Pyrimido-diazepinone compounds and methods of treating disorders
The present invention relates to novel pyrimido-diazepinone compounds, methods of modulating protein kinases, including MPS1 (TTK), ERK5 (BMK1, MAPK7), LRKK2, EphA2, polo kinase 1, 2, 3, or 4, Ack1, Ack2, Abl, DCAMKL1, ABL1, Abl mutants, DCAMKL2, ARK5, BRK, MKNK2, FGFR4, TNK1, PLK1, ULK2, PLK4, PRKD1, PRKD2, PRKD3, ROS1, RPS6KA6, TAOK1, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, Axl, Bmx, BTK, c-kit, CHK2, Flt3, MST2, p70S6K, PDGFR, PKB, PKC, Raf, ROCK-H, Rsk1, SGK, TrkA, TrkB and TrkC, and the use of such compounds in the treatment of various diseases, disorders or conditions.
1. A compound having the formula:
or a pharmaceutically acceptable salt thereof,
wherein,
R′ is H or methyl;
L is absent, SO 2 , or CO;
X is H, methyl, fluoro, chloro, phenyl, pyridinyl, thiophenyl, —NH—CO—CH═CH—CH 2 —N(CH 3 ) 2 , —S(O) 2 —N(CH 3 ) 2 , or
Z is NH or N—C1-C3 alkyl;
R 2 is hydrogen or methyl;
R 6 is hydrogen; and
R 1 is H, C═O(CH 3 ),
2. The compound of claim 1 , wherein the compound is selected from the group consisting of:
3. A compound selected from the group consisting of:
4. The compound
or a pharmaceutically acceptable salt thereof.
5. The compound
or a pharmaceutically acceptable salt thereof.