AR032319A1 - METHOD FOR INHIBITING CATEPSINA S, 4-AMINO-AZEPAN-3-ONAS, TREATMENT METHODS THAT UNDERSTAND YOUR ADMINISTRATION AND USE OF THE SAME IN THE MANUFACTURE OF MEDICINES - Google Patents

METHOD FOR INHIBITING CATEPSINA S, 4-AMINO-AZEPAN-3-ONAS, TREATMENT METHODS THAT UNDERSTAND YOUR ADMINISTRATION AND USE OF THE SAME IN THE MANUFACTURE OF MEDICINES

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AR032319A1
AR032319A1 ARP010101786A ARP010101786A AR032319A1 AR 032319 A1 AR032319 A1 AR 032319A1 AR P010101786 A ARP010101786 A AR P010101786A AR P010101786 A ARP010101786 A AR P010101786A AR 032319 A1 AR032319 A1 AR 032319A1
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Argentina
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alkyl
het
group
cycloalkyl
azepan
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ARP010101786A
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Spanish (es)
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Smithkline Beecham Corp
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    • 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
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    • 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
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    • C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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Abstract

Un método para inhibir la Catepsina S que comprende administrarle a un animal que lo necesita, una cantidad eficaz de una de 4-amino-azepan-3-ona de Formula (1), en la que: R1 se selecciona del grupo formado por las formulas (2), (3) y (4); R2 se selecciona del grupo formado por H, alquilo C1-6, cicloalquil C3-6-alquilo C0-6, Ar-alquilo C0-6, Het-alquilo C0-6, R9C(O)-, R9C(S)-, R9SO2-, R9OC(O)-, R9R11NC(O)-, R9R11NC(S)-, R9(R11)NSO2-, formulas(5), (6) y (7); R3 se selecciona del grupo formado por: H, alquilo C1-6, cicloalquil C3-6-alquilo C0-6, alquenilo C2-6, alquinilo C2-6, Het-alquilo C0-6, Ar-alquilo C0-6, Ar-Ar-alquilo C0-6, Ar-Het-alquilo C0-6, Het-Ar-alquilo C0-6 y Het-Het-alquilo C0-6; R3 y R' pueden estar unidos dos para formar un anillo de pirrolidina, piperidina o morfolina; R4 se selecciona del grupo formado por: H, alquilo C1-6, cicloalquil C3-6-alquilo C0-6, Ar-alquilo C0-6, Het-alquilo C0-6, R5C(O)-, R5C(S)-, R5SO2-, R5OC(O)-, R5R13NC(O)- y R5R13NC(S)-; R5 se selecciona del grupo formado por: H, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquil C3-6-alquilo C0-6, Ar-alquilo C0-6 y Het-alquilo C0-6; R6 se selecciona del grupo formado por: H, alquilo C1-6, cicloalquil C3-6-alquilo C0-6, Ar-alquilo C0-6 y Het-alquilo C0-6, R7 se selecciona del grupo formado por: H, alquilo C1-6, cicloalquil C3-6-alquilo C0-6, Ar-alquilo C0-6, Het-alquilo C0-6, R10C(O)-, R10C(S)-, R10SO2-, R10OC(O)-, R10R14NC(O)- y R10R14NC(S)-; R8 se selecciona del grupo formado por: H; alquilo C1-6, alquenilo C2-6, alquinilo C2-6, Het-alquilo C0-6 y Ar-alquilo C0-6; R9 se selecciona del grupo formado por: alquilo C1-6, cicloalquil C3-6-alquilo C0-6, Ar-alquilo C0-6 y Het-alquilo C0-6; R10 se selecciona del grupo formado por: alquilo C1-6, cicloalquil C3-6-alquilo C0-6, Ar-alquilo C0-6 y Het-alquilo C0-6; R11 se selecciona del grupo formado por: H, alquilo C1-6, Ar-alquilo C0-6 y Het-alquilo C0-6, R12 se selecciona del grupo formado por: H, alquilo C1-6, Ar-alquilo C0-6 y Het-alquilo C0-6, R13 se selecciona del grupo formado por: H, alquilo C1-6, Ar-alquilo C0-6 y Het-alquilo C0-6; R14 se selecciona del grupo formado por H, alquilo C1-6, Ar-alquilo C0-6 y Het-alquilo C0-6; R' se selecciona del grupo formado por: H, alquilo C1-6, Ar-alquilo C0-6 y Het-alquilo C0-6; R'' se selecciona del grupo formado por: H, alquilo C1-6, Ar-alquilo C0-6 o Het-alquilo C0-6, R''' se selecciona del grupo formado por: H, alquilo C1-6, cicloalquil C3-6-alquilo C0-6, Ar-alquilo C0-6 y Het-alquilo C0-6; X se selecciona del grupo formado por: CH2, S y O; Z se selecciona del grupo formado por: C(O) y CH2; y sus sales, hidratos y solvatos farmacéuticamente aceptables. Además, se dan a conocer 4-amino-azepan-3-onas, métodos de tratamiento que comprenden su administracion, y uso de las mismas en la fabricacion de medicamentos para el tratamiento o prevencion de enfermedad autoinmune y para la prevencion de lesiones ateroscleroticas; inhibicion de una respuesta asmática, inhibicion de una respuesta alérgica, inhibicion de respuesta inmune contra un organo o tejido trasplantado, o inhibicion de la actividad de elastasa en ateroma.A method for inhibiting cathepsin S which comprises administering to an animal in need thereof, an effective amount of a 4-amino-azepan-3-one of Formula (1), in which: R1 is selected from the group consisting of formulas (2), (3) and (4); R2 is selected from the group consisting of H, C1-6 alkyl, C3-6 cycloalkyl-C0-6 alkyl, Ar-C0-6 alkyl, Het-C0-6 alkyl, R9C (O) -, R9C (S) -, R9SO2-, R9OC (O) -, R9R11NC (O) -, R9R11NC (S) -, R9 (R11) NSO2-, formulas (5), (6) and (7); R3 is selected from the group consisting of: H, C1-6 alkyl, C3-6 cycloalkyl-C0-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Het-C0-6 alkyl, Ar-C0-6 alkyl, Ar -Ar-C0-6 alkyl, Ar-Het-C0-6 alkyl, Het-Ar-C0-6 alkyl and Het-Het-C0-6 alkyl; R3 and R 'can be joined together to form a pyrrolidine, piperidine or morpholine ring; R4 is selected from the group consisting of: H, C1-6 alkyl, C3-6 cycloalkyl-C0-6 alkyl, Ar-C0-6 alkyl, Het-C0-6 alkyl, R5C (O) -, R5C (S) - , R5SO2-, R5OC (O) -, R5R13NC (O) - and R5R13NC (S) -; R5 is selected from the group consisting of: H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl-C0-6 alkyl, Ar-C0-6 alkyl and Het-C0-6 alkyl; R6 is selected from the group consisting of: H, C1-6 alkyl, C3-6 cycloalkyl-C0-6 alkyl, Ar-C0-6 alkyl and Het-C0-6 alkyl, R7 is selected from the group consisting of: H, alkyl C1-6, C3-6 cycloalkyl-C0-6 alkyl, Ar-C0-6 alkyl, Het-C0-6 alkyl, R10C (O) -, R10C (S) -, R10SO2-, R10OC (O) -, R10R14NC (O) - and R10R14NC (S) -; R8 is selected from the group consisting of: H; C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Het-C0-6 alkyl and Ar-C0-6 alkyl; R9 is selected from the group consisting of: C1-6 alkyl, C3-6 cycloalkyl-C0-6 alkyl, Ar-C0-6 alkyl and Het-C0-6 alkyl; R10 is selected from the group consisting of: C1-6 alkyl, C3-6 cycloalkyl-C0-6 alkyl, Ar-C0-6 alkyl and Het-C0-6 alkyl; R11 is selected from the group consisting of: H, C1-6 alkyl, Ar-C0-6 alkyl and Het-C0-6 alkyl, R12 is selected from the group consisting of: H, C1-6 alkyl, Ar-C0-6 alkyl and Het-C0-6 alkyl, R13 is selected from the group consisting of: H, C1-6 alkyl, Ar-C0-6 alkyl and Het-C0-6 alkyl; R14 is selected from the group consisting of H, C1-6 alkyl, Ar-C0-6 alkyl and Het-C0-6 alkyl; R 'is selected from the group consisting of: H, C1-6 alkyl, Ar-C0-6 alkyl and Het-C0-6 alkyl; R '' is selected from the group consisting of: H, C1-6 alkyl, Ar-C0-6 alkyl or Het-C0-6 alkyl, R '' 'is selected from the group consisting of: H, C1-6 alkyl, cycloalkyl C3-6-C0-6 alkyl, Ar-C0-6 alkyl and Het-C0-6 alkyl; X is selected from the group consisting of: CH2, S and O; Z is selected from the group consisting of: C (O) and CH2; and its pharmaceutically acceptable salts, hydrates and solvates. In addition, 4-amino-azepan-3-ones, methods of treatment comprising their administration, and use thereof in the manufacture of medicaments for the treatment or prevention of autoimmune disease and for the prevention of atherosclerotic lesions are disclosed; inhibition of an asthmatic response, inhibition of an allergic response, inhibition of immune response against a transplanted organ or tissue, or inhibition of elastase activity in atheroma.

