US 11,912,710 B2
Substituted pyrimido[4,5-b][1,4]diazepines as PLK1 degradation inducers
Soo Hee Ryu, Incheon (KR); Im Suk Min, Gyeonggi-do (KR); Han Kyu Lee, Gyeonggi-do (KR); Seong Hoon Kim, Incheon (KR); Hye Guk Ryu, Incheon (KR); Keum Young Kang, Incheon (KR); Sang Youn Kim, Incheon (KR); So Hyun Chung, Incheon (KR); Jun Kyu Lee, Gyeonggi-do (KR); and Gibbeum Lee, Gyeonggi-do (KR)
Assigned to UPPTHERA, INC., Incheon (KR)
Appl. No. 18/019,047
Filed by UPPTHERA, INC., Incheon (KR)
PCT Filed Aug. 10, 2022, PCT No. PCT/KR2022/011963
§ 371(c)(1), (2) Date Jan. 31, 2023,
PCT Pub. No. WO2023/018238, PCT Pub. Date Feb. 16, 2023.
Claims priority of application No. 10-2021-0105358 (KR), filed on Aug. 10, 2021; application No. 10-2021-0106488 (KR), filed on Aug. 12, 2021; application No. 10-2021-0117389 (KR), filed on Sep. 3, 2021; application No. 10-2021-0126757 (KR), filed on Sep. 24, 2021; application No. 10-2022-0008456 (KR), filed on Jan. 20, 2022; application No. 10-2022-0020996 (KR), filed on Feb. 17, 2022; application No. 10-2022-0054880 (KR), filed on May 3, 2022; and application No. 10-2022-0075838 (KR), filed on Jun. 21, 2022.
Prior Publication US 2023/0219966 A1, Jul. 13, 2023
Int. Cl. A61K 31/519 (2006.01); C07D 487/04 (2006.01); A61K 47/55 (2017.01); C07D 519/00 (2006.01)
CPC C07D 487/04 (2013.01) [A61K 47/55 (2017.08); C07D 519/00 (2013.01)] 12 Claims
 
1. A compound represented by the following Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein:
X, is CH or N;
ring U is phenylene or 5- or 6-membered heteroarylene, wherein the phenylene or 5- or 6-membered heteroarylene is optionally substituted with one or more independently selected RU substituents;
each RU is independently halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 aminoalkyl, C1-4 hydroxyalkyl, or OC1-4 alkyl;
LU is a bond, —(CH2)x—, —(CH2)xNH—, —(CH2)xO—, —C(O)—, or phenylene;
L1 is a bond or heterocycloalkylene;
wherein the heterocycloalkylene contains at least one nitrogen ring heteroatom; and
wherein the heterocycloalkylene is optionally substituted with one or more substituents independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, OH, OC1-4 alkyl, or ═O;
L2 is a bond, —(CH2)y1—, —(CD2)y1-, —(CH2)y2—C(O)—(CH2)y3—, —(CH2)y2—NH—(CH2)y3—, —(CH2)y2—N(C1-4 alkyl)-(CH2)y3—, or —(CH2)y1—(OC1-4 alkylene)z-OC1-4 alkylene-;
L3 is a bond, cycloalkylene, or heterocycloalkylene;
wherein the heterocycloalkylene contains at least one nitrogen ring heteroatom; and
wherein the cycloalkylene or heterocycloalkylene is optionally substituted with one or more substituents independently selected from halo, C1-4 alkyl, or C1-4 haloalkyl:
LP is —(CH2)p—NH—C(O)— or —(CH2)p—O—, wherein the —C(O)— or —O— of LP is bonded to the phenyl ring bearing R6;
p is 0, 1, or 2;
x is 0, 1, 2, 3, or 4;
y1 is 0, 1, 2, 3, 4, 5, or 6;
y2 is 0, 1, 2, 3, 4, 5, or 6;
y3 is 0, 1, 2, 3, 4, 5, or 6;
z is 0, 1, 2, 3, 4, 5, or 6;
Y is CR7;
R6 is halo, C1-4 alkyl, or OC1-4 alkyl;
R7 is H or halo;
R1 is 3- to 7-membered cycloalkyl;
R2 is H or C1-4 alkyl;
R3 is H, halo, or C1-4 alkyl;
R4 is H, halo, or C1-4 alkyl; and
R5 is C1-4 alkyl.
 
7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof.