US 12,331,038 B2
Hexone glucokinase inhibitor and use thereof
Bin Liu, Jinan (CN); and Bo Chen, Jinan (CN)
Assigned to SHANDONG XUANZHU PHARMA CO., LTD., Jinan (CN); and XUANZHU BIOPHARMACEUTICAL CO., LTD., Shijiazhuang (CN)
Appl. No. 17/426,675
Filed by SHANDONG XUANZHU PHARMA CO., LTD., Jinan (CN); and XUANZHU BIOPHARMACEUTICAL CO., LTD., Shijiazhuang (CN)
PCT Filed Jan. 22, 2020, PCT No. PCT/CN2020/073813
§ 371(c)(1), (2) Date Jul. 29, 2021,
PCT Pub. No. WO2020/156445, PCT Pub. Date Aug. 6, 2020.
Claims priority of application No. 201910085547.9 (CN), filed on Jan. 29, 2019; application No. 201910316417.1 (CN), filed on Apr. 19, 2019; and application No. 201910985433.X (CN), filed on Oct. 17, 2019.
Prior Publication US 2022/0106299 A1, Apr. 7, 2022
Int. Cl. C07D 403/14 (2006.01); C07D 401/14 (2006.01); C07D 403/04 (2006.01)
CPC C07D 403/14 (2013.01) [C07D 401/14 (2013.01); C07D 403/04 (2013.01)] 9 Claims
 
1. A compound represented by general formula (I), a pharmaceutically acceptable salt, an ester, or a stereoisomer thereof:

OG Complex Work Unit Chemistry
wherein,
X, Y, and Z are each —N—;
ring A is a 4-7 membered cycloalkyl;
R1 is selected from hydrogen, halogen, nitro group, cyano group, -(L)m-C(O)ORa, -(L)m-CONRaRb, -(L)m-CONHSO2Ra, -(L)m-SO2Ra, -(L)m-SO2NHCORa, -(L)m-ORa, -(L)m-SRa, -(L)m-NRaRb, -(L)m-C(O)Ra, -(L)m-OC(O)Ra, -(L)m-OC(O)ORa, -(L)m-OC(O)NRaRb, -(L)m-NRaC(O)Rb, -(L)m-NRaC(O)ORb, -(L)m-OS(O)Ra, -(L)m-OS(O)ORa, -(L)m-OS(O)NRaRb, -(L)m-S(O)NRaRb, -(L)m-NRaS(O)Rb, -(L)m-OS(O)2Ra, -(L)m-S(O)2NRaRb, -(L)m-NRaS(O)2Rb; and the following groups optionally substituted with one or more Q1 groups: -(L)m-C1-6 alkyl, -(L)m-C1-6 alkoxy, -(L)m-C3-12 cycloalkyl, -(L)m-C3-12 heterocyclyl, -(L)m-C6-12 aryl, and -(L)m-C5-12 heteroaryl;
L is selected from C1-6 alkylene and haloC1-6 alkylene;
R2 is selected from the following groups optionally substituted by one or more Q2 groups: 3-12 membered heterocyclic group, 3-12 membered cycloalkyl group, 5-12 membered heteroaryl, 6-12 membered aryl, 5-12 membered spirocyclic group, 5-12 membered spiro heterocyclic group, 5-12 membered bridged group, 5-12 membered bridged heterocyclic group, N(C1-6 alkyl)2, N(C1-6 alkyl)(C3-8 cycloalkyl), NH(C1-6 alkyl), and NH(C3-8 cycloalkyl);
each R3 is independently selected from hydrogen, halogen, nitro group, cyano group, amino group, hydroxyl, carboxy; and the following groups optionally substituted with one or more Q3 groups: C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, di(C1-6 alkyl)amino, halo C1-6 alkyl, hydroxy C1-6 alkyl, amino C1-6 alkyl, halo C1-6 alkoxy, 3-12 membered cycloalkyl group, 3-12 membered heterocyclic group, 6-12 membered aryl, and 5-12 membered heteroaryl;
each of Ra and Rb is independently selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, di(C1-6 alkyl)amino, halo C1-6 alkyl, hydroxy C1-6 alkyl, amino C1-6 alkyl, and halo C1-6 alkoxy;
each of Q1, Q2, Q3 and Q4 groups is independently selected from hydroxyl, amino group, halogen, nitro group, cyano group, carboxy, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, di(C1-6 alkyl)amino, halo C1-6 alkyl, hydroxy C1-6 alkyl, amino C1-6 alkyl, halo C1-6 alkoxy, 3-10 membered cycloalkyl group, 3-10 membered heterocyclic group, 6-10 membered aryl, and 5-10 membered heteroaryl; and
m and n are each independently an integer from 0 to 8.