Claims for Patent: 9,994,575

Summary for Patent: 9,994,575

Title:	Compositions useful for treating disorders related to kit
Abstract:	Compounds and compositions useful for treating disorders related to mutant KIT are described herein.
Inventor(s):	Hodous; Brian L. (Cambridge, MA), Kim; Joseph L. (Wayland, MA), Wilson; Kevin J. (Boston, MA), Wilson; Douglas (Ayer, MA), Zhang; Yulian (Acton, MA)
Assignee:	BLUEPRINT MEDICINES CORPORATION (Cambridge, MA)
Application Number:	14/887,614
Patent Claims:	1. A compound of Formula II: ##STR00232## or a pharmaceutically acceptable salt thereof, wherein: Ring A is selected from monocyclic or bicyclic aryl, monocyclic or bicyclic heteroaryl, cycloalkyl, and heterocyclyl; Z is selected from C.sub.1-C.sub.6 alkyl, cycloalkyl, monocyclic or bicyclic aryl, monocyclic or bicyclic aralkyl, monocyclic or bicyclic heteroaryl, monocyclic or bicyclic heterocyclyl, and monocyclic or bicyclic heterocyclylalkyl, wherein each of C.sub.1-C.sub.6 alkyl, cycloalkyl, monocyclic or bicyclic aryl, monocyclic or bicyclic aralkyl, monocyclic or bicyclic heteroaryl, monocyclic or bicyclic heterocyclyl, and monocyclic or bicyclic heterocyclylalkyl is independently substituted with 0-5 occurrences of R.sup.C; L is selected from a bond, --(C(R.sup.2)(R.sup.2)).sub.m--, --(C.sub.2-C.sub.6 alkynylene)-, --(C.sub.2-C.sub.6 alkenylene)-, --(C.sub.1-C.sub.6 haloalkylene)-, --(C.sub.1-C.sub.6 heteroalkylene)-, --(C.sub.1-C.sub.6 hydroxyalkylene)-, --C(O)--, --O--, --S--, --S(O), --S(O).sub.2--, --N(R.sup.2)--, --O--(C.sub.1-C.sub.6 alkylene)-, --(C.sub.1-C.sub.6 alkylene)-O--, --N(R.sup.2)--C(O)--, --C(O)--N(R.sup.2)--, --(C.sub.1-C.sub.6 alkylene)-N(R.sup.2)--, --N(R.sup.2)--(C.sub.1-C.sub.6 alkylene)-, --N(R.sup.2)--C(O)--(C.sub.1-C.sub.6 alkylene)-, --C(O)--N(R.sup.2)--(C.sub.1-C.sub.6 alkylene)-, --N(R.sup.2)--S(O).sub.2--, --S(O).sub.2--N(R.sup.2)--, --N(R.sup.2)--S(O).sub.2--(C.sub.1-C.sub.6 alkylene)-, and --S(O).sub.2--N(R.sup.2)--(C.sub.1-C.sub.6 alkylene)-; each R.sup.A and R.sup.B is independently selected from C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 heterocyclyl, halo, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 hydroxyalkyl, C.sub.1-C.sub.6 heteroalkyl, monocyclic or bicyclic aralkyl, --N(R.sup.2)(R.sup.2), cyano, and --OR.sup.2; each R.sup.C is independently selected from C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkynyl, halo, C.sub.1-C.sub.6 heteroalkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, C.sub.1-C.sub.6 hydroxyalkyl, cycloalkyl, monocyclic or bicyclic aryl, monocyclic or bicyclic aryloxy, monocyclic or bicyclic aralkyl, monocyclic or bicyclic heterocyclyl, monocyclic or bicyclic heterocyclylalkyl, nitro, cyano, --C(O)R.sup.2, --OC(O)R.sup.2, --C(O)OR.sup.2, --SR.sup.2, --S(O).sub.2R.sup.2, --S(O).sub.2--N(R.sup.2)(R.sup.2), --(C.sub.1-C.sub.6 alkylene)-S(O).sub.2--N(R.sup.2)(R.sup.2), --N(R.sup.2)(R.sup.2), --C(O)--N(R.sup.2)(R.sup.2), --N(R.sup.2)(R.sup.2)--C(O)R.sup.2, --(C.sub.1-C.sub.6 alkylene)-N(R.sup.2)--C(O)R.sup.2, --NR.sup.2S(O).sub.2R.sup.2, --P(O)(R.sup.2)(R.sup.2), and --OR.sup.2, wherein each of C.sub.1-C.sub.6 heteroalkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkynyl, cycloalkyl, monocyclic or bicyclic aryl, monocyclic or bicyclic aryloxy, monocyclic or bicyclic aralkyl, monocyclic or bicyclic heterocyclyl, and monocyclic or bicyclic heterocyclylalkyl is independently substituted with 0-5 occurrences of R.sup.a; or 2 R.sup.C together with the carbon atom(s) to which they are attached form a cycloalkyl or heterocyclyl ring substituted with 0-5 occurrences of R.sup.a; each R.sup.2 is independently selected from hydrogen, hydroxyl, halo, thiol, C.sub.1-C.sub.6 thioalkyl, --NR''R'', C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 hydroxyalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl, wherein each of C.sub.1-C.sub.6 alkyl, cycloalkyl, and heterocyclyl is independently substituted with 0-5 occurrences of R.sup.b, or 2 R.sup.2 together with the atoms to which they are attached form a cycloalkyl or heterocyclyl ring; each R.sup.a and R.sup.b is independently selected from hydrogen, halo, cyano, hydroxyl, C.sub.1-C.sub.6 alkoxyl, --C(O)R', C(O)OR', C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 heteroalkyl, C.sub.1-C.sub.6 hydroxyalkyl, --NR'R', and cycloalkyl, wherein cycloalkyl is substituted with 0-5 occurrences of R'; each R' is hydrogen, hydroxyl, or C.sub.1-C.sub.6 alkyl; each R'' is hydrogen, C.sub.1-C.sub.6 alkyl, --C(O)--C.sub.1-C.sub.6 alkyl, --C(O)--NR'R'; or --C(S)--NR'R'; and m, p, and q are each independently 0, 1, 2, 3, or 4. 2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula III: ##STR00233## 3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein L is --(C(R.sup.2)(R.sup.2)).sub.m--. 4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein A is monocyclic or bicyclic aryl. 5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Z is monocyclic or bicyclic aryl. 6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Z is monocyclic or bicyclic heteroaryl. 7. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Z is monocyclic heteroaryl. 8. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Z is selected from pyrazolyl, isoxazolyl, thiophenyl, thiazolyl, and pyridyl. 9. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Z is phenyl. 10. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Z is monocyclic or bicyclic heterocyclyl. 11. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R.sup.A is fluoro and q is 1. 12. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof. 13. A method of treating mastocytosis, the method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 14. A method of treating gastrointestinal stromal tumor, the method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 15. A method of treating acute myeloid leukemia, the method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. 16. The method of claim 13, wherein the mastocytosis is selected from cutaneous mastocytosis (CM) and systemic mastocytosis (SM). 17. The method of claim 16, wherein the systemic mastocytosis is selected from indolent systemic mastocytosis (ISM), smoldering systemic mastocytosis (SSM), aggressive systemic mastocytosis (ASM), SM with associated hematologic non-mast cell lineage disease (SM-AHNMD), and mast cell leukemia (MCL). 18. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein L is --(C(R.sup.2)(R.sup.2)).sub.m--. 19. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein Z is monocyclic or bicyclic heteroaryl. 20. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein R.sup.A is fluoro and q is 1.