AR059980A1 - METHODS OF TREATMENT WITH INHIBITORS OF THE PROTEIN OF TRANSFER OF ESTER DE COLESTEROL (CETP) - Google Patents

METHODS OF TREATMENT WITH INHIBITORS OF THE PROTEIN OF TRANSFER OF ESTER DE COLESTEROL (CETP)

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Publication number
AR059980A1
AR059980A1 ARP070101123A ARP070101123A AR059980A1 AR 059980 A1 AR059980 A1 AR 059980A1 AR P070101123 A ARP070101123 A AR P070101123A AR P070101123 A ARP070101123 A AR P070101123A AR 059980 A1 AR059980 A1 AR 059980A1
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Argentina
Prior art keywords
alkyl
halo
alkoxy
disease
amino
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ARP070101123A
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Spanish (es)
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Roger Benjamin Ruggeri
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Pfizer Prod Inc
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Publication of AR059980A1 publication Critical patent/AR059980A1/en

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    • A—HUMAN NECESSITIES
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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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—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
    • A61K31/4025—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 not condensed and containing further heterocyclic rings, e.g. cromakalim
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • 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
    • A61P25/28—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
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    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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    • A61P33/10—Anthelmintics
    • A61P33/12—Schistosomicides
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    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • 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
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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Abstract

