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AR032624A1 - Derivados de fenilamina ciclica, uso de los mismos para la fabricacion de medicamentos y composicion farmaceutica - Google Patents

Derivados de fenilamina ciclica, uso de los mismos para la fabricacion de medicamentos y composicion farmaceutica

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Publication number
AR032624A1
AR032624A1 ARP010103382A ARP010103382A AR032624A1 AR 032624 A1 AR032624 A1 AR 032624A1 AR P010103382 A ARP010103382 A AR P010103382A AR P010103382 A ARP010103382 A AR P010103382A AR 032624 A1 AR032624 A1 AR 032624A1
Authority
AR
Argentina
Prior art keywords
alkyl
substituted
halogen
het
mono
Prior art date
Application number
ARP010103382A
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English (en)
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Wyeth Corp
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Filing date
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Publication of AR032624A1 publication Critical patent/AR032624A1/es

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    • 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
    • C07D401/10—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 linked by a carbon chain containing aromatic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • A61P3/08—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
    • 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
    • A—HUMAN NECESSITIES
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • 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
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/56—Nitrogen atoms
    • C07D211/58—Nitrogen atoms attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D223/12—Nitrogen atoms not forming part of a nitro radical
    • 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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • C07D401/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Ophthalmology & Optometry (AREA)
  • Diabetes (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Obesity (AREA)
  • Vascular Medicine (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Emergency Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Fodder In General (AREA)
  • Hydrogenated Pyridines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Derivados de fenilamina cíclica, que comprenden un compuesto de la Formula (1) en la cual: A es Ar o Het; X es -OCH2-, -SCH2-, o un enlace; T1 es (CH2)m; T2 es (CH2)n; T es un enlace, alquilo C1-6 sustituido en forma opcional con R11, alquenilo C2-7 sustituido en forma opcional con R11, alquinilo C2-7, alquiltio C1-6, alquilamino C1-6, alcoxoalquilo C1-6 por grupo funcional alquilo, alquiltioalquilo C1-6 por grupo funcional alquilo, alcoxi C1-6, alcoxialquilo C1-6, alquiloxoalquilo C1-6 por grupo funcional alquilo, acilo C2-7, o alquenilcarbonilo C3-8; R1, R2 y R3 son, cada uno, en forma independiente, hidrogeno, alquilo C1-6, cicloalquilo C3-8, hidroxi, halogeno, trifluorometilo, alcoxi C1-6, benciloxi, aliloxi, propargiloxi, aciloxi C2-7, ciano, nitro, amino, aminocarbonilo, alquilamino C1-6, dialquilamino C1-6 por grupo alquilo, formamido, ureido, acilamino C2-7, alquilsulfoniloamino C1-6, arilsulfoniloamino, dialquiloxifosforilamino C1-6 por grupo alquilo, dihidroxifosforilamino, -CO2-alquilo C1-6, o Ar sustituido en forma opcional con R11; R4 es hidrogeno, alquilo C1-6, halogeno, hidroxi, alquiloxi C1-6, alquiltio C1-6, amino, alquilamino C1-6, carboxi, acilo C2-7, ArCO-, alcoxicarbonilo C2-7, aminocarbonilo, alquilaminocarbonilo C2-7, alquilsulfonilo C1-6, o alquilsulfonilamino C1-6; R5 se selecciona entre las formulas (2) a (12); Aa es (i) un amino ácido, en el cual el nitrogeno del amino ácido está aherido al carbonilo adyacente de R5; o (ii) un éster de alquilo de un amino ácido, en el cual el nitrogeno del amino ácido está adherido al carbonilo adyacente de R5, y el grupo funcional alquilo del éster de alquilo contiene C1-6;Y y Z son, cada uno, en forma independiente, NR7, O, o S; X1 y X2 son, cada uno, en forma independiente, CO o SO2; una línea de puntos representa un doble enlace opcional; R6, R7 y R8 son, cada uno, en forma independiente, hidrogeno, alquilo C1-6 sustituido o no por R11, R12 y R13; alquenilo C2-7 sustituido o no por R11, R12 y R13; alquinilo C2-7 sustituido o no por R11; cicloalquilo C3-8 