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AR057776A1 - Derivados de 1,4-benzotiazepinas para prevenir y tratar trastornos que in-volucran la modulacion de los receptores ryr; procesos de obtencion y composiciones farmaceuticas - Google Patents

Derivados de 1,4-benzotiazepinas para prevenir y tratar trastornos que in-volucran la modulacion de los receptores ryr; procesos de obtencion y composiciones farmaceuticas

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Publication number
AR057776A1
AR057776A1 ARP060103693A ARP060103693A AR057776A1 AR 057776 A1 AR057776 A1 AR 057776A1 AR P060103693 A ARP060103693 A AR P060103693A AR P060103693 A ARP060103693 A AR P060103693A AR 057776 A1 AR057776 A1 AR 057776A1
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Argentina
Prior art keywords
alkyl
aryl
heterocyclyl
alkylaryl
heteroaryl
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ARP060103693A
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English (en)
Inventor
Andrew R Marks
Donald W Landry
Shixian Deng
Zhen Zhuang Cheng
Stephan E Lehnart
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Univ Columbia
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Publication of AR057776A1 publication Critical patent/AR057776A1/es

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    • C07D281/02—Seven-membered rings
    • C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
    • C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
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    • A61K31/554—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
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    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
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    • C07D417/12—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 chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
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    • 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

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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)

