IP Library › Granted Patent US 12,479,820

Granted Patent B2

US 12,479,820 · App. 17/620,520 · Granted Nov 25, 2025

Pyridin-3-yl derivatives

Inventors: Martin Bolli (Allschwil, CH); Christine Brotschi (Allschwil, CH); Cyrille Lescop (Allschwil, CH)

Assignee: IDORSIA PHARMACEUTICALS LTD

C07D401/12 A61P9/14 C07D401/14 C07D405/14

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Quick Facts

Patent No.: US 12,479,820
App. No.: 17/620,520
Granted: Nov 25, 2025
Kind: B2

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Abstract

The present invention relates to pyridin-3-yl derivatives of Formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , Ar 1 , L, m and n are as described in the description, their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of Formula (I), and especially to their use as LPA1 receptor modulators.

Claims (291)

1 . A compound of Formula (I),

wherein

R 1 is hydrogen, halogen, methyl, or trifluoromethyl;

R 2 is C 1-3 -alkoxy, cyclopropyloxy or methoxy-C 2-3 -alkoxy;

Ar 1 represents phenyl, or 6-membered heteroaryl containing one or two nitrogen atoms, wherein said group Ar 1 is substituted with R 3 and R 4 , wherein

R 3 is n-propyl, isopropyl, or C 3-6 -cycloalkyl; and

R 4 represents one substituent independently selected from hydrogen, fluoro, methyl and methoxy;

m and n independently represent the integer 1 or 2; and

the group -L-R 5 represents

hydrogen;

—C 1-4 -alkyl;

—C 0-6 -alkylene-C 3-6 -cycloalkyl; wherein the C 3-6 -cycloalkyl independently is unsubstituted or mono-substituted with halogen;

—CO—H;

-L 1 —CO—R C11 wherein R C11 independently represents hydroxy; —O-benzyl; —O—C 1-6 -alkyl; C 1 -fluoroalkyl; or —NR N11 R N12 ; wherein independently R N11 is hydrogen or C 1-4 -alkyl, and R N12 is hydrogen, C 1-4 -alkyl, —SO 2 —C 1-6 -alkyl, or —O—R O11 , wherein R O11 independently represents hydrogen, C 1-6 -alkyl, or benzyl; and

-L 1 -independently represents

—C 1-6 -alkylene-, —CO—C 1-6 -alkylene-, —SO 2 —C 1-6 -alkylene-, —CO—O—C 1-6 -alkylene-, —CO—NH—C 1-6 -alkylene-, or —SO 2 —NH—C 1-6 -alkylene-;

—C 1-6 -alkylene-, —CO—C 1-6 -alkylene-, or —SO 2 —C 1-6 -alkylene-; wherein in the above groups said C 1-6 -alkylene independently is mono-substituted with hydroxy, C 1-3 -alkoxy, —O—CO—C 1-4 -alkyl, or —NR N13 R N14 ; wherein independently R N13 is hydrogen or C 1-4 -alkyl, and R N14 is hydrogen, C 1-4 -alkyl or —CO—O—C 1-4 -alkyl;

—C 2-6 -alkylene-, —CO—C 2-6 -alkylene-, or —SO 2 —C 2-6 -alkylene-; wherein in the above groups said C 2-6 -alkylene independently is di-substituted wherein the substituents are independently selected from hydroxy and —NR N15 R N16 , wherein independently R N15 is hydrogen or C 1-4 -alkyl, and R N16 is hydrogen, C 1-4 -alkyl or —CO—O—C 1-4 -alkyl;

—C 0-4 -alkylene-C 3-8 -cycloalkylene-C 0-4 -alkylene-, —CO—C 0-4 -alkylene-C 3-8 -cycloalkylene-C 0-4 -alkylene-, —SO 2 —C 0-4 -alkylene-C 3-8 -cycloalkylene-C 0-4 -alkylene-, —CO—NH—C 0-4 -alkylene-C 3-8 -cycloalkylene-C 0-4 -alkylene-, or —CO—O—C 0-4 -alkylene-C 3-8 -cycloalkylene-C 0-4 -alkylene-;

—C 0-4 -alkylene-Cy 1 -C 0-4 -alkylene-, —CO—C 0-4 -alkylene-Cy 1 -C 0-4 -alkylene-, —CO—O—C 0-4 -alkylene-Cy 1 -C 0-4 -alkylene-, —CO—NH—C 0-4 -alkylene-Cy 1 -C 0-4 -alkylene-, —SO 2 —C 0-4 -alkylene-Cy 1 -C 0-4 -alkylene-, or —SO 2 —NH—C 0-4 -alkylene-Cy 1 -C 0-4 -alkylene-; wherein Cy 1 independently represents a C 3-6 -heterocycloalkylene containing one ring oxygen atom, or one ring nitrogen atom, wherein said ring nitrogen, in case it has a free valency, independently is mono-substituted with H, C 1-4 -alkyl or —CO—O—C 1-4 -alkyl;

—C 2-4 -alkylene-O—C 2-4 -alkylene-O—C 1-4 -alkylene-, or —CO—C 1-4 -alkylene-O—C 2-4 -alkylene-O—C 1-4 -alkylene-;

—C 2-4 -alkylene-X 11 —C 1-4 -alkylene-, —CO—O—C 2-4 -alkylene-X 11 —C 1-4 -alkylene-, —CO—NH—C 2-4 -alkylene-X 11 —C 1-4 -alkylene-, or —SO 2 —NH—C 2-4 -alkylene-X 11 —C 1-4 -alkylene-; wherein X 11 independently represents oxygen, or a nitrogen atom which is independently mono-substituted with H, C 1-4 -alkyl, C 3-6 -cycloalkyl, or —CO—O—C 1-4 -alkyl;

—CO—C 1-4 -alkylene-X 12 —C 1-4 -alkylene-, —SO 2 —C 1-4 -alkylene-X 12 —C 1-4 -alkylene-, or —CO—C 1-4 -alkylene-X 12 —C 0-4 -alkylene-C 3-6 -cycloalkylene-C 0-4 -alkylene-; wherein X 12 independently represents oxygen, or a nitrogen atom which is independently mono-substituted with H, C 1-4 -alkyl, C 3-6 -cycloalkyl, —CO—O—C 1-4 -alkyl, or C 1-3 -alkoxy-C 2-4 -alkyl;

