EA201591793A1 - Лактамные соединения в качестве селективных агонистов ep4-рецепторов для применения при лечении опосредованных ep4 заболеваний и состояний - Google Patents

Лактамные соединения в качестве селективных агонистов ep4-рецепторов для применения при лечении опосредованных ep4 заболеваний и состояний

Info

Publication number
EA201591793A1
EA201591793A1 EA201591793A EA201591793A EA201591793A1 EA 201591793 A1 EA201591793 A1 EA 201591793A1 EA 201591793 A EA201591793 A EA 201591793A EA 201591793 A EA201591793 A EA 201591793A EA 201591793 A1 EA201591793 A1 EA 201591793A1
Authority
EA
Eurasian Patent Office
Prior art keywords
treatment
receptors
states
mediated diseases
selective agonists
Prior art date
Application number
EA201591793A
Other languages
English (en)
Inventor
Стефен Дуглас Баррет
Джозеф Майкл Коломбо
Брэдли Дэвид Джермейн
Грегори Уилльям Эндрес
Андрий Корнилов
Джеймс Бернард Крамер
Адам Узибло
Фред Лоренс Циске
Кирк М. Макси
Джеймс Пол О'Малли
Томас Аллен Оуэн
Original Assignee
Кайман Кемикал Компани, Инк.
МАЙОМЕТРИКС ЭлЭлСи
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Кайман Кемикал Компани, Инк., МАЙОМЕТРИКС ЭлЭлСи filed Critical Кайман Кемикал Компани, Инк.
Publication of EA201591793A1 publication Critical patent/EA201591793A1/ru

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/12—Oxygen or sulfur atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Ophthalmology & Optometry (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Transplantation (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Epidemiology (AREA)
  • Cosmetics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

В заявке раскрыты соединения формулы (I)где L, L, L, L, R, R, R, Rи s определены в описании. Соединения формулы (I) представляют собой агонисты ЕР4, пригодные при лечении глаукомы, остеопороза, перелома кости, потери периодонтальной костной ткани, ортопедической имплантации, алопеции, нейропатической боли и сопутствующих нарушений. Также описаны фармацевтические композиции и способы лечения состояний и нарушений.
EA201591793A 2013-03-15 2014-03-14 Лактамные соединения в качестве селективных агонистов ep4-рецепторов для применения при лечении опосредованных ep4 заболеваний и состояний EA201591793A1 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361793736P 2013-03-15 2013-03-15
PCT/US2014/029057 WO2014144584A2 (en) 2013-03-15 2014-03-14 Lactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated diseases and conditions

Publications (1)

Publication Number Publication Date
EA201591793A1 true EA201591793A1 (ru) 2016-01-29

Family

ID=50897877

Family Applications (1)

Application Number Title Priority Date Filing Date
EA201591793A EA201591793A1 (ru) 2013-03-15 2014-03-14 Лактамные соединения в качестве селективных агонистов ep4-рецепторов для применения при лечении опосредованных ep4 заболеваний и состояний

Country Status (17)

Country Link
US (1) US9688627B2 (ru)
EP (2) EP3235817B1 (ru)
JP (2) JP6317807B2 (ru)
KR (1) KR20150130326A (ru)
CN (1) CN105143217A (ru)
AU (1) AU2014228973B2 (ru)
BR (1) BR112015023080A2 (ru)
CA (1) CA2906134A1 (ru)
DK (1) DK2989098T3 (ru)
EA (1) EA201591793A1 (ru)
ES (1) ES2635635T3 (ru)
HK (1) HK1222170A1 (ru)
IL (2) IL240988A (ru)
PH (1) PH12015502165A1 (ru)
PT (1) PT2989098T (ru)
SG (1) SG11201507470WA (ru)
WO (1) WO2014144584A2 (ru)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106748951B (zh) 2012-07-19 2020-07-24 开曼化学股份有限公司 作为在治疗ep4介导的疾病和病状中使用的ep4受体选择性激动剂的二氟内酰胺化合物
KR20160048054A (ko) 2013-07-19 2016-05-03 카이맨 케미칼 컴파니 인코포레이티드 골 성장의 촉진을 위한 방법, 시스템 및 조성물
CN107365329B (zh) * 2016-05-12 2019-02-01 华东师范大学 一种3-甲基-2-氧代-5-庚炔基磷酸二甲酯的制备方法
MX2020006307A (es) 2017-12-25 2020-09-17 Asahi Kasei Pharma Corp Compuesto ciclico de 6 miembros que contiene nitrogeno.
WO2020205867A1 (en) 2019-04-02 2020-10-08 Aligos Therapeutics, Inc. Compounds targeting prmt5

