PT1437131E - Utilização de ramipril para a prevenção de diabetes num doente sem insuficiência cardíaca congestiva pré-existente - Google Patents

Utilização de ramipril para a prevenção de diabetes num doente sem insuficiência cardíaca congestiva pré-existente Download PDF

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PT1437131E
PT1437131E PT04006330T PT04006330T PT1437131E PT 1437131 E PT1437131 E PT 1437131E PT 04006330 T PT04006330 T PT 04006330T PT 04006330 T PT04006330 T PT 04006330T PT 1437131 E PT1437131 E PT 1437131E
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diabetes
chf
heart failure
stroke
congestive heart
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PT04006330T
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Norbert Bender
Badrudin Rangoonwala
Gilles Dagenais
Hertzel Gerstein
Anders Ljunggren
Salim Yusuf
Bernward Schoelkens
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Sanofi Aventis Deutschland
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • 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
    • 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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    • 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
    • A61K31/4164—1,3-Diazoles
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    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Description

DESCRIÇÃO "UTILIZAÇÃO DE RAMIPRIL PARA A PREVENÇÃO DE DIABETES NUM DOENTE SEM INSUFICIÊNCIA CARDÍACA CONGESTIVA PRÉ-EXISTENTE"
CAMPO DA INVENÇÃO A presente invenção refere-se à utilização de ramipril ou um seu sal f armaceuticamente aceitável, na preparação de um medicamento para a prevenção ou redução do início da diabetes num doente sem insuficiência cardíaca congestiva (CHF) pré-existente e em que o doente está em elevado risco de vir a sofrer um evento cardiovascular, devido a um historial anterior de doença cardíaca isquémica, acidente vascular cerebral ou doença arterial periférica.
ANTECEDENTES DA INVENÇÃO
Os compostos que interferem com o RAS são bem conhecidos na técnica e são utilizados para tratar doenças cardiovasculares, em particular, hipertensão arterial e insuficiência cardíaca. Principalmente, pode-se interferir no RAS pela inibição das enzimas sintetizadoras das angiotensinas ou pelo bloqueio dos receptores correspondentes nos locais efectores. Estão actualmente disponíveis inibidores da enzima de conversão da angiotensina (ACE) e antagonistas do receptor tipo 1 da angiotensina II (AT II). 1
Os inibidores da ACE são compostos que inibem a conversão da angiotensina I na angiotensina II activa, bem como a degradação do vasodilatador activo bradicinina. Ambos estes mecanismos conduzem à vasodilatação. Tais compostos têm sido descritos, por exemplo, nos documentos EP 158927, EP 317878, US 4743450 e US 4857520. O ramipril (divulgado no documento EP-A-079022) é um inibidor da ACE de acção prolongada. O seu metabolito activo é o diácido livre ramiprilato, que é obtido in vivo após administração de ramipril. Em doentes hipertensos, sabe-se que a administração de ramipril provoca uma redução na resistência arterial periférica e, assim, uma redução da pressão sanguínea sem um aumento compensatório na taxa cardíaca. Está a ser utilizado actualmente no tratamento da hipertensão e CHF. Além disso, o ramipril tem demonstrado reduzir a mortalidade em doentes com sinais clínicos de insuficiência cardíaca congestiva após terem sobrevivido a um enfarte do miocárdio agudo. Tem sido sugerido que o ramipril tem uma vantagem adicional sobre muitos outros inibidores da ACE, devido à sua pronunciada inibição da ACE em tecidos, resultando em efeitos protectores nos órgãos e. g., coração, rim e vasos sanguíneos.
Os compostos que interferem com o RAS, incluindo os inibidores da ACE e antagonistas da AT II, são utilizados correntemente no tratamento de vários distúrbios cardiovasculares, especialmente em doentes que apresentam uma elevada pressão sanguínea. A utilização dos referidos compostos na prevenção de distúrbios cardiovasculares é muito menos comum e a utilização dos referidos compostos na prevenção de acidente vascular cerebral, diabetes e/ou CHF é, até aqui, desconhecida. 2
SUMARIO DA INVENÇÃO A presente invenção refere-se à utilização de ramipril ou um seu sal f armaceut icamente aceitável, na preparação de um medicamento para a prevenção ou redução do início da diabetes num doente sem insuficiência cardíaca congestiva (CHF) pré-existente e em que o doente está em elevado risco de vir a sofrer um evento cardiovascular, devido a um historial anterior de doença cardíaca isquémica, acidente vascular cerebral ou doença arterial periférica, especialmente em doentes que apresentam uma pressão sanguínea normal ou baixa.
DESCRIÇÃO DETALHADA DA INVENÇÃO
Verificou-se, de forma surpreendente, que a diabetes pode ser prevenida pela utilização de ramipril. A presente invenção é especialmente surpreendente no facto de que, especialmente os doentes com uma função cardíaca essencialmente normal e/ou que apresentam uma pressão sanguínea normal ou baixa, beneficiam acentuadamente da acção preventiva do ramipril.
Os doentes que apresentam uma pressão sanguínea normal ou baixa são conhecidos como doentes normotensos. Exemplos de directrizes que definem os valores de pressão sanguínea, para grupos diferentes de doentes, incluindo diferentes idades, incluem as directrizes publicadas pela OMS e JNC (USA) . Na presente invenção, pode ser encontrada uma definição adequada de uma pressão sanguínea normal ou baixa em JNC VI.
Na presente invenção, "diabetes" refere-se a diabetes de tipo II, também conhecida como diabetes mellitus não dependente 3 de insulina (NIDDM).
Formulações farmacêuticas São descritas formulações farmacêuticas compreendendo ramipril ou um sal farmaceuticamente aceitável como ingrediente activo, incluindo metabolitos, para utilização na prevenção ou redução do início da diabetes.
Para utilização clínica, o ramipril é formulado numa formulação farmacêutica para administração oral, intravenosa, subcutânea, traqueal, brônquica, intranasal, pulmonar, transdérmica, bocal, rectal, parentérica ou qualquer outro modo de administração. A formulação farmacêutica pode conter o inibidor em mistura com um adjuvante, diluente e/ou veículo farmaceuticamente aceitável.
Na preparação das formulações farmacêuticas, o ingrediente activo pode ser misturado com ingredientes sólidos em pó, tais como lactose, sacarose, sorbitol, manitol, amido, amilopectina, derivados da celulose, gelatina ou outro ingrediente adequado, bem como com agentes de desintegração e agentes lubrificantes, tais como estearato de magnésio, estearato de cálcio, estearilfumarato de sódio e ceras de polietilenoglicol. A mistura pode depois ser processada em grânulos ou prensada em comprimidos. 0 ingrediente activo pode ser pré-misturado separadamente com os outros ingredientes não-activos, antes de ser misturado para formar uma formulação. 4
As cápsulas de gelatina mole podem ser preparadas com cápsulas contendo uma mistura do ingrediente activo da invenção, óleo vegetal, gordura ou outro veiculo adequado para cápsulas de gelatina mole. As cápsulas de gelatina dura podem conter grânulos dos ingredientes activos. As cápsulas de gelatina dura podem também conter os ingredientes activos em combinação com ingredientes sólidos em pó, tais como lactose, sacarose, sorbitol, manitol, amido de batata, amido de milho, amilopectina, derivados de celulose ou gelatina.
As unidades de dosagem para administração rectal podem ser preparadas (i) na forma de supositórios que contêm a substância activa misturada com uma base gorda neutra; (ii) na forma de uma cápsula rectal de gelatina que contém a substância activa numa mistura com um óleo vegetal, óleo de parafina ou outro veículo adequado para cápsulas de gelatina rectais; (iii) na forma de uma microenema pronto a utilizar; ou (iv) na forma de uma formulação em microenema seca para ser reconstituída num solvente adequado, mesmo antes da administração.
