AR040955A1 - Analogos de ghrelina - Google Patents

Analogos de ghrelina

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Publication number
AR040955A1
AR040955A1 ARP030102647A ARP030102647A AR040955A1 AR 040955 A1 AR040955 A1 AR 040955A1 AR P030102647 A ARP030102647 A AR P030102647A AR P030102647 A ARP030102647 A AR P030102647A AR 040955 A1 AR040955 A1 AR 040955A1
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aib
acc
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dap
dab
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Sod Conseils Rech Applic
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    • C07K14/60Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
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Abstract

La presente comprende análogos de peptidilo que poseen actividad de Ghrelina agonista o antagonista, junto con usos terapéuticos y no terapéuticos de los mismos. Reivindicación 1: Un compuesto conforme a la fórmula: (R2R3)-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, en donde: A1 es Gly, Aib, Ala, beta-Ala, o Acc; A2 es Ser, Aib, Act, Ala, Acc, Abu, Act, Ava, Thr, o Val; A3 es Ser, Ser(C(O)-R4), Asp(O-R8), Asp(NH-R9); Cys(S-R14), Dap(S(O)2-R10), Dab(S(O)2-R11), Glu(O-R6), Glu(NH-R7), Thr, Thr(C(O)-R5), o HN-CH((CH2)n-N(R12R13))-C(O); A4 es Phe, Acc, Aic, Cha, 2Fua, 1Nal, 2Nal, 2Pal, 3Pal, 4Pal, hPhe, (X1, X2, X3, X4, X5)Phe, Taz, 2Thi, 3Thi, Trp, o Tyr; A5 es Leu, Abu, Acc, Aib, Ala, Cha, lle, hLeu, Nle, Nva, Phe, Tle, o Val; A6 es Ser, Abu, Acc, Act, Aib, Ala, Gly, Thr, o Val; A7 es Pro, Dhp, Dmt, 3Hyp, 4Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, o eliminado; A8 es Glu, Acc, Aib, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn, HN-CH((CH2)n-N(R12R13))-C(O), o eliminado; A9 es His, Apc, Aib, Acc, 2Fua, 2Pal, 3Pal, 4Pal, Taz, 2Thi, 3Thi, (X1, X2, X3, X4, X5-)Phe, o eliminado; A10 es Gln, Acc, Aib, Asn, Asp, Glu, o eliminado; A11 es Arg, Apc, hArg, Dab, Dap, Lys, Orn, HN-CH((CH2)n-N(R12R13))-C(O), o eliminado; A12 es Val, Abu, Acc, Aib, Ala, Cha, Nva, Gly, lle, Leu, Nle, Tle, Cha, o eliminado; A13 es Gln, Acc, Aib, Asn, Asp, Glu, o eliminado; A14 es Gln, Acc, Aib, Asn, Asp, Glu, o eliminado; A15 es Arg, hArg, Acc, Aib, Apc, Dab, Dap, Lys, Orn, HN-CH((CH2)n-N(R12R13))-C(O), o eliminado; A16 es, Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn, HN-CH((CH2)n-(N(R12R13))-C(O), o eliminado; A17 es Glu, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn, HN-CH((CH2)n-N(R12R13))-C(O), o eliminado; A18 es Ser, Abu, Acc, Act, Aib, Ala, Thr, Val, o eliminado; A19 es Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn, HN-CH((CH2)n-N(R12R13))-C(O), o eliminado; A20 es Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn, HN-CH((CH2)n-N(R12R13))-C(O), o eliminado; A21 es Pro, Dhp, Dmt, Inc, 3Hyp, 4Hyp, Ktp, Oic, Pip, Thz, Tic, o eliminado; A22 es Pro, Dhp, Dmt, 3Hyp, 4Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, o eliminado; A23 es Abu, Acc, Act, Aib, Ala, Apc, Gly, Nva, Val, o eliminado; A24 es Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn, HN-CH((CH2)n-N(R12R13))-C(O), o eliminado; A25 es Leu, Abu, Acc, Aib, Ala, Cha, lle, hleu, Nle, Nva, Phe, Tle, Val, o eliminado; A26 es Gln, Aib, Asn, Asp, Glu, o eliminado; A27 es Pro, Dhp, Dmt, 3Hyp, 4Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, o eliminado; A28 es Acc, Aib, Apc, Arg, hArg, Dab, Dap, Lys, Orn, HN-CH((CH2)n-N(R12R13))-C(O), o eliminado; R1 es -OH, -NH2, -alcoxi (C1-30), o NH-X6-CH2-Z0, en donde X6 es un alquilo (C1-12), alquenilo (C2-12), y Z0 es -H, -OH, -CO2H o -C(O)-NH2; R2 y R3 son, cada un en forma independiente para cada aparición, H, alquilo (C1-20) o acilo (C1-20); R4, R5, R6, R7, R8, R9 , R10, R11 y R14 son, cada uno en forma independiente para cada aparición, alquilo (C1-40), alquenilo (C2-40), alquilo (C1-40) sustituido, alquenilo (C2-40) sustituido, alquilarilo, alquilarilo sustituido, arilo o arilo sustituido; R12 y R13 son, cada uno en forma independiente para cada aparición, H, alquilo (C1-40), acilo (C1-40), alquilsulfonilo (C1-30) o -C(NH)-NH2, en donde cuando R12 es acilo (C1-40), alquilsulfonilo (C1-30), o -C(NH)-NH2, entonces R13 es H o alquilo (C1-40); n es, en forma independiente para cada aparición 1, 2, , 3, 4, ó 5; X1, X2, X3, X4 y X5 son, cada uno en forma independiente para cada aparición, H, F, Cl, Br, I, alquilo (C1-10), alquilo (C1-10) sustituido, arilo, arilo sustituido, OH, NH2, NO2, o CN; siempre que el péptido contenga por lo menos un aminoácido seleccionado entre los grupos que consiste en: A2 es Aib, Acc, o Act; A3 es Dap(S(O)2-R10), Dab(S(O)2-R11), Glu(NH-Hexil), o Cys(S-Decil); A5 es Abu, Acc, Aib, Ala, Cha, lle, hLeu, Nle, Nva, Phe, Tle, o Val; A6 es Abu, Acc, Act, Aib, Ala, Gly, Thr, o Val; A7 es Dhp, Dmt, 3Hyp, 4Hyp, Inc, Ktp, Oic, Pip, Thz, o Tic; A8 es Acc, Aib, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn, o HN-CH((CH2)n-N(R12R13))-C(O); A9 es Aib, Acc, Apc, 2Fua, 2Pal, 3Pal, 4Pal, Taz, 2Thi, 3Thi, o (X1, X2, X3, X4, X5-)Phe; y A10 es Acc, Aib, Asn, Asp, o Glu; y además, siempre que el péptido no sea (Lys8)hGhrelina(1-8)-NH2 o (Arg8)Hgrelina(1-8)-NH2, o una sal farmacéuticamente aceptable de los mismos.
ARP030102647A 2002-07-23 2003-07-23 Analogos de ghrelina AR040955A1 (es)