—C 2-4 -alkylene-X 13 —C 1-4 -alkylene-; wherein X 13 represents —NH—CO—, and wherein said C 2-4 -alkylene independently is unsubstituted, or mono-substituted with hydroxy;

—C 1-4 -alkylene-X 14 —C 1-4 -alkylene-; wherein X 14 represents —CO—NH—;

—CO—C 2-6 -alkenylene- or —SO 2 —C 2-6 -alkenylene-; or

—CO—C 2-6 -fluoroalkylene-;

-L 2 -hydroxy; wherein -L 2 - represents

—CO—C 1-6 -alkylene- or —SO 2 —C 1-6 -alkylene-; wherein in the above groups said C 1-6 -alkylene independently is unsubstituted, or mono-substituted with hydroxy, C 1 -fluoroalkyl, or —NR N21 R N22 wherein independently R N21 is hydrogen or C 1-4 -alkyl, and R N22 is hydrogen, C 1-4 -alkyl or —CO—O—C 1-4 -alkyl;

—C 2-6 -alkylene-, —CO—O—C 2-6 -alkylene-, —CO—NH—C 2-6 -alkylene-, or —SO 2 —NH—C 2-6 -alkylene-, wherein in the above groups said C 2-6 -alkylene independently is unsubstituted, or mono-substituted with hydroxy, C 1 -fluoroalkyl, or —NR N23 R N24 wherein independently R N23 is hydrogen or C 1-4 -alkyl, and R N24 is hydrogen, C 1-4 -alkyl or —CO—O—C 1-4 -alkyl;

—C 0-4 -alkylene-C 3-6 -cycloalkylene-C 0-4 -alkylene-, —CO—C 0-4 -alkylene-C 3-6 -cycloalkylene-C 0-4 -alkylene-, or —SO 2 —C 0-4 -alkylene-C 3-6 -cycloalkylene-C 0-4 -alkylene-;

—C 0-4 -alkylene-Cy 2 -C 0-4 -alkylene-, —CO—C 0-4 -alkylene-Cy 2 -C 0-4 -alkylene-, or —SO 2 —C 0-4 -alkylene-Cy 2 -C 0-4 -alkylene-; wherein Cy 2 independently represents a C 3-6 -heterocycloalkylene group containing one ring oxygen atom, or one ring nitrogen atom; wherein said ring nitrogen, in case it has a free valency, is independently mono-substituted with H, C 1-4 -alkyl or —CO—O—C 1-4 -alkyl;

—C 2-4 -alkylene-(O—C 2-4 -alkylene) p - or —CO—C 1-4 -alkylene-(O—C 2-4 -alkylene) p -; wherein p independently represents the integer 1 or 2;

—C 2-4 -alkylene-X 21 —C 2-4 -alkylene-; wherein X 21 represents a nitrogen atom which is mono-substituted with H, C 1-4 -alkyl, C 3-6 -cycloalkyl, or —CO—O—C 1-4 -alkyl;

—CO—C 1-4 -alkylene-X 22 —C 2-4 -alkylene-, —CO—C 1-4 -alkylene-X 22 —C 1-4 -alkylene-C 3-6 -cycloalkylene-, or —SO 2 —C 1-4 -alkylene-X 22 —C 2-4 -alkylene-; wherein X 22 represents a nitrogen atom which is independently mono-substituted with H, C 1-4 -alkyl, C 3-6 -cycloalkyl, or —CO—O—C 1-4 -alkyl;

—C 2-4 -alkylene-X 23 —C 1-4 -alkylene-; wherein X 23 represents —NH—CO—, and wherein said C 2-4 -alkylene independently is unsubstituted, or mono-substituted with hydroxy;

—C 1-4 -alkylene-X 24 —C 2-4 -alkylene-; wherein X 24 represents —CO—NH—, and wherein said C 2-4 -alkylene independently is unsubstituted, or mono-substituted with hydroxy; or

3,4-dioxocyclobut-1-ene-1,2-diyl;

-L 3 -O—R O31 wherein R O31 is-C 1-4 -alkyl, —CO—C 1-4 -alkyl or —CO—C 2-4 -alkenyl; and

-L 3 -independently represents

—C 2-6 -alkylene-, —CO—C 1-6 -alkylene- or —SO 2 —C 1-6 -alkylene-, —CO—O—C 2-6 -alkylene-, —CO—NH—C 2-6 -alkylene-, or —SO 2 —NH—C 2-6 -alkylene-;

-L 4 -NR N1 R N2 wherein independently R N1 is hydrogen or C 1-4 -alkyl; and R N2 is hydrogen; C 1-4 -alkyl; C 1-3 -fluoroalkyl; C 3-6 -cycloalkyl; C 1-3 -alkoxy-C 2-4 -alkylene; —CO—C 1-4 -alkyl; —SO 2 -C 1-4 -alkyl; or —SO 2 -C 1 -fluoroalkyl; and

-L 4 -independently represents

—C 2-6 -alkylene-, —CO—C 1-6 -alkylene-, —SO 2 —C 1-6 -alkylene-, —CO—O—C 2-6 -alkylene-, —CO—NH—C 2-6 -alkylene-, or —SO 2 —NH—C 2-6 -alkylene-; or

—C 0-4 -alkylene-Cy 4 -C 0-4 -alkylene-, —CO—C 0-4 -alkylene-Cy 4 -C 0-4 -alkylene-, or —SO 2 —C 0-4 -alkylene-Cy 4 -C 0-4 -alkylene-; wherein Cy 4 independently represents a C 3-6 -heterocycloalkylene group containing one ring oxygen atom;

-L 5 -NR N3 R N4 wherein R N3 is hydrogen, C 1-4 -alkyl, or C 1-3 -alkoxy-C 2-4 -alkylene; and R N4 is-CO—O—C 1-4 -alkyl; —CO—NR N51 R N52 wherein R N51 and R N52 are independently selected from hydrogen and C 1-4 -alkyl; or —SO 2 —NR N53 R N54 wherein independently R N53 is hydrogen or C 1-4 -alkyl, and R N54 is hydrogen, C 1-4 -alkyl, or —CO—C 1-4 -alkyl;

and -L 5 -independently represents

—C 2-6 -alkylene-, —CO—C 1-6 -alkylene- or —SO 2 —C 1-6 -alkylene-, —CO—O—C 2-6 -alkylene-, —CO—NH—C 2-6 -alkylene-, or —SO 2 —NH—C 2-6 -alkylene-;

