Pyrrolotriazine derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis

A compound of formula (I)

• wherein
• R1 is selected from the group consisting of aryl, benzyl, and heteroaryl,
• wherein aryl and heteroaryl can be optionally substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of
• (C1-C4)alkyl, wherein (C1-C4)alkyl can be substituted with 0, 1, 2 or 3 halogen, 0 or 1 heterocyclyl, or 0 or 1 (C1-C3)alkoxy, wherein
• (C1-C3)alkoxy can be optionally substituted with (C1-C3)alkylamino,
• (C1-C3)alkoxy, wherein (C1-C3)alkoxy can be optionally substituted with (C1-C3)alkylamino,
• halogen,
• trifluoromethyl,
• trifluoromethoxy,
• (C3-C6)cycloalkyl,
• phenyl optionally substituted with 1 or 2 halogen,
• wherein X is CH2, O, S or NR1-1 and wherein R1-1 is hydrogen or (C1-C6)alkyl,
• nitro,
• cyano,
• (C1-C3)alkylthio,
• trifluoromethylthio,
• (C1-C3)alkylcarbonyl,
• (C1-C6)alkoxycarbonyl, and
• phenoxy, wherein phenoxy can optionally be substituted with 0, 1 or 2 substituents independently selected from the group consisting of (C1-C6)alkyl, (C1-C6)alkoxy, trifluoromethoxy, and halogen,
• and
• wherein benzyl can be substituted with 0, 1, 2 or 3 groups selected from halogen, (C1-C3)alkyl, and (C1-C3)alkoxy;
• R2 is selected from the group consisting of hydrogen, halogen, (C1-C4)alkyl and (C1-C4)alkoxy;
• R3 is selected from the group consisting of
• carboxyl,
• formyl,
• (C1-C6)alkylcarbonyl optionally substituted with 0, 1, 2, or 3 groups selected from fluorine, chlorine, hydroxy, (C1-C6)alkoxy, and heterocycle,
• (C3-C6)cycloalkylcarbonyl,
• (C1-C6)alkoxycarbonyl optionally substituted with 0, 1, 2, or 3 groups selected from amino, and (C1-C6)alkoxycarbonyl,
• aminocarbonyl,
• (C1-C6)alkylaminocarbonyl, wherein (C1-C6)alkylaminocarbonyl can optionally be substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of (C3-C6)cycloalkyl, halogen, amino, (C1-C6)alkylamino, hydroxy, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkylthio, (C1-C6)alkoxycarbonylamino, and methylsulfonyl, and wherein (C1-C6)alkylaminocarbonyl can optionally be substituted with or 0 or 1 heterocyclyl, wherein heterocyclyl can optionally be substituted with 0 or 1 (C1-C6)alkyl, and wherein (C1-C6)alkylaminocarbonyl can optionally be substituted with 0 or 1 phenyl, wherein phenyl can optionally be substituted with 0 or 1 halogen, (C1-C6)alkyl, or (C1-C6)alkoxy,
• heterocyclylcarbonyl optionally substituted with 0 or 1 amino, (C1-C6)alkylamino, cycloalkyl, or (C1-C6)alkyl, wherein (C1-C6)alkyl can optionally be substituted with 0 or 1 amino or (C1-C6)alkylamino,
• (C1-C6)alkyl optionally substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of
• a) hydroxyl,
• b) amino,
• c) (C1-C6)alkylamino, wherein (C1-C6)alkylamino can be substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, amino, alkylamino, methoxy, methylthio, and methylsulfonyl,
• d) arylamino, wherein arylamino can be substituted with 0, 1 or 2 substituents independently selected from the group consisting of (C1-C6)alkyl, (C1-C6)alkoxy, and trifluoromethyl,
• e) heterocyclyl, wherein heterocyclyl can be substituted with 0, 1 or 2 (C1-C6)alkyl, wherein (C1-C6)alkyl can be substituted with 0, 1 or 2 hydroxy, methoxy or pyridyl,
• f) imidazolyl,
• g) pyridylamino,
• h) (C1-C3)alkoxy optionally substituted by fluoro up to the perfluoro level, or by heterocycle, wherein heterocycle can optionally be substituted by 0 or 1 (C1-C6)alkyl,
• i) (C1-C3)alkoxy(C2-C3)alkoxy, and
• j) (C1-C6)alkoxycarbonyl,
• k) (C3-C6)cycloalkyl,
• l) cyano,
• (C1-C6)alkoxy optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of amino, (C1-C6)alkylamino, and heterocyclyl, wherein heterocyclyl can be substituted with 0, 1, 2 or 3 (C1-C6)alkyl,
• (C3-C6)cycloalkylaminocarbonyl optionally substituted with (C1-C3)alkyl,
• cyano,
• heteroaryl, wherein heteroaryl can be substituted with 0, 1, 2, or 3 groups independently selected from the group consisting of
• a) (C1-C6)alkyl, wherein (C1-C6)alkyl can be substituted with 0, 1, 2, or 3 halogen, 0 or 1 heterocyclyl, 0 or 1 alkylamino, or 0 or 1 hydroxy or methoxy,
• b) halogen,
• c) amino,
• d) alkylamino,
• e) (C1-C6)alkoxycarbonyl, and
• f) (C3-C6)cycloalkyl,
• heteroarylcarbonyl, which can be substituted with 0, 1, 2, or 3 groups independently selected from the group consisting of (C1-C6)alkyl, (C3-C6)cycloalkyl and halogen,
• heterocyclyl, wherein heterocyclyl can be substituted with 0, 1, 2, or 3 groups independently selected from the group consisting of (C1-C6)alkyl and (C1-C6)alkoxycarbonyl;
• and
• R4 is selected from the group consisting of hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy and halogen;
• or a pharmaceutically acceptable salt thereof.