Abstract

La presente se refiere a sus sales, hidratos, solvatos, complejos y prodrogas. Se proveen además, métodos para sintetizar. Composiciones farmacéuticas que comprenden los compuestos y métodos para usar las composiciones farmacéuticas de la formula (1) para el tratamiento y prevencion de trastornos y enfermedades asociados con los receptores RyR que regulan al funcionamiento de los canales de calcio en las células. Reivindicacion 1: Un compuesto de formula (1), en donde, n es 0, 1 o 2; q es 0, 1, 2, 3 o 4; cada R se selecciona, de forma independiente, del grupo formado por halogeno, -OH, -NH2, -NO2, -CN, -CF3, -OCF3, -N3, -SO3H, -S(=O)2alquilo, -S(=O)alquilo, -OS(=O)2CF3, acilo, -O-acilo, alquilo, alcoxilo, alquilamino, alquilarilamino, alquiltio, cicloalquilo, alquilarilo, arilo, heteroarilo, heterociclilo, heterociclilalquilo, alquenilo, alquinilo, (hetero-)arilo, (hetero-)ariltio, y (hetero-)arilamino; en donde cada acilo, -O-acilo, alquilo, alcoxilo, alquilamino, alquilarilamino, alquiltio, cicloalquilo, alquilarilo, arilo, heteroarilo, heterociclilo, heterociclilalquilo, alquenilo, alquinilo, (hetero-)arilo, (hetero-)ariltio, y (hetero-) arilamino puede estar sustituido o no sustituido; R1 se selecciona del grupo formado por H, oxo, alquilo, alquenilo, arilo, alquilarilo, cicloalquilo, heteroarilo y heterociclilo; en donde cada alquilo, alquenilo, arilo, alquilarilo, cicloalquilo, heteroarilo y heterociclilo puede estar sustituido o no sustituido; R2 se selecciona del grupo formado por H, -C(=O)R5, -C(=S)R6, -SO2R7, -P(=O)R8R9, -(CH2)m-R10, alquilo, arilo, alquilarilo, heteroarilo, cicloalquilo, cicloalquilalquilo, y heterociclilo; en donde cada alquilo, arilo, alquilarilo, heteroarilo, cicloalquilo, cicloalquilalquilo, y heterociclilo puede estar sustituido o no sustituido; R3 se selecciona del grupo formado por H, -CO2Y, C(=O)NHY, acilo, -O-acilo, alquilo, alquenilo, arilo, alquilarilo, cicloalquilo, heteroarilo y heterociclilo; en donde cada acilo, alquilo, alquenilo, arilo, alquilarilo, cicloalquilo, heteroarilo y heterociclilo puede estar sustituido o no sustituido; y en donde Y se selecciona del grupo formado por H, alquilo, arilo, alquilarilo, cicloalquilo, heteroarilo y heterociclilo; y en donde cada alquilo, arilo, alquilarilo, cicloalquilo, heteroarilo y heterociclilo puede estar sustituido o no sustituido; R4 se selecciona del grupo formado por H, alquilo, alquenilo, arilo, alquilarilo, cicloalquilo, heteroarilo y heterociclilo; en donde cada alquilo, alquenilo, arilo, alquilarilo, cicloalquilo, heteroarilo y heterociclilo puede estar sustituido o no sustituido; R5 se selecciona del grupo formado por -NR15R16, - (CH2)qNR15R16, -NHNR15R16, NHOH, -OR15, -C(=O)NHNR15R16, -CO2R15, -C(=O)NR15R16, CH2X, acilo, alquilo, alquenilo, arilo, alquilarilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heterociclilo, y heterociclilalquilo; en donde cada acilo, alquilo, alquenilo, arilo, alquilarilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heterociclilo, y heterociclilalquilo puede estar sustituido o no sustituido, y en donde q es 1, 2, 3, 4, 5 o 6; R6 se selecciona del grupo formado por -OR15, NHNR15R16, - NHOH, -NR15R16, -CH2X, acilo, alquenilo, alquilo, arilo, alquilarilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heterociclilo, y heterociclilalquilo; en donde cada acilo, alquenilo, alquilo, arilo, alquilarilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heterociclilo, y heterociclilalquilo puede estar sustituido o no sustituido; R7 se selecciona del grupo formado por -OR15, -NR15R16, NHNR15R16, -NHOH, -CH2X, alquilo, alquenilo, alquinilo, arilo, alquilarilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heterociclilo, y heterociclilalquilo; en donde cada alquilo, alquenilo, alquinilo, arilo, alquilarilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heterociclilo, y heterociclilalquilo puede estar sustituido o no sustituido; R8 y R9 se seleccionan, de forma independiente, del grupo formado por OH, acilo, alquenilo, alcoxilo, alquilo, alquilamino, arilo, alquilarilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heterociclilo, y heterociclilalquilo; en donde cada acilo, alquenilo, alcoxilo, alquilo, alquilamino, arilo, alquilarilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heterociclilo, y heterociclilalquilo puede estar sustituido o no sustituido; R10 se selecciona del grupo formado por -NR15R16, OH, -SO2R11, - NHSO2R11, C(=O)(R12), NHC=O(R12), -OC=O(R12), y -P(=O)R13R14; R11, R12, R13, y R14 se seleccionan, de forma independiente, del grupo formado por H, OH, NH2, -NHNH2, -NHOH, acilo, alquenilo, alcoxilo, alquilo, alquilamino, arilo, alquilarilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heterociclilo, y heterociclilalquilo; en donde cada acilo, alquenilo, alcoxilo, alquilo, alquilamino, arilo, alquilarilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heterociclilo, y heterociclilalquilo puede estar sustituido o no sustituido; X se selecciona del grupo formado por halogeno, -CN, -CO2R15, -C(=O)NR15R16, -NR15R16, -OR15, -SO2R7, y -P(=O)R8R9; y R15 y R16 se seleccionan, de forma independiente, del grupo formado por H, acilo, alquenilo, alcoxilo, OH, NH2, alquilo, alquilamino, arilo, alquilarilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heterociclilo, y heterociclilalquilo; en donde cada acilo, alquenilo, alcoxilo, alquilo, alquilamino, arilo, alquilarilo, cicloalquilo, cicloalquilalquilo, heteroarilo, heterociclilo, y heterociclilalquilo puede estar sustituido o no sustituido; y opcionalmente R15 y R16 junto con el N al cual están unidos, pueden formar un heterociclo que puede estar sustituido; el nitrogeno en el anillo benzotiazepina puede ser opcionalmente un nitrogeno cuaternario; y enantiomeros, diastereomeros, tautomeros, sales, hidratos, solvatos, complejos y prodrogas aceptables para uso farmacéutico de los mismos; con la condicion que cuando q es 0 y n es 0, entonces R2 no es H, Et, -C(=O)NH2, (=O)NHPh, -C(=S)NH-nButilo, -C(=O)NHC(= O)CH2Cl, -C(=O)H, -C(=O)Me, -C(=O)Et, -C(=O)CH=CH2, -S(=O)2Me o -S(=O)2Et; con la condicion que cuando q es 0 y n es 1 o 2, entonces R2 no es -C(=O)Me, -C(=O)Et, -S(=O)2Et; con la condicion adicional que cuando q es 1, y R es Me, Cl o F en la posicion 6 del anillo benzotiazepeno, entonces R2 no es H, Me, -C(=O)H, -C(=O)Me, -C(=O)Et, -C(=O)Ph, -S(=O)2Me o -S(=O)Et; y con la condicion adicional que cuando q es 1, n es 0, y R es OCT3, OH, alcoxilo C1-3 en la posicion 7 del anillo benzotiazepeno, entonces R2 no es H, -C(=O)CH=CH2, o un resto de formula (2).
ARP060103693A 2005-08-25 2006-08-24 Derivados de 1,4-benzotiazepinas para prevenir y tratar trastornos que in-volucran la modulacion de los receptores ryr; procesos de obtencion y composiciones farmaceuticas AR057776A1 (es)

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US7879840B2 (en) * 2005-08-25 2011-02-01 The Trustees Of Columbia University In The City Of New York Agents for preventing and treating disorders involving modulation of the RyR receptors
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