US 12,344,597 B2
Alkoxy-substituted pyridinyl derivatives as LPA1 receptor antagonists and their use in the treatment of fibrosis
Martin Bolli, Allschwil (CH); Christine Brotschi, Allschwil (CH); Cyrille Lescop, Allschwil (CH); and Jodi T. Williams, Allschwil (CH)
Assigned to IDORSIA PHARMACEUTICALS LTD, Allschwil (CH)
Appl. No. 16/972,878
Filed by IDORSIA PHARMACEUTICALS LTD, Allschwil (CH)
PCT Filed Jun. 5, 2019, PCT No. PCT/EP2019/064690
§ 371(c)(1), (2) Date Dec. 7, 2020,
PCT Pub. No. WO2019/234115, PCT Pub. Date Dec. 12, 2019.
Claims priority of application No. PCT/EP2018/065016 (WO), filed on Jun. 7, 2018.
Prior Publication US 2021/0246116 A1, Aug. 12, 2021
Int. Cl. C07D 401/12 (2006.01); A61P 9/14 (2006.01); C07D 401/14 (2006.01)
CPC C07D 401/12 (2013.01) [A61P 9/14 (2018.01); C07D 401/14 (2013.01)] 21 Claims
 
1. A compound of Formula (I),

OG Complex Work Unit Chemistry
wherein
W represents N, and Z represents CH; or
Z represents N, and W represents CH;
R1 is hydrogen or fluoro;
R2 is hydrogen, halogen, methyl, ethyl, methoxy or ethoxy;
R3 is C1-3-fluoroalkoxy;
Ar1 represents phenyl, wherein said group Ar1 is substituted with R4 and R5, wherein
R4 is n-propyl, isopropyl, C3-6-cycloalkyl optionally containing a ring oxygen atom, or cyclopent-1-en-1-yl; and
R5 represents one substituent independently selected from hydrogen, fluoro, methyl or methoxy;
m and n represent the integer 1; and
the group -L—R6 represents
-L1-COOH; wherein
-L1- represents
-C1-6-alkylene-, —CO—C1-6-alkylene-, —SO2-C1-6-alkylene-, —CO—O-C1-6-alkylene-, —CO—NH-C1-6-alkylene-, or —SO2—NH-C1-6-alkylene-;
—CO-C1-6-alkylene-; wherein said C1-6-alkylene is mono-substituted with hydroxy;
-C0-4-alkylene-C3-8-cycloalkylene-C0-4-alkylene-, —CO-C0-4-alkylene-C3-8-cycloalkylene-C0-4-alkylene-, —SO2-C0-4-alkylene-C3-8-cycloalkylene-C0-4-alkylene-, or —CO-O-C0-4-alkylene-C3-8-cycloalkylene-C0-4-alkylene-;
—CO-C0-4-alkylene-Cy1-C0-4-alkylene-; wherein Cy1 independently represents a C3-6-heterocycloalkylene containing one ring oxygen atom;
—CO-C1-4-alkylene-X12-C1-4-alkylene-; wherein X12 independently represents a nitrogen atom which is unsubstituted, or mono-substituted with C1-4-alkyl;
—CO-C2-6-alkenylene- or —SO2-C2-6-alkenylene-; or
—CO-C2-6-fluoroalkylene-;
-L2-hydroxy; wherein -L2- represents
-C2-6-alkylene-, wherein the C2-6-alkylene is unsubstituted, or mono-substituted with hydroxy; or
—CO-C1-4-alkylene-X22-C2-4-alkylene-; wherein X22 represents a nitrogen atom which is independently unsubstituted, or mono-substituted with C1-4-alkyl or C3-6-cycloalkyl; or
-L9-HET1, wherein HET1 represents 5- or 6-membered heteroaryl selected from pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, furanyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyrimidinyl, pyridazinyl, and pyrazinyl; wherein said HET1 independently is unsubstituted or mono-, or di-substituted wherein the substituents are independently selected from C1-4-alkyl; halogen; cyano; hydroxy; hydroxymethyl; -C0-2-alkylene-Cy91-COORO91 wherein RO91 is hydrogen or C1-4-alkyl, and wherein Cy91 represents a C3-6-cycloalkylene group; or -C0-2-alkylene-COORO92 wherein RO92 is hydrogen or C1-4-alkyl; and
-L9- independently represents
-C0-6-alkylene-, or —CO-C0-6-alkylene-;
or a pharmaceutically acceptable salt thereof.