As preparações líquidas podem ser preparadas na forma de xaropes ou suspensões, e. g., soluções ou suspensões contendo os ingredientes activos e o restante consistindo, por exemplo, de açúcar ou álcoois de açúcares e uma mistura de etanol, água, glicerol, propilenoglicol e polietilenoglicol. Se desejado, tais preparações liquidas podem conter agentes corantes, agentes aromatizantes, conservantes, sacarina e carboximetilcelulose ou outros agentes espessantes. As preparações líquidas podem também ser preparadas na forma de um pó seco para ser reconstituído, antes da utilização, com um solvente adequado. 5
As soluções para administração parentérica podem ser preparadas como uma solução de uma formulação da invenção num solvente farmaceuticamente aceitável. Estas soluções podem conter também ingredientes de estabilização, conservantes e/ou ingredientes tamponantes. As soluções para administração parentérica podem também ser preparadas como uma preparação seca para ser reconstituída, antes da utilização, com um solvente adequado. A quantidade total de ingrediente activo está, de um modo adequado, dentro na gama de cerca de 0,1% (p/p) a cerca de 95% (p/p) da formulação, de um modo adequado, de 0,5% a 50% (p/p) e, de um modo preferido, de 1% a 25% (p/p).
As formulações farmacêuticas podem conter entre cerca de 0,1 mg e cerca de 1000 mg do ingrediente activo, de um modo preferido, entre 1 mg e 100 mg do ingrediente activo. A dose do ingrediente activo a ser administrada irá depender da indicação relevante, da idade, peso e sexo do doente e pode ser determinada por um médico. A dosagem irá, de um modo adequado, estar na gama de cerca de 0,01 mg/kg a cerca de 20 mg/kg, de um modo preferido, entre 0,1 mg/kg e 10 mg/kg. A dose diária típica do ingrediente activo varia dentro de uma vasta gama e irá depender de vários factores, tais como a indicação relevante, a via de administração, a idade, peso e sexo do doente e pode ser determinada por um médico. Em geral, dosagens e, especialmente, dosagens orais e parentéricas, irão estar na gama de cerca de 0,1 a cerca de 100 mg por dia do ingrediente activo, de um modo preferido, entre 1 e 50 mg por dia do ingrediente activo. 6 0 Exemplo seguinte tem como intenção ilustrar a invenção.
EXEMPLO
Foi concebido um ensaio clinico de larga escala para examinar o efeito do inibidor da ACE ramipril versus placebo na redução de eventos cardiovasculares. 0 estudo foi realizado em 267 centros em 19 países durante um período de seis anos e incluiu 9541 participantes gue estavam em elevado risco de eventos cardiovasculares devido a um historial de anterior doença cardíaca isguémica, acidente vascular cerebral, doença arterial periférica ou indivíduos com diabetes. A pressão sanguínea sistólica no momento da inclusão dos doentes foi, em média, de 13 8 mm Hg e, assim, os doentes eram normotensos no início do estudo. Após um mês de terapia com ramipril ou placebo, a pressão sanguínea sistólica diminuiu em 5,48 mm Hg e 1,59 mm Hg, respectivamente. 0 ponto final primário do estudo foi enfarte do miocárdio (MI), acidente vascular cerebral e morte cardiovascular (CV) (mortalidade). 0 estudo foi interrompido mais cedo devido a uma nítida redução no ponto final combinado de mortes cardiovasculares, atagues cardíacos e acidentes vasculares cerebrais em doentes a tomar o ramipril. Além dos benefícios acima, verificou-se também uma redução de entre um guarto e um guinto na necessidade de procedimentos de revascularização (tais como cirurgia de bypass 7 da artéria coronária por enxerto, angioplastia de balão, etc.) e complicações relacionadas com a diabetes.
Verificou-se uma redução nítida em 32% no grupo do ramipril no número de doentes que desenvolveram acidente vascular cerebral e isto é surpreendente uma vez que os doentes eram normotensos quando recrutados para o estudo. 0 número de doentes que desenvolveram CHF foi reduzido significativamente em 21% no grupo do ramipril, o que foi inesperado uma vez que os doentes não evidenciavam sinais ou sintomas de CHF no início do estudo.
Igualmente surpreendente foi a redução acentuada de 36% no número de doentes que desenvolveram diabetes no grupo do ramipril.
Abreviaturas ACE = enzima de conversão da angiotensina
AT II = receptor tipo 1 da angiotensina II CHF = insuficiência cardíaca congestiva IDMM = diabetes mellitus dependente de insulina JNC = Joint National Committee
MI enfarte do miocárdio
NIDDM = diabetes mellitus nao dependente de insulina OMS =
Organizaçao Mundial de Saúde
Lisboa, 4 de Julho de 2012 9

Claims (2)

  1. REIVINDICAÇÕES 1. Utilização de ramipril ou um seu sal farmaceuticamente aceitável, na preparação de um medicamento para a prevenção ou redução do início da diabetes num doente sem insuficiência cardíaca congestiva (CHF) pré-existente e em que o doente está em elevado risco de vir a sofrer um evento cardiovascular, devido a um historial anterior de doença cardíaca isquémica, acidente vascular cerebral ou doença arterial periférica.
  2. 2. Utilização de acordo com a reivindicação 1, em que o doente apresenta pressão sanguínea normal ou baixa. Lisboa, 4 de Julho de 2012 1
PT04006330T 1999-08-27 2000-08-25 Utilização de ramipril para a prevenção de diabetes num doente sem insuficiência cardíaca congestiva pré-existente PT1437131E (pt)

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PL353199A1 (en) * 1999-08-30 2003-11-03 Aventis Pharma Deutschland Gmbh Use of inhibitors of the renin-angiotensin system in the prevention of cardiovascular events
EP1375500A1 (en) * 2001-03-26 2004-01-02 Kotobuki Pharmaceutical Co., Ltd. Isoquinuclidine derivative, process for producing the same, and medicinal composition containing the same
WO2003032965A2 (en) * 2001-10-17 2003-04-24 King Pharmaceuticals Research And Development, Inc Use of ace inhibitors for reducing type 2 diabetes in high risk patients
US6844361B2 (en) 2002-02-04 2005-01-18 Aventis Pharma Deutschland Gmbh Pharmaceutical composition comprising a sodium hydrogen exchange inhibitor and an angiotensin converting enzyme inhibitor
DE10230272A1 (de) * 2002-07-05 2004-01-22 Solvay Pharmaceuticals Gmbh AT1-Rezeptorantagonisten zur Prävention von Folgeschlaganfällen
EP1382334A1 (en) * 2002-07-11 2004-01-21 Université de Picardie Jules Verne Use of angiotensin II AT1-receptor blockers (ARB), alone or combined with thiazide or angiotensin II for the treatment of stroke
US7232828B2 (en) * 2002-08-10 2007-06-19 Bethesda Pharmaceuticals, Inc. PPAR Ligands that do not cause fluid retention, edema or congestive heart failure
DE10306179A1 (de) * 2003-02-13 2004-08-26 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verwendung von Dipyridamol in Kombination mit Acetylsalicylsäure und einem Angiotensin II-Antagonisten zur Schlaganfall-Prophylaxe
US20040229901A1 (en) * 2003-02-24 2004-11-18 Lauren Otsuki Method of treatment of disease using an adenosine A1 receptor antagonist
CA2458288A1 (en) * 2003-03-11 2004-09-11 Institut De Cardiologie De Montreal / Montreal Heart Institute Method and compound to reduce the incidence of diabetes in a subject with chronic heart failure
AR044069A1 (es) 2003-04-25 2005-08-24 Nova Cardia Inc Un metodo de diuresis mejorada en individuos con funcion renal deteriorada
MXPA06005547A (es) 2003-11-18 2006-08-17 Solvay Pharm Gmbh Composiciones farmaceuticas para el tratamiento de disfuncion, enfermedad o trastorno renal, en particular, en pacientes diabeticos.
