US 11,028,054 B2Granted

1, 4, 6-trisubstituted-2-alkyl-1H-benzo[d]imidazole derivatives as dihydroorotate oxygenase inhibitors

AssigneeMerck Patent GmbH

InventorsSiva Sanjeeva Rao Thunuguntla, Subramanya Hosahalli, Sunil Kumar Panigrahi, Matthias Schwarz, Michael Arit

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Abstract

The present invention provides 1, 4, 6-trisubstituted-2-alkyl-1H-benzo[d]imidazole derivatives as dihydroorotate oxygenase inhibitor compounds of formula (I), which may be therapeutically useful as DHODH inhibitors, in which R1 to R3 and ‘m’ have the meanings given in the specification, and pharmaceutically acceptable salts or stereoisomer thereof that are useful in the treatment and prevention in diseases or disorder, in particular their use in diseases or disorder where there is an advantage in inhibiting DHODH. The present invention also provides methods for synthesizing 1, 4, 6-trisubstituted-2-alkyl-1H-benzo[d]imidazole derivatives of formula (I). The present invention also provides pharmaceutical formulations comprising at least one of the DHODH inhibitor compound of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient.

Claims16

Dependent claims

A compound of formula (I):

or a pharmaceutically acceptable salt, solvate, tautomer, hydrate, stereoisomer and mixture of isomers, or N-oxide thereof;
wherein;
R1 is hydrogen or linear or branched C1-C6 alkyl;
R2 is an optionally substituted Cb, an optionally substituted Het or —O—(CH2)pCb′;
wherein the optional substituent, at each occurrence, is independently selected from one or more occurrences of R4;
R3 is hydrogen, halogen, linear or branched C1-C6 alkyl or —OR5;
R4 is independently selected from hydrogen, halogen, linear or branched C1-C6 alkyl, —(CH2)pO(CH2)qR7, —(CH2)pS(═O)xR5, —C(R5)═NOR5, —(CH2)pHet′ and —(CH2)pNR5(CH2)qR6;
R5 is independently selected from hydrogen and linear or branched C1-C6 alkyl;
R6 is independently selected from hydrogen, linear or branched C1-C6 alkyl, —(CO)Het, Cb′, Het′, —CF3, —C≡CR5, —N(R5)2, —S(═O)xR5 and OR5;
R7 is independently selected from hydrogen, linear or branched C1-C6 alkyl, Cb′, Het′, —CF3, —C≡CR5, —N(R5)2 or —S(═O)xR5;
Cb and Cb′ independently represents a monocyclic, a fused or non-fused bicyclic, saturated, unsaturated or aromatic carbocyclic ring system having 3 to 14 carbon atoms;
wherein the Cb and Cb′ are optionally substituted with ‘n’ occurrences of R7;
Het and Het′ independently represents a 3- to 14-membered, monocyclic, a fused or non-fused bicyclic, saturated, unsaturated or aromatic heterocyclic ring system having at least 1 to 4 heteroatom or heterogroup selected from N, O, S, CO, NH, SO and SO2;
wherein the Het and Het′ are optionally substituted with ‘n’ occurrences of R8;
R8, at each occurrence, is independently selected from halogen, hydroxy, oxo and linear or branched C1-C6 alkyl;
‘m’ is 0 to 4;
‘n’, ‘p’ and ‘q’ independently represents 0 to 3;
and ‘x’ is 0 to 2.

15 more elements

A compound, or a pharmaceutically acceptable salt or a stereoisomer thereof, selected from one or more of the following:

Example
No
IUPAC names
1.
6-([1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid;
2.
6-(3',5'-difluoro-[1,1'-biphenyl]-4-yl)-2-
methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
3.
6-(3',4'-difluoro-[1,1'-biphenyl]-4-yl)-2-
methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
4.
6-(2',3'-difluoro-[1,1'-biphenyl]-4-yl)-2-
methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
5.
6-(2'-fluoro-[1,1'-biphenyl]-4-yl)-2-methyl-
1H-benzo[d]imidazole-4-carboxylic
acid;
6.
6-(4'-fluoro-[1,1'-biphenyl]-4-yl)-2-methyl-
1H-benzo[d]imidazole-4-carboxylic
acid;
7.
2-methyl-6-(4-(pyridin-3-yl)phenyl)-1H-
benzo[d]imidazole-4-carboxylic acid;
8.
6-(3'-fluoro-[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic
acid.;
9.
2-methyl-6-(4-(pyridin-4-yl)phenyl)-1H-
benzo[d]imidazole-4-carboxylic acid;
10.
6-(3'-methoxy-[1,1'-biphenyl]-4-yl)-2-methyl-
1H-benzo[d]imidazole-4-carboxylic
acid;
11.
2-methyl-6-(3'-(trifluoromethoxy)-[1,1'-
biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid;
12.
6-(2',5'-difluoro-[1,1'-biphenyl]-4-yl)-2-
methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
13.
2-methyl-6-(4'-(trifluoromethoxy)-[1,1'-
biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid;
14.
6-(4'-methoxy-[1,1'-biphenyl]-4-yl)-2-methyl-
1H-benzo[d]imidazole-4-carboxylic
acid;
15.
6-(3'-(benzyloxy)-[1,1'-biphenyl]-4-yl)-2-
methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
16.
6-(3'-hydroxy-[1,1'-biphenyl]-4-yl)-2-methyl-
1H-benzo[d]imidazole-4-carboxylic
acid;
17.
6-(2'-(benzyloxy)-[1,1'-biphenyl]-4-yl)-2-
methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
18.
6-(2'-methoxy-[1,1'-biphenyl]-4-yl)-2-methyl-
1H-benzo[d]imidazole-4-carboxylic
acid;
19.
6-(4'-(benzyloxy)-[1,1'-biphenyl]-4-yl)-2-
methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
20.
6-(4'-hydroxy-[1,1'-biphenyl]-4-yl)-2-methyl-
1H-benzo[d]imidazole-4-carboxylic
acid;
21.
6-(2'-fluoro-3'-methoxy-[1,1'-biphenyl]-4-yl)-
2-methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
22.
6-(3'-(benzyloxy)-5'-fluoro-[1,1'-biphenyl]-
4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid;
23.
6-(2'-hydroxy-[1,1'-biphenyl]-4-yl)-2-methyl-
1H-benzo[d]imidazole-4-carboxylic
acid;
24.
2-methyl-6-(3'-methyl-[1,1'-biphenyl]-4-yl)-
1H-benzo[d]imidazole-4-carboxylic
acid;
25.
2-methyl-6-(2'-methyl-[1,1'-biphenyl]-4-yl)-
1H-benzo[d]imidazole-4-carboxylic
acid;
26.
2-methyl-6-(4'-(piperidin-1-ylmethyl)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
27.
6-(4'-((isopropylamino)methyl)-[1,1'-
biphenyl]-4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
28.
2-methyl-6-(4'-(pyrrolidin-1-ylmethyl)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
29.
2-methyl-6-(4'-(thiomorpholinomethyl)-[1,1'-
biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
30.
6-(4'-((3,3-difluoropiperidin-1-yl)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
31.
2-methyl-6-(3'-(piperidin-1-ylmethyl)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
32.
2-methyl-6-(3'-(pyrrolidin-1-ylmethyl)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
33.
2-methyl-6-(3'-(thiomorpholinomethyl)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid;
34.
6-(3'-((isopropylamino)methyl)-[1,1'-
biphenyl]-4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
35.
2-methyl-6-(3'-(morpholinomethyl)-[1,1'-
biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
36.
6-(3'-((1,1-dioxidothiomorpholino)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
37.
6-(3'-((3,3-difluoropiperidin-1-yl)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
38.
6-(3'-((dipropylamino)methyl)-[1,1'-biphenyl]-
4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
39.
6-(3'-((tert-butylamino)methyl)-[1,1'-biphenyl]-
4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
40.
6-(3'-((cycloheptylamino)methyl)-[1,1'-
biphenyl]-4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
41.
6-(3'-((3-hydroxyazetidin-1-yl)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
42.
2-methyl-6-(2'-(piperidin-1-ylmethyl)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
43.
6-(2'-((isopropylamino)methyl)-[1,1'-
