US 11,655,238 B2
MMPL3 inhibitors, compositions and uses thereof
Zihe Rao, Shanghai (CN); Jun Li, Shanghai (CN); Bing Zhang, Shanghai (CN); and Haitao Yang, Shanghai (CN)
Assigned to SHANGHAITECH UNIVERSITY, Shanghai (CN)
Appl. No. 17/295,227
Filed by SHANGHAITECH UNIVERSITY, Shanghai (CN)
PCT Filed Nov. 20, 2019, PCT No. PCT/CN2019/119668
§ 371(c)(1), (2) Date May 19, 2021,
PCT Pub. No. WO2020/103856, PCT Pub. Date May 28, 2020.
Claims priority of application No. PCT/CN2018/116350 (WO), filed on Nov. 20, 2018.
Prior Publication US 2022/0017492 A1, Jan. 20, 2022
Int. Cl. C07D 403/04 (2006.01); C07D 207/327 (2006.01); C07D 231/14 (2006.01); C07D 233/90 (2006.01); C07D 249/10 (2006.01); C07D 333/38 (2006.01); C07D 401/04 (2006.01); C07D 405/04 (2006.01)
CPC C07D 403/04 (2013.01) [C07D 207/327 (2013.01); C07D 231/14 (2013.01); C07D 233/90 (2013.01); C07D 249/10 (2013.01); C07D 333/38 (2013.01); C07D 401/04 (2013.01); C07D 405/04 (2013.01)] 28 Claims
 
1. A compound of the below Formula III:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, tautomer, isotopically enriched analog, stereoisomer, or mixture of stereoisomers thereof,
wherein:
X1, X2, and X3 are C; X4 and X5 are N;
L1 is *—N(R1b)CO—, *—(CH2)k—N(R1b)CO—, *—(CH2)n—N(R1c)—(CH2)k—N(R1b)CO—, *—(CH2)n-(O(CH2)m)p—O(CH2)k—N(R1b)CO—, *—(CH2)m—CO-L1a-CO—, *—(CH2)m-L1a-CO—, *—(CH2)n—NHCONH—(CH2)m—, *—(CH2)n—N(R1c)—(CH2)k—N(R1b)—(CH2)m—, *—(CH2)n—CON(R1b)—(CH2)m—, *—(CH2)p—N(R1c)—(CH2)n—CON(R1b)—(CH2)m—, *—(CH2)p—N(R1c)—(CH2)n—SO2N(R1b)—(CH2)m—, *—(CH2)n—SO2N(R1b)—(CH2)m—, *—(CH2)n—OCO—, *—(CH2)n-L1a-(CH2)m—, *—N(R1c)—(CH2)m—N(R1b)—(CH2)m—, or —N(R1c)—(CH2)n—N(R1b)—N(R1b)—(CO)—; wherein
* represents the point of connection with R1;
L1a is 5-, 6- or 7-membered heterocyclylene;
each R1b is independently H or C1-3 alkyl;
each R1c is independently H or C1-3 alkyl;
k is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and
each m, n and p is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
R1 is adamantly substituted with one to ten R1a, bicyclo[2.2.1]heptyl substituted with one to ten R1a or unsubstituted adamantyl;
each R1a is independently selected from —CN, —NO2, C1-3 alkyl, C1-3 haloalkyl, —OR6, —SR6, —N(R6)2, —C(O)R6, —C(O)OR6, —S(O)R6, —S(O)2R6, —C(O)N(R6)2, —NR6C(O)R6, —NR6C(O)OR6, —NR6C(O)N(R6)2, —NHS(O)R6, —S(O)(NH)R6, cycloalkyl, aryl, heterocyclyl, heteroaryl, or a combination thereof;
R2 is C1-3 alkyl;
each R3b and R3c is independently H or R3a; and
each R4b and R4c is independently H or R4a;
R3a and R4a is independently selected form halo and C1-3 alkyl;
R5 is absent;
each R6 is independently hydrogen, C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, aryl, heteroaryl, or heterocyclyl.