COMBINATION OF A PHOSPHATIDYLINOSITOL-3-KINASE (PI3K) INHIBITOR AND A MTOR INHIBITOR

摘要

The invention relates to a pharmaceutical combination which comprises (a) a phosphoinositide 3-kinase inhibitor compound of formula (I) and (b) a mTOR inhibitor for the treatment of a target of rapamycin (mTOR) kinase dependent disease, especially a cancer disease; a pharmaceutical composition comprising such a combination; the use of such a combination for the preparation of a medicament for the treatment of a proliferative disease; a commercial package or product comprising such a combination as a combined preparation for simultaneous, separate or sequential use; and to a method of treatment of a warm-blooded animal, especially a human.

主权项

1. A pharmaceutical combination comprising
a) a compound of formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein, W is CRw or N, wherein Rw is selected from the group consisting of (1) hydrogen, (2) cyano, (3) halogen, (4) methyl, (5) trifluoromethyl, (6) sulfonamido; R1 is selected from the group consisting of (1) hydrogen, (2) cyano, (3) nitro, (4) halogen, (5) substituted and unsubstituted alkyl, (6) substituted and unsubstituted alkenyl, (7) substituted and unsubstituted alkynyl, (8) substituted and unsubstituted aryl, (9) substituted and unsubstituted heteroaryl, (10) substituted and unsubstituted heterocyclyl, (11) substituted and unsubstituted cycloalkyl, (12) —COR1a, (13) —CO2R1a, (14) —CONR1aR1b, (15) —NR1aR1b, (16) —NR1aCOR1b, (17) —NR1aSO2R1b, (18) —OCOR1a, (19) —OR1a, (20) —SR1a, (21) —SOR1a, (22) —SO2R1a, and (23) —SO2NR1aR1b, wherein R1a, and R1b are independently selected from the group consisting of (a) hydrogen, (b) substituted or unsubstituted alkyl, (c) substituted and unsubstituted aryl, (d) substituted and unsubstituted heteroaryl, (e) substituted and unsubstituted heterocyclyl, and (f) substituted and unsubstituted cycloalkyl; R2 is selected from the group consisting (1) hydrogen, (2) cyano, (3) nitro, (4) halogen, (5) hydroxy, (6) amino, (7) substituted and unsubstituted alkyl, (8) —COR2a, and (9) —NR2aCOR2b, wherein R2a, and R2b are independently selected from the group consisting of (a) hydrogen, and (b) substituted or unsubstituted alkyl; R3 is selected from the group consisting of (1) hydrogen, (2) cyano, (3) nitro, (4) halogen, (5) substituted and unsubstituted alkyl, (6) substituted and unsubstituted alkenyl, (7) substituted and unsubstituted alkynyl, (8) substituted and unsubstituted aryl, (9) substituted and unsubstituted heteroaryl, (10) substituted and unsubstituted heterocyclyl, (11) substituted and unsubstituted cycloalkyl, (12) —COR3a, (13) —NR3aR3b, (14) —NR3aCOR3b, (15) —NR3aSO2R3b, (16) —OR3a, (17) —SR3a, (18) —SOR3a, (19) —SO2R3a, and (20) —SO2NR3aR3b, wherein R3a, and R3b are independently selected from the group consisting of (a) hydrogen, (b) substituted or unsubstituted alkyl, (c) substituted and unsubstituted aryl, (d) substituted and unsubstituted heteroaryl, (e) substituted and unsubstituted heterocyclyl, and (f) substituted and unsubstituted cycloalkyl; and R4 is selected from the group consisting of (1) hydrogen, and (2) halogenand
b) at least one mTOR inhibitor.