GEP201706690B - Novel process for making compounds for use in treatment of cancer - Google Patents

Novel process for making compounds for use in treatment of cancer

Info

Publication number
GEP201706690B
GEP201706690B GEAP201313824A GEAP2013013824A GEP201706690B GE P201706690 B GEP201706690 B GE P201706690B GE AP201313824 A GEAP201313824 A GE AP201313824A GE AP2013013824 A GEAP2013013824 A GE AP2013013824A GE P201706690 B GEP201706690 B GE P201706690B
Authority
GE
Georgia
Prior art keywords
cancer
treatment
novel process
making compounds
compounds
Prior art date
Application number
GEAP201313824A
Other languages
English (en)
Inventor
Sriram Naganathan
Nathan Guz
Matthew Pfeiffer
C Gregory Sowell
Tracy Bostick
Jason Yang
Amit Srivastava
Original Assignee
Exelixis Inc
Genentech Inc
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 Exelixis Inc, Genentech Inc filed Critical Exelixis Inc
Publication of GEP201706690B publication Critical patent/GEP201706690B/en

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Hydrogenated Pyridines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
GEAP201313824A 2012-10-12 2013-10-14 Novel process for making compounds for use in treatment of cancer GEP201706690B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201261713104P 2012-10-12 2012-10-12

Publications (1)

Publication Number Publication Date
GEP201706690B true GEP201706690B (en) 2017-06-26

Family

ID=49474740

Family Applications (1)

Application Number Title Priority Date Filing Date
GEAP201313824A GEP201706690B (en) 2012-10-12 2013-10-14 Novel process for making compounds for use in treatment of cancer

Country Status (31)

Country Link
US (4) US9771347B2 (2)
EP (1) EP2909188B1 (2)
JP (2) JP6300042B2 (2)
KR (1) KR102204520B1 (2)
CN (2) CN108948043B (2)
AU (1) AU2013328929B2 (2)
BR (1) BR112015008113B1 (2)
CA (1) CA2889466C (2)
CL (1) CL2015000926A1 (2)
CR (2) CR20200237A (2)
EA (1) EA030613B1 (2)
ES (1) ES2671502T3 (2)
GE (1) GEP201706690B (2)
HK (1) HK1213567A1 (2)
HR (1) HRP20180670T1 (2)
IL (1) IL238116B (2)
IN (1) IN2015DN03928A (2)
MA (1) MA38085B1 (2)
MX (2) MX372708B (2)
MY (1) MY186549A (2)
NZ (1) NZ706723A (2)
PE (3) PE20151494A1 (2)
PH (1) PH12015500785A1 (2)
PL (1) PL2909188T3 (2)
SA (1) SA515360271B1 (2)
SG (1) SG11201502795VA (2)
SI (1) SI2909188T1 (2)
TR (1) TR201807861T4 (2)
UA (1) UA115455C2 (2)
WO (1) WO2014059422A1 (2)
ZA (1) ZA201502349B (2)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MA38085B1 (fr) 2012-10-12 2018-11-30 Exelixis Inc Nouveau procédé pour la production de composés à utiliser dans le traitement du cancer
US9532987B2 (en) 2013-09-05 2017-01-03 Genentech, Inc. Use of a combination of a MEK inhibitor and an ERK inhibitor for treatment of hyperproliferative diseases
AR105483A1 (es) 2015-06-30 2017-10-11 Exelixis Inc Sal de fumarato cristalina de (s)-[3,4-difluoro-2-(2-fluoro-4-yodofenilamino)fenil][3-hidroxi-3-(piperidin-2-il)azetidin-1-il]-metanona
CA2987912C (en) 2015-06-30 2023-01-24 Genentech, Inc. Immediate-release tablets containing a drug and processes for forming the tablets
CN105330643B (zh) * 2015-12-09 2017-12-05 苏州明锐医药科技有限公司 卡比替尼的制备方法
CN106045969B (zh) * 2016-05-27 2019-04-12 湖南欧亚药业有限公司 一种卡比替尼的合成方法
AU2017311585A1 (en) 2016-08-12 2019-02-28 Genentech, Inc. Combination therapy with a MEK inhibitor, a PD-1 axis inhibitor, and a VEGF inhibitor
AU2017335839A1 (en) 2016-09-29 2019-04-18 Genentech, Inc. Combination therapy with a MEK inhibitor, a PD-1 axis inhibitor, and a taxane
WO2020187674A1 (en) 2019-03-15 2020-09-24 Sandoz Ag Crystalline (s)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl][3-hydroxy-3-(piperidin-2-yl)azetidin-1-yl]methanone hemisuccinate
JP2024509269A (ja) 2021-03-09 2024-02-29 ジェネンテック， インコーポレイテッド 脳がんの治療における使用のためのベルバラフェニブ
EP4319749A1 (en) 2021-04-06 2024-02-14 Genentech, Inc. Combination therapy with belvarafenib and cobimetinib or with belvarafenib, cobimetinib, and atezolizumab