NZ586285A (en) * 2004-03-17 2011-12-22 Novartis Ag Use of aliskiren in monotherapy for treating diabetes and metabolic disorder (syndrome X)
CA2586760A1 (en) * 2004-11-05 2006-05-18 Edward S. Wilson Stabilized ramipril compositions and methods of making
US20070208041A1 (en) * 2005-10-13 2007-09-06 Stamler Jonathan S Compositions for the treatment and prevention of heart disease and methods of using same
EP2059242A1 (en) * 2006-08-28 2009-05-20 Sanofi-Aventis Deutschland GmbH Methods of lowering glucose levels
DK2180787T3 (da) 2007-08-01 2014-02-03 Univ Pittsburgh Nitrooliesyremodulering af type ii-diabetes
JP2011519373A (ja) 2008-05-01 2011-07-07 コンプレクザ インコーポレイテッド ビニル置換脂肪酸
US8686038B2 (en) 2008-06-19 2014-04-01 The Univsersity of Utah Research Foundation Use of nitrated lipids for treatment of side effects of toxic medical therapies
US20140024713A1 (en) 2008-06-19 2014-01-23 University Of Utah Research Foundation Use of nitrated lipids for treatment of side effects of toxic medical therapies
WO2010022249A2 (en) 2008-08-20 2010-02-25 Ensemble Discovery Corporation Macrocyclic compounds for inhibition of tumor necrosis factor alpha
CA2769624C (en) 2009-07-31 2018-09-11 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Electrophilic fatty acid derivatives as anti-inflammatory agents
US8686167B2 (en) 2009-10-02 2014-04-01 Complexa, Inc. Heteroatom containing substituted fatty acids
MY174431A (en) 2010-05-14 2020-04-17 Univ Sabanci An apparatus for using hydrodynamic cavitation in medical treatment
EP2744491B1 (en) * 2011-08-19 2020-07-29 The University of Utah Research Foundation Combination therapy with nitrated lipids and inhibitors of the renin-angiotensin-aldosterone system
WO2016176338A1 (en) * 2015-04-30 2016-11-03 The Trustees Of Columbia University In The City Of New York Small molecule ras ligands
AU2016289856B2 (en) 2015-07-07 2020-11-26 H. Lundbeck A/S PDE9 inhibitors with imidazo triazinone backbone and imidazo pyrazinone backbone for treatment of peripheral diseases
SG10201913953UA (en) 2015-10-02 2020-03-30 Complexa Inc Prevention, treatment and reversal of disease using therapeutically effective amounts of activated fatty acids
CN110833620A (zh) * 2018-08-15 2020-02-25 王镕 血管紧张素转化酶抑制剂在防治自身免疫性疾病及相应的并发症中的用途
KR20230137654A (ko) * 2022-03-22 2023-10-05 주식회사 메디포럼 뇌졸중의 예방 및 치료용 조성물

Family Cites Families (256)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5612114B2 (pt) * 1974-06-07 1981-03-18
US4231938A (en) * 1979-06-15 1980-11-04 Merck & Co., Inc. Hypocholesteremic fermentation products and process of preparation
US4444784A (en) * 1980-08-05 1984-04-24 Merck & Co., Inc. Antihypercholesterolemic compounds
MX7065E (es) * 1980-06-06 1987-04-10 Sankyo Co Un procedimiento microbiologico para preparar derivados de ml-236b
US4450171A (en) * 1980-08-05 1984-05-22 Merck & Co., Inc. Antihypercholesterolemic compounds
ZA817261B (en) * 1980-10-23 1982-09-29 Schering Corp Carboxyalkyl dipeptides,processes for their production and pharmaceutical compositions containing them
DE3226768A1 (de) * 1981-11-05 1983-05-26 Hoechst Ag, 6230 Frankfurt Derivate der cis, endo-2-azabicyclo-(3.3.0)-octan-3-carbonsaeure, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung
US4448784A (en) * 1982-04-12 1984-05-15 Hoechst-Roussel Pharmaceuticals, Inc. 1-(Aminoalkylphenyl and aminoalkylbenzyl)-indoles and indolines and analgesic method of use thereof
US4739073A (en) * 1983-11-04 1988-04-19 Sandoz Pharmaceuticals Corp. Intermediates in the synthesis of indole analogs of mevalonolactone and derivatives thereof
US4722810A (en) 1984-08-16 1988-02-02 E. R. Squibb & Sons, Inc. Enkephalinase inhibitors
DE3413710A1 (de) 1984-04-12 1985-10-24 Hoechst Ag, 6230 Frankfurt Verfahren zur behandlung der herzinsuffizienz
US5684016A (en) * 1984-04-12 1997-11-04 Hoechst Aktiengesellschaft Method of treating cardiac insufficiency
US5231080A (en) * 1985-10-15 1993-07-27 Hoechst Aktiengesellschaft Method for the treatment of atherosclerosis, thrombosis, and peripheral vessel disease
EP0241201A3 (en) * 1986-04-07 1990-05-23 Merck & Co. Inc. Angiotensin converting enzyme inhibitors useful in prolonging survival of mammalians with congestive heart failure
US4681893A (en) * 1986-05-30 1987-07-21 Warner-Lambert Company Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis
US4749688A (en) 1986-06-20 1988-06-07 Schering Corporation Use of neutral metalloendopeptidase inhibitors in the treatment of hypertension
CA1334092C (en) 1986-07-11 1995-01-24 David John Carini Angiotensin ii receptor blocking imidazoles
DE3633496A1 (de) * 1986-10-02 1988-04-14 Hoechst Ag Kombination von angiotensin-converting-enzyme-hemmern mit calciumantagonisten sowie deren verwendung in arzneimitteln
FR2607004B1 (fr) * 1986-11-20 1990-06-01 Synthelabo Compositions pharmaceutiques contenant du diltiazem et un inhibiteur de l'enzyme de conversion de l'angiotensine
DE3704661A1 (de) 1987-02-14 1988-08-25 Hoechst Ag Annelierte azepinon- und azocinon-derivate, verfahren zu ihrer herstellung, diese enthaltende mittel und ihre verwendung, sowie zwischenprodukte bei ihrer herstellung
US4743450A (en) 1987-02-24 1988-05-10 Warner-Lambert Company Stabilized compositions
DE3739690A1 (de) * 1987-11-24 1989-06-08 Hoechst Ag Stabilisierte arzneistoffe, verfahren zu ihrer herstellung sowie stabile arzneizubereitungen
US5015651A (en) 1988-01-07 1991-05-14 E. I. Du Pont De Nemours And Company Treatment of hypertension with 1,2,4-angiotensin II antagonists
CA1338238C (en) 1988-01-07 1996-04-09 David John Carini Angiotensin ii receptor blocking imidazoles and combinations thereof with diuretics and nsaids
EP0331014A3 (de) * 1988-03-02 1991-10-23 THERA - Patent Verwaltungs-GmbH Verwendung von ACE-Inhibitoren für die Diabetesprophylaxe