-L 6 -N(R N61 )—O—R O61 wherein R N61 is hydrogen, —CO—C 1-4 -alkyl, or —CO—O—C 1-4 -alkyl; and R O61 independently represents hydrogen, C 1-6 -alkyl, or benzyl;

and -L 6 -independently represents

—C 2-6 -alkylene-, —CO—C 1-6 -alkylene-, —SO 2 —C 1-6 -alkylene-, —CO—O—C 2-6 -alkylene-, —CO—NH—C 2-6 -alkylene-, or —SO 2 —NH—C 2-6 -alkylene-;

-L 7 -NR N5 R N6 wherein R N5 is hydrogen or C 1-4 -alkyl; R N6 is hydrogen, C 1-4 -alkyl, —CO—C 1-4 -alkyl, C 1-3 -fluoroalkyl, or C 3-6 -cycloalkyl; and

-L 7 -independently represents

—CO—, or —SO 2 —;

-L 8 —SO 2 —R S81 wherein R S81 independently represents —C 1-6 -alkyl; C 1 -fluoroalkyl; hydroxy; —NR N81 R N82 wherein independently R N81 is hydrogen or C 1-4 -alkyl, and R N82 is hydrogen, C 1-4 -alkyl, —CO—C 1-6 -alkyl; and

-L 8 -independently represents

—C 1-6 -alkylene-, —CO—C 1-6 -alkylene-, —SO 2 —C 1-6 -alkylene-, —CO—O—C 2-6 -alkylene-, —CO—NH—C 1-6 -alkylene-, or —SO 2 —NH—C 1-6 -alkylene-;

-L 9 -HET 1 , wherein HET 1 represents 5- or 6-membered heteroaryl, wherein said HET 1 independently is unsubstituted or mono-, or di-substituted, wherein the substituents are independently selected from C 1-4 -alkyl; halogen; cyano; hydroxy; hydroxymethyl; —C 0-2 -alkylene-Cy 91 —COOR O91 wherein R O91 is hydrogen or C 1-4 -alkyl, and wherein Cy 91 represents a C 3-6 -cycloalkylene group; or -C 0-2 -alkylene-COOR O92 wherein R O92 is hydrogen or C 1-4 -alkyl; and

-L 9 -independently represents

—C 0-6 -alkylene-, —CO—C 0-6 -alkylene-, —SO 2 —C 0-6 -alkylene-, —CO—O—C 1-6 -alkylene-, —CO—NH—C 1-6 -alkylene-, or —SO 2 —NH—C 1-6 -alkylene-;

-L 10 -C 4-6 -heterocyclyl, wherein the C 4-6 -heterocyclyl independently contains one or two ring heteroatoms independently selected from nitrogen, sulfur and oxygen; wherein in the above groups said C 4-6 -heterocyclyl independently is unsubstituted, or mono-, di-, or tri-substituted wherein the substituents are independently selected from:

one or two oxo substituents each attached to a ring carbon atom in alpha position to a ring nitrogen atom; and/or

two methyl substituents attached to a ring carbon atom in alpha position to a ring nitrogen atom or a ring oxygen atom; and/or

two oxo substituents at a ring sulfur atom; and/or

C 1-4 -alkyl, C 1-3 -alkoxy-C 2-4 -alkyl, C 2-3 -fluoroalkyl, or —CO—C 1-4 -alkyl attached to a ring nitrogen atom having a free valency; and

-L 10 -independently represents

—C 0-6 -alkylene-, —CO—C 0-6 -alkylene-, —SO 2 —C 0-6 -alkylene-, —CO—O—C 1-6 -alkylene-, —CO—NH—C 1-6 -alkylene-, or —SO 2 —NH—C 1-6 -alkylene-;

-L 11 -cyano; wherein -L 11 - represents —CO—C 1-6 -alkylene-, —SO 2 —C 1-6 -alkylene, or —C 0-6 -alkylene-;

-L 12 -NO 2 ; wherein -L 12 - represents —C 2-6 -alkylene-; or

-L 13 -C 1-4 -alkyl; wherein -L 13 - represents —CO—, —CO—O—, or —SO 2 —;

or a pharmaceutically acceptable salt thereof.

2 . A compound according to claim 1 , wherein R 1 is halogen; or a pharmaceutically acceptable salt thereof.

3 . A compound according to claim 1 , wherein R 2 is C 1-3 -alkoxy;

or a pharmaceutically acceptable salt thereof.

4 . A compound according to claim 1 , wherein Ar 1 represents phenyl;

wherein said phenyl group is substituted with R 3 and R 4 , wherein

R 3 represents isopropyl; and

R 4 represents hydrogen;

or a pharmaceutically acceptable salt thereof.

5 . A compound according to claim 1 , wherein the fragment:

represents a ring independently selected from:

or a pharmaceutically acceptable salt thereof.

6 . A compound according to claim 1 , wherein m and n both are 1;

or a pharmaceutically acceptable salt thereof.