Family Cites Families (71)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1563587A (en) * 1924-09-20 1925-12-01 Raney Murray Method of preparing catalytic material
US1628190A (en) * 1926-05-14 1927-05-10 Raney Murray Method of producing finely-divided nickel
US1915473A (en) * 1930-12-31 1933-06-27 Raney Murray Method of preparing catalytic material
US4510139A (en) 1984-01-06 1985-04-09 Sterling Drug Inc. Substituted aminobenzamides and their use as agents which inhibit lipoxygenase activity
US5155110A (en) 1987-10-27 1992-10-13 Warner-Lambert Company Fenamic acid hydroxamate derivatives having cyclooxygenase and 5-lipoxygenase inhibition
CA2186947A1 (en) 1994-04-01 1995-10-12 Kazuo Ueda Oxime derivative and bactericide containing the same as active ingredients
WO1997012613A1 (en) 1995-10-05 1997-04-10 Warner-Lambert Company Method for treating and preventing inflammation and atherosclerosis
WO1998037881A1 (en) 1997-02-28 1998-09-03 Warner Lambert Company Method of treating or preventing septic shock by administering a mek inhibitor
US6310060B1 (en) * 1998-06-24 2001-10-30 Warner-Lambert Company 2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives and their use as MEK inhibitors
NZ501276A (en) 1997-07-01 2000-10-27 Warner Lambert Co 4-bromo or 4-iodo phenylamino benzhydroxamic acid derivatives and their use as MEK inhibitors in treating proliferative disorders
CA2290509A1 (en) 1997-07-01 1999-01-14 Warner-Lambert Company 2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives and their use as mek inhibitors
US6974878B2 (en) 2001-03-21 2005-12-13 Symyx Technologies, Inc. Catalyst ligands, catalytic metal complexes and processes using same
AU2180500A (en) 1998-12-15 2000-07-03 Warner-Lambert Company Use of a mek inhibitor for preventing transplant rejection
AU776788C (en) 1998-12-16 2005-10-27 Warner-Lambert Company Treatment of arthritis with MEK inhibitors
PL348326A1 (en) 1998-12-22 2002-05-20 Warner Lambert Co Combination chemotherapy
KR20000047461A (ko) 1998-12-29 2000-07-25 성재갑 트롬빈 억제제
JP2002534380A (ja) 1999-01-07 2002-10-15 ワーナー−ランバート・カンパニー Ｍｅｋ阻害剤による喘息の治療
AU2203800A (en) 1999-01-07 2000-07-24 Warner-Lambert Company Antiviral method using mek inhibitors
CA2348236A1 (en) 1999-01-13 2000-07-20 Stephen Douglas Barrett 4-arylamino, 4-aryloxy, and 4-arylthio diarylamines and derivatives thereof as selective mek inhibitors
EP1150950A2 (en) 1999-01-13 2001-11-07 Warner-Lambert Company Anthranilic acid derivatives
CA2349832A1 (en) 1999-01-13 2000-07-20 Warner-Lambert Company Benzenesulfonamide derivatives and their use as mek inhibitors
CA2355470C (en) 1999-01-13 2008-09-30 Warner-Lambert Company Benzoheterocycles and their use as mek inhibitors
