US 12,441,706 B2
Protein degradation agent compound preparation method and application
Hongfu Lu, Shanghai (CN); Weiqiang Xing, Shanghai (CN); Baojian Qi, Shanghai (CN); Jianbiao Peng, Shanghai (CN); and Haibing Guo, Shanghai (CN)
Assigned to SHANGHAI JEMINCARE PHARMACEUTICALS CO., LTD., Shanghai (CN); and JIANGXI JEMINCARE GROUP CO., LTD., Nanchang (CN)
Appl. No. 17/788,154
Filed by SHANGHAI JEMINCARE PHARMACEUTICALS CO., LTD., Shanghai (CN); and JIANGXI JEMINCARE GROUP CO., LTD., Nanchang (CN)
PCT Filed Dec. 23, 2020, PCT No. PCT/CN2020/138572
§ 371(c)(1), (2) Date Jun. 22, 2022,
PCT Pub. No. WO2021/129653, PCT Pub. Date Jul. 1, 2021.
Claims priority of application No. 201911342649.0 (CN), filed on Dec. 23, 2019; application No. 202010200682.6 (CN), filed on Mar. 20, 2020; application No. 202010496353.0 (CN), filed on Jun. 3, 2020; and application No. 202011486334.6 (CN), filed on Dec. 16, 2020.
Prior Publication US 2023/0111119 A1, Apr. 13, 2023
Int. Cl. C07D 401/14 (2006.01); A61P 15/00 (2006.01); A61P 25/28 (2006.01); A61P 35/00 (2006.01)
CPC C07D 401/14 (2013.01) [A61P 15/00 (2018.01); A61P 25/28 (2018.01); A61P 35/00 (2018.01); C07B 2200/07 (2013.01)] 31 Claims
 
1. A compound represented by formula (I), an optical isomer thereof, or a pharmacologically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein:
X is C(R) or N;
T1, T2, T3 and T4 are each independently C(R) or N;
T5 is —(C═O)— or —CH2—;
R1, R2, R3 and R4 are each independently selected from the group consisting of CN, halogen, C1-6 alkyl and C1-6 alkoxy, wherein the C1-6 alkyl and C1-6 alkoxy are optionally substituted by 1, 2 or 3 R;
L1, L2 and L3 are each independently selected from the group consisting of single bond, O, S, NH, C(═O), S(═O), S(═O)2, C1-6 alkyl, —C1-6 alkyl-O—, —C1-6 alkyl-NH—, —O—C1-6 alkyl-O—, —O—C1-6 alkyl-O—C1-6 alkyl-, —O—C2-3 alkenyl, C2-3 alkynyl, C3-10 cycloalkyl, 3- to 10-membered heterocycloalkyl, phenyl, and 5- to 9-membered heteroaryl; wherein the C1-6 alkyl, —C1-6 alkyl-O—, —C1-6 alkyl-NH—, —O—C1-6 alkyl-O—, —O—C1-6 alkyl-O—C1-6 alkyl-, C2-3 alkenyl, C2-3 alkynyl, C3-10 cycloalkyl, 3- to 10-membered heterocycloalkyl, phenyl, and 5- to 9-membered heteroaryl are optionally substituted by 1, 2 or 3 RL;
RL are each independently selected from the group consisting of H, halogen, OH, NH2, CN,

OG Complex Work Unit Chemistry
C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkyl-C(═O)—, C1-6 alkoxy, C1-6 alkylthio and C1-6 alkylamino; wherein the C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 alkylthio, and C1-6 alkylamino are optionally substituted by 1, 2 or 3 R′;
R′ is F, Cl, Br, I, OH, NH2,

OG Complex Work Unit Chemistry
CH3, CH2CH3, CH2F, CHF2, or CF3;
R is H, F, Cl, Br, I, OH, or C1-6 alkyl;
CH3, CH2CH3, CH2F, CHF2, or CF3;
R5 is H, halogen, or C1-6 alkyl;
the 3- to 10-membered heterocycloalkyl or 5- to 9-membered heteroaryl contains 1, 2 or 3 heteroatoms or heteroatomic groups independently selected from the group consisting of —O—, —NH—, —S—, —C(═O)—, —C(═O)O—, —S(═O)—, —S(═O)2—, and N.