Patent AR-069461-A1 (AR)
Title: Uso de melanocortinas para tratar la sensibilidad a insulina
Filed: 2008-11-05
Abstract: Se refiere a ligandos péptidos de los receptores de melanocortina, en particular, el receptor de melanocortina 4, y como tales, son utiles en el tratamiento de trastornos sensibles a la activacion de este receptor, tales como la resistencia a la insulina. Reivindicacion 1: Uso de un agonista del receptor de melanocortina 4 caracterizado porque es para la manufactura de un medicamento util para el tratamiento de la resistencia a la insulina en un sujeto que lo necesita. Reivindicacion 2: El uso de acuerdo con la reivindicacion 1, donde dicho agonista de receptor de melanocortina 4 util para el tratamiento de la resistencia a la insulina se selecciona del grupo que consiste en: Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-b-Ala-Lys)-NH2, SEQ. ID. Ns 1; Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH2, SEQ. ID. NRO,: 1; Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2, SEQ. ID. Ns 2; D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH2, SEQ. ID. Ns 3; D-Phe-c(Cys-His-D-Phe-Arg-Trp-b-AIa-D-Cys)-Thr-NH2, SEQ. ID. Ns 3; D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2, SEQ. ID. Ns 3; Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2, SEQ. ID. Ns 2; Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2, SEQ. ID. Ns 4; Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 5; Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 6; Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 6; Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 6; Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 7; Ac-Nle-c(Cys-b-Ala-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 7; Ac-NIe-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 7; Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 7; Ac-NIe-c(Cys-GIy-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 7; Ac-NIe-c(D-Cys-AIa-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 8; Ac-NIe-c(D-Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 8; Ac-NIe-c(D-Cys-b-AIa-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 8; Ac-NIe-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 8; Ac-NIe-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 8; Ac-NIe-c(D-Cys-GIy-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 8; Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-D-Cys)-NH2, SEQ. ID. Ns 9; Ac-NIe-c(Cys-b-AIa-His-D-Phe-Arg-Trp-D-Cys)-NH2, SEQ. ID. Ns 9; Ac-NIe-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2, SEQ. ID. Ns 9; Ac-NIe-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2, SEQ. ID. Ns 9; Ac-NIe-c(Cys-GIy-His-D-Phe-Arg-Trp-D-Cys)-NH2, SEQ. ID. Ns 9; Ac-NIe-c(D-Cys-AIa-His-D-Phe-Arg-Trp-D-Cys)-NH2, SEQ. ID. Ns 10; Ac-NIe-c(D-Cys-D-AIa-His-D-Phe-Arg-Trp-D-Cys)-NH2, SEQ. ID. Ns 10; Ac-NIe-c(D-Cys-b-AIa-His-D-Phe-Arg-Trp-D-Cys)-NH2, SEQ. ID. Ns 10; Ac-NIe-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2, SEQ. ID. Ns 10; Ac-NIe-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2, SEQ. ID. Ns 10; Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 11; Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 11; Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 11; Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEC. ID. Ns 11; Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 11; Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 11; Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 11; Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 11; Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 11; Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 11; n-butanoiI-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 SEQ. ID. Ns 12; Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 11; Ac-b-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 11; Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 11; Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-AIa-Lys)-NH2, SEQ. ID. Ns 13; Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-AIa-Lys)-NH2, SEQ. ID. Ns 13; Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-AIa-Lys)-NH2, SEC. ID. Ns 13; Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-AIa-Lys)-NH2, SEQ. ID. Ns 13; Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-AIa-Lys)-NH2, SEQ. ID. Ns 13; Ac-NIe-c(Asp-His-D-Phe-Arg-D-Trp-D-AIa-Lys)-NH2, SEQ. ID. Ns 14; Ac-NIe-c(Asp-His-D-Phe-Arg-D-Trp-b-AIa-Lys)-NH2, SEQ. ID. Ns 14; Ac-NIe-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 14; Ac-NIe-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2, SEQ. ID. Ns 14; Ac-NIe-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2, SEQ. ID. Ns 14; Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH2, SEQ. ID. Ns 15; Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2, SEQ. ID. Ns 15; Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH2, SEQ. ID. Ns 15; Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-b-AIa-Cys)-NH2, SEQ. ID. Ns 15; Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-D-AIa-Cys)-NH2, SEQ. ID. Ns 15; Ac-NIe-c(Cys-D-AIa-His-D-2-NaI-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 16; Ac-NIe-c(Cys-D-AIa-His-D-2-NaI-Arg-2-NaI-Cys)-NH2, SEQ. ID. Ns 16; Ac-NIe-c(Cys-D-AIa-His-D-2-NaI-Arg-1-NaI-Cys)-NH2, SEQ. ID. Ns 16; n-butanoil-NIe-c(Cys-D-AIa-His-D-Phe-Arg-2-NaI-Cys)-NH2, SEQ. ID. Ns 17; n-butanoil-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 17; Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-2-NaI-Cys)-NH2, SEQ. ID. Ns 18; Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-NaI-Cys)-NH2, SEQ. ID. Ns 18; Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-BaI-Cys)-NH2, SEQ. ID. Ns 18; Ac-NIe-c(Cys-D-GIu-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 59; Ac-NIe-c(Asp-His-D-Phe-Arg-Trp-D-AIa-LYS)-NH2, SEQ. ID. Ns 19; Ac-NIe-c(Cys-D-AIa-Hs-D-2-NaI-Arg-BaI-Cys)-NH2, SEQ. ID. Ns 20; Ac-NIe-c(Pen-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 21; Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-NH2, SEQ. ID. Ns 22; Ac-NIe-c(Pen-D-AIa-His-D-Phe-Arg-Trp-Pen)-NH2, SEQ. ID. Ns 22; D-Phe-c(Cys-His-D-Phe-hArg-Trp-b-AIa-D-Cys)-Thr-NH2, SEQ. ID. Ns 23; D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-b-AIa-D-Cys)-Thr-NH2, SEQ. ID. Ns 24; D-Phe-c(Cys-His-D-Phe-Arg-Bip-b-AIa-D-Cys)-Thr-NH2, SEQ. ID. Ns 25; D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-b-AIa-D-Cys)-Thr-NH2, SEQ. ID. Ns 24; D-Phe-c(Cys-His-D-Phe-hArg-Bip-b-AIa-D-Cys)-Thr-NH2, SEQ. ID. Ns 26; D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-b-AIa-D-Cys)-Thr-NH2, SEQ. ID. Ns 26; NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2, SEQ. ID. Ns 27; Ac-NIe-c(Asp-D-AIa-His-D-Phe-Arg-Trp-Lys)-NH2, SEQ. ID. Ns 28; Ac-NIe-c(Asp-D-AIa-His-D-Phe-Arg-BaI-Lys)-NH2, SEQ. ID. Ns 28; Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-OH, SEQ. ID. Ns 29; Ac-NIe-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 30; Ac-NIe-c(Cys-D-VaI-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID, Ns 30; Ac-NIe-c(Cys-D-IIe-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 30; Ac-NIe-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 30; Ac-NIe-c(Cys-D-TIe-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 30; Ac-NIe-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 30; Ac-NIe-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2, SEQ. ID. Ns 31; Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2, SEQ. ID. Ns 32; Ac-NIe-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2, SEQ. ID. Ns 32; Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2, SEQ. ID. Ns 33; Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2, SEQ. ID. Ns 33; Ac-IIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2, SEC. ID. Ns 33; Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2, SEQ. ID. Ns 33; Ac-VaI-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2, SEQ. ID. Ns 33; Ac-2-NaI-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2, SEQ. ID. Ns 33; NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2, SEQ. ID. Ns 34; Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2, SEQ. ID. Ns 34; Ac-NIe-c(Cys-3-PaI-D-Phe-Arg-Trp-Gaba-Cys)-NH2, SEQ. ID. Ns 35; Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-OH SEQ. ID. Ns 36; Ac-NIe-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH2, SEQ. ID. Ns 37; Ac-NIe-c(Asp-His-D-2-NaI-Arg-Trp-AIa-Lys)-NH2, SEQ. ID. Ns 38; Ac-Nle-c(Asp-Hs-D-2-NaI-Arg-Trp-b-AIa-Lys)-NH2, SEQ, ID. Ns 38; Ac-NIe-c(Cys-His-D-2-NaI-Arg-Trp-Gaba-Cys)-NH2, SEQ. ID. Ns 39; Ac-NIe-c(Cys-His-D-2-NaI-Arg-Trp-Ahx-Cys)-NH2, SEQ. ID. Ns 39; Ac-hPhe-c(Asp-His-D-2-NaI-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 40; Ac-Cha-c(Asp-His-D-2-NaI-Arg-Trp-Gaba-Lys)-NH2, SEQ. ID. Ns 40; Ac-NIe-c(Asp-Hs-D-Phe-Arg-Trp-b-AIa-Lys)-OH SEQ. ID. Ns 41; Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH SEQ. ID. Ns 42; D-Phe-c(Cys-His-D-Phe-Arg-Trp-AIa-D-Cys)-Thr-OH SEQ. ID. Ns 43; D-Phe-c(Cys-His-D-Phe-Arg-Trp-b-AIa-D-Cys)-Thr-OH SEQ. ID. Ns 43; D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-thr-OH SEQ. ID. Ns 43; Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH SEQ. ID. Ns 42; Ac-NIe-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH SEQ. ID. Ns 41; Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH SEQ. ID. Ns 44; Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH SEQ. ID. Ns 44; Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH SEQ. ID. Ns 44; Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH SEQ. ID. Ns 44; Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH SEQ. ID. Ns 44; Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH SEQ. ID. Ns 44; Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH SEQ. ID. Ns 44; Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH SEQ. ID. Ns 45; Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-OH SEQ. ID. Ns 45; Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-b-AIa-Cys)-OH SEQ. ID. Ns 45; Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-D-AIa-Cys)-OH SEQ. ID. Ns 45; Ac-NIe-c(Cys-D-Ala-His-D-2-NaI-Arg-Trp-Cys)-OH SEQ. ID. Ns 46; Ac-NIe-c(Cys-D-AIa-His-D-2-NaI-Arg-2-NaI-Cys)-OH SEC. ID. Ns 46; Ac-NIe-c(Cys-D-AIa-His-D-2-NaI-Arg-1-NaI-Cys)-OH SEQ. ID. Ns 46; Ac-NIe-c(Cys-D-AIa-His-D-2-NaI-Arg-BaI-Cys)-OH SEQ. ID. Ns 46; Ac-NIe-c(Pen-D-AIa-His-D-Phe-Arg-Trp-Cys)-OH SEQ. ID. Ns 47; Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-OH SEQ. ID. Ns 48; Ac-Arg-c(Cys-D-AIa-His-D-2-NaI-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 49; Ac-Arg-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 50; Ac-D-Arg-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2, SEQ. ID. Ns 50; Ac-D-Arg-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-NH2, SEQ. ID. Ns 51; Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2, SEQ. ID. Ns 52; Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2, SEQ. ID. Ns 52; Ac-Arg-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-NH2, SEQ. ID. Ns 51; Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-AIa-Lys)-NH2, SEQ. ID. Ns 53; Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-AIa-Lys)-NH2, SEQ. ID. Ns 53; Ac-NIe-c(Cys-3-PaI-D-Phe-Arg-Trp-Gaba-Cys)-NH2, SEQ. ID. Ns 35; Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-GIy-Cys)-NH2, SEQ. ID. N