HUP0105092A3 (en) 1999-01-13 2003-12-29 Warner Lambert Co 1-heterocycle substituted diarylamines and medicaments containing them
EP1202732A2 (en) 1999-07-16 2002-05-08 Warner-Lambert Company Llc Method for treating chronic pain using mek inhibitors
JP2003504400A (ja) 1999-07-16 2003-02-04 ワーナー−ランバート・カンパニー Ｍｅｋ阻害剤を用いた慢性痛の治療方法
CA2377092A1 (en) 1999-07-16 2001-01-25 Warner-Lambert Company Method for treating chronic pain using mek inhibitors
JP2003504401A (ja) 1999-07-16 2003-02-04 ワーナー−ランバート・カンパニー Ｍｅｋ阻害剤を用いる慢性疼痛の治療方法
DE60040676D1 (de) 1999-09-17 2008-12-11 Millennium Pharm Inc BENZAMIDE UND ÄHNLICHE INHIBITOREN VON FAKTOR Xa
BR0109188A (pt) 2000-03-15 2003-03-18 Warner Lambert Co Diarilaminas 5-amida substituìdas como inibidores de mex
AR033517A1 (es) 2000-04-08 2003-12-26 Astrazeneca Ab Derivados de piperidina, proceso para su preparacion y uso de estos derivados en la fabricacion de medicamentos
DZ3401A1 (fr) 2000-07-19 2002-01-24 Warner Lambert Co Esters oxygenes d'acides 4-iodophenylamino benzhydroxamiques
KR20030059115A (ko) * 2000-08-25 2003-07-07 워너-램버트 캄파니 엘엘씨 Ｎ-아릴-안트라닐산 및 그의 유도체의 제조 방법
US7105682B2 (en) 2001-01-12 2006-09-12 Amgen Inc. Substituted amine derivatives and methods of use
IL149462A0 (en) 2001-05-09 2002-11-10 Warner Lambert Co Method of treating or inhibiting neutrophil chemotaxis by administering a mek inhibitor
US20040039208A1 (en) * 2001-07-20 2004-02-26 Chen Michael Huai Gu Process for making n-aryl-anthranilic acids and their derivatives
DE10141266A1 (de) 2001-08-21 2003-03-06 Syntec Ges Fuer Chemie Und Tec Elektrolumineszierende Derivate der 2,5-Diamino-terephthalsäure und deren Verwendung in organischen Leuchtdioden
US7085492B2 (en) 2001-08-27 2006-08-01 Ibsen Photonics A/S Wavelength division multiplexed device
CN1568184A (zh) 2001-10-31 2005-01-19 辉瑞产品公司 烟碱乙酰胆碱受体激动剂在治疗多动腿综合征中的用途
EP1467968A1 (en) 2002-01-23 2004-10-20 Warner-Lambert Company LLC N-(4-substituted phenyl)-anthranilic acid hydroxamate esters
DOP2003000556A (es) 2002-01-23 2003-10-31 Warner Lambert Co Esteres hidroxamato de acido n-(4-fenil-sustituido)-antranilico.
SG2013013339A (en) 2002-03-13 2014-12-30 Array Biopharma Inc N3 alkylated benzimidazole derivatives as mek inhibitors
EP1482944A4 (en) 2002-03-13 2006-04-19 Array Biopharma Inc NZ ALKYL BENZIMIDAZOLE DERIVATIVES AS MEK INHIBITORS
US7235537B2 (en) 2002-03-13 2007-06-26 Array Biopharma, Inc. N3 alkylated benzimidazole derivatives as MEK inhibitors
EP1515727A4 (en) 2002-06-11 2009-04-08 Merck & Co Inc (HALO-BENZO CARBONYL) HETEROBICYCLIC P38 KINASE INHIBITION
GB0214268D0 (en) 2002-06-20 2002-07-31 Celltech R&D Ltd Chemical compounds
AU2003248813A1 (en) 2002-07-05 2004-01-23 Beth Israel Deaconess Medical Center Combination of mtor inhibitor and a tyrosine kinase inhibitor for the treatment of neoplasms
