LIU, Yi,REN, Pingda,JESSEN, Katayoun,GUO, Xin,ROMMEL, Christian
申请号：
ES12779459
公开号：
ES2618489T3
申请日:
2012.05.04
申请国别(地区):
ES
年份:
2017
代理人:
摘要：
A combination of a first agent and an mTOR inhibitor for use in treating a proliferative disorder in a subject in need thereof comprising administering to the subject said first agent followed by administration of the mTOR inhibitor, wherein said first agent is paclitaxel, wherein said mTOR inhibitor is a compound of formula I-C1a: ** ** formula or a pharmaceutically acceptable salt thereof wherein: E2 is -H X1 and X2 are N R1 is -L-C1-10 alkyl, -L-C3-8cycloalkyl, -L-alkylheterocyclyl C1-10, or -L-heterocyclyl, each of which is unsubstituted or substituted with one or more independent R3 L is absent, - (C> = O) -, -C (> = O) O-, -C (> = O) N (R31) -, -S-, -S (O) -, -S ( O) 2-, -S (O) 2N (R31) -, or -N (R31) - R3 is hydrogen, -OH, -OR31, -NR31R32, -C (O) R31, -C (> = O) NR31R32, -C (> = O) NR34R35, aryl, heteroaryl, C1-4 alkyl, C1- 10, C3-8 cycloalkyl, or heterocyclyl wherein each said aryl or heteroaryl is unsubstituted or substituted independently with one or more alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, -OH, -R 31, -CF3, -OCF3, -OR31, -NR31R32, -NR34R35, -C (O) R31, -CO2R31, -C (> = O) NR31R32, -C (> = O ) NR34R35, -NO 2, -CN, -S (O) 0-2R31, -SO2NR31R32, -SO2NR34R35, -NR31C (> = O) R32, -NR31C (> = O) OR 32, NR31C (> = O) NR32R33, -NR31S (O) 0-2R32, -C (> = S) OR31, -C (> = O) SR31, -NR31C (> = NR32) NR33R32, -NR31C (> = NR32) OR33, -NR31C (> = NR32) SR33, -OC (> = O) OR33, -OC (> = O) NR31R32, -O (> = O) SR31, -SC (> = O) OR31, -P (O) OR31OR32, o-SC (> = O) NR31R32, and wherein each of said alkyl, cycloalkyl, or heterocyclyl is unsubstituted or substituted with one or more alkyl, heteroalkyl, alkenyl, alkyn yl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, -OH, -R 31, -CF3, -OCF3, -OR31, -O-aryl, -NR31R32, -NR34R35, -C (O) R31, - CO2R31, -C (> = O) NR34R35, or -C (> = O) NR31R32 - (W2) k- is -NH-, -N (H) C (O) - or -N (H) S (O) 2- R2 is hydrogen, hal