7 . A compound according to claim 1 , wherein the group -L-R 5 represents

hydrogen;

—C 1-4 -alkyl;

—C 0-6 -alkylene-C 3-6 -cycloalkyl; wherein the C 3-6 -cycloalkyl independently is unsubstituted or mono-substituted with halogen;

—CO—H;

-L 1 —CO—R C11 wherein R C11 independently represents hydroxy; or —O—C 1-6 -alkyl; and

-L 1 -independently represents

—C 1-6 -alkylene-, —CO—C 1-6 -alkylene-, or —CO—NH—C 1-6 -alkylene-;

-L 2 -hydroxy; wherein -L 2 - represents

—CO—C 1-6 -alkylene- or —SO 2 —C 1-6 -alkylene-;

—C 2-6 -alkylene-, —CO—NH—C 2-6 -alkylene-, or —SO 2 —NH—C 2-6 -alkylene-, wherein in the above groups said C 2-6 -alkylene independently is unsubstituted, or mono-substituted with hydroxy; or

3,4-dioxocyclobut-1-ene-1,2-diyl;

-L 3 -O—R O31 wherein R O31 is-C 1-4 -alkyl or —CO—C 2-4 -alkenyl; and

-L 3 -independently represents

—SO 2 —C 1-6 -alkylene-, —CO—O—C 2-6 -alkylene-, —CO—NH—C 2-6 -alkylene-, or —SO 2 —NH—C 2-6 -alkylene-;

-L 4 -NR N1 R N2 wherein independently R N1 is hydrogen or C 1-4 -alkyl; and R N2 is hydrogen; C 1-4 -alkyl; or —SO 2 —C 1-4 -alkyl; and

-L 4 -independently represents

—C 2-6 -alkylene-, —CO—C 1-6 -alkylene-, or —SO 2 —C 1-6 -alkylene-;

-L 5 -NR N3 R N4 wherein R N3 is hydrogen, or C 1-4 -alkyl; and R N4 is-SO 2 —NR N53 R N54 wherein independently R N53 is hydrogen or C 1-4 -alkyl, and R N54 is hydrogen, or C 1-4 -alkyl;

and -L 5 -independently represents

—C 2-6 -alkylene-, —CO—C 1-6 -alkylene- or —SO 2 —C 1-6 -alkylene-;

-L 7 -NR N5 R N6 wherein R N5 is hydrogen or C 1-4 -alkyl; R N6 is hydrogen, C 1-4 -alkyl, or C 3-6 -cycloalkyl; and

-L 7 -independently represents

—CO—, or —SO 2 —;

-L 8 —SO 2 —R S81 wherein R S81 independently represents —C 1-6 -alkyl; C 1 -fluoroalkyl; or hydroxy; and

-L 8 -independently represents

—C 1-6 -alkylene-, —CO—C 1-6 -alkylene-, or —SO 2 —C 1-6 -alkylene-;

-L 9 -HET 1 , wherein HET 1 represents 5- or 6-membered heteroaryl, wherein said HET 1 independently is unsubstituted or mono-, or di-substituted wherein the substituents are independently selected from C 1-4 -alkyl; halogen; cyano; hydroxy; hydroxymethyl; and -C 0-2 -alkylene-COOR O92 wherein R O92 is hydrogen or C 1-4 -alkyl; and

-L 9 -independently represents

—C 0-6 -alkylene-, —CO—C 0-6 -alkylene-, or —SO 2 —C 0-6 -alkylene;

-L 10 -C 4-6 -heterocyclyl, wherein the C 4-6 -heterocyclyl independently contains one or two ring heteroatoms independently selected from nitrogen and oxygen; wherein in the above groups said C 4-6 -heterocyclyl independently is unsubstituted, or mono-, or di-substituted wherein the substituents are independently selected from:

one or two oxo substituents each attached to a ring carbon atom in alpha position to a ring nitrogen atom; and/or

two methyl substituents attached to a ring carbon atom in alpha position to a ring nitrogen atom or a ring oxygen atom; and

-L 10 -independently represents

—C 0-6 -alkylene-, —CO—C 0-6 -alkylene-, or —SO 2 —C 0-6 -alkylene-; or

-L 13 -C 1-4 -alkyl; wherein -L 13 - represents —CO—, —CO—O—, or —SO 2 —;

or a pharmaceutically acceptable salt thereof.

8 . A compound according to claim 1 , wherein the group -L-R 5 represents hydrogen;

isopropyl, isobutyl;

cyclobutyl;

—CO—H;

-L 1 —COOH; wherein -L 1 - represents

*—CH 2 —C(CH 3 ) 2 —, *—CH 2 —CH 2 —C(CH 3 ) 2 —, *—CH 2 —CH 2 —CH 2 —C(CH 3 ) 2 —, or *—CO—CH 2 —C(CH 3 ) 2 —;

-L 2 -hydroxy; wherein -L 2 - represents

—CH 2 —CH 2 —, *—CH 2 —CH(OH)—CH 2 —;

*—CO—NH—CH 2 —CH 2 —; or

*—SO 2 —CH 2 —CH 2 —;

-L 3 -O—CH 3 , or -L 3 -O—CO—C(CH 3 )—CH 2 , wherein -L 3 - represents

*—CO—NH—CH 2 —CH 2 —;

-L 7 -NH 2 , -L 7 -NH—CH 3 , -L 7 -NH—CH 2 —CH 3 , -L 7 -NH—CH(CH 3 ) 2 , or -L 7 -NH-cyclopropyl; wherein -L 7 - represents

—CO—, or —SO 2 —;

-L 9 -HET 1 ; wherein -L 9 -HET 1 represents

-L 10 -C 4-6 -heterocyclyl; wherein -L 10 -C 4-6 -heterocyclyl represents

-L 13 -methyl; wherein -L 13 - represents —CO—, or —SO 2 —;

wherein in the above groups the asterisks indicate the bond which is connected to the rest of the molecule;

or a pharmaceutically acceptable salt thereof.

9 . A compound according to claim 1 , wherein the group -L-R 5 represents —SO 2 —NH 2 ;

or a pharmaceutically acceptable salt thereof.

10 . A compound, wherein said compound is selected from the group consisting of:

N-(6-fluoro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

3-(2-isopropylphenyl)-N-(4-methoxypyridin-3-yl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-bromo-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-ethoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-isopropoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-cyclopropoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-(2-methoxyethoxy)pyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

(S)—N-(6-chloro-4-((1-methoxypropan-2-yl)oxy)pyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-4-(2-isopropylphenyl)piperidine-4-carboxamide;

3-(2-isopropylphenyl)-N-(4-methoxy-6-methylpyridin-3-yl)azetidine-3-carboxamide;

3-(2-isopropylphenyl)-N-(4-methoxy-6-(trifluoromethyl)pyridin-3-yl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-fluoro-6-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(5-fluoro-2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(3-isopropylpyridin-2-yl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(6-fluoro-3-isopropylpyridin-2-yl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-cyclopentylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-isopropyl-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-isobutyl-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(2-hydroxyethyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

1-(2-(1H-tetrazol-5-yl)ethyl)-N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

