C - Chemistry – Metallurgy – 07 – D
Patent
C - Chemistry, Metallurgy
07
D
C07D 471/04 (2006.01) A61K 31/435 (2006.01) A61K 31/495 (2006.01) A61K 31/535 (2006.01) A61K 31/675 (2006.01) C07D 519/00 (2006.01) C07F 9/6561 (2006.01) C07D 519/00 (2006.01)
Patent
CA 2180730
The present invention relates to compound of formula (I) wherein A is benzene, naphthalene, 5,6,7,8,-tetrahydronaphthalene, quinoline, isoquinoline, indole or 7-azaindole; R1 is -H, -CN, -SO3R4, -SO2NHR5, (i), -COOR6, - CONHCH2(CHOH)nCH2OH, (ii), -NR7R8, -N(CH2CH2OH)2, -NHCH2(CHOH)nCH2OH, - NHCONH2, -NH-C(NH2)=NH, -NHCO(CH)OH)nCH2OH, (iii), -NHSO2R9, -OR10, - OCH2(CHOH)nCH2OH, -OOC(CHOH)nCH2OH, -OPO(OH)2, -CH2NH2, -C(NH2)=NH, - CH2NHC(NH2)=NH, (iv), -CH2OH, -CH2OOC(CHOH)nCH2OH, -CH2OPO(OH)2 or -PO(OH)2; R2 is C1-C6 alkyl, halogen, or hydroxy; R3 is -H or C1-C6 alkyl; R4 is -H, C1- C6 alkyl or -CH2(CHOH)nCH2OH; R5 is -H, C1-C6 alkyl, -CH2(CHOH)nCH2OH or - (CH2)mNMe2; R6 is -H, C1-C6 alkyl or -CH2(CHOH)nCH2OH; each of R7 and R8 independently is -H or C1-C6 alkyl; R9 is methyl or tolyl; R10 is -H, C1-C6 alkyl or C2-C6 alkanoyl; Z is CH2, 0, NH or NCH2CH2OH; n is zero or 1; m is 2 or 3; p is 1, 2 or 3; q is zero, 1 or 2; and the pharmaceutically acceptable salt thereof, for use as tyrosine kinase inhibitors.
La présente invention concerne un composé de la formule (I) ainsi qu'un sel de celui-ci, acceptable sur le plan pharmacologique. Dans cette formule, A représente benzène, naphtalène, 5,6,7,8-tétrahydronaphtalène, quinoline, isoquinoline, indole ou 7-aza-indole; R¿1? représente -H, -CN, -SO¿3?R¿4?, -SO¿2?NHR¿5?, (i), -COOR¿6?, -CONHCH¿2?(CHOH)¿n?CH¿2?OH, (ii), -NR¿7?R¿8?, -N(CH¿2?CH¿2?OH)¿2?, -NHCH¿2?(CHOH)¿n?CH¿2?OH, -NHCONH¿2?, -NH-C(NH¿2?)=NH, -NHCO(CHOH)¿n?CH¿2?OH, (iii), -NHSO¿2?R¿9?, -OR¿10?, -OCH¿2?(CHOH)¿n?CH¿2?OH, -OOC(CHOH)¿n?CH¿2?OH, -OPO(OH)¿2?, -CH¿2?NH¿2?; -C(NH¿2?)=NH, -CH¿2?NHC(NH¿2?)=NH, (iv), -CH¿2?OH, -CH¿2?OOC(CHOH)¿n?CH¿2?OH, -CH¿2?OPO(OH)¿2? ou -PO(OH)¿2?; R¿2? représente alkyle C¿1?-C¿6?, halogène ou hydroxy; R¿3? représente -H ou alkyle C¿1?-C¿6?; R¿4? représente -H, alkyle C¿1?-C¿6? ou -CH¿2?-(CHOH)¿n?CH¿2?OH; R¿5? représente -H, alkyle C¿1?-C¿6?, -CH¿2?(CHOH)¿n?CH¿2?OH ou -(CH¿2?)¿m?NMe¿2?; R¿6? représente -H, alkyle C¿1?-C¿6? ou -CH¿2?(CHOH)¿n?CH¿2?OH; chacun des R¿7? et R¿8? représente indépendamment -H ou alkyle C¿1?-C¿6?; R¿9? représente méthyle ou tolyle; R¿10? représente -H, alkyle C¿1?-C¿6? ou alcanoyle C¿2?-C¿6?; Z représente ?CH¿2?, ?O, ?NH ou ?NCH¿2?CH¿2?OH; n vaut zéro ou 1; m vaut 2 ou 3; p vaut 1, 2 ou 3 et q vaut zéro, 1 ou 2. Ces composés sont utiles en tant qu'inhibiteurs des tyrosines kinases.
Ballinari Dario
Brasca Gabriella Maria
Buzzetti Franco
Longo Antonio
Pharmacia S.p.a.
Smart & Biggar
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