SUBSTITUTED BENZOTHIENYL - PYRROLOTRIAZINES AND USES THEREOF IN THE TREATMENT CANCER

摘要

This invention relates to novel substituted 5-(1-benzothiophen-2-yl)pyrrolo[2,1-fJ[1,2,4]triazin-4-amine derivatives having protein tyrosine kinase inhibitory activities, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for treating proliferative disorders, in particular cancer and tumor diseases.;

主权项

1. A compound of formula (I) wherein R1 is hydrogen, chloro, methyl or methoxy, R2 is hydrogen or methoxy,
with the proviso that at least one of R1 and R2 is other than hydrogen, andG represents the group —CH2—OR3, —C(═O)—OR3, —CH2—NR4R5 or —C(═O)—NR4R6, wherein
R3 is hydrogen or (C1-C4)-alkyl optionally substituted with cyano, hydroxy, (C1-C4)-alkoxy, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, amino, mono(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, pyrrolidino, piperidino, morpholino, aminocarbonyl, mono-(C1-C4)-alkylaminocarbonyl, di-(C1-C4)alkylaminocarbonyl or up to three fluoro atoms, R4 is hydrogen or (C1-C4)-alkyl, R5 is hydrogen, (C1-C4)-alkyl, (C1-C4)-alkylcarbonyl, (C3-C6)-cycloalkyl or 4- to 6-membered heterocycloalkyl, wherein
(i) said (C1-C4)-alkyl is optionally substituted with cyano, hydroxy, (C1-C4)-alkoxy, (C1-C4)-alkoxycarbonyl, aminocarbonyl, mono(C1-C4)-alkylamino carbonyl, di-(C1-C4)-alkylamino carbonyl, (C1-C4)alkylcarbonylamino or up to three fluoro atoms,
and(ii) said (C3-C6)-cycloalkyl is optionally substituted with one or two substituents independently selected from the group consisting of (C1-C4)alkyl, hydroxy, amino and (C1-C4)-alkylcarbonylamino,
and(iii) said 4- to 6-membered heterocycloalkyl is optionally substituted with one or two substituents independently selected from the group consisting of (C1-C4)-alkyl, hydroxy, oxo, amino and (C1-C4)-alkylcarbonylamino, R6 is hydrogen, (C1-C4)-alkyl, (C3-C6)-cycloalkyl or 4- to 6-membered heterocycloalkyl, wherein
(i) said (C1-C4)-alkyl is optionally substituted with hydroxy, (C1-C4)alkoxy, (C1-C4)-alkoxycarbonyl, amino, aminocarbonyl, mono(C1-C4)-alkylamino carbonyl, di-(C1-C4)-alkylamino carbonyl or (C1-C4)-alkylcarbonylamino,
and(ii) said (C3-C6)-cycloalkyl is optionally substituted with one or two substituents independently selected from the group consisting of (C1-C4)alkyl, hydroxy, amino and (C1-C4)-alkylcarbonylamino,
and(iii) said 4- to 6-membered heterocycloalkyl is optionally substituted with one or two substituents independently selected from the group consisting of (C1-C4)-alkyl, hydroxy, oxo, amino and (C1-C4)-alkylcarbonylamino,
or R4 and R5, or R4 and R6, respectively, are joined and, taken together with the nitrogen atom to which they are attached, form a monocyclic, saturated 4- to 7-membered heterocycloalkyl ring which may contain a second ring heteroatom selected from N(R7), O, S and S(O)2, and which may be substituted on ring carbon atoms with up to three substituents independently selected from the group consisting of fluoro, (C1-C4)-alkyl, oxo, hydroxy, (C1-C4)-alkoxy, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino and aminocarbonyl, and wherein
R7 is hydrogen, (C1-C4)-alkyl, cyclopropyl, cyclobutyl, formyl, (C1-C4)-alkylcarbonyl or (C1-C4)-alkoxycarbonyl, or a pharmaceutically acceptable salt, hydrate and/or solvate thereof.