1-(3-(1H-tetrazol-5-yl)propyl)-N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

2-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)acetic acid;

1-(2-aminoethyl)-N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-cyclobutyl-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(oxetan-3-yl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-((1-fluorocyclopropyl)methyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

(R)—N-(6-chloro-4-methoxypyridin-3-yl)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

(R)—N-(6-chloro-4-methoxypyridin-3-yl)-1-(2,3-dihydroxypropyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

1-((1H-pyrazol-3-yl)methyl)-N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

1-((1H-pyrazol-4-yl)methyl)-N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

1-((1H-1,2,3-triazol-4-yl)methyl)-N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

methyl 4-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethylbutanoate;

4-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethylbutanoic acid;

methyl 4-(3-((6-chloro-4-ethoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethylbutanoate;

4-(3-((6-chloro-4-ethoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethylbutanoic acid;

4-(3-((6-chloro-4-isopropoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethylbutanoic acid;

methyl 4-(4-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-4-(2-isopropylphenyl)piperidin-1-yl)-2,2-dimethylbutanoate;

4-(4-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-4-(2-isopropylphenyl)piperidin-1-yl)-2,2-dimethylbutanoic acid;

4-(3-((6-bromo-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethylbutanoic acid;

ethyl 5-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethylpentanoate;

5-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethylpentanoic acid;

ethyl 5-(3-((6-chloro-4-ethoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethylpentanoate;

5-(3-((6-chloro-4-ethoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethylpentanoic acid;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(2-(sulfamoylamino)ethyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(3-hydroxypropanoyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

1-acetyl-N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-formyl-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(oxetane-3-carbonyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(3-hydroxyisoxazole-5-carbonyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(5-hydroxy-1,2,4-oxadiazole-3-carbonyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

1-(2-(2H-1,2,3-triazol-2-yl)acetyl)-N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(2-(4-methyl-1H-1,2,3-triazol-1-yl)acetyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(2-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)acetyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

1-(2-(2H-tetrazol-2-yl)acetyl)-N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

1-(2-(1H-1,2,3-triazol-1-yl)acetyl)-N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(2-(3-hydroxy-1H-pyrazol-4-yl)acetyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(2-(3-hydroxy-1H-pyrazol-5-yl)acetyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(sulfamoylglycyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-((methylsulfonyl)glycyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(2-(methylsulfonyl)acetyl)azetidine-3-carboxamide;

methyl 4-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethyl-4-oxobutanoate;

4-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethyl-4-oxobutanoic acid;

4-(3-((6-bromo-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethyl-4-oxobutanoic acid;

4-(4-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-4-(2-isopropylphenyl)piperidin-1-yl)-2,2-dimethyl-4-oxobutanoic acid;

4-(3-((6-chloro-4-ethoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethyl-4-oxobutanoic acid;

4-(3-((6-fluoro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2,2-dimethyl-4-oxobutanoic acid;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(methylsulfonyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-((2-methoxyethyl)sulfonyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-((2-(dimethylamino)ethyl)sulfonyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(oxetan-3-ylsulfonyl)azetidine-3-carboxamide;

N-(6-fluoro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide;

N-(6-chloro-4-ethoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide;

N-(6-chloro-4-isopropoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide;

N-(6-chloro-4-cyclopropoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide;

N-(6-chloro-4-(2-methoxyethoxy)pyridin-3-yl)-3-(2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide;

(S)—N-(6-chloro-4-((1-methoxypropan-2-yl)oxy)pyridin-3-yl)-3-(2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-4-(2-isopropylphenyl)-1-sulfamoylpiperidine-4-carboxamide;

N-(6-bromo-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide;

3-(2-isopropylphenyl)-N-(4-methoxy-6-methylpyridin-3-yl)-1-sulfamoylazetidine-3-carboxamide;

3-(2-isopropylphenyl)-N-(4-methoxy-6-(trifluoromethyl)pyridin-3-yl)-1-sulfamoylazetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-cyclopentylphenyl)-1-sulfamoylazetidine-3-carboxamide

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(N-methylsulfamoyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(N-cyclopropylsulfamoyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-fluoro-6-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(5-fluoro-2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(3-isopropylpyridin-2-yl)-1-sulfamoylazetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(6-fluoro-3-isopropylpyridin-2-yl)-1-sulfamoylazetidine-3-carboxamide;

3-(2-isopropylphenyl)-N-(4-methoxypyridin-3-yl)-1-sulfamoylazetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(N-(2-methoxyethyl)sulfamoyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(N-(2-hydroxyethyl)sulfamoyl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N3-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-1,3-dicarboxamide;

N3-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-N1-methylazetidine-1,3-dicarboxamide;

N3-(6-chloro-4-methoxypyridin-3-yl)-N1-ethyl-3-(2-isopropylphenyl)azetidine-1,3-dicarboxamide;

N3-(6-chloro-4-methoxypyridin-3-yl)-N1-isopropyl-3-(2-isopropylphenyl)azetidine-1,3-dicarboxamide;

(S)-N3-(6-chloro-4-((1-methoxypropan-2-yl)oxy)pyridin-3-yl)-N1-cyclopropyl-3-(2-isopropylphenyl)azetidine-1,3-dicarboxamide;

N3-(6-chloro-4-methoxypyridin-3-yl)-N1-cyclopropyl-3-(3-isopropylpyridin-2-yl)azetidine-1,3-dicarboxamide;

2-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidine-1-carboxamido)ethyl methacrylate;

N3-(6-chloro-4-methoxypyridin-3-yl)-N1-(2-hydroxyethyl)-3-(2-isopropylphenyl)azetidine-1,3-dicarboxamide;

N3-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-N1-(2-methoxyethyl)azetidine-1,3-dicarboxamide;

ethyl (3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidine-1-carbonyl)glycinate;

(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidine-1-carbonyl)glycine;

ethyl 3-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidine-1-carboxamido)propanoate;

3-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidine-1-carboxamido)propanoic acid;

N3-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-N1,N1-dimethylazetidine-1,3-dicarboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(morpholine-4-carbonyl)azetidine-3-carboxamide;

methyl 3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidine-1-carboxylate;