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US (3) US7589058B2 (es)
EP (2) EP2258381A3 (es)
JP (2) JP2006515271A (es)
KR (1) KR101065471B1 (es)
AR (2) AR040955A1 (es)
AT (1) ATE496940T1 (es)
AU (1) AU2003254119B2 (es)
BR (1) BR0312871A (es)
CA (1) CA2491946C (es)
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EP1750745A1 (en) * 2004-05-11 2007-02-14 The United States of America, represented by the Secretary, Department of Health and Human Services Methods of inhibiting proinflammatory cytokine expression using ghrelin
CA2625920C (en) 2005-09-28 2014-12-23 Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R Analogs of ghrelin
PT1937262T (pt) * 2005-09-29 2019-08-21 Ipsen Pharma Sas Composição para utilização no tratamento de dismotilidade gastrointestinal
WO2007092023A1 (en) * 2006-02-11 2007-08-16 Boston Biomedical Research Institute Compositions and methods for binding or inactivating ghrelin
WO2007106385A2 (en) 2006-03-10 2007-09-20 Societe De Conseils De Recherches Et D'applications Scientifiques S.A.S. Use of a ghrelin agonist to improve the catabolic effects of glucocorticoid treatment
CA2645844C (en) * 2006-03-13 2016-04-26 Liat Mintz Use of ghrelin splice variant for treating cachexia and/or anorexia and/or anorexia-cachexia and/or malnutrition and/or lipodystrophy and/or muscle wasting and/or appetite-stimulation
CN101541341B (zh) * 2006-09-27 2013-06-05 益普生制药两合公司 N末端取代的生长素释放肽类似物
WO2008067831A2 (en) * 2006-12-05 2008-06-12 Charite Universitätsmedizin - Berlin Use of ghrelin, an analogue thereof or a pharmaceutically acceptable salt thereof
TW200916113A (en) * 2007-08-08 2009-04-16 Sod Conseils Rech Applic Method for inhibiting inflammation and pro-inflammatory cytokine/chemokine expression using a ghrelin analogue
US8883721B2 (en) * 2009-05-12 2014-11-11 Mcgill University Methods of inhibiting the ghrelin/growth hormone secretatogue receptor pathway and uses thereof
US9724381B2 (en) 2009-05-12 2017-08-08 The Administrators Of The Tulane Educational Fund Methods of inhibiting the ghrelin/growth hormone secretatogue receptor pathway and uses thereof
US20110105389A1 (en) 2009-10-30 2011-05-05 Hoveyda Hamid R Macrocyclic Ghrelin Receptor Antagonists and Inverse Agonists and Methods of Using the Same
CA2805406A1 (en) * 2010-06-16 2011-12-22 Mcgill University Growth hormone secretatogue receptor antagonists and uses thereof
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