Inhibidores de la proteína de transferencia de éster de colesterol (CETP), a composiciones farmacéuticas que contienen dichos inhibidores y al uso de dichos inhibidores para tratar ciertas enfermedades/afecciones opcionalmente en asociacion con ciertos agentes terapéuticos por ej., inhibidores de la HMG CoA reductasa. Reivindicacion 1: Un método de tratamiento de un trastorno o afeccion seleccionada de: trastornos cardiovasculares, angina, isquemia, isquemia cardiaca, apoplejía, lesion de revascularizacion, restenosis angioplástica, hipertension arterial, complicaciones vasculares de la diabetes, obesidad, endotoxemia, enfermedad cerebrovascular, arteriopatía coronaria, hipertension arterial, disfuncion ventricular, arritmia cardiaca, vasculopatía pulmonar, insuficiencia venosa periférica, enfermedad renovascular, enfermedad renal, vasculopatía visceral, enfermedad hemostática vascular, diabetes, enfermedad inflamatoria, trastornos autoinmunitarios y otras indicaciones de enfermedades sistémicas, modulacion de la funcion inmunologica, enfermedad pulmonar, enfermedad de antioxidantes, disfuncion sexual, disfuncion cognitiva, esquistosomiasis y cáncer en un mamífero, que comprende administrar a dicho mamífero una cantidad terapéuticamente eficaz de un compuesto de la formula (1), o una sal farmacéuticamente aceptable de dicho compuesto, en el que: R1 es Y, W-O-Y o W-Y; en donde W es un carbonilo; Y para cada caso es independientemente Z o alquilo C1-10 en el que uno de los carbonos se puede reemplazar con S, O o N y cuando Y es alquilo C1-10 entonces Y está opcionalmente sustituido con uno o nueve sustituyentes seleccionados independientemente de: halo, hidroxi, oxo, amino, amido, carboxi y Z; en el que Z es un sistema de anillo de tres a ocho miembros o de anillo bicíclico, parcialmente saturado, completamente saturado o completamente insaturado, opcionalmente con uno a cuatro heteroátomos seleccionados de O, S y N, en el que Z está opcionalmente sustituido con uno, dos o tres sustituyentes seleccionados independientemente de: halo, alquilo C1-6, hidroxi, alcoxi C1-6, amino, amido, ciano, oxo, carboxi, (alquil C1-6)oxicarbonilo, mono-N- y di-N,N-(alquil C1-6)amino en el que dicho sustituyente alquilo C1-6 está opcionalmente sustituido con uno, dos o tres sustituyentes seleccionados independientemente de: halo, hidroxi, alcoxi C1-6, ciano, oxo, amino, amido, carboxi, mono-N- y di-N,N-(alquil C1-6)amino y (alquil C1- 6)oxicarbonilo, dicho sustituyente alquilo C1-6 o alcoxi C1-6 está también opcionalmente sustituido con desde uno o nueve fluoruros; R2 es alquilo C1-4 o cicloalquilo C1-6; R4 es: V0, -COO(alquilo C1-4), ciano, -CHO, -CONH2 o -CO(alquilo C1-4); en el que V0 es: tetrazolilo, triazolilo, imidazolilo, pirazolilo, oxadiazolilo, isoxazolilo, furanilo, tiadiazolilo, isotiazolilo, tiofenilo, pirimidinilo o piridinilo; en el que V0 está opcionalmente sustituido con (R0)n en el que n es 1, 2, 3 o 4 y cada R0 es independientemente: halo, alquilo C1-6, hidroxi, alcoxi C1-6, amino, amido, ciano, oxo, carboxamoilo, carboxi o (alquil C1-6)oxicarbonilo, en el que dicho sustituyente alquilo C1-6 o alcoxi C1-6 está opcionalmente independientemente sustituido con uno o dos oxo, uno o dos hidroxi o uno o nueve halo; y R5, R6, R7 y R8 son independientemente: hidrogeno, ciano, halo, alcoxi C1-4 o alquilo C1-4 en el que dicho alquilo C1-4 y alcoxi C1-4 están opcionalmente sustituidos independientemente con desde uno a siete halo; con la condicion de que cuando R4 es distinto de V0 entonces R1 no es alquilo C1-6 y R1 tiene un sustituyente amido o sustituyente carboxi; opcionalmente en asociacion con un inhibidor de HMG CoA reductasa o una sal farmacéuticamente aceptable del mismo, en cantidades que hacen eficaces a los agentes activos en el tratamiento de dicho trastorno o afeccion. Reivindicacion 6: El método de acuerdo a la reivindicacion 4, en el que el inhibidor de la HMG CoA reductasa es atorvastatina o una sal farmacéuticamente aceptable de dicho compuesto.Cholesterol ester transfer protein (CETP) inhibitors, pharmaceutical compositions containing said inhibitors and the use of said inhibitors to treat certain diseases / conditions optionally in association with certain therapeutic agents eg, HMG CoA reductase inhibitors . Claim 1: A method of treating a disorder or condition selected from: cardiovascular disorders, angina, ischemia, cardiac ischemia, stroke, revascularization injury, angioplastic restenosis, arterial hypertension, vascular complications of diabetes, obesity, endotoxemia, cerebrovascular disease, coronary artery disease, arterial hypertension, ventricular dysfunction, cardiac arrhythmia, pulmonary vasculopathy, peripheral venous insufficiency, renovascular disease, renal disease, visceral vasculopathy, hemostatic vascular disease, diabetes, inflammatory disease, autoimmune disorders and other indications of systemic diseases, function modulation immunological, lung disease, antioxidant disease, sexual dysfunction, cognitive dysfunction, schistosomiasis and cancer in a mammal, comprising administering to said mammal a therapeutically effective amount of a compound of the formula (1), or a sa l pharmaceutically acceptable of said compound, wherein: R1 is Y, W-O-Y or W-Y; where W is a carbonyl; And for each case it is independently Z or C1-10 alkyl in which one of the carbons can be replaced with S, O or N and when Y is C1-10 alkyl then Y is optionally substituted with one or nine substituents independently selected from: halo, hydroxy, oxo, amino, amido, carboxy and Z; wherein Z is a three to eight member ring or bicyclic ring system, partially saturated, completely saturated or completely unsaturated, optionally with one to four heteroatoms selected from O, S and N, in which Z is optionally substituted with one, two or three substituents independently selected from: halo, C1-6 alkyl, hydroxy, C1-6 alkoxy, amino, amido, cyano, oxo, carboxy, (C1-6 alkyl) oxycarbonyl, mono-N- and di-N , N- (C1-6 alkyl) amino in which said C1-6 alkyl substituent is optionally substituted with one, two or three substituents independently selected from: halo, hydroxy, C1-6 alkoxy, cyano, oxo, amino, amido, carboxy, mono-N- and di-N, N- (C1-6 alkyl) amino and (C1-6 alkyl) oxycarbonyl, said substituent C1-6 alkyl or C1-6 alkoxy is also optionally substituted with from one or nine fluorides ; R2 is C1-4 alkyl or C1-6 cycloalkyl; R4 is: V0, -COO (C1-4 alkyl), cyano, -CHO, -CONH2 or -CO (C1-4 alkyl); wherein V0 is: tetrazolyl, triazolyl, imidazolyl, pyrazolyl, oxadiazolyl, isoxazolyl, furanyl, thiadiazolyl, isothiazolyl, thiophenyl, pyrimidinyl or pyridinyl; wherein V0 is optionally substituted with (R0) n where n is 1, 2, 3 or 4 and each R0 is independently: halo, C1-6 alkyl, hydroxy, C1-6 alkoxy, amino, amido, cyano, oxo, carboxamoyl, carboxy or (C1-6 alkyl) oxycarbonyl, wherein said substituent C1-6 alkyl or C1-6 alkoxy is optionally independently substituted with one or two oxo, one or two hydroxy or one or nine halo; and R5, R6, R7 and R8 are independently: hydrogen, cyano, halo, C1-4 alkoxy or C1-4 alkyl in which said C1-4 alkyl and C1-4 alkoxy are optionally substituted independently with from one to seven halo; with the proviso that when R4 is different from V0 then R1 is not C1-6 alkyl and R1 has an amido substituent or carboxy substituent; optionally in association with an HMG CoA reductase inhibitor or a pharmaceutically acceptable salt thereof, in amounts that make the active agents effective in the treatment of said disorder or condition. Claim 6: The method according to claim 4, wherein the HMG CoA reductase inhibitor is atorvastatin or a pharmaceutically acceptable salt of said compound.