US20050004186A1 (en) 2002-12-20 2005-01-06 Pfizer Inc MEK inhibiting compounds
CA2517517C (en) 2003-03-03 2012-12-18 Array Biopharma, Inc. P38 inhibitors and methods of use thereof
TW200505834A (en) 2003-03-18 2005-02-16 Sankyo Co Sulfamide derivative and the pharmaceutical composition thereof
JP2005162727A (ja) 2003-03-18 2005-06-23 Sankyo Co Ltd スルファミド誘導体及びその医薬組成物
GB0308185D0 (en) 2003-04-09 2003-05-14 Smithkline Beecham Corp Novel compounds
EP1641804A1 (en) 2003-06-20 2006-04-05 Celltech R & D Limited Thienopyridone derivatives as kinase inhibitors
WO2005000818A1 (en) 2003-06-27 2005-01-06 Warner-Lambert Company Llc 5-substituted-4-`(substituted phenyl)!amino!-2-pyridone deviatives for use as mek inhibitors
US20050049276A1 (en) 2003-07-23 2005-03-03 Warner-Lambert Company, Llc Imidazopyridines and triazolopyridines
CA2532067C (en) 2003-07-24 2010-12-21 Stephen Douglas Barrett N-methyle-substituted benzamidazoles
US7538120B2 (en) 2003-09-03 2009-05-26 Array Biopharma Inc. Method of treating inflammatory diseases
US7144907B2 (en) 2003-09-03 2006-12-05 Array Biopharma Inc. Heterocyclic inhibitors of MEK and methods of use thereof
US8084645B2 (en) 2003-09-19 2011-12-27 Chugai Seiyaku Kabushiki Kaisha 4-phenylamino-benzaldoxime derivatives and uses thereof as mitogen-activated protein kinase kinase (MEK) inhibitors
CA2546353A1 (en) 2003-11-19 2005-06-09 Array Biopharma Inc. Bicyclic inhibitors of mek and methods of use thereof
US7517994B2 (en) 2003-11-19 2009-04-14 Array Biopharma Inc. Heterocyclic inhibitors of MEK and methods of use thereof
CA2547804A1 (en) 2003-12-08 2005-06-30 F. Hoffmann-La Roche Ag Novel thiazole derivatives
MY144232A (en) 2004-07-26 2011-08-15 Chugai Pharmaceutical Co Ltd 5-substituted-2-phenylamino benzamides as mek inhibitors
MX2007004781A (es) 2004-10-20 2007-05-11 Applied Research Systems Derivados de 3-arilamino piridina.
WO2006061712A2 (en) 2004-12-10 2006-06-15 Pfizer Inc. Use of mek inhibitors in treating abnormal cell growth
US7547782B2 (en) 2005-09-30 2009-06-16 Bristol-Myers Squibb Company Met kinase inhibitors
HRP20110498T1 (hr) * 2005-10-07 2011-08-31 Exelixis Azetidini kao inhibitori mek za liječenje proliferativnih bolesti
CN101528231A (zh) 2006-08-16 2009-09-09 埃克塞利希斯股份有限公司 在癌症的治疗中使用pi3k和mek调控剂
WO2008076415A1 (en) 2006-12-14 2008-06-26 Exelixis, Inc. Methods of using mek inhibitors
MA38085B1 (fr) 2012-10-12 2018-11-30 Exelixis Inc Nouveau procédé pour la production de composés à utiliser dans le traitement du cancer
JP6451652B2 (ja) 2014-02-07 2019-01-16 住友化学株式会社 （ｒ）−１，１，３−トリメチル−４−アミノインダンの製造方法
AR105483A1 (es) 2015-06-30 2017-10-11 Exelixis Inc Sal de fumarato cristalina de (s)-[3,4-difluoro-2-(2-fluoro-4-yodofenilamino)fenil][3-hidroxi-3-(piperidin-2-il)azetidin-1-il]-metanona

