S. Katz Methods and systems for diagnosing and treating fibromyalgia
RU2736722C2 (ru) 2016-07-29 2020-11-19 Джапан Тобакко Инк. Способ получения соединения пиразоламида
WO2018181859A1 (ja) * 2017-03-31 2018-10-04 東レ株式会社 抗がん剤誘発末梢神経障害の治療剤又は予防剤

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AUPP608898A0 (en) 1998-09-23 1998-10-15 Fujisawa Pharmaceutical Co., Ltd. New use of prostaglandin E2 antagonists
US6437146B1 (en) * 1998-09-25 2002-08-20 Fujisawa Pharmaceutical Co., Ltd. Oxazole compounds as prostaglandin e2 agonists or antagonists
WO2000066562A1 (en) * 1999-05-03 2000-11-09 Dr. Reddy's Research Foundation Pyrazoles having antiinflammatory activity
JP2006503025A (ja) * 2002-09-05 2006-01-26 サイオス インク． ｐ３８ＭＡＰキナーゼの抑制による疼痛治療
JPWO2007111323A1 (ja) * 2006-03-27 2009-08-13 東レ株式会社 ウレイド誘導体およびその医薬用途
CN101511802A (zh) * 2006-09-13 2009-08-19 阿斯利康(瑞典)有限公司 螺唑烷酮化合物及其作为代谢型谷氨酸受体增效剂的用途
US20080171762A1 (en) * 2007-01-16 2008-07-17 Ockert David M Treatment of pain with naloxone
WO2008105383A1 (ja) 2007-02-26 2008-09-04 Toray Industries, Inc. ピラゾール誘導体およびその医薬用途
TWI435874B (zh) * 2008-10-31 2014-05-01 Toray Industries 環己烷衍生物及其醫藥用途

Also Published As

Publication number Publication date
RU2012146325A (ru) 2014-05-10
JP5751168B2 (ja) 2015-07-22
KR20130052536A (ko) 2013-05-22
BR112012022947A2 (pt) 2020-07-28
AU2011237072A1 (en) 2012-10-18
AU2011237072B2 (en) 2014-09-04
JPWO2011125836A1 (ja) 2013-07-11
CA2793709C (en) 2017-09-12
CN102822148A (zh) 2012-12-12
BR112012022947B1 (pt) 2021-06-15
EP2554541A4 (en) 2013-10-09
EP2554541B1 (en) 2015-12-09
MX2012010767A (es) 2012-10-15
KR101738471B1 (ko) 2017-05-22
RU2560168C2 (ru) 2015-08-20
US8957094B2 (en) 2015-02-17
CN102822148B (zh) 2015-03-11
US20130190503A1 (en) 2013-07-25
PL2554541T3 (pl) 2016-06-30
WO2011125836A1 (ja) 2011-10-13
CA2793709A1 (en) 2011-10-13
EP2554541A1 (en) 2013-02-06

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