Family Cites Families (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3975399A (en) 1974-08-06 1976-08-17 E. I. Du Pont De Nemours And Company 1,5-Disubstituted-2-pyrrolidinones, -3-pyrrolin-2-ones, and -4-pyrrolin-2-ones
DE2517771A1 (de) 1975-04-18 1976-10-28 Schering Ag Neue prostaglandin-acetylen-analoga und verfahren zu ihrer herstellung
DE2528664A1 (de) 1975-06-27 1977-01-13 Hoechst Ag Pyrrolidone und verfahren zu ihrer herstellung
CA1085859A (en) 1975-06-27 1980-09-16 Wilhelm Bartmann Pyrrolidones and process for their manufacture
DE2619638A1 (de) 1976-05-04 1977-11-17 Hoechst Ag Pyrrolidone und verfahren zu ihrer herstellung
US4268522A (en) 1976-06-14 1981-05-19 Pfizer Inc. 13,14-Dihydro-15-alkenyl- and 13,14-dihydro-15-alkynyl prostaglandins and analogs thereof
US4320136A (en) 1980-08-11 1982-03-16 E. I. Du Pont De Nemours And Company 8-Aza-16,16-difluoroprostanoids
US6043275A (en) 1998-04-16 2000-03-28 Ono Pharmaceutical Co., Ltd. 3,7-dithiaprostanoic acid derivative
US6894175B1 (en) 1999-08-04 2005-05-17 The Procter & Gamble Company 2-Decarboxy-2-phosphinico prostaglandin derivatives and methods for their preparation and use
TWI247606B (en) 1999-11-24 2006-01-21 Ono Pharmaceutical Co Treating agent for osteopenic diseases
EE200200355A (et) 1999-12-22 2003-10-15 Pfizer Products Inc. EP4 retseptori selektiivsed agonistid osteoporoosi raviks
US20010056060A1 (en) 2000-02-07 2001-12-27 Cameron Kimberly O. Treatment of osteoporsis with EP2/EP4 receptor selective agonists
WO2002024647A1 (fr) 2000-09-21 2002-03-28 Ono Pharmaceutical Co., Ltd. Agonistes du recepteur de l'ep4 comprenant comme principe actif des derives de la 8-azaprostaglandine
MXPA03004623A (es) * 2000-11-27 2003-09-05 Pfizer Prod Inc Agonistas selectivos del receptor ep4 en el tratamiento de la osteoporosis.
CA2451393C (en) 2001-07-16 2011-01-04 F. Hoffmann-La Roche Ag 2 pyrrolidone derivatives as prostanoid agonists
EP1409455B1 (en) 2001-07-16 2006-01-04 F. Hoffmann-La Roche Ag Prostaglandin analogues-as ep4 receptor agonists
WO2003009872A1 (en) 2001-07-23 2003-02-06 Ono Pharmaceutical Co., Ltd. Remedies for diseases with bone mass loss having ep4 agonist as the active ingredient
DE60226051T2 (de) 2001-10-23 2009-05-20 Laboratoires Serono S.A., Coinsins Pyrazolidinon-verbindungen als liganden des ep2 und/oder ep4 prostaglandin-rezeptoren
US20040204590A1 (en) 2001-12-03 2004-10-14 Ogidigben Miller J. Ep4 receptor agonist, compositions and methods thereof
CA2466757A1 (en) 2001-12-03 2003-06-12 Merck & Co., Inc. Method for treating ocular hypertension
