US 12,202,844 B2
MAP4K1 inhibitors
Jason D. Brubaker, Cambridge, MA (US); Joshua T. Close, Cambridge, MA (US); Thomas A. Dineen, Cambridge, MA (US); Chandrasekhar V. Miduturu, Cambridge, MA (US); and Emanuele Perola, Cambridge, MA (US)
Assigned to Blueprint Medicines Corporation, Cambridge, MA (US)
Filed by Blueprint Medicines Corporation, Cambridge, MA (US)
Filed on Jul. 13, 2022, as Appl. No. 17/864,106.
Claims priority of provisional application 63/221,825, filed on Jul. 14, 2021.
Prior Publication US 2023/0112729 A1, Apr. 13, 2023
Int. Cl. C07D 519/00 (2006.01); A61P 35/00 (2006.01); C07D 491/052 (2006.01)
CPC C07D 519/00 (2013.01) [A61P 35/00 (2018.01); C07D 491/052 (2013.01)] 30 Claims
 
1. A compound of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein:
T is selected from

OG Complex Work Unit Chemistry
and 4-5 membered heterocycle containing

OG Complex Work Unit Chemistry
wherein said heterocycle of T is optionally substituted with 1-2 R6;
Z is absent, O or NH;
Ring A is C4-6 cycloalkyl or 4-6 membered heterocycle containing nitrogen, wherein said cycloalkyl or heterocycle of Ring A is optionally substituted with 1-2 R6;
L1 is selected from bond and C1-C3 alkylene, wherein said alkylene of L1 is optionally substituted with 1-2 R11;
L2 is selected from bond and C1-C3 alkylene;
B is O or NH;
Q is N or CH;
x is 0, 1, or 2;
n is 0, 1, 2, 3, or 4;
R1 and R2 are each independently selected from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, and 4 to 6-membered heterocycle, wherein said alkyl of R1 and R2 is optionally substituted with 1-2 R3;
each R3 is independently selected from halogen, hydroxyl and OR4;
each R4 is independently selected from C1-3 alkyl, CF3, CH2F, and CHF2;
each R5 is independently selected from C1-2 alkyl, CF3, CH2F, and CHF2, or
two R5 attached to the same carbon atom taken together with the carbon atom to which they attach form C3-5 cycloalkyl; or two R5 attached to two adjacent carbon atoms taken together with the two adjacent carbon atoms to which they attach form C4-6 cycloalkyl;
each R6 is independently selected from CH3, methoxy, CF3, CH2F, and CHF2;
R7 is selected from C1-3 alkyl, C3-6 cycloalkyl, OC1-4 alkyl, NR9R10, and 3-5 membered heterocycle containing nitrogen or oxygen, wherein said alkyl, cycloalkyl, or heterocycle of R7 is optionally substituted with 1-3 R8;
each R8 is independently selected from halogen, C1-3 alkyl, hydroxyl and OC1-3 alkyl, wherein said alkyl of R8 is optionally substituted with 1-3 R12;
R9 is selected from C1-2 alkyl;
R10 is selected from C1-2 alkyl;
each R11 is independently selected from halogen, methoxy, C1-2 alkyl, CH2F, CHF2 and CF3, or two R11 taken together with the two adjacent carbon atoms to which they attach form cyclopropyl; and
each R12 is halogen.