2-methoxyethyl 3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidine-1-carboxylate;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(3-methylpyridin-4-yl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(3-fluoropyridin-4-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(3-fluoro-2-methylpyridin-4-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(5-fluoro-2-methylpyridin-4-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(2-methylpyridin-4-yl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(2,6-dimethylpyridin-4-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(4-fluoropyridin-2-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(5-cyanopyrimidin-2-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(5-fluoropyrimidin-2-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(5-fluoropyrimidin-4-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(pyrimidin-4-yl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(2-methylpyrimidin-4-yl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(5-methylpyrimidin-4-yl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(6-methylpyrimidin-4-yl)azetidine-3-carboxamide;

1-(6-chloro-2-methylpyrimidin-4-yl)-N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(5-fluoro-2-methylpyrimidin-4-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(5-fluoropyrimidin-4-yl)-4-(2-isopropylphenyl)piperidine-4-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-1-(5-fluoro-2-methylpyrimidin-4-yl)-4-(2-isopropylphenyl)piperidine-4-carboxamide;

methyl 5-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)pyrazine-2-carboxylate;

5-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)pyrazine-2-carboxylic acid;

methyl 6-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)nicotinate;

methyl 2-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)pyrimidine-5-carboxylate;

2-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)pyrimidine-5-carboxylic acid;

methyl 6-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)pyridazine-3-carboxylate;

ethyl 2-(3-((6-chloro-4-methoxypyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)oxazole-4-carboxylate;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(1H-tetrazol-5-yl)azetidine-3-carboxamide;

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-(4-oxo-4,5-dihydrooxazol-2-yl)azetidine-3-carboxamide; and

N-(6-chloro-4-methoxypyridin-3-yl)-1-(2-hydroxy-3,4-dioxocyclobut-1-en-1-yl)-3-(2-isopropylphenyl)azetidine-3-carboxamide;

or a pharmaceutically acceptable salt thereof.

11 . A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

12 . A compound, wherein said compound is:

N-(6-chloro-4-methoxypyridin-3-yl)-3-(2-isopropylphenyl)-1-sulfamoylazetidine-3-carboxamide;

or a pharmaceutically acceptable salt thereof.

13 . A pharmaceutical composition comprising the compound according to claim 12 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

14 . A pharmaceutical composition comprising a compound according to claim 10 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

15 . A method for the treatment of pulmonary fibrosis or systemic sclerosis; comprising administering to a subject in need thereof an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

16 . A method for the treatment of pulmonary fibrosis or systemic sclerosis; comprising administering to a subject in need thereof an effective amount of a compound according to claim 10 , or a pharmaceutically acceptable salt thereof.

17 . A method for the treatment of pulmonary fibrosis or systemic sclerosis; comprising administering to a subject in need thereof an effective amount of the compound according to claim 12 , or a pharmaceutically acceptable salt thereof.

Assignments (2)

PATENT SECURITY AGREEMENT Recorded Jun 25, 2026

From: IDORSIA PHARMACEUTICALS LTD

To: BIOPHARMA CREDIT PLC, AS COLLATERAL AGENT

Reel/Frame 076038/0461 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 13, 2022

From: BOLLI, MARTIN; BROTSCHI, CHRISTINE; LESCOP, CYRILLE

To: IDORSIA PHARMACEUTICALS LTD

Reel/Frame 059249/0340 →

Priority Claims (1)

WO PCT/EP2019/065963 · Jun 18, 2019 · international

Continuity (1)

Related Publication 20220251068A1 · Aug 11, 2022

References Cited (104)

US 3097209A · Jannsen · 1963 [cited by applicant]

US 6734184B1 · Barlaam et al. · 2004 [cited by applicant]

US 7855290B2 · Matsushima et al. · 2010 [cited by applicant]

US 12344597B2 · Bolli et al. · 2025 [cited by applicant]

US 20040067908A1 · Nakade et al. · 2004 [cited by applicant]

US 20070078120A1 · Ban et al. · 2007 [cited by applicant]

US 20080207573A1 · Yager et al. · 2008 [cited by applicant]

US 20080319188A1 · Matsushima et al. · 2008 [cited by applicant]

US 20120232026A1 · Curtis et al. · 2012 [cited by applicant]

US 20210246116A1 · Bolli et al. · 2021 [cited by applicant]

US 20230000846A1 · Birker et al. · 2023 [cited by applicant]

EP 1364659A1 · 2003 [cited by applicant]

EP 2481725A1 · 2012 [cited by applicant]

JP 2008110971A1 · 2008 [cited by applicant]

WO WO1996011940A1 · 1996 [cited by applicant]

WO WO2000012478A1 · 2000 [cited by applicant]

WO WO2001032173A1 · 2001 [cited by applicant]

WO WO2001077077A1 · 2001 [cited by applicant]

WO WO2002062389A1 · 2002 [cited by applicant]

WO WO2003088908A2 · 2003 [cited by applicant]

WO WO2004085385A2 · 2004 [cited by applicant]

WO WO2004110350A2 · 2004 [cited by applicant]

WO WO2005023761A2 · 2005 [cited by applicant]

WO WO2005037269A1 · 2005 [cited by applicant]

WO WO2005049605A1 · 2005 [cited by applicant]

WO WO2006073967A1 · 2006 [cited by applicant]

WO WO2006091862A2 · 2006 [cited by applicant]

WO WO2007058990A2 · 2007 [cited by applicant]

WO WO2007146712A2 · 2007 [cited by applicant]

WO WO2008115281A2 · 2008 [cited by applicant]

WO WO2009051715A1 · 2009 [cited by applicant]

WO WO2009131940A1 · 2009 [cited by applicant]

WO WO2009135590A1 · 2009 [cited by applicant]

WO WO2010023181A1 · 2010 [cited by applicant]

WO WO2011037192A1 · 2011 [cited by applicant]

WO WO2012017359A1 · 2012 [cited by applicant]

WO WO2012055995A1 · 2012 [cited by applicant]

WO WO2012078805A1 · 2012 [cited by applicant]

WO WO2012082817A1 · 2012 [cited by applicant]

WO WO2012120399A1 · 2012 [cited by applicant]

WO WO2013096771A1 · 2013 [cited by applicant]

WO WO2014079805A1 · 2014 [cited by applicant]