sustituido o no por R11, R12 y R13; bicicloalquilo C7-11 sustituido o no por R11, R12 y R13; -CO2-alquilo C1-6; Het sustituido o no por R11, R12 y R13; o Ar sustituido o no por R11, R12 y R13; o cuando R6 y R7 están incluidos en un nitrogeno comun, pueden unirse para formar un heterociclo saturado de 5-7 elementos que está sustituido o no por R11; R9 y R10 son, cada uno, en forma independiente, alquilo sustituido o no por R11, R12 y R13; Ar es, en forma opcional, mono-, di-, o tri-sustituido por R15; Ar fusionado a un anillo de cicloalquilo C3-8, y, en forma opcional mono-, di-, o tri-sustituido por R15; o Het, en forma opcional, mono-, di-, o tri-sustituido por R15; R11, R12, o R13 son, cada uno, en forma independiente, alquilo C1-6, halogeno, alquenilo C2-7, alquinilo C2-7, cicloalquilo C3-8, Ar-alquilo C1-6, Ar sustituido o no por R14, Het sustituido o no por R14, hidroxi, alcoxi C1-6, Ar-oxi, oxo, -CN, -CHO, -CO2H, -OCO2-alquilo C1-6, -CO2-alquilo C1-6, -CO2-Ar-, -CO2-alquil C1-6-Ar, -OCO2-Ar, -CONH2, -CONHOH, amino, alquilamino C1-6, dialquilamino C1-6, -NHCONH-alquilo C1-6, -NHSO2-alquilo C1-6, -NHSO2-Ar, o -NHSO2-Het; o cuando R11 y R12 están incluidos en un átomo de carbono comun de un grupo funcional alquilo, pueden unirse para formar un anillo espiro cicloalquilo C3-8; R14 es halogeno, alcoxi C1-6, alquilo C1-6, alquenilo C2-7, alquinilo C2-7, hidroxi, acilo C2-7, -SO2-alquilo C1-6, -CO2-alquilo C1-6, o alcoxicarbonilalquilo C3-13; R15 es (a) hidroxi, halogeno, -CN, -NR16R16, -OR16, -SR16, trifluorometilo, alquilo C1-6, -SO2R17, -O-alquil C1-6-CO2R17, -CO2R17, -OCOR17, -NR16COR17, -COR17, -NR16SO2R17, o -NR16CO2R16; o (b) alquilo C1-6 mono- o di-sustituido con hidroxi, halogeno, -CN, -NR16NR16, -OR16, -SR16, trifluorometilo, alquilo C1-6, -SO2R17, -CO2R17, -OCOR17, -NR16COR17, -COR17, -NR16SO2R17, -NR16CO2R16, Ar que puede en ser o no, mono- o di-sustituido por R16, -OR16, -NR16R16, o halogeno, o Het que puede ser o no, mono- o di-sustituido por R16, -OR16, -NR16R16, o halogeno; (c) Het que puede ser o no, mono- o di-sustituido por R16, -OR16, -NR16R16, o halogeno; o (d) Ar que puede ser o no, mono- o di-sustituido por R16, -OR16, -NR16R16, o halogeno; R16 es hidrogeno, alquilo C1-6, cicloalquilalquilo C4-14, bencilo, Ar o Het, en los cuales los grupos funcionales Ar o Het pueden ser, en forma opcional, mono-, di-, o tri-sustituidos con halogeno, nitro, alquilamino C1-6, dialquilamino C1-6, trifluorometilo, alquilo C1-6, alcoxi C1-6, alquiltio C1-6, -CO2H, -CO2alquilo C1-6, o -SO2alquilo C1-6; R17 es R16 o -NR16R16; Het es un heterociclo monocíclico o bicíclico de 5-10 átomos en el anillo, que tiene 1-4 heteroátomos seleccionados de oxígeno, nitrogeno, y azufre; en el cual el heterociclo puede ser saturado, insaturado o parcialmente saturado; y puede estar, en forma opcional fusionado a un anillo de fenilo; Ar es un sistema aromático que contiene 1-2 anillos aromáticos carbocíclicos C6-10; m = 1-3; y n = 1-3; o una de sus sales aceptables para uso farmacéutico; el uso de dichos derivados para la fabricacion de un medicamento para uso farmacéutico, que son utiles en el tratamiento o la inhibicion de trastornos metabolicos relacionados con la resistencia a la insulina o la hiperglucemia (asociados normalmente con la obesidad o intolerancia a la glucosa), ateroesclerosis, trastornos gastrointestinales, inflamacion neurogenética, glaucoma, hipertension ocular y necesidad frecuente de orinar; y son de particular utilidad en el tratamiento o la inhibicion de la diabetes tipo II y composiciones farmacéuticas que los comprenden.
ARP010103382A 2000-07-17 2001-07-16 Derivados de fenilamina ciclica, uso de los mismos para la fabricacion de medicamentos y composicion farmaceutica AR032624A1 (es)

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US21862700P 2000-07-17 2000-07-17

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Country Status (10)

Country Link
US (2) US6525202B2 (es)
EP (1) EP1301482A1 (es)
JP (1) JP2004504299A (es)
CN (1) CN1455771A (es)
AR (1) AR032624A1 (es)
AU (1) AU2002222930A1 (es)
BR (1) BR0112522A (es)
CA (1) CA2416245A1 (es)
MX (1) MXPA03000518A (es)
WO (1) WO2002006232A1 (es)

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US6525202B2 (en) 2003-02-25
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EP1301482A1 (en) 2003-04-16
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