US5217958A (en) * 1988-03-03 1993-06-08 E. R. Squibb & Sons, Inc. 1,2-hydroxy phosphonates and derivatives thereof
US4804770A (en) * 1988-04-29 1989-02-14 E. R. Squibb & Sons, Inc. Process for preparing a keto-phosphonate intermediate useful in preparing HMG-CoA reductase inhibitors
DE3818245A1 (de) * 1988-05-28 1989-12-07 Hoechst Ag Kombination von angiotensin-converting-enzyme-hemmern mit kaliumkanal-modulatoren sowie deren verwendung in arzneimitteln
EP0444156A4 (en) * 1988-11-21 1992-12-09 Abbott Laboratories Method for treating vascular diseases
IE64514B1 (en) 1989-05-23 1995-08-09 Zeneca Ltd Azaindenes
IL94390A (en) 1989-05-30 1996-03-31 Merck & Co Inc The 6-membered trans-nitrogen-containing heterocycles are compressed with imidazo and pharmaceutical preparations containing them
US5064825A (en) 1989-06-01 1991-11-12 Merck & Co., Inc. Angiotensin ii antagonists
CA2016467A1 (en) * 1989-06-05 1990-12-05 Martin Eisman Method for treating peripheral atherosclerotic disease employing an hmg coa reductase inhibitor and/or a squalene synthetase inhibitor
ATE250587T1 (de) 1989-06-14 2003-10-15 Smithkline Beecham Corp Imidazoalkensäure
EP0403158A3 (en) 1989-06-14 1991-12-18 Smithkline Beecham Corporation Imidazolyl-alkenoic acids
DK0479903T3 (da) 1989-06-30 1996-03-18 Du Pont Substituerede imidazoler og deres anvendelse som angiotensin II hæmmere
AU645022B2 (en) 1989-06-30 1994-01-06 E.I. Du Pont De Nemours And Company Fused-ring aryl substituted imidazoles
US5164407A (en) 1989-07-03 1992-11-17 Merck & Co., Inc. Substituted imidazo-fused 5-membered ring heterocycles and their use as angiotensin ii antagonsists
CA2020073A1 (en) 1989-07-03 1991-01-04 Eric E. Allen Substituted quinazolinones as angiotensin ii antagonists
EP0407342A3 (en) 1989-07-06 1991-07-10 Ciba-Geigy Ag Pyrimidine derivatives
EP0409332A3 (en) 1989-07-19 1991-08-07 Merck & Co. Inc. Substituted triazoles as angiotensin ii antagonists
FI94339C (fi) * 1989-07-21 1995-08-25 Warner Lambert Co Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi
EP0412594B1 (en) 1989-07-28 1996-01-03 Merck & Co. Inc. Substituted triazolinones, triazolinethiones, and triazolinimines as angiotensin II antagonists
ATE113281T1 (de) 1989-08-02 1994-11-15 Takeda Chemical Industries Ltd Pyrazol-derivate, verfahren zu deren herstellung und anwendung.
EP0412848B1 (en) 1989-08-11 1995-01-18 Zeneca Limited Quinoline derivatives, process for their preparation and their use as medicaments
DE3926606A1 (de) * 1989-08-11 1991-02-14 Hoechst Ag Verfahren zur behandlung der cardialen sowie der vasculaeren hypertrophie und hyperplasie
US5100897A (en) 1989-08-28 1992-03-31 Merck & Co., Inc. Substituted pyrimidinones as angiotensin ii antagonists
EP0415886A3 (en) 1989-08-30 1991-10-23 Ciba-Geigy Ag Aza compounds
IE70593B1 (en) 1989-09-29 1996-12-11 Eisai Co Ltd Biphenylmethane derivative the use of it and pharmacological compositions containing same
EP0424317A3 (en) 1989-10-19 1991-09-25 Ciba-Geigy Ag Pyrimidines
US5212165A (en) * 1989-10-23 1993-05-18 E. R. Squibb & Sons, Inc. Method for rehabilitating the vasorelaxant action of the coronary arteries impaired through atherosclerosis or hypercholesterolemia employing an ace inhibitor
US5061694A (en) * 1989-10-23 1991-10-29 E. R. Squibb & Sons, Inc. Method for stabilizing or causing regression of atherosclerosis in coronary arteries employing an ace inhibitor
IL95975A (en) 1989-10-24 1997-06-10 Takeda Chemical Industries Ltd N-benzyl- 2-alkylbenzimidazole derivatives, their production and pharmaceutical compositions containing them
CA2027937A1 (en) 1989-10-25 1991-04-26 Richard M. Keenan Substituted 5-¬ (tetrazolyl)alkenyl|imidazoles
CA2026686A1 (en) * 1989-10-30 1991-05-01 Werner Tschollar Method for preventing onset of type ii diabetes employing an ace inhibitor
IL96019A0 (en) 1989-10-31 1991-07-18 Fujisawa Pharmaceutical Co Imidazole derivatives,processes for the preparation thereof and pharmaceutical compositions containing the same
CA2028925A1 (en) 1989-11-06 1991-05-07 Gerald R. Girard Substituted n-(imidazolyl)alkyl alanine derivatives
PT95899A (pt) 1989-11-17 1991-09-13 Glaxo Group Ltd Processo para a preparacao de derivados indole
IE903911A1 (en) 1989-11-20 1991-05-22 Ici Plc Diazine derivatives
US5073566A (en) 1989-11-30 1991-12-17 Eli Lilly And Company Angiotensin ii antagonist 1,3-imidazoles and use thereas
GB8927277D0 (en) 1989-12-01 1990-01-31 Glaxo Group Ltd Chemical compounds
EP0430709A3 (en) 1989-12-01 1992-02-12 Glaxo Group Limited Benzthiophen derivatives
EP0430300A3 (en) 1989-12-01 1992-03-25 Takeda Chemical Industries, Ltd. Xanthine derivatives, their production and use
US5104891A (en) 1989-12-11 1992-04-14 G. D. Searle & Co. Cycloheptimidazolone compounds as angiotensin ii antagonists for control of hypertension
EP0434038A1 (en) 1989-12-22 1991-06-26 Takeda Chemical Industries, Ltd. Fused imidazole derivatives, their production and use
EP0435827A3 (en) 1989-12-28 1991-11-13 Ciba-Geigy Ag Diaza compounds
CA2032289A1 (en) 1989-12-29 1991-06-30 Joseph A. Finkelstein Substituted 5-(alkyl) carboxamide imidazoles
CA2075637A1 (en) 1990-02-13 1991-08-14 William J. Greenlee Angiotensin ii antagonists incorporating a substituted benzyl element
CA2075621A1 (en) 1990-02-13 1991-08-14 William J. Greenlee Imidazole angiotensin ii antagonists incorporating a substituted benzyl element
EP0515546A4 (en) 1990-02-13 1993-05-12 Merck & Co. Inc. Triazole angiotensin ii antagonists incorporating a substituted benzyl element
ES2081365T3 (es) 1990-02-14 1996-03-01 Siemens Ag Procedimiento para la desmodulacion de señales de television en color codificadas-secam con ciclo acoplado de lineas y disposicion de circuito para la realizacion del procedimiento.