BR0308166A (pt) 2002-03-05 2005-01-18 Ono Pharmaceutical Co Compostos de derivados de 8-azaprostaglandina e drogas contendo os compostos como o ingrediente ativo
EP1490055A1 (en) 2002-03-18 2004-12-29 Pfizer Products Inc. Use of selective ep4 receptor agonists for the treatment of liver failure, loss of patency of the ductus arteriosus, glaucoma or ocular hypertension
ES2268327T3 (es) 2002-03-18 2007-03-16 Pfizer Products Inc. Uso de un selectivo de un receptor de ep4 para el tratamiento de enfermedades.
US6573294B1 (en) 2002-05-14 2003-06-03 Allergan, Inc. 8-azaprostaglandin analogs as agents for lowering intraocular pressure
AU2003237520B2 (en) 2002-06-10 2009-01-08 Laboratoires Serono Sa Gamma lactams as prostaglandin agonists and use thereof
JP2006505572A (ja) 2002-10-25 2006-02-16 メルク フロスト カナダ アンド カンパニー Ｅｐ４受容体アゴニストとしての２−ピロリドン
JP4582456B2 (ja) 2003-01-21 2010-11-17 小野薬品工業株式会社 ８−アザプロスタグランジン誘導体およびその医薬用途
ATE394372T1 (de) * 2003-03-03 2008-05-15 Serono Lab G-lactamderivate als prostaglandinagonisten
US7169807B2 (en) 2004-04-09 2007-01-30 Allergan, Inc. 10-Hydroxy-11-dihydroprostaglandin analogs as selective EP4 agonists
JP4888775B2 (ja) 2004-08-10 2012-02-29 小野薬品工業株式会社 Ｅｐ４アゴニストを含有してなる下部尿路系疾患の予防および／または治療剤
US20080234337A1 (en) 2004-08-10 2008-09-25 Ono Pharmaceutical Co., Ltd. Preventive and/or Remedy for Hyperkalemia Containing Ep4 Agonist
BRPI0611079A2 (pt) * 2005-06-03 2010-08-03 Ono Pharmaceutical Co agentes para a regeneração e/ou proteção de nervos
US20070232660A1 (en) 2006-04-04 2007-10-04 Allergan, Inc. Therapeutic and delivery methods of prostaglandin ep4 agonists
RU2009145280A (ru) 2007-05-08 2011-06-20 Нэшнл Юниверсити Корпорейшн, Хамамацу Юниверсити Скул Оф Медсин (Jp) Активатор цитотоксических т-клеток, включающий агонист ep4
NZ585103A (en) 2007-10-23 2012-04-27 Allergan Inc Substituted lactams derivatives and their uses for glaucoma and ocullar hypertension
US20120270934A1 (en) 2009-07-03 2012-10-25 Concert Pharmaceuticals, Inc. Prostacyclin derivatives
CA2815179A1 (en) 2010-11-10 2012-05-18 Actelion Pharmaceuticals Ltd Lactam derivatives useful as orexin receptor antagonists
US20120283293A1 (en) 2011-05-06 2012-11-08 The Board Of Trustees Of The Leland Stanford Junior University Methods of neuroprotection involving Prostaglandin E2 EP4 (PGE2 EP4) receptor activation
MX2014000971A (es) 2011-08-02 2014-02-27 Ono Pharmaceutical Co Agente mejorador de la funcion diastolica ventricular izquierda.
CN106748951B (zh) 2012-07-19 2020-07-24 开曼化学股份有限公司 作为在治疗ep4介导的疾病和病状中使用的ep4受体选择性激动剂的二氟内酰胺化合物

