US 11,970,493 B2
Autotaxin inhibitor compounds
Sung-Ku Choi, Hwaseong-si (KR); Yoon-Suk Lee, Hwaseong-si (KR); Sung-Wook Kwon, Hwaseong-si (KR); Kyung-Sun Kim, Hwaseong-si (KR); Jeong-Geun Kim, Hwaseong-si (KR); Jeong-Ah Kim, Hwaseong-si (KR); An-Na Moon, Hwaseong-si (KR); Sun-Young Park, Hwaseong-si (KR); Jun-Su Ban, Hwaseong-si (KR); Dong-Keun Song, Hwaseong-si (KR); Kyu-Sic Jang, Hwaseong-si (KR); Ju-Young Jung, Hwaseong-si (KR); and Soo-Jin Lee, Hwaseong-si (KR)
Assigned to ILDONG PHARMACEUTICAL CO., LTD., Seoul (KR)
Filed by ILDONG PHARMACEUTICAL CO., LTD., Seoul (KR)
Filed on Oct. 4, 2021, as Appl. No. 17/493,456.
Claims priority of provisional application 63/088,219, filed on Oct. 6, 2020.
Prior Publication US 2022/0106311 A1, Apr. 7, 2022
Int. Cl. C07D 471/04 (2006.01)
CPC C07D 471/04 (2013.01) 51 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or isomer thereof,
wherein:
X1, X2, and X3 are independently selected from C—R1 and N;
Z1, Z2, and Z3 are independently selected from C—R1 and N;
each R1 is independently selected from —H, -halogen, optionally substituted —(C1-C6)alkyl and optionally substituted —(C1-C6)alkoxy;
Y is selected from S, O, and N—R2, wherein R2 is selected from —H, and optionally substituted —(C1-C6)alkyl;
R3 is selected from optionally substituted R4—C(O)—(C1-C3)alkyl-, R4C(O)—, optionally substituted monocyclic or bicyclic carbocycle, optionally substituted monocyclic or bicyclic heterocycle, R5R6HC—, and R5R6N—;
R4 is selected from H2N—, HO—, R5R6N—, optionally substituted (C1-C10)alkyl-, optionally substituted (C1-C10)alkoxy-, optionally substituted monocyclic or bicyclic carbocycle, optionally substituted monocyclic or bicyclic heterocycle, optionally substituted cycloalkyl-(C1-C6)alkylene-, and optionally substituted heterocycle-(C1-C6)alkylene-;
R5 and R6 are independently selected from H—, H2N—, HO—, optionally substituted (C1-C10)alkyl-, optionally substituted monocyclic or bicyclic carbocycle, optionally substituted monocyclic or bicyclic heterocycle, optionally substituted R4C(O)—(C1-C10)alkyl-, R4C(O)—, R4—, and substituted amino; or R5 and R6 together with the nitrogen or carbon atom to which they are attached are cyclically linked to form an optionally substituted carbocycle or an optionally substituted heterocycle;
R7 is selected from H—, and optionally substituted (C1-C6)alkyl-;
R8 is selected from —H, -halogen, and optionally substituted —(C1-C6)alkyl;
R9 and each R10 are independently selected from —H, -halogen, —CN, —OH, optionally substituted —(C1-C6)alkoxy, —NH2, substituted amino, optionally substituted —(C1-C6)alkyl-NH2 and optionally substituted —(C1-C6)alkyl; and
n is 0, 1, 2, 3, 4, or 5;
with the proviso that:
a) when i) X1, X2, and X3 are C—H, or X1 and X2 are C—H and X3 is C—CH3 or N,
ii) R3 is R4-C(O)—(C1-C3)alkyl-, and iii) R4 is R5R6N—:
R5 and R6 are independently selected from H—, H2N—, HO—, optionally substituted (C1-C10)alkyl-, optionally substituted monocyclic or bicyclic carbocycle, optionally substituted monocyclic or bicyclic heterocycle, optionally substituted R4C(O)—(C1-C10)alkyl-, R4C(O)—, R4-, and substituted amino; or
R5 and R6 together with the nitrogen atom to which they are attached are cyclically linked to form an unsubstituted heterocycle;
b) when i) X1 is C—F and X2 and X3 are C—H, ii) R3 is R4-C(O)-(C1-C3)alkyl- or R4-C(O)—, and iii) R4 is R5R6N—:
R5 and R6 are independently selected from H—, H2N—, HO—, optionally substituted (C1-C10)alkyl-, optionally substituted monocyclic or bicyclic carbocycle, optionally substituted monocyclic or bicyclic heterocycle, optionally substituted R4C(O)-(C1-C10)alkyl-, R4C(O)—, R4-, and substituted amino; or
R5 and R6 together with the nitrogen atom to which they are attached are cyclically linked to form an unsubstituted heterocycle; and
c) when i) X1 and X3 are C—H and X2 is N and, ii) R3 is R4-C(O)-(C1-C3)alkyl-, R4-C(O)—, or R5R6N—, wherein iii) R4 is R5R6N—:
R5 and R6 are independently selected from H—, H2N—, HO—, optionally substituted (C1-C10)alkyl-, optionally substituted monocyclic or bicyclic carbocycle, optionally substituted monocyclic or bicyclic heterocycle, optionally substituted R4C(O)-(C1-C10)alkyl-, R4C(O)—, R4-, and substituted amino; or
R5 and R6 together with the nitrogen atom to which they are attached are cyclically linked to form an unsubstituted heterocycle;
wherein:
when one of R5 and R6 is H—:
the other one of R5 and R6 is independently selected from H2N—, HO—, unsubstituted (C1-C10)alkyl-, optionally substituted monocyclic or bicyclic carbocycle, optionally substituted monocyclic heterocycle, optionally substituted R4C(O)-(C1-C10)alkyl-, R4C(O)—, R4-, and substituted amino.