ATE169915T1 (de) 1990-02-15 1998-09-15 Takeda Chemical Industries Ltd Pyrimidindionderivate, deren herstellung und verwendung
ATE134624T1 (de) 1990-02-19 1996-03-15 Ciba Geigy Ag Acylverbindungen
CA2036618C (en) 1990-02-22 2002-10-29 Akira Morimoto Fused thiophene derivatives, their production and use
DE4006693A1 (de) 1990-03-01 1991-09-05 Schering Ag Neue benzimidazolderivate, verfahren zu ihrer herstellung und ihre pharmazeutische verwendung
US5044166A (en) 1990-03-05 1991-09-03 Membrane Technology & Research, Inc. Refrigeration process with purge and recovery of refrigerant
CA2037630C (en) 1990-03-07 2001-07-03 Akira Morimoto Nitrogen-containing heterocylic compounds, their production and use
GB9005354D0 (en) 1990-03-09 1990-05-02 Glaxo Group Ltd Chemical compounds
FR2659655B1 (fr) 1990-03-19 1992-07-24 Union Pharma Scient Appl Nouveaux derives d'oxypyrazole antagonistes des recepteurs a l'angiotensine ii ; leurs procedes de preparation, compositions pharmaceutiques les contenant.
TW201738B (pt) 1990-03-20 1993-03-11 Sanofi Co
US5223516A (en) 1990-03-22 1993-06-29 E. R. Squibb & Sons, Inc. 3,3,3-trifluoro-2-mercaptomethyl-N-tetrazolyl substituted propanamides and method of using same
CA2079344A1 (en) 1990-03-30 1991-10-01 Eric E. Allen Substituted pyrimidines, pyrimidinones and pyridopyrimidines
JPH05505822A (ja) 1990-03-30 1993-08-26 メルク・エンド・カムパニー・インコーポレーテツド ピラゾール類、イソキサゾール類及びイソチアゾール置換体
DE4010797A1 (de) 1990-04-04 1991-10-10 Hoechst Ag Substituierte azole, verfahren zu deren herstellung, diese enthaltende mittel und deren verwendung
CA2077897A1 (en) 1990-04-13 1991-10-14 Robert G. Franz Substituted benzimidazoles
GB2244054B (en) 1990-04-19 1994-04-06 Ici Plc Pyridine derivatives
US5196444A (en) 1990-04-27 1993-03-23 Takeda Chemical Industries, Ltd. 1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate and compositions and methods of pharmaceutical use thereof
US5703110A (en) 1990-04-27 1997-12-30 Takeda Chemical Industries, Ltd. Benzimidazole derivatives, their production and use
US5098920A (en) 1990-05-04 1992-03-24 G. D. Searle & Co. 1h-substituted-1,2,4-triazole compounds and methods of use thereof for treatment of cardiovascular disorders
GB9010394D0 (en) 1990-05-09 1990-06-27 Ici Plc Heterocyclic compounds
CA2041763A1 (en) 1990-05-11 1991-11-12 Sheih-Shung T. Chen Microbial transformation process for antihypertensive products
US5298497A (en) * 1990-05-15 1994-03-29 E. R. Squibb & Sons, Inc. Method for preventing onset of hypertension employing a cholesterol lowering drug
EP0531382A1 (en) 1990-05-25 1993-03-17 G.D. Searle & Co. N-substituted-1,2,4-triazolone compounds for treatment of cardiovascular disorders
US5140012A (en) * 1990-05-31 1992-08-18 E. R. Squibb & Sons, Inc. Method for preventing onset of restenosis after angioplasty employing pravastatin
US5166143A (en) * 1990-05-31 1992-11-24 E. R. Squibb & Sons, Inc. Method for preventing onset of restenosis after angioplasty employing an ace inhibitor
DK0461039T3 (da) 1990-06-08 1999-06-14 Hoechst Marion Roussel Inc Nye benzimidazolafledte forbindelser, fremgangsmåde til deres fremstilling, de opnåede mellemprodukter, deres anvendelse so
AU653524B2 (en) 1990-06-08 1994-10-06 Roussel-Uclaf New imidazole derivatives, their preparation process, the new intermediates obtained, their use as medicaments and the pharmaceutical compositions containing them
US5622985A (en) * 1990-06-11 1997-04-22 Bristol-Myers Squibb Company Method for preventing a second heart attack employing an HMG CoA reductase inhibitor
WO1991019715A1 (en) 1990-06-15 1991-12-26 G.D. Searle & Co. 1H-SUBSTITUTED-IMIDAZO[4,5-d]PYRIDAZINE COMPOUNDS FOR TREATMENT OF CARDIOVASCULAR DISORDERS
CA2051705A1 (en) 1990-06-19 1991-12-20 Kiyoaki Katano Pyridine derivatives having angiotensin ii antagonism
CA2085584C (en) 1990-06-22 2003-02-11 David John Carini Treatment of chronic renal failure with imidazole angiotensin-ii receptor antagonists
NZ238688A (en) 1990-06-28 1992-05-26 Smithkline Beecham Corp Substituted histidines: pharmaceutical compositions, preparation and uses thereof
IE912114A1 (en) 1990-07-02 1992-01-15 Union Pharma Scient Appl Novel pyrimidine derivatives which are angiotensin ii¹receptor antagonists, their methods of preparation and¹pharmaceutical compositions in which they are present
IL98319A (en) 1990-07-05 1997-04-15 Roussel Uclaf Sulphurous derivatives of imidazole, their preparation process, and pharmaceutical compositions containing them
US5137902A (en) 1990-07-13 1992-08-11 E. I. Du Pont De Nemours And Company 4-alkylimidazole derivatives and anti-hypertensive use thereof
CA2044806A1 (en) 1990-07-18 1992-01-19 Roland Jaunin Purine derivatives
CA2047029A1 (en) 1990-07-19 1992-01-20 Shieh-Shung T. Chen Microbial transformation process for antihypertensive products
DE4023215A1 (de) 1990-07-21 1992-01-23 Hoechst Ag Substituierte azole, verfahren zu deren herstellung, sie enthaltende mittel und deren verwendung
RU1836357C (ru) 1990-07-23 1993-08-23 Др.Карл Томэ ГмбХ Производные бензимидазола, их изомеры, смеси изомеров, гидраты или их физиологически переносимые соли, обладающие антагонистическими в отношении ангиотензина свойствами
NZ239161A (en) 1990-07-31 1994-01-26 Smithkline Beecham Corp Substituted [1h-imidazol-5-yl] alkanoic acid derivatives; medicaments,
EP0470543A1 (de) 1990-08-10 1992-02-12 Dr. Karl Thomae GmbH Heterocyclische Imidazole, diese Verbindungen enthaltende Arzneimittel und Verfahren zur ihrer Herstellung
US5217985A (en) 1990-08-28 1993-06-08 G. D. Searle & Co. Renal-selective biphenylalkyl 1h-substituted-1,2,4-triazole angiotensin ii antagonists for treatment of hypertension
AU8405691A (en) 1990-09-04 1992-03-30 Yamanouchi Pharmaceutical Co., Ltd. Novel tetrahydrobenzazole derivative
CA2048699A1 (en) * 1990-09-04 1992-03-05 Abraham Sudilovsky Method for preventing or treating cerebro-vascular disease employing ceronapril
IL99246A0 (en) 1990-09-10 1992-07-15 Abbott Lab Angiotensin ii receptor antagonists and pharmaceutical compositions containing them
IL99372A0 (en) 1990-09-10 1992-08-18 Ciba Geigy Ag Azacyclic compounds
US5140036A (en) 1990-09-19 1992-08-18 G. D. Searle & Co. 1,3,5-trisubstituted-1,2,4-triazole compounds for treatment of circulatory disorders
US5210092A (en) 1990-09-25 1993-05-11 Fujisawa Pharmaceutical Co., Ltd. Angiotensin ii antagonizing heterocyclic derivatives
US5242939A (en) 1990-09-28 1993-09-07 Warner-Lambert Company Anilide derivatives with angiotensin ii antagonist properties
EP0481614A1 (en) 1990-10-01 1992-04-22 Merck & Co. Inc. Substituted pyridopyrimidinones and related heterocycles as angiotensin II antagonists
US5126342A (en) 1990-10-01 1992-06-30 Merck & Co., Inc. Imidazole angiotensin ii antagonists incorporating acidic functional groups
US5260322A (en) 1990-10-08 1993-11-09 Merck & Co., Inc. Angiotension II antagonists in the treatment of hyperuricemia
US5470975A (en) * 1990-10-16 1995-11-28 E.R. Squibb & Sons, Inc. Dihydropyrimidine derivatives
CA2053148A1 (en) 1990-10-16 1992-04-17 Karnail Atwal Dihydropyrimidine derivatives
US5430145A (en) 1990-10-18 1995-07-04 Merrell Dow Pharmaceuticals Inc. Mercaptoacetylamide derivatives useful as inhibitors of enkephalinase and ace
CA2053340C (en) 1990-10-18 2002-04-02 Timothy P. Burkholder Mercaptoacetylamide derivatives useful as inhibitors of enkephalinase and ace
CA2052014A1 (en) * 1990-10-19 1992-04-20 Henry Y. Pan Method for preventing diabetic complications employing a cholesterol lowering drug alone or in combination with an ace inhibitor
US5190970A (en) * 1990-10-19 1993-03-02 E. R. Squibb & Sons, Inc. Method for preventing onset of or treating Type II diabetes employing a cholesterol lowering drug alone or in combination with an ace inhibitor
US5130333A (en) * 1990-10-19 1992-07-14 E. R. Squibb & Sons, Inc. Method for treating type II diabetes employing a cholesterol lowering drug
AU9024591A (en) 1990-10-25 1992-05-26 G.D. Searle & Co. Biphenylalkyl xanthine compounds for treatment of cardiovascular disorders
AU636066B2 (en) 1990-10-30 1993-04-08 Takeda Chemical Industries Ltd. Thienoimidazole derivatives, their production and use
US5087634A (en) 1990-10-31 1992-02-11 G. D. Searle & Co. N-substituted imidazol-2-one compounds for treatment of circulatory disorders
PH31175A (en) 1990-10-31 1998-03-20 Squibb & Sons Inc Indole and benzimi-dazole-substituted imidazole and benzimidazole derivatives.