ARP010101786A 2000-04-18 2001-04-17 METHOD FOR INHIBITING CATEPSINA S, 4-AMINO-AZEPAN-3-ONAS, TREATMENT METHODS THAT UNDERSTAND YOUR ADMINISTRATION AND USE OF THE SAME IN THE MANUFACTURE OF MEDICINES AR032319A1 (en)

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CN1708293A (en) 2002-09-24 2005-12-14 诺瓦提斯公司 S1p receptor agonist for treating demyelinate disease
AU2003273697A1 (en) * 2002-10-08 2004-05-04 Merck Frosst Canada Ltd 4-amino-azepan-3-one compounds as cathepsin k inhibitors useful in the treatment of osteoporosis
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JPWO2009054454A1 (en) * 2007-10-24 2011-03-03 国立大学法人 東京医科歯科大学 Modulator of signal transduction of Toll-like receptor containing cathepsin inhibitor as an active ingredient
EP3545953A1 (en) 2008-06-20 2019-10-02 Novartis AG Paediatric compositions for treating1 multiple sclerosis
LV15485B (en) * 2018-09-13 2020-06-20 Latvijas Organiskās Sintēzes Institūts Selenophene chromenone hydroxamic acids, their production and use in angiogenesis inhibition

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PL366040A1 (en) 2005-01-24
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CZ20023460A3 (en) 2004-03-17
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NO20025005L (en) 2002-12-06
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AU9050701A (en) 2001-12-03
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CA2406829A1 (en) 2001-11-29
MXPA02010276A (en) 2003-04-25

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