Also Published As

Publication number Publication date
KR20150067339A (ko) 2015-06-17
HK1213878A1 (en) 2016-07-15
EA030613B1 (ru) 2018-08-31
JP2018052973A (ja) 2018-04-05
PE20200387A1 (es) 2020-02-24
AU2013328929B2 (en) 2018-01-04
CR20200237A (es) 2020-07-26
BR112015008113B1 (pt) 2022-05-24
EP2909188A1 (en) 2015-08-26
IL238116B (en) 2018-06-28
TR201807861T4 (tr) 2018-06-21
EA201590700A1 (ru) 2015-09-30
US10793541B2 (en) 2020-10-06
HRP20180670T1 (hr) 2018-07-13
US20150210668A1 (en) 2015-07-30
US9771347B2 (en) 2017-09-26
PH12015500785B1 (en) 2015-06-15
US10239858B2 (en) 2019-03-26
MX2015004660A (es) 2015-08-07
NZ706723A (en) 2018-07-27
CR20150245A (es) 2015-11-19
PE20191818A1 (es) 2019-12-27
PL2909188T3 (pl) 2018-08-31
BR112015008113A2 (pt) 2017-07-04
AU2013328929A1 (en) 2015-04-30
CN104837826B (zh) 2018-07-27
ES2671502T3 (es) 2018-06-06
JP6300042B2 (ja) 2018-03-28
MA38085B1 (fr) 2018-11-30
US20190185447A1 (en) 2019-06-20
CL2015000926A1 (es) 2015-08-28
MA38085A1 (fr) 2018-08-31
CA2889466C (en) 2021-09-14
CA2889466A1 (en) 2014-04-17
IN2015DN03928A (2) 2015-10-02
MX2020005533A (es) 2020-10-12
PE20151494A1 (es) 2015-11-06
ZA201502349B (en) 2019-12-18
CN108948043B (zh) 2021-05-04
CN108948043A (zh) 2018-12-07
SA515360271B1 (ar) 2016-05-19
EP2909188B1 (en) 2018-03-07
UA115455C2 (uk) 2017-11-10
HK1213567A1 (zh) 2016-07-08
MX372708B (es) 2020-05-29
US11414396B2 (en) 2022-08-16
WO2014059422A1 (en) 2014-04-17
US20200392104A1 (en) 2020-12-17
CN104837826A (zh) 2015-08-12
SG11201502795VA (en) 2015-05-28
US20170349569A1 (en) 2017-12-07
SI2909188T1 (en) 2018-07-31
MY186549A (en) 2021-07-26
KR102204520B1 (ko) 2021-01-20
JP2015533175A (ja) 2015-11-19
PH12015500785A1 (en) 2015-06-15

Similar Documents

Publication Publication Date Title
GEP201706690B (en) Novel process for making compounds for use in treatment of cancer
TN2014000138A1 (en) Substituted benzylindazoles for use as bub1 kinase inhibitors in the treatment of hyperproliferative diseases.
MY177344A (en) Compounds and their methods of use
EA201400178A1 (ru) Лечение рака молочной железы
EA201491149A1 (ru) Пиразолопиридиновые производные, способы их получения и их терапевтическое применение
MX2013010898A (es) Novedoso derivados de la pirimidina.
NZ723971A (en) Methods and compositions for treating ewings sarcoma family of tumors
MX2014012477A (es) Inhibidores pirrolopirazona de tanquirasa.
MY174883A (en) Treatment of brain cancer
PH12015501088A1 (en) Dimeric compounds
NZ711192A (en) Process for making benzoxazepin compounds
MX2014002832A (es) Nuevas imidazol-aminas como moduladores de la actividad de cinasas.
MX2016008259A (es) Metodo de proceso para inhibidores de fosfatidilinositol 3-cinasa.
GEP201706626B (en) Synthesis of (s)-nifuratel
NI201200195A (es) Procedimiento de preparación de la sal de l - arginina de perindoprilo
PH12014501712A1 (en) Novel morpholinyl derivatives useful as mogat-2-inhibitors
GB201107985D0 (en) Process
MX2013014488A (es) Metodos y composiciones para tratar el cancer cerebral.
PH12015500061A1 (en) Method for preparing substituted triazolopyridines
IN2013MU01113A (2)
GB201209015D0 (en) Novel compounds
TN2015000095A1 (en) Macrolide derivatives, preparation thereof and therapeutic use thereof
EA033160B1 (ru) Соединения для лечения заболеваний, связанных с ишемией-реперфузией
MX2015007460A (es) Agentes para el tratamiento del dolor y usos de los mismos.
NZ715554A (en) Method of treating hypertrophic cardiomyopathy