DE4036645A1 (de) 1990-11-16 1992-05-21 Hoechst Ag Substituierte azole, verfahren zu deren herstellung, deren enthaltende mittel und deren verwendung
DE4036706A1 (de) 1990-11-17 1992-05-21 Hoechst Ag Verfahren zur behandlung der cardialen sowie der vasculaeren hypertrophie und hyperplasie
GB9025123D0 (en) 1990-11-19 1991-01-02 Ici Plc Nitrogen compounds
GB9026006D0 (en) 1990-11-29 1991-01-16 Glaxo Group Ltd Chemical compounds
AU9055391A (en) 1990-11-30 1992-06-25 Smithkline Beecham Corporation Substituted 5-aryl imidazoles
CA2057089A1 (en) 1990-12-07 1992-06-08 Eric E. Allen Substituted pyrazolopyrimidines and imidazopyridazines as angiotensin ii antagonists
AU657498B2 (en) 1990-12-14 1995-03-16 Novartis Ag Biphenylyl compounds
DE69133019T2 (de) 1990-12-14 2002-11-28 Smithkline Beecham Corp Imidazolyl-alkencarbonsäuren
US5175180A (en) 1990-12-20 1992-12-29 G. D. Searle & Co. N-substituted n-(alpha-triazolyl-toluyl)pyrrole compounds and use for treatment of circulatory disorders
CA2058198A1 (en) 1991-01-04 1992-07-05 Adalbert Wagner Azole derivatives, process for their preparation, and their use
US5124335A (en) 1991-01-30 1992-06-23 Merck & Co., Inc. Substituted pyrollo-fused 6 membered heterocycles as angiotensin ii antagonists
US5290780A (en) 1991-01-30 1994-03-01 American Cyanamid Co. Angiotensin II receptor blocking 2,3,6 substituted quinazolinones
AT395853B (de) 1991-01-31 1993-03-25 Chem Pharm Forsch Gmbh Neue imidazolderivate, verfahren zu ihrer herstellung und ihre verwendung
SI9210098B (sl) 1991-02-06 2000-06-30 Dr. Karl Thomae Benzimidazoli, zdravila, ki te spojine vsebujejo, in postopek za njihovo pripravo
IL100555A (en) 1991-02-07 2000-08-31 Hoechst Marion Roussel Inc N-substituted quinoline derivatives their preparation their use for the preparation of medicaments and the pharmaceutical compositions containing them
ATE156120T1 (de) 1991-02-07 1997-08-15 Roussel Uclaf Bizyklische stickstoffverbindungen, ihre herstellung, erhaltene zwischenprodukte, ihre verwendung als arzneimittel und diese enthaltende pharmazeutische zusammensetzungen
MX9200299A (es) 1991-02-07 1992-12-01 Roussel Uclaf Nuevos derivados biciclicos nitrogenados, su procedimiento de preparacion los nuevos compuestos intermedios obtenidos su aplicacion como medicamentos y las composiciones farmaceuticas que los contienen.
GB9102804D0 (en) 1991-02-11 1991-03-27 Ici Plc Heterocyclic derivatives
GB9102803D0 (en) 1991-02-11 1991-03-27 Ici Plc Pyridine compounds
IE920175A1 (en) 1991-02-11 1992-08-12 Zeneca Ltd Nitrogen heterocycles
IL100917A0 (en) 1991-02-16 1992-11-15 Fisons Plc Pyridinone and pyrimidinone derivatives,their preparation and pharmaceutical compositions containing them
FR2672892B1 (fr) 1991-02-20 1994-01-14 Synthelabo Derives de 4-pyrimidinones, leur preparation et leur application en therapeutique.
IS1756B (is) 1991-02-21 2000-12-28 Sankyo Company Limited Hliðstæðuaðferð til framleiðslu 1-Biphenylmethylimidazole afleiða
CA2061159A1 (en) 1991-02-26 1992-08-27 Michael A. Poss Imidazole and benzimidazole derivatives
FR2673427B1 (fr) 1991-03-01 1993-06-18 Sanofi Elf Derives heterocycliques diazotes n-substitues par un groupement biphenylmethyle, leur preparation, les compositions pharmaceutiques en contenant.