WO WO2017177004A1 · 2017 [cited by applicant]

WO WO2019234115A1 · 2019 [cited by applicant]

WO WO2021110805A1 · 2021 [cited by applicant]

U.S. Appl. No. 16/972,878, filed Dec. 7, 2020 (371(c) Date), Bolli et al. [cited by applicant]

Abu El-Asrar, A. et al., “Expression of Autotaxin and Acylglycerol Kinase in Proliferative Vitreoretinal Epiretinal Membranes,” Acta Ophthainiologica, 2012, 90, e84-e89. [cited by applicant]

An, S. et al., “Molecular Cloning of the Human Edg2 Protein and Its Identification as a Functional Cellular Receptor for Lysophosphatidic Acid,” Biochemical and Biophysical Research Communications, 1997, 231, 619-622. [cited by applicant]

Baker, D. et al., “Direct Quantitative Analysis of Lysophosphatidic Acid Molecular Species by Stable Isotope Dilution Electrospray Ionization Liquid Chromatography-Mass Spectrometry,” Analytical Biochemistry, 2001, 292,… [cited by applicant]

Boucharaba, A. et al., “Platelet-Derived Lysophosphatidic Acid Supports the Progression of Osteolytic Bone Metastases in Breast Cancer,” The Journal of Clinical Investigation, 2004, 114 (12), 1714-1725. [cited by applicant]

Boucharaba, A. et al., “The Type 1 Lysophosphatidic Acid Receptor is a Target for Therapy in Bone Metastases,” Proceedings of the National Academy of Sciences, 2006, 103 (25), 9643-9648. [cited by applicant]

Bremner, D. et al., “The Synthesis of Thienopyridines from ortho-Halogenated Pyridine Derivatives,” Synthesis, 1992, 6, 528-530. [cited by applicant]

Brindley, D., “Lipid Phosphate Phosphatases and Related Proteins: Signaling Functions in Development, Cell Division, and Cancer,” Journal of Cellular Biochemistry, 2004, 92, 900-912. [cited by applicant]

Castelino, F. et al., “Amelioration of Dermal Fibrosis by Genetic Deletion or Pharmacologic Antagonism of Lysophosphatidic Acid Receptor 1 in a Mouse Model of Scleroderma,” Arthritis & Rheumatism, 2011, 63 (5), 1405-141… [cited by applicant]

Choi, J. et al., “LPA Receptors: Subtypes and Biological Actions,” Annual Review of Pharmacology and Toxicology, 2010, 50, 157-186. [cited by applicant]

Choi, J. et al., “Lysophospholipids and Their Receptors in the Central Nervous System,” Biochimica et Biophysica Acta, 2013, 1831, 20-32. [cited by applicant]

Chun, J. et al., Eds., Lysophospholipid Receptors: Signaling and Biochemistry, 2013, John Wiley & Sons, Inc., ISBN: 978-0-470-56905-4. [cited by applicant]

Dollé, V. et al., “Studies Towards 4-C-Alkylation of Pyridin-2(1H)-one Derivatives,” Tetrahedron, 1997, 53 (37), 12505-12524. [cited by applicant]

D'Souza, K. et al., “Lysophosphatidic Acid Signaling in Obesity and Insulin Resistance,” Nutrients, 2018, 10, 399, 20 pages, doi:10.3390/nu10040399. [cited by applicant]

Fujiwara, Y. et al., “Identification of Residues Responsible for Ligand Recognition and Regioisomeric Selectivity of Lysophosphatidic Acid Receptors Expressed in Mammalian Cells,” The Journal of Biological Chemistry, 20… [cited by applicant]

Georas, S. et al., “Lysophosphatidic Acid is Detectable in Human Bronchoalveolar Lavage Fluids at Baseline and Increased After Segmental Allergen Challenge,” Clinical and Experimental Allergy, 2006, 37 (3), 311-322. [cited by applicant]

Gill, M. et al., “Pigments of Fungi. LIX*† Synthesis of (1S,3S)- and (1R,3R)- Austrocortilutein and (1S,3S)-Austrocortirubin from Citramalic Acid,” Australian Journal of Chemistry, 2000, 53, 245-256. [cited by applicant]

Goetzl, E. et al., “Lysophospholipid Growth Factors and Their G Protein-Coupled Receptors in Immunity, Coronary Artery Disease, and Cancer,” The Scientific World Journal, 2002, 2, 324-338. [cited by applicant]

Greene, T. et al., Eds., “Protective Groups in Organic Synthesis,” Wiley-Interscience, 1999. [cited by applicant]

Guo, C. et al., “Mitogenic Signaling in Androgen Sensitive and Insensitive Prostate Cancer Cell Lines,” The Journal of Urology, 2000, 163, 1027-1032. [cited by applicant]

Hecht, J. et al., “ [cited by applicant]

Inoue, M. et al., “Initiation of Neuropathic Pain Requires Lysophosphatidic Acid Receptor Signaling,” Nature Medicine, 2004, 10 (7), 712-718 and Erratum. [cited by applicant]

Kerins, F. et al., “Generation of Substituted Styrenes via Suzuki Cross-Coupling of Aryl Halides with 2,4,6-Trivinylcyclotriboroxane,” Journal of Organic Chemistry, 2002, 67, 4968-4971. [cited by applicant]

Kocienski, P., Protecting Groups, George Thieme Verlag Stuttgart, New York, 1994. [cited by applicant]

Komachi, M. et al., “Orally Active Lysophosphatidic Acid Receptor Antagonist Attenuates Pancreatic Cancer Invasion and Metastasis In Vivo,” Cancer Science, 2012, 103 (6), 1099-1104. [cited by applicant]

Kropp, B. et al., “Characterization of Cultured Bladder Smooth Muscle Cells: Assessment of In Vitro Contractility,” The Journal of Urology, 1999, 162, 1779-1784. [cited by applicant]

Kuner, R., “Central Mechanisms of Pathological Pain,” Nature Medicine, 2010, 16 (11), 1258-1266. [cited by applicant]

Li, H. et al., “Blocking Lysophosphatidic Acid Receptor 1 Signaling Inhibits Diabetic Nephropathy in db/db Mice,” Kidney International, 2017, 91, 1362-1373. [cited by applicant]

