US 12,391,690 B2
Compounds as autotaxin inhibitors and pharmaceutical compositions comprising the same
Dae Yon Lee, Daejeon (KR); Sang Eun Chae, Daejeon (KR); Eun Mi Jung, Daejeon (KR); Eun Hye Yang, Daejeon (KR); Yoon Jeong Choi, Daejeon (KR); Chul-Woong Chung, Daejeon (KR); Ju Hyun Shin, Daejeon (KR); Yun Ki Kim, Daejeon (KR); Hyun Jin Kwon, Daejeon (KR); Jeong Hee Ryu, Daejeon (KR); Eun Hye Ban, Daejeon (KR); Yong Zu Kim, Daejeon (KR); Yeong Soo Oh, Daejeon (KR); and Jeiwook Chae, Daejeon (KR)
Assigned to LigaChem Biosciences Inc., Daejeon (KR)
Filed by LigaChem Biosciences Inc., Daejeon (KR)
Filed on Dec. 1, 2022, as Appl. No. 18/073,120.
Application 18/073,120 is a continuation of application No. 16/098,748, granted, now 11,548,883, previously published as PCT/KR2018/005516, filed on May 15, 2018.
Claims priority of application No. 10-2017-0060940 (KR), filed on May 17, 2017.
Prior Publication US 2023/0123569 A1, Apr. 20, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 471/04 (2006.01); C07D 239/42 (2006.01); C07D 401/14 (2006.01); C07D 403/14 (2006.01); C07D 413/12 (2006.01); C07D 413/14 (2006.01); C07D 471/10 (2006.01); C07D 498/10 (2006.01); C07D 513/04 (2006.01); C07D 519/00 (2006.01)
CPC C07D 471/04 (2013.01) [C07D 239/42 (2013.01); C07D 401/14 (2013.01); C07D 403/14 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01); C07D 471/10 (2013.01); C07D 498/10 (2013.01); C07D 513/04 (2013.01); C07D 519/00 (2013.01)] 11 Claims
 
1. A compound represented by the following chemical formula 1, or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein:
X is CR′ and Y is N;
R′ is hydrogen, C1-C10 alkyl, or C6-C12 aryl;
R is indanyl, C6-C12arC1-C10 alkyl, or C6-C12arC3-C10 cycloalkenyl;
said aralkyl and arcycloalkenyl of above R may be further substituted with one or more substituents that are selected from halogen, C1-C10 alkoxy, and halo-substituted C1-C10 alkoxy;
A is C2-C12 heteroaryl, carboxyl-substituted C1-C10 alkyl, C6-C12 aryl, C6-C12arC1-C10 alkyl, C2-C12 heterocycloalkyl, or NR1R2;
said heteroaryl, aryl, aralkyl, and heterocycloalkyl of above A may be further substituted with one or more substituents that are selected from hydroxy, carboxyl, carbamoyl, aminosulfonyl, C1-C10 alkylsulfonylamino, C6-C12 arylsulfonylamino, aminosulfonylamino (—NHSO2NH2), —C(═O) CH2OH and amino,
R1 and R2 are each independently hydrogen or carboxyl-substituted C1-C10 alkyl, or R1 and R2 may be linked to each other to form a monocycle, a polycycle, or a spiro ring that is either saturated or unsaturated;
said ring formed as above may contain one or more hetero atoms that are selected from nitrogen, oxygen, and sulfur and may contain a C═C double bond, a C═N double bond, or a N═N double bond, and a CH2 in said ring formed as above may be substituted with oxo, and also in which said ring as formed above may be substituted with or further substituted with one or more substituents that are selected from hydroxy, carboxyl, carbamoyl, aminosulfonyl, C1-C10 alkylsulfonylamino, C6-C12 arylsulfonylamino, aminosulfonylamino (—NHSO2NH2), hydrazide and amino;
L is a single bond, —(CR3R4)aC(═O)—, —C(═O)—(CR3R4)a—, —C(═O)—(CR5R6)b—NH—(CR7R8)c—, —NH—(CR7R8)c—C(═O)—(CR5R6)b—, —C(═NR9)—(CR3R4)a—, C2-C12 heteroarylene, —(CR3R4)a—C2-C12 heterocycloalkylene-, —C2-C12 heterocycloalkenylene-(CR3R4)a—, —C2-C12 heterocycloalkylene-(CR3R4)a—(NH)d—,

OG Complex Work Unit Chemistry
R3 to R8 are each independently hydrogen or C1-C10 alkyl;
R9 is hydroxy, C1-C10 alkoxy, or mono- or di-C1-C10 alkylamino;
Y1 is NR10, O, or S;
each R10 is independently hydrogen or C1-C10 alkyl;
a is an integer of from 1 to 5;
b and c are each independently an integer of from 0 to 5;
d is an integer of 0 or 1;
Q is selected from the following structures:

OG Complex Work Unit Chemistry
and
said heteroaryl, heteroarylene, heterocycloalkylene, heterocycloalkenylene, and heterocycloalkyl contain at least one hetero atom that is selected from nitrogen, oxygen, and sulfur;
provided that, when Q is carbonyl, L or A contains a nitrogen atom directly bonded to Q.