EP0502575A1 (en) 1991-03-06 1992-09-09 Merck & Co. Inc. Substituted 1-(2H)-isoquinolinones
US5202328A (en) 1991-03-06 1993-04-13 Merck & Co., Inc. Substituted fused pyrimidinones
EP0503838A3 (en) 1991-03-08 1992-10-07 Merck & Co. Inc. Heterocyclic compounds bearing acidic functional groups as angiotensin ii antagonists
EP0505098A1 (en) 1991-03-19 1992-09-23 Merck & Co. Inc. Imidazole derivatives bearing acidic functional groups as angiotensin II antagonists
US5196537A (en) 1991-03-21 1993-03-23 G. D. Searle & Co. 5-apylheteroarylalkyl-1,3,5-trisubstituted-1,2,4-triazole compounds for treatment of circulatory disorders
US5187179A (en) 1991-03-22 1993-02-16 Merck & Co., Inc. Angiotensin II antagonists incorporating a substituted imidazo [1,2-b][1,2,4]triazole
US5128327A (en) 1991-03-25 1992-07-07 Merck & Co., Inc. Angiotensin II antagonists incorporating a nitrogen containing six membered ring heterocycle
WO1992016552A1 (en) 1991-03-25 1992-10-01 Glaxo Group Limited 1-imidazolgemethyl benzofuran derivatives as inhibitors of angiotensin ii activity
US5177074A (en) 1991-03-26 1993-01-05 Merck & Co., Inc. Angiotensin ii antagonists incorporating a substituted thiophene or furan
DE4110019C2 (de) 1991-03-27 2000-04-13 Merck Patent Gmbh Imidazopyridine, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zubereitungen
US5157025A (en) * 1991-04-01 1992-10-20 E. R. Squibb & Sons, Inc. Method for lowering serum cholesterol employing a phosphorus containing ace inhibitor alone or in combination with a cholesterol lowering drug
US5164403A (en) 1991-04-05 1992-11-17 G. D. Searle & Co. N-arylheteroarylalkyl imidazol-2-one compounds for treatment of circulatory disorders
US5157040A (en) 1991-04-05 1992-10-20 Merck & Co., Inc. Substituted quinolines as angiotensin ii antagonists
US5151435A (en) 1991-04-08 1992-09-29 Merck & Co., Inc. Angiotensin ii antagonists incorporating an indole or dihydroindole
US5155117A (en) 1991-04-12 1992-10-13 G. D. Searle & Co. 1-arylheteroarylalkyl substituted-1h-1,2,4-triazole compounds for treatment of circulatory disorders
TW274551B (pt) 1991-04-16 1996-04-21 Takeda Pharm Industry Co Ltd
DE4200954A1 (de) 1991-04-26 1992-10-29 Bayer Ag Heterocyclisch substituierte phenylessigsaeurederivate
US5252574A (en) 1991-04-26 1993-10-12 Merck & Co., Inc. Angiotensin II antagonists incorporating a substituted thiophene or furan
EP0511767A1 (en) 1991-04-29 1992-11-04 Merck & Co. Inc. Tablets containing compound DUP753
GB9109246D0 (en) 1991-04-30 1991-06-19 Ici Plc Nitrogen derivatives
US5198438A (en) 1991-05-07 1993-03-30 Merck & Co., Inc. Angiotensin ii antagonists incorporating a substituted thiophene or furan
US5162325A (en) 1991-05-07 1992-11-10 Merck & Co., Inc. Angiotensin ii antagonists incorporating a substituted benzyl element
US5506361A (en) * 1991-05-08 1996-04-09 Theupjohn Company Imidazobenzoquinones and composition for preventing or treating hypertension or congestive heart failure containing the same
JPH05112533A (ja) * 1991-05-08 1993-05-07 Upjohn Co:The イミダゾベンゾキノン類およびこれを有効成分とする高血圧・鬱血性心不全の予防・治療剤
US5238942A (en) 1991-05-10 1993-08-24 Merck & Co., Inc. Substituted quinazolinones bearing acidic functional groups as angiotensin ii antagonists
US5223501A (en) 1991-05-10 1993-06-29 Merck & Co., Inc. Substituted pyrimidinones bearing acidic functional groups as angiotensin ii antagonists
US5162340A (en) 1991-05-10 1992-11-10 Merck & Co., Inc. Substituted 1-(2h)-isoquinolinones bearing acidic functional groups as angiotensin ii antagonists
GB9110532D0 (en) 1991-05-15 1991-07-03 Smithkline Beecham Corp Chemical compounds
EP0514192A1 (en) 1991-05-16 1992-11-19 Glaxo Group Limited Antihypertensive benzofuran derivatives, substituted by varied N-pyrimidinyl- or N-imidazolyl-methyl groups
GB9110636D0 (en) 1991-05-16 1991-07-03 Glaxo Group Ltd Chemical compounds
GB9110635D0 (en) 1991-05-16 1991-07-03 Glaxo Group Ltd Chemical compounds
GB9110625D0 (en) 1991-05-16 1991-07-03 Glaxo Group Ltd Chemical compounds
GB9110623D0 (en) 1991-05-16 1991-07-03 Glaxo Group Ltd Chemical compounds
CA2068756A1 (en) 1991-05-16 1992-11-17 Barry C. Ross Benzofuran derivatives
FR2676734B1 (fr) 1991-05-23 1995-05-19 Roussel Uclaf Nouveaux derives de la pyrimidine, leur procede de preparation, les nouveaux intermediaires obtenus, leur application a titre de medicaments et les compositions pharmaceutiques les renfermant.
AU1625192A (en) 1991-05-31 1992-12-03 Zeneca Limited Heterocyclic derivatives
WO1992021666A1 (fr) 1991-05-31 1992-12-10 Laboratoires Upsa Derives de thiazole antagonistes de recepteurs a l'angiotensine ii
US5175164A (en) 1991-06-05 1992-12-29 Merck & Co., Inc. Angiotensin ii antagonists incorporating a substituted indole or dihydroindole
JPH05213884A (ja) 1991-06-14 1993-08-24 Upjohn Co:The 新規な４−アミノキノリン類およびこれを有効成分とする高血圧・鬱血性心不全の予防・治療剤
US5210211A (en) 1991-06-21 1993-05-11 Warner-Lambert Company 4-(1h-pyrrol-1-yl) imidazoles with angiotension ii antagonist activity
GB9113628D0 (en) 1991-06-25 1991-08-14 Ici Plc Heterocyclic derivatives
GB9113626D0 (en) 1991-06-25 1991-08-14 Ici Plc Heterocyclic compounds
IL102183A (en) 1991-06-27 1999-11-30 Takeda Chemical Industries Ltd The heterocyclic compounds are converted into biphenyl groups, their production and the pharmaceutical compositions containing them
CA2072775A1 (en) 1991-07-03 1993-01-04 Wallace T. Ashton Substituted triazolinones
FR2678618B1 (fr) 1991-07-05 1993-11-05 Upsa Laboratoires Nouveaux derives de triazolo pyrimidine antagonistes des recepteurs a l'angiotensine ii; leurs procedes de preparation, compositions pharmaceutiques les contenant.
WO1993003033A1 (en) 1991-07-26 1993-02-18 G. D. Searle & Co. CARBONATE-SUBSTITUTED IMIDAZO[4,5-d] PYRIDAZINE COMPOUNDS FOR TREATMENT OF CARDIOVASCULAR DISORDERS
IT1250749B (it) 1991-08-02 1995-04-21 Luso Farmaco Inst Composti eterociclici ad attivita' a ii antagonista
WO1993003040A1 (en) 1991-08-05 1993-02-18 Taisho Pharmaceutical Co., Ltd. Thienopyrimidin-4-one derivative
US5225401A (en) 1991-08-12 1993-07-06 E. R. Squibb & Sons, Inc. Treatment of congestive heart failure
US5246944A (en) 1991-08-13 1993-09-21 Merck & Co., Inc. Quinoline angiotensin ii antagonists incorporating a substituted benzyl element
DK0528762T3 (da) 1991-08-15 1997-08-25 Ciba Geigy Ag N-acyl-N-heterocyclyl- eller naphthylalkyl-aminosyrer som angiotensin II antagonister
DE534263T1 (de) 1991-09-20 1993-09-02 L.G.L. Electronics S.P.A., Bergamo, It Selbstregulierende fadenbremse fuer eine schussfadenliefervorrichtung.