Lin, S et al., “Lysophosphatidic Acid Receptor 1 is Important for Intestinal Epithelial Barrier Function and Susceptibility to Colitis,” The American Journal of Pathology, Accepted Manuscript, 2017, doi: 10.1016/j.ajpat… [cited by applicant]

Liu, Y. et al. “Highly Controlling Selectivity of Copper(I)-catalyzed Azide/Alkyne Cycloaddition (CuAAC) between Sulfonyl Azids and Normal Alkynes or Propynoates,” Tetrahedron, 2011, 67, 6294-6299. [cited by applicant]

Matsushita, H. et al., “Palladium-Catalyzed Reactions of Allylic Electrophiles with Organometallic Reagents. A Regioselective 1,4-Elimination and a Regio- and Stereoselective Reduction of Allylic Derivatives,” Journal o… [cited by applicant]

Möbus, K. et al., “Hydrogenation of Aromatic Nitrogroups with Precious Metal Powder Catalysts: Influence of Modifier on Selectivity and Activity,” Topics in Catalysis, 2010, 53, 1126-1131. [cited by applicant]

Montalbetti, C. et al., “Amide Bond Formation and Peptide Coupling,” Tetrahedron, 2005, 61, 10827-10852. [cited by applicant]

Moolenaar, W. et al., “The Ins and Outs of Lysophosphatidic Acid Signaling,” BioEssays, 2004, 26, 870-881. [cited by applicant]

Nagai, J. et al., “Autotaxin and Lysophosphatidic Acid [cited by applicant]

Onorato, J. et al., “Challenges in Accurate Quantitation of Lysophosphatidic Acids in Human Biofluids,” Journal of Lipid Research, 2014, 55, 1784-1796. [cited by applicant]

Pradère, J-P. et al., “LPA [cited by applicant]

Rancoule, C. et al., “Lysophosphatidic Acid-1-receptor Targeting Agents for Fibrosis,” Expert Opinion on Investigational Drugs, 2011, 20 (5), 657-667. [cited by applicant]

Remington, The Science and Practice of Pharmacy, 21st Edition, 2005, Part 5, “Pharmaceutical Manufacturing,” published by Lippincott Williams & Wilkins. [cited by applicant]

Rockey, D. et al., “Fibrosis—A Common Pathway to Organ Injury and Failure,” New England Journal of Medicine, 2015, 372 (12), 1138-1149. [cited by applicant]

Sakamoto, K. et al., “Effect of ASP6432, a Novel Type 1 Lysophosphatidic Acid Receptor Antagonist, on Urethral Function and Prostate Cell Proliferation” The Journal of Pharmacology and Experimental Therapeutics, 2018, 3… [cited by applicant]

Simon, M. et al., “Lysophosphatidic Acid Inhibits Adipocyte Differentiation via Lysophosphatidic Acid 1 Receptor-dependent Down-regulation of Peroxisome Proliferator-activated Receptor γ2*,” The Journal of Biological Ch… [cited by applicant]

Sperry, J. et al., “A Safe and Practical Procedure for the Difluoromethylation of Methyl 4-Hydroxy-3-iodobenzoate,” Organic Process Research & Development, 2011, 15, 721-725. [cited by applicant]

Stahl, P. et al., Eds., Handbook of Pharmaceutical Salts. Properties, Selection and Use, Wiley-VCH, 2008. [cited by applicant]

Stepan, A. et al., “Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Ring Bioisostere in the Design of a Potent and Orally Active γ-Secretase Inhibitor,” Journal of Medicinal Chemistry, 2012, 55 (… [cited by applicant]

Stoddard, N. et al., “Promising Pharmacological Directions in the World of Lysophosphatidic Acid Signaling,” Biomolecules & Therapeutics, 2015, 23 (1), 1-11. [cited by applicant]

Tager, A. et al., “The Lysophosphatidic Acid Receptor LPA [cited by applicant]

Thomoson, C. et al., “Use of Fluoroform as a Source of Difluorocarbene in the Synthesis of N-CF2H Heterocycles and Difluoromethoxypyridines,” Journal of Fluorine Chemistry, 2014, 168, 34-39. [cited by applicant]

Valeur, E. et al., “Amide Bond Formation: Beyond the Myth of Coupling Reagents,” Chemical Society Reviews, 2009, 38, 606-631. [cited by applicant]

Van Leeuwen, F. et al., “Lysophosphatidic Acid: Mitogen and Motility Factor,” Biochemical Society Transactions, 2003, 31 (6), 1209-1212. [cited by applicant]

Watanabe, N. et al., “Both Plasma Lysophosphatidic Acid and Serum Autotaxin Levels are Increased in Chronic Hepatitis C,” Journal of Clinical Gastroenterology, 2007, 41 (6), 616-623. [cited by applicant]

Watanabe, N. et al., “Plasma Lysophosphatidic Acid Level and Serum Autotaxin Activity are Increased in Liver Injury in Rats in Relation to Its Severity,” Life Sciences, 2007, 81, 1009-1015. [cited by applicant]

Wouters, J. et al., Eds., Pharmaceutical Salts and Co-crystals, RSC Publishing, 2012. [cited by applicant]

Yamada, T. et al., “Lysophosphatidic Acid Stimulates the Proliferation and Motility of Malignant Pleural Mesothelioma Cells Through Lysophosphatidic Acid Receptors, LPA [cited by applicant]

Yang, C. et al., “The Role of Lysophosphatidic Acid Receptor (LPA [cited by applicant]

Zeng, Y. et al., “Gene expression Profiles of Lysophosphatidic Acid-Related Molecules in the Prostate: Relevance to Prostate Cancer and Benign Hyperplasia,” The Prostate, 2009, 69, 283-292. [cited by applicant]

Zhao, Y. et al., “Lysophosphatidic Acid (LPA) and Its Receptors: Role in Airway Inflammation and Remodeling,” Biochimica et Biophysica Acta, 2013, 1831, 86-92. [cited by applicant]

Pending Claims for U.S. Appl. No. 16/972,878, filed Nov. 14, 2024, 22 pages. [cited by applicant]

U.S. Appl. No. 17/782,530, filed Jun. 3, 2022 (371(c) Date), Birker et al. [cited by applicant]