Also Published As

Publication number Publication date
JP2016516050A (ja) 2016-06-02
PT2989098T (pt) 2017-08-16
US20160060216A1 (en) 2016-03-03
JP2017186356A (ja) 2017-10-12
US9688627B2 (en) 2017-06-27
EP3235817A1 (en) 2017-10-25
IL250077A0 (en) 2017-03-30
EP2989098B1 (en) 2017-05-10
HK1222170A1 (zh) 2017-06-23
ES2635635T3 (es) 2017-10-04
WO2014144584A2 (en) 2014-09-18
CA2906134A1 (en) 2014-09-18
AU2014228973A1 (en) 2015-09-17
BR112015023080A2 (pt) 2017-07-18
SG11201507470WA (en) 2015-10-29
JP6352497B2 (ja) 2018-07-04
AU2014228973B2 (en) 2018-11-08
KR20150130326A (ko) 2015-11-23
PH12015502165A1 (en) 2016-01-25
DK2989098T3 (en) 2017-08-28
JP6317807B2 (ja) 2018-04-25
WO2014144584A3 (en) 2014-11-20
IL240988A (en) 2017-05-29
IL240988A0 (en) 2015-11-30
EP3235817B1 (en) 2018-12-12
CN105143217A (zh) 2015-12-09
EP2989098A2 (en) 2016-03-02

Similar Documents

Publication Publication Date Title
PH12016500105A1 (en) Sulfonamides as modulators of sodium channels
EA201992878A1 (ru) Соединения для лечения болезни хантингтона
EA201390772A1 (ru) Новые соли и полиморфные формы афатиниба
PH12015501740A1 (en) Sodium channel modulators for the treatment of pain
EA201300471A1 (ru) Замещенные 6-аминоникотинамиды в качестве модуляторов kcnq2/3
PH12015502854A1 (en) Methods, systems, and compositions for promoting bone growth
MX2015009591A (es) Amidas como moduladores de canales de sodio.
EA201100654A1 (ru) Соединения для лечения офтальмологических заболеваний и расстройств
EA201170922A1 (ru) Производные сульфонамида
EA200970747A1 (ru) Антагонисты активина-actriia и применение для стимуляции роста кости у больных раком
MX368833B (es) Derivados de quinolina y quinazolina amidas como inhibidores de canales de sodio nav1.8 y el uso de los mismos en el tratamiento del dolor.
EA201391720A1 (ru) Замещенные диоксопиперидинилфталимидные производные
EA200970913A1 (ru) 2-пиридинкарбоксамидные производные в качестве модуляторов натриевых каналов
EA201390682A1 (ru) Спирооксиндольные антагонисты mdm2
EA200870569A1 (ru) Соединения и способы модуляции fxr
EA201071045A1 (ru) Соединения оксадиазоантрацена для лечения диабета
EP2381957A4 (en) THERAPEUTIC MODULATION OF VAGINAL EPITHELIUM LIMITING LUBRICATION
WO2015157559A3 (en) 10',11'-modified saxitoxins useful for the treatment of pain
EA201071038A1 (ru) Производные 1-бензил-3-гидроксиметилиндазола и их применение для лечения заболеваний, основанных на экспрессии mcp-1, cx3cr1 и p40
EA201591793A1 (ru) Лактамные соединения в качестве селективных агонистов ep4-рецепторов для применения при лечении опосредованных ep4 заболеваний и состояний
EA201692049A1 (ru) Гетероарилзамещенные гетероциклилсульфоны
EA201891377A1 (ru) ПРИМЕНЕНИЕ МОДУЛЯТОРОВ КАНАЛОВ Kv3.1/Kv3.2/Kv3.3 ДЛЯ ЛЕЧЕНИЯ БОЛИ
EA201591541A1 (ru) Ингибиторы бета-секретазы 1 (bace 1)
EA201300988A1 (ru) Мягкая фармацевтическая композиция на водной основе, содержащая тапентадол
CY1116234T1 (el) Υποκατεστημενα 2-οξυ-κινολινο-3-καρβοξαμιδια σαν διαμορφωτες kcnq2/3