AR024463A1

AR024463A1 - SOMATOSTATINE AGONISTS

Info

Publication number: AR024463A1
Application number: ARP000103155A
Authority: AR
Original assignee: Scient S C R A S Soc De Conseils De Rech S Et D Applic S
Priority date: 1999-06-25
Filing date: 2000-06-23
Publication date: 2002-10-02
Also published as: WO2001000676A1; RU2263677C2; IL146941A0; JP2003503369A; CZ20014534A3; AU770958B2; HUP0201696A3; CA2377265A1; EP1189942A1; AU6200000A; JP4041311B2; BR0011919A; MXPA01013127A; PL352763A1; CN1367792A; HUP0201696A2

Abstract

Se refiere a péptidos cíclicos de formula (1): X-A1-ciclo(D-Cys-A3-A4-Lys-A6-A7)-A8-Y o su sal farmacéuticamente aceptable, en donde: X es H, formula (2) oformula (3); A1 y A3 son cada uno independientemente el isomero D- o L- de un aminoácidoselecc ionado entre el grupo que consiste en Phe, Tyr, Tyr(I), Trp,3-Pal, 4-Pal, Cpa y NaI; A4 es L-Trp, D-Trp, L-beta-metil-Trp o D-beta-metil-Trp; A6 es -NH-(CHR1)n-CO-, donde n es 2, 3 o 4; A7 es L- o D-Cys; A8 es elisomero D o L de un aminoácidoselecci onado entre el grupo que consiste en Phe, Tyr, Tyr(I), Trp, NaI, Cpa, Val, Leu, IIe, Ser y Thr; Y es NR2R3 donde R2 y R3son cada uno independientemente H o alquilo C1-5; R1 se selecciona entre el grupo que consiste en H, alquilo C1-4 y-CH2-arilo; en donde dicho arilo es unaporcion optativamente sustituida seleccionada entre el grupo que consiste en fenilo, 1-naftilo y 2-naftilo, en donde dicha porcion optativamente sustituida esoptativamente sustituida con uno o más sustituyentescada uno selec cionado independientemente entre el grupo que consiste en alquiloC1-6, alquenilo C2-6,alquinilo C2-6, arilo, arilalquilo C1-6, alcoxi C1-6, -N(R4R5), -COOH, -CON(R4R5), halo, -OH, -CN, y -NO2; R4 y R5 cada uno es, independientementepara cadaaparicio n, H o alquilo C1-3; donde el Cys de A2 está unido al Cys de A7 por un enlace di-sulfuro formado de los grupos tiol de cada Cys; composicionesfarmacéuticas que comprenden dichos péptidos y el uso de las mismas como un agonista delos subtipos del rec eptor de somatostatina. Los péptidos de la presentese unen selectivamente al tipo 5 del receptor de los subtipos de somatostatina y producen un efecto agonista de los receptores de subtipo de somatostatina alas cuales se unenlos péptidos.Refers to cyclic peptides of formula (1): X-A1-cycle (D-Cys-A3-A4-Lys-A6-A7) -A8-Y or its pharmaceutically acceptable salt, wherein: X is H, formula ( 2) oformula (3); A1 and A3 are each independently the D- or L- isomer of an amino acid selected from the group consisting of Phe, Tyr, Tyr (I), Trp, 3-Pal, 4-Pal, Cpa and NaI; A4 is L-Trp, D-Trp, L-beta-methyl-Trp or D-beta-methyl-Trp; A6 is -NH- (CHR1) n-CO-, where n is 2, 3 or 4; A7 is L- or D-Cys; A8 is the D or L elisomer of an amino acid selected from the group consisting of Phe, Tyr, Tyr (I), Trp, NaI, Cpa, Val, Leu, IIe, Ser and Thr; Y is NR2R3 where R2 and R3 are each independently H or C1-5 alkyl; R1 is selected from the group consisting of H, C1-4 alkyl and -CH2-aryl; wherein said aryl is an optionally substituted portion selected from the group consisting of phenyl, 1-naphthyl and 2-naphthyl, wherein said optionally substituted portion is optionally substituted with one or more substituents each one independently selected from the group consisting of C1-alkyl. 6, C2-6 alkenyl, C2-6 alkynyl, aryl, C1-6 arylalkyl, C1-6 alkoxy, -N (R4R5), -COOH, -CON (R4R5), halo, -OH, -CN, and -NO2 ; R4 and R5 each is, independently for each space n, H or C1-3 alkyl; where the Cys of A2 is linked to the Cys of A7 by a di-sulfide bond formed from the thiol groups of each Cys; Pharmaceutical compositions comprising said peptides and their use as an agonist of the subtypes of the somatostatin receptor. The peptides of the present selectively bind to type 5 receptor somatostatin subtypes and produce an agonist effect of somatostatin subtype receptors to which peptides bind.