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AR061780A1 - Analogos de ghrelina sustituidos en el extremo n- terminal - Google Patents

Analogos de ghrelina sustituidos en el extremo n- terminal

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Publication number
AR061780A1
AR061780A1 ARP070104255A ARP070104255A AR061780A1 AR 061780 A1 AR061780 A1 AR 061780A1 AR P070104255 A ARP070104255 A AR P070104255A AR P070104255 A ARP070104255 A AR P070104255A AR 061780 A1 AR061780 A1 AR 061780A1
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Argentina
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acc
apc
dap
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Sod Conseils Rech Applic
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    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C07K14/60—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
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Abstract

Peptidil análogos de la ghrelina que tienen mayor estabilidad, que son activos en el receptor de GHS de acuerdo con las formulas representadas a continuacion: (R2)-A1-A2-A3-A4-A5-A6-A7-A8-A9-A10-A11-A12-A13-A14-A15-A16-A17-A18-A19-A20-A21-A22-A23- A24-A25-A26-A27-A28-R1 donde las definiciones de A1 a A28, R1 y R2 se proporcionan en la memoria descriptiva, con la excepcion de que el aminoácido N-terminal debe seleccionarse del grupo que consiste en Inp, 1-Apc y 4-Apc, sus sales aceptables para uso farmacéutico y composiciones farmacéuticas que comprenden una cantidad efectiva de dicho compuesto junto con sus usos terapéuticos y no terapéuticos. Reivindicacion 1: Un compuesto análogo de ghrelina de acuerdo con la formula (1): (R2)-A1-A2- A3-A4-A5-A6-A7-A8-A9-A10-A11-A12-A13-A14-A15-A16-A17-A18-A19-A20-A21-A22-A23-A24-A25-A26-A27-A28-R1donde: A1 es Inp, 1-Apc o 4-Apc; A2 es Ser, Abu, Acc, Act, Aib, Ala, Ava, Thr o Val; A3 es Ser, Asp(NH-R3), Asp(O-R4), Cys(S-R5), Dab(S(O)2-R6), Dap(S(O)2-R7), Glu(NH-R8), Glu(O-R9), Ser(C(O)-R10), Thr(C(O)-R11) o HN-CH((CH2)n-N(R12R13))-C(O); A4 es Phe, Acc, Aic, Cha, 2-Fua, 1-Nal, 2-Nal, 2-Pal, 3-Pal, 4-Pal, hPhe, (X1,X2,X3,X4,X5)Phe, Taz, 2-Thi, 3-Thi, Trp o Tyr; A5 es Leu, Abu, Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, TIe o Val; A6 es Ser, Abu, Acc, Act, Aib, Ala, Gly, Thr o Val; A7 es Pro, Dhp, Dmt, 3-Hyp, 4-Hyp, lnc, Ktp, Oic, Pip, Thz o Tic; A8 es Glu, Acc, Aib, Arg, Asn, Asp, Dab, Dap, GIn, Lys, Orn o HN-CH((CH2)n- N(R12R13))-C(O); A9 es His, Acc, Apc, Aib, 2-Fua, 2-Pal, 3-Pal, 4-Pal, (X1,X2,X3,X4,X5-)-Phe, Taz, 2-Thi o 3-Thi; A10 es Gln, Acc, Aib, Asn, Asp o Glu; A11 es Arg, Apc, hArg, Dab, Dap, Lys, Orn o HN-CH((CH2)n-N(R12R13))-C(O); A12 es Val, Abu, Acc, Aib, Ala, Cha, Gly, Ile, Leu, NIe, Nva o TIe; A13 es GIn, Acc, Aib, Asn, Asp o Glu; A14 es Gln, Acc, Aib, Asn, Asp o Glu; A15 es Arg, Acc, Aib, Apc, hArg, Dab, Dap, Lys o Orn; A16 es Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn o está suprimido; A17 es Glu, Arg, Asn, Asp, Dab, Dap, Gin, Lys, Orn, Asp(NH-R3), Asp(O-R4), Cys(S-R5), Dab(S(O)2-R6), Dap(S(O)2-R7), GIu(NH-R8), Glu(O-R9), Ser(C(O)-R10), Thr(C(O)-R11), HN-CH((CH2)n-N(R12R13))-C(O) o está suprimido; A18 es Ser, Abu, Acc, Act, Aib, Ala, Thr, Val o está suprimido; A19 es Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn o está suprimido; A20 es Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn o está suprimido; A21 es Pro, Dhp, Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic o está suprimido; A22 es Pro, Dhp, Dmt, 3-Hyp, 4-Hyp, lnc, Ktp, Oic, Pip, Thz, Tic o está suprimido; A23 es Ala, Abu, Acc, Act, Aib, Apc, Gly, Nva, Val o está suprimido; A24 es Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn, HN-CH((CH2)n-N(R12R13))-C(O) o está suprimido; A25 es Leu, Abu, Acc, Aib, Ala, Cha, Ile, hLeu, NIe, Nva, Phe, TIe, Val o está suprimido; A26 es Gln, Aib, Asn, Asp, Glu o está suprimido; A27 es Pro, Dhp, Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic o está suprimido; A28 es Arg, Acc, Aib, Apc, hArg, Dab, Dap, Lys, Orn, HN-CH((CH2)n-N(R12R13))-C(O) o está suprimido; R1 es -OH, -NH2, -alcoxi C1-30 o NH-X6-CH2-Z0, donde X6 es un alquilo C1-12 o alquenilo C2-12 y Z0 es -H, -OH, -CO2H o -C(O)-NH2; R2 es H, alquilo C1-30, heteroalquilo C1-30, acilo C1-30, alquenilo C2-30, alquinilo C2-30, arilalquilo C1-30, arilacilo C1-30, alquilo C1-30 sustituido, heteroalquilo C1-30 sustituido, acilo C2-30 sustituido, alquenilo C2-30 sustituido, arilalquilo C1-30 sustituido, alquinilo C2-30 sustituido o arilacilo C1-30 sustituido; cada uno de R3, R4, R5, R6, R7, R8, R9, R10 y R11, independientemente para cada una de sus apariciones, se selecciona del grupo que consiste en alquilo C1-40, alquenilo C2-40, alquilo C1-40 sustituido, alquenilo C2-40 sustituido, alquilarilo, alquilarilo sustituido arilo y arilo sustituido; cada uno de R12 y R13, independientemente para cada una de sus apariciones, se selecciona del grupo que consiste en H, alquilo C1-40, heteroalquilo C1-40, acilo C1-40, alquenilo C2-40, alquinilo C2-40, arilalquilo C1-40, arilacilo C1-40; alquilo C1-40 sustituido, heteroalquilo C1-40 sustituido, acilo C1-40 sustituido, alquenilo C2-40 sustituido, alquinilo C2-40 sustituido, arilalquilo C1-40 sustituido, arilacilo C1-40 sustituido, alquilsulfonilo C1-40 o -C(NH)-NH2; n es, independientemente para cada una de sus apariciones, 1, 2, 3, 4 o 5; cada uno de X1, X2, X3, X4, y X5, independientemente para cada una de sus apariciones, se selecciona del grupo que consiste en H, F, CI, Br, I, alquilo C1-10, alquilo C1-10 sustituido, arilo, arilo sustituido, OH, NH2, NO2 y CN; con la salvedad de que: cuando R12 es acilo C1-40, arilacilo C1-40, acilo C1-40 sustituido, arilacilo C1-40 sustituido, alquilsulfonilo C1-40, o -C(NH)-NH2, entonces R13 es H o alquilo C1-40, heteroalquilo C1-40, alquenilo C2-40, alquinilo C2-40, arilalquilo C1-40, alquilo C1-40 sustituido, heteroalquilo C1-40 sustituido, alquenilo C2-40 sustituido, alquinilo C2-40 sustituido o arilalquilo C1-40 sustituido; o una de sus sales aceptables para uso farmacéutico.
ARP070104255A 2006-09-27 2007-09-26 Analogos de ghrelina sustituidos en el extremo n- terminal AR061780A1 (es)

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EP (1) EP2083842B1 (es)
JP (1) JP5134627B2 (es)
KR (1) KR101197541B1 (es)
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AR (1) AR061780A1 (es)
AU (1) AU2007300526B2 (es)
BR (1) BRPI0717169C1 (es)
CA (1) CA2664558C (es)
ES (1) ES2436419T3 (es)
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MX (1) MX2009003246A (es)
NZ (1) NZ576470A (es)
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