biphenyl]-4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
44.
2-methyl-6-(2'-(thiomorpholinomethyl)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
45.
2-methyl-6-(2'-(morpholinomethyl)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
46.
2-methyl-6-(2'-(pyrrolidin-1-ylmethyl)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
47.
6-(2'-((1,1-dioxidothiomorpholino)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
48.
6-(2'-((cyclopropylamino)methyl)-[1,1'-
biphenyl]-4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
49.
6-(2'-((dimethylamino)methyl)-[1,1'-biphenyl]-
4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
50.
6-(2'-((3,3-difluoropiperidin-1-yl)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
51.
6-(2'-((cycloheptylamino)methyl)-[1,1'-biphenyl]-
4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
52.
2-methyl-6-(2,3,5,6-tetrafluoro-[1,1'-biphenyl]-
4-yl)-1H-benzo[d]imidazole-4-
carboxylic acid;
53.
2-methyl-6-(2,3,5,6-tetrafluoro-2'-(piperidin-
1-ylmethyl)-[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
54.
2-methyl-6-(2,3,5,6-tetrafluoro-2'-
(thiomorpholinomethyl)-[1,1'-biphenyl]-4-yl)-
1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
55.
2-methyl-6-(2,3,5,6-tetrafluoro-2'-
((isopropylamino)methyl)-[1,1'-biphenyl]-4-yl)-
1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
56.
2-methyl-6-(2,3,5,6-tetrafluoro-3'-(piperidin-
1-ylmethyl)-[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
57.
2-methyl-6-(2,3,5,6-tetrafluoro-3'-
(hydroxymethyl)-[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
58.
2-methyl-6-(2,3,5,6-tetrafluoro-3'-
(pyrrolidin-1-ylmethyl)-[1,1'-biphenyl]-4-yl)-
1H-benzo[d]imidazole-4-carboxylic acid;
59.
2-methyl-6-(2,3,5,6-tetrafluoro-3'-
((isopropylamino)methyl)-[1,1'-biphenyl]-4-yl)-
1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
60.
6-(3'-((cyclopropylamino)methyl)-2,3,5,6-
tetrafluoro-[1,1'-biphenyl]-4-yl)-2-
methyl-1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
61.
2-methyl-6-(2,3,5,6-tetrafluoro-4'-(piperidin-1-
ylmethyl)-[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
62.
2-methyl-6-(2,3,5,6-tetrafluoro-4'-(pyrrolidin-
1-ylmethyl)-[1,1'-biphenyl]-4-yl)-
1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
63.
2-methyl-6-(2,3,5,6-tetrafluoro-4'-
(thiomorpholinomethyl)-[1,1'-biphenyl]-4-yl)-
1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
64.
6-(4'-((3,3-difluoropiperidin-1-yl)methyl)-
2,3,5,6-tetrafluoro-[1,1'-biphenyl]-4-yl)-
2-methyl-1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
65.
6-(4'-((1,1-dioxidothiomorpholino)methyl)-
2,3,5,6-tetrafluoro-[1,1'-biphenyl]-4-
yl)-2-methyl-1H-benzo[d]imidazole-4-
carboxylic acid.2,2,2-trifluoroacetic acid;
66.
2-methyl-6-(2,3,5,6-tetrafluoro-4'-
((isopropylamino)methyl)-[1,1'-biphenyl]-4-yl)-
1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
67.
6-(4-(2,5-dimethyl-1H-pyrrol-1-yl)-
2,3,5,6-tetrafluorophenyl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid;
68.
6-([1,1'-biphenyl]-4-yl)-1,2-dimethyl-1H-
benzo[d]imidazole-4-carboxylic acid;
69.
6-(4-(benzyloxy)phenyl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid;
70.
2-methyl-6-(4'-(piperidin-4-ylmethoxy)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
71.
2-methyl-6-(4'-(2-(piperidin-4-yl)ethoxy)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
72.
2-methyl-6-(3'-(piperidin-4-ylmethoxy)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
73.
2-methyl-6-(3'-(piperidin-4-yloxy)-[1,1'-
biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
74.
2-methyl-6-(4'-(2-morpholinoethoxy)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
75.
2-methyl-6-(3'-(2-(piperidin-4-yl)ethoxy)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
76.
2-methyl-6-(3'-(2-(tetrahydro-2H-pyran-4-
yl)ethoxy)-[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
77.
(S)-2-methyl-6-(3'-(pyrrolidine-2-
carboxamido)-[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
78.
2-methyl-6-(3'-(piperidine-4-carboxamido)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
79.
2-methyl-6-(2'-(methylsulfonyl)-[1,1'-
biphenyl]-4-yl)-1H-benzo[d]imidazole-4-
