PHARMACEUTICAL COMBINATIONS COMPRISING A PYRIDO [4,3-D] PYRIMIDINE DERIVED HSP90-INHIBITOR AND A HER2 INHIBITOR

摘要

A pharmaceutical combination comprising an Hsp90 inhibitor and an HER2 inhibitor, and methods of using the combination to treat proliferative disorders.

主权项

1. A pharmaceutical combination comprising an HSP90 inhibitor and a HER2 inhibitor, wherein the HSP90 inhibitor is
(A) a compound of formula (E) wherein R3 is selected from ethylaminocarbonyl CH3CH2NHC(═O)— or isopropylaminocarbonyl (CH3)2CHNHC(═O)—), R8 is selected from ethyl, isopropyl, bromo, or chloro; and R9 is —CH2NR10R11 or —NR10R11 wherein the substituted amino group —NR10R11 is a morpholinyl, piperidinyl, piperazinyl, pyrrolidinyl, ethylamino, isopropylamino, diethylamino, cyclohexylamino, cyclopentylamino, methoxyethylamino, piperidin-4-yl, N-acetylpiperazinyl, N-methylpiperazinyl, methylsulfonylamino, thiomorpholinyl, thiomorpholinyl-dioxide, 4-hydroxyethylpiperidinyl or 4-hydroxypiperidinyl, or pharmaceutically acceptable salt or prodrug thereof; or (B) compound according to Formula (I) wherein Ra is selected from the group consisting of (1) hydrogen, (2) halogen, (3) hydroxyl, (4) C1-C6 alkoxy, (5) thiol, (6) C1-C6 alkylthiol, (7) substituted or unsubstituted C1-C6 alkyl, (8) amino or substituted amino, (9) substituted or unsubstituted aryl, (10) substituted or unsubstituted heteroaryl, and (11) substituted or unsubstituted heterocyclyl; R is selected from the group consisting of (1) hydrogen, (2) substituted or unsubstituted C1-C6 alkyl, (3) substituted or unsubstituted C2-C6 alkenyl, (4) substituted or unsubstituted C2-C6 alkynyl, (5) substituted or unsubstituted C3-C7 cycloalkyl, (6) substituted or unsubstituted C5-C7 cycloalkenyl, (7) substituted or unsubstituted aryl, (8) substituted or unsubstituted heteroaryl, and (9) substituted or unsubstituted heterocyclyl; Rb is selected from the group consisting of (1) substituted or unsubstituted C3-C7 cycloalkyl, (2) substituted or unsubstituted C5-C7 cycloalkenyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heteroaryl, and (5) substituted or unsubstituted heterocyclyl; and with the proviso that when Ra is amino, then Rb is not phenyl, 4-alkyl-phenyl, 4-alkoxy-phenyl, or 4-halo-phenyl, or a pharmaceutically acceptable salt or prodrug thereof.