US5256667A (en) * 1991-09-25 1993-10-26 Merck & Co., Inc. Quinazolinones and pyridopyrimidinones
US5202322A (en) * 1991-09-25 1993-04-13 Merck & Co., Inc. Quinazolinone and pyridopyrimidine a-II antagonists
CA2078759C (en) 1991-09-27 2003-09-16 Alan M. Warshawsky Novel carboxyalkyl derivatives useful as inhibitors of enkephalinase and ace
AU657793B2 (en) 1991-09-27 1995-03-23 Merrell Pharmaceuticals Inc. Novel 2-substituted indane-2-carboxyalkyl derivatives useful as inhibitors of enkephalinase and ACE
JPH06107661A (ja) * 1991-10-24 1994-04-19 Upjohn Co:The イミダゾール誘導体およびこれを有効成分とする医薬組成物
US5219856A (en) * 1992-04-06 1993-06-15 E. I. Du Pont De Nemours And Company Angiotensin-II receptor blocking, heterocycle substituted imidazoles
US5977160A (en) * 1992-04-10 1999-11-02 Brigham And Women's Hospital, Inc. Methods for reducing risk of repeat myocardial infarction and increasing survival in heart attack victims
US5972990A (en) * 1992-04-10 1999-10-26 Brigham And Women's Hospital, Inc. Methods for reducing risk of repeat myocardial infarction and increasing survival in heart attack victims
US5552397A (en) 1992-05-18 1996-09-03 E. R. Squibb & Sons, Inc. Substituted azepinone dual inhibitors of angiotensin converting enzyme and neutral exdopeptidase
JP3360079B2 (ja) 1992-05-15 2002-12-24 メレルダウファーマスーティカルズ インコーポレイテッド エンケファリナーゼ及びＡＣＥの阻害剤として有用な新規なメルカプトアセチルアミドピリダゾ［１，２］ピリダジン、ピラゾロ［１，２］ピリダジン、ピリダゾ［１，２‐ａ］［１，２］ジアゼピン、及びピラゾロ［１，２‐ａ］［１，２］ジアゼピン誘導体類
EP0668864A1 (en) * 1992-07-17 1995-08-30 Merck & Co. Inc. Substituted biphenylmethylimidazopyridines
US5266583A (en) * 1992-09-01 1993-11-30 Merck & Co., Inc. Angitotensin II antagonist
US5504080A (en) 1992-10-28 1996-04-02 Bristol-Myers Squibb Co. Benzo-fused lactams
DE4308504A1 (de) * 1993-03-18 1994-09-22 Knoll Ag Neue Verwendung einer Kombination aus Verapamil und Trandolapril
DE4309553A1 (de) * 1993-03-24 1994-09-29 Bayer Ag Verfahren zur Herstellung von 3R,5S-(+)-Natrium-erythro-(E)-7-(4-(4-flurophenyl)-2,6-diisopropyl-5-methoxymethyl-pyrid-3-yl)-3,5-dihydroxy-hept-6-enoat
CN1110865A (zh) 1993-06-11 1995-10-25 卫材株式会社 氨基酸衍生物
US5508272A (en) 1993-06-15 1996-04-16 Bristol-Myers Squibb Company Compounds containing a fused bicycle ring and processes therefor
US5362727A (en) 1993-07-26 1994-11-08 Bristol-Myers Squibb Substituted azepino[2,1-a]isoquinoline compounds
US5525723A (en) 1993-11-18 1996-06-11 Bristol-Myers Squibb Co. Compounds containing a fused multiple ring lactam
US6369103B1 (en) * 1994-01-18 2002-04-09 Bristol-Myers Squibb Company Method for preventing or reducing risk of onset of cardiovascular events employing an HMG CoA reductase inhibitor
ES2079315B1 (es) * 1994-02-24 1996-10-16 Uriach & Cia Sa J Nuevas imidazopiridinas.
ES2105939B1 (es) * 1994-08-02 1998-07-01 Uriach & Cia Sa J Nuevos pirazoles con actividad antagonista de la angiotensina ii.
US5612359A (en) 1994-08-26 1997-03-18 Bristol-Myers Squibb Company Substituted biphenyl isoxazole sulfonamides
AU5354196A (en) * 1995-02-10 1996-08-27 G.D. Searle & Co. Combination of angiotensin converting enzyme inhibitor and side-effect-reduced amount of aldosterone antagonist
EP0738510A3 (fr) * 1995-04-20 2005-12-21 L'oreal Utilisation d'un inhibiteur d'HMG-coenzyme A-reductase pour lutter contre le vieillissement de la peau et pour traiter l'acné. Composition comprenant au moins un inhibiteur HMG-coenzyme A reductase et au moins un actif possédant des propriétes desquamantes
US5656603A (en) * 1995-05-31 1997-08-12 Loyola University Of Chicago Aminopeptidase P inhibitors and uses thereof
TW442301B (en) * 1995-06-07 2001-06-23 Sanofi Synthelabo Pharmaceutical compositions containing irbesartan
GB2308064A (en) * 1995-10-31 1997-06-18 Merck & Co Inc Treatment of congestive heart failure with a growth hormone secretagogue
AU2252297A (en) * 1996-01-31 1997-08-22 Technology Licensing Co., L.L.C. Method of diagnosis and treatment and related compositions and apparatus
EP0795327A1 (en) * 1996-03-13 1997-09-17 Pfizer Inc. Use of Amlodipine for the treatment and prophylaxis of congestive cardiac failure of non-ischaemic origin
ATE216881T1 (de) * 1996-06-24 2002-05-15 Merck & Co Inc Zusammensetzung auf basis von enalapril und losartan
KR20000070046A (ko) * 1997-01-10 2000-11-25 폴락 돈나 엘. 심부전증을 치료하기 위한, 안지오텐신 ⅱ 길항제를 포함하는 약제학적 조성물
US6180660B1 (en) * 1997-08-26 2001-01-30 Merck & Co., Inc. Cholesterol-lowering therapy
CA2306216C (en) * 1997-10-17 2011-06-07 Eurogene Limited The use of inhibitors of the renin-angiotensin system for the treatment of cachexia and wasting
US6097772A (en) * 1997-11-24 2000-08-01 Ericsson Inc. System and method for detecting speech transmissions in the presence of control signaling
JPH11222439A (ja) * 1998-02-03 1999-08-17 Dainippon Pharmaceut Co Ltd 脳血管攣縮抑制薬
CN1291888A (zh) * 1998-03-04 2001-04-18 武田药品工业株式会社 Aⅱ拮抗剂的缓释制剂、其制备和用途
RU2450813C2 (ru) * 1998-07-10 2012-05-20 Новартис Аг Гипотензивная комбинация валсартана и блокатора кальциевых каналов
DE19913528A1 (de) * 1998-12-21 2000-06-29 Sanol Arznei Schwarz Gmbh Neue Verwendung von Moexipril
AU5016200A (en) * 1999-05-21 2000-12-12 Myriad Genetics, Inc. Diabetes gene
PL353199A1 (en) * 1999-08-30 2003-11-03 Aventis Pharma Deutschland Gmbh Use of inhibitors of the renin-angiotensin system in the prevention of cardiovascular events
GB0020691D0 (en) * 2000-08-22 2000-10-11 Boehringer Ingelheim Pharma Pharmaceutical combination
US20030158090A1 (en) * 2001-07-23 2003-08-21 Ulrik Pedersen-Bjergaard Renin-angiotensin system in diabetes mellitus
US20050065203A1 (en) * 2001-10-17 2005-03-24 Salim Yusuf Method of reducing type 2 diabetes in high risk patients
JP2005511631A (ja) * 2001-11-23 2005-04-28 ゾルファイ　ファーマスーティカルズ　ゲゼルシャフト　ミット　ベシュレンクテル　ハフツング 脳血管障害発作の急性期における高血圧症の治療
ITBO20030050A1 (it) * 2003-02-06 2004-08-07 Ima Spa Macchina per il trattamento di prodotti farmaceutici.

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