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AR057772A1 - Derivados de imidazol como inhibidores de sintasa de aldosterona y aromatasa. composiciones farmaceuticas - Google Patents

Derivados de imidazol como inhibidores de sintasa de aldosterona y aromatasa. composiciones farmaceuticas

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Publication number
AR057772A1
AR057772A1 ARP060103664A ARP060103664A AR057772A1 AR 057772 A1 AR057772 A1 AR 057772A1 AR P060103664 A ARP060103664 A AR P060103664A AR P060103664 A ARP060103664 A AR P060103664A AR 057772 A1 AR057772 A1 AR 057772A1
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AR
Argentina
Prior art keywords
alkyl
alkoxy
hydrogen
aryl
group
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Application number
ARP060103664A
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English (en)
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Novartis Ag
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=37610275&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR057772(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Novartis Ag filed Critical Novartis Ag
Publication of AR057772A1 publication Critical patent/AR057772A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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
    • A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
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    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/32—Antioestrogens
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
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    • A—HUMAN NECESSITIES
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    • A61P9/00—Drugs for disorders of the cardiovascular system
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
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  • Organic Chemistry (AREA)
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  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
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  • Epidemiology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
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  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
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  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Este compuesto es inhibidor de la sintasa de aldosterona y de la aromatasa, y por lo tanto, se puede emplear para el tratamiento de un trastorno y de una enfermedad mediada por la sintasa de aldosterona o por la aromatasa. De conformidad con lo anterior, se puede utilizar en el tratamiento de hipocalemia, hipertension, insuficiencia cardíaca congestiva, fibrilacion auricular, insuficiencia renal, en particular insuficiencia renal cronica, restenosis, ateroesclerosis, síndrome X, obesidad, nefropatía, infarto post-miocardial, enfermedades cardíacas coronarias, inflamacion, mayor formacion de colágeno, fibrosis, tales como fibrosis cardíaca o miocardíaca, y remodelacion en seguida de hipertension y disfuncion endotelial, ginecomastia, osteoporosis, cáncer de prostata, endometriosis, fibroides uterinos, hemorragia uterina disfuncional, hiperplasia endometrial, enfermedad de ovario poliquístico, infertilidad, enfermedad de mama fibroquística, cáncer de mama, y mastopatía fibroquística. Finalmente, la presente también proporciona una composicion farmacéutica. Reivindicacion 1: Un compuesto de formula (1), en donde: n es 1, o 2, o 3; R es hidrogeno, alquilo C1-7, o alquenilo C1-7, estando el alquilo C1-7 y el alquenilo C1-7 opcionalmente sustituidos por 1 a 5 sustituyentes independientemente seleccionados a partir del grupo que consiste en -O-R8 y -N(R8)(R9), en donde R8 y R9 se seleccionan independientemente a partir del grupo que consiste en hidrogeno, alquilo C1-7, acilo, arilo y heteroarilo, cada uno de los cuales está además opcionalmente sustituido por 1 a 4 sustituyentes independientemente seleccionados a partir del grupo que consiste en halogeno, alcoxilo C1-7 y alquilo C1-7; o R es -C(O)O- R10, o -C(O)N(R11)(R12), en donde R10, R11 y R12 se seleccionan independientemente a partir del grupo que consiste en hidrogeno, alquilo C1-7, cicloalquilo C3-8, arilo, aril-alquilo C1-7, haloalquilo C1-7 y heteroarilo, cada uno de los cuales está además opcionalmente sustituido por 1 a 4 sustituyentes independientemente seleccionados a partir del grupo que consiste en halogeno, hidroxilo, alcoxilo C1-7, alquilo C1-7, y arilo, en donde R11 y R12, tomados junto con el átomo de nitrogeno con el que están unidos, forman opcionalmente un anillo de 3 a 8 miembros; R1, R2, R3, R4, y R5 se seleccionan independientemente a partir del grupo que consiste en hidrogeno, alquenilo C1-7, alquilo C1-7, cicloalquilo C3-8, halogeno, ciano, nitro, H2N-, haloalquilo C1-7, alcoxilo C1-7, cicloalcoxilo C3-8, ariloxilo, arilo, heteroarilo, -C(O)OR10, y -N(R13)(R14), estando el alquilo C1-7, alquenilo C1-7, alcoxilo C1-7, arilo y heteroarilo además opcionalmente sustituidos por 1 a 3 sustituyentes seleccionados a partir de alquilo C1-7, hidroxilo, halogeno, alcoxilo C1-7, nitro, ciano, dialquilo C1-7-amino, alcoxilo C1-7-alquilo C1-7-, y haloalquilo C1-7, teniendo el R10 el mismo significado que se define anteriormente, y R13 y R14 se seleccionan independientemente a partir del grupo que consiste en hidrogeno, alquilo C1-7, cicloalquilo C3-8, haloalquilo C1-7, haloalcoxilo C1-7, arilo y ciano, con la condicion de que no más de tres de R1, R2, R3, R4, y R5 son simultáneamente hidrogeno; R13 y R14, tomados junto con el átomo de nitrogeno con el que están unidos, forman opcionalmente un anillo de 3-8 miembros; R y R1, tomados juntos, forman opcionalmente un anillo de 5 a 6 miembros que contiene 0 o 1 heteroátomo seleccionado a partir de O, N, o S; R6 y R7 son independientemente hidrogeno, hidroxilo, alquilo C1-7, alcoxilo C1-7, fenilo, o bencilo, en donde fenilo y bencilo están opcionalmente sustituidos por 1 a 4 sustituyentes independientemente seleccionados a partir del grupo que consiste en halogeno, alcoxilo C1-7 y alquilo C1-7; cuando R6 y R7 están unidos al mismo átomo de carbono, opcionalmente forman una fraccion formula (2), en donde Ra y Rb son independientemente hidrogeno, alquilo C1-7, alcoxilo C1-7, acilo, -COOR15 o -COR15, siendo el R15 hidrogeno, alquilo C1-7, haloalquilo C1-7, arilo, o -NH2; o cuando R6 y R7 están unidos al mismo átomo de carbono, tomados junto con ese átomo de carbono, forman opcionalmente un anillo de 3 a 8 miembros; o una sal farmacéuticamente aceptable del mismo; o un isomero optico del mismo, o una mezcla de isomeros opticos.
ARP060103664A 2005-08-25 2006-08-23 Derivados de imidazol como inhibidores de sintasa de aldosterona y aromatasa. composiciones farmaceuticas AR057772A1 (es)

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US (4) US8314097B2 (es)
EP (3) EP2256118B1 (es)
JP (2) JP5225086B2 (es)
KR (3) KR101324872B1 (es)
CN (2) CN101248078B (es)
AR (1) AR057772A1 (es)
AU (1) AU2006283105C1 (es)
BR (1) BRPI0615095B8 (es)
CA (1) CA2619660C (es)
DK (1) DK1919916T3 (es)
EA (1) EA014940B1 (es)
EC (1) ECSP088201A (es)
ES (2) ES2527209T3 (es)
GT (1) GT200600381A (es)
HR (1) HRP20130797T1 (es)
IL (2) IL189024A (es)
JO (1) JO2882B1 (es)
MA (1) MA29771B1 (es)
MX (1) MX2008002545A (es)
MY (1) MY151601A (es)
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NZ (1) NZ565476A (es)
PE (2) PE20070517A1 (es)
PH (1) PH12013502342A1 (es)
PL (1) PL1919916T3 (es)
PT (1) PT1919916E (es)
SG (1) SG165319A1 (es)
SI (1) SI1919916T1 (es)
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