ARP070101123A 2006-03-22 2007-03-20 METHODS OF TREATMENT WITH INHIBITORS OF THE PROTEIN OF TRANSFER OF ESTER DE COLESTEROL (CETP) AR059980A1 (en)

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Publication number Priority date Publication date Assignee Title
WO2008038098A1 (en) * 2006-09-25 2008-04-03 Pfizer Products Inc. Crystalline form of 7 [5-cyclopropyl)-4-o-fluorobenzylcarbamoyl)-2-(4-fluorophenyl)-imidazol-1-yl]-3r,5r-dihydroxyheptanoic
WO2009059943A1 (en) 2007-11-05 2009-05-14 Novartis Ag 4-benzylamino-1-carboxyacyl-piperidine derivatives as cetp inhibitors useful for the treatment of diseases such as hyperlipidemia or arteriosclerosis
ATE528289T1 (en) 2007-12-03 2011-10-15 Novartis Ag 1,2-DISUBSTITUTED 4-BENZYLAMINOPYRROLIDINE DERIVATIVES AS CETP INHIBITORS SUITABLE FOR THE TREATMENT OF DISEASES SUCH AS HYPERLIPIDEMIA OR ARTERIOSCLEROSIS
EP3261628A4 (en) * 2015-02-24 2018-10-31 King Abdullah University Of Science And Technology Cholesteryl ester transfer protein (cetp) inhibition in the treatment of cancer

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Publication number Priority date Publication date Assignee Title
US6147090A (en) * 1998-09-17 2000-11-14 Pfizer Inc. 4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines
US7071210B2 (en) * 2002-07-02 2006-07-04 Pfizer Inc. CETP inhibitors in combination with antihypertensive agents and uses thereof
UA90269C2 (en) * 2004-04-02 2010-04-26 Мицубиси Танабе Фарма Корпорейшн Tetrahydroquinoline derivatives and a process for preparing the same
MXPA06011657A (en) * 2004-04-16 2007-04-23 Warner Lambert Co Novel imidazoles.
EA200700119A1 (en) * 2004-06-24 2007-10-26 Эли Лилли Энд Компани CONNECTIONS AND METHODS OF TREATMENT OF DYSLIPIDEMIA
WO2006033004A1 (en) * 2004-09-23 2006-03-30 Pfizer Products Inc. Quinoline compounds as cetp inhibitors
US20060063803A1 (en) * 2004-09-23 2006-03-23 Pfizer Inc 4-Amino substituted-2-substituted-1,2,3,4-tetrahydroquinoline compounds
AP2007003979A0 (en) * 2004-11-23 2007-06-30 Warner Lambert Co 7-(2h-pyrazol-3-yl)-3,5-dihyroxy-heptanoic acid derivatives as hmg co-a reductase inhibitors for thetreatment of lipidemia
US20060270675A1 (en) * 2005-03-10 2006-11-30 Groneberg Robert D Inhibitors of cholesterol ester transfer protein

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