AR078258A1

AR078258A1 - DERIVATIVES OF 5,6,7,8-TETRAHYDROINDOLIZINE AS INHIBITORS OF HSP90, COMPOSITIONS THAT CONTAIN THEM AND USE

Info

Publication number: AR078258A1
Application number: ARP100103218A
Authority: AR
Inventors: Herve Minoux; Patrick Mailliet; Jean-Marie Ruxer; Luc Bertin
Original assignee: Sanofi Aventis
Priority date: 2009-09-03
Filing date: 2010-09-02
Publication date: 2011-10-26
Also published as: FR2949467B1; WO2011027081A3; WO2011027081A2; FR2949467A1

Abstract

Se refiere a nuevos productos de formula (1): Het y Het' representan un heterociclo aromático o parcialmente insaturado -de tipo dihidro o tetrahidro- mono o bicíclico, de 5 a 11 eslabones que contiene de 1 a 4 heteroátomos, elegidos entre N, O o S, eventualmente sustituido por uno o varios radicales R1 o R'1 idénticos o diferentes tal como se describe a continuacion, X representa NH-CO o CO-NH, R1 y/o R'1 son del grupo constituido por: H, halogeno, CF3, nitro, ciano, alquilo, hidroxi, mercapto, amino, alquilamino, dialquilamino, alcoxi, alquiltio, carboxi libre o esterificado por un radical alquilo, carboxamida, CO-NH(alquilo), CON(alquilo)2, NH-CO-alquilo, sulfonamida, NH-SO2-alquilo, S(O)2-NHalquilo, S(O2)-N(alquilo)2, estando todos los radicales alquilo, alcoxi y alquiltio opcionalmente sustituidos por uno o varios radicales iguales o diferentes, elegido(s) entre: halogeno, hidroxi, alcoxi, amino, alquilamino y dialquiamino; estando estos productos en todas las formas isomeras y las sales, como medicamentos para tumores. Reivindicacion 1: Productos de formula (1): en los que: Het representa un heterociclo aromático o parcialmente insaturado -de tipo dihidro o tetrahidro- mono o bicíclico, de 5 a 11 eslabones, que contiene de 1 a 4 heteroátomos, elegidos entre N, O o S, sustituido opcionalmente con uno o varios radicales R1 o R'1 idénticos o diferentes, tal como se describen a continuacion, X representa NH-CO o CO-NH, Het' representa un heterociclo aromático o parcialmente insaturado -de tipo dihidro o tetrahidro- mono o bicíclico, de 5 a 11 eslabones, que contiene de 1 a 4 heteroátomos, elegidos entre N, O o S, sustituido opcionalmente por uno o varios radicales R1 o R'1 idénticos o diferentes tal como se describen más adelante, R1 y/o R'1 son del grupo constituido por: H, halogeno, CF3, nitro, ciano, alquilo, hidroxi, mercapto, amino, alquilamino, dialquilamino, alcoxi, alquiltio, carboxi libre o esterificado por un radical alquilo, carboxamida, CO-NH(alquilo), CON(alquilo)2, NHCO-alquilo, sulfonamida, NH-SO2-alquilo, S(O)2-NHalquilo, S(O2)-N(alquilo)2, estando todos los radicales alquilo, alcoxi y alquiltio opcionalmente sustituidos por uno o varios radicales iguales o diferentes, elegido(s) entre: halogeno, hidroxi, alcoxi, amino, alquilamino y dialquilamino; estando dichos productos de formula (1) en todas las formas tautomeras e isomeras posibles, racémicas, enantiomeras y diastereoisomeras, así como sales de adicion con los ácidos minerales y orgánicos o con las bases minerales y orgánicas de los productos de formula (1), así como los profármacos de los productos de formula general (1).It refers to new products of formula (1): Het and Het 'represent an aromatic or partially unsaturated heterocycle - dihydro or tetrahydro-mono or bicyclic, of 5 to 11 links containing 1 to 4 heteroatoms, chosen from N, O or S, optionally substituted by one or more identical or different R1 or R'1 radicals as described below, X represents NH-CO or CO-NH, R1 and / or R'1 are of the group consisting of: H , halogen, CF3, nitro, cyano, alkyl, hydroxy, mercapto, amino, alkylamino, dialkylamino, alkoxy, alkylthio, free carboxy or esterified by an alkyl radical, carboxamide, CO-NH (alkyl), CON (alkyl) 2, NH -CO-alkyl, sulfonamide, NH-SO2-alkyl, S (O) 2-NHalkyl, S (O2) -N (alkyl) 2, all alkyl, alkoxy and alkylthio radicals being optionally substituted by one or more equal radicals or different, chosen from: halogen, hydroxy, alkoxy, amino, alkylamino and dialkylamino; these products being in all isomeric forms and salts, as medicines for tumors. Claim 1: Products of formula (1): in which: Het represents an aromatic or partially unsaturated heterocycle - dihydro or tetrahydro-mono or bicyclic, of 5 to 11 links, containing 1 to 4 heteroatoms, chosen from N , O or S, optionally substituted with one or several identical or different R1 or R'1 radicals, as described below, X represents NH-CO or CO-NH, Het 'represents an aromatic or partially unsaturated heterocycle -of type dihydro or tetrahydro-mono or bicyclic, 5 to 11 links, containing 1 to 4 heteroatoms, chosen from N, O or S, optionally substituted by one or more identical or different R1 or R'1 radicals as described further Further, R1 and / or R'1 are from the group consisting of: H, halogen, CF3, nitro, cyano, alkyl, hydroxy, mercapto, amino, alkylamino, dialkylamino, alkoxy, alkylthio, free carboxy or esterified by an alkyl radical, carboxamide, CO-NH (alkyl), CON (alkyl) 2, NHCO-alkyl, su lfonamide, NH-SO2-alkyl, S (O) 2-NHalkyl, S (O2) -N (alkyl) 2, all alkyl, alkoxy and alkylthio radicals being optionally substituted by one or more identical or different radicals, chosen (s) ) between: halogen, hydroxy, alkoxy, amino, alkylamino and dialkylamino; said products of formula (1) being in all possible tautomeric and isomeric, racemic, enantiomeric and diastereoisomeric forms, as well as addition salts with the mineral and organic acids or with the mineral and organic bases of the products of formula (1), as well as the prodrugs of the products of general formula (1).