carboxylic acid.2,2,2-trifluoroacetic acid;
80.
2-methyl-6-(3'-(methylsulfonyl)-[1,1'-
biphenyl]-4-yl)-1H-benzo[d]imidazole-4-
carboxylic acid;
81.
2-methyl-6-(4'-(methylsulfonyl)-[1,1'-
biphenyl]-4-yl)-1H-benzo[d]imidazole-4-
carboxylic acid.2,2,2-trifluoroacetic acid;
82.
6-(2'-((benzylamino)methyl)-[1,1'-
biphenyl]-4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
83.
6-(4'-(methoxymethyl)-[1,1'-biphenyl]-4-
yl)-2-methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
84.
2-methyl-6-(2,3,5,6-tetrafluoro-3'-
(morpholinomethyl)-[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
85.
2-methyl-6-(4'-((methylsulfonyl)methyl)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid;
86.
2-methyl-6-(4'-((methylthio)methyl)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid;
87.
6-(3'-((benzylamino)methyl)-[1,1'-biphenyl]-
4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid;
88.
6-(2'-(hydroxymethyl)-[1,1'-biphenyl]-4-yl)-
2-methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
89.
2-methyl-6-(4'-methyl-[1,1'-biphenyl]-4-yl)-
1H-benzo[d]imidazole-4-carboxylic
acid;
90.
6-(3'-(hydroxymethyl)-[1,1'-biphenyl]-4-yl)-
2-methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
91.
6-(4'-((benzylamino)methyl)-2,3,5,6-tetrafluoro-
[1,1'-biphenyl]-4-yl)-2-methyl-
1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
92.
2-methyl-6-(2,3,5,6-tetrafluoro-4'-(methylthio)-
[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid;
93.
2-methyl-6-(2,3,5,6-tetrafluoro-4'-(methylsulfonyl)-
[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid;
94.
6-(2'-((4-hydroxypiperidin-1-yl)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
95.
(R)-6-(3'-((3-hydroxypyrrolidin-1-yl)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
96.
2-methyl-6-(4'-(piperidin-1-yl)-[1,1'-biphenyl]-
4-yl)-1H-benzo[d]imidazole-4-
carboxylic acid.2,2,2-trifluoroacetic acid;
97.
2-methyl-6-(3'-((4-methylpiperidin-1-yl)methyl)-
[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
98.
6-(3'-((cyclopentylamino)methyl)-[1,1'-
biphenyl]-4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
99.
6-(3'-(((cyclopropylmethyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
100.
6-(3'-((4-hydroxypiperidin-1-yl)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
101.
6-(4'-(hydroxymethyl)-[1,1'-biphenyl]-
4-yl)-2-methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
102.
6-(2'-((3-hydroxyazetidin-1-yl)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid;
103.
6-(2'-((dipropylamino)methyl)-[1,1'-biphenyl]-
4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid;
104.
6-(2'-(((2-methoxyethyl)amino)methyl)-[1,1'-
biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid;
105.
2-methyl-6-(2'-((2-oxoazepan-1-yl)methyl)-
[1,1'-biphenyl]-4-yl)-1H-benzo[d]
imidazole-4-carboxylic acid;
106.
6-(2'-((tert-butylamino)methyl)-[1,1'-biphenyl]-
4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
107.
(R)-6-(2'-((3-hydroxypyrrolidin-1-yl)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
108.
2-methyl-6-(2'-((4-methylpiperidin-1-
yl)methyl)-[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
109.
2-methyl-6-(2'-((2-oxopyrrolidin-1-yl)methyl)-
[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
110.
6-(2'-(((cyclopropylmethyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
111.
6-(4-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl)-
2-methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
112.
6-(3'-(((2-methoxyethyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
113.
2-methyl-6-(3'-((prop-2-yn-1-ylamino)methyl)-
[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
114.
2-methyl-6-(3'-(((2-(methylsulfonyl)ethyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-
1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
115.
(R)-6-(3'-((3-fluoropyrrolidin-1-yl)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
116.
2-methyl-6-(2'-(((l-methylpiperidin-4-yl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
117.
(R)-6-(2'-((3-fluoropyrrolidin-1-yl)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
118.
6-(2'-((cyclohexylamino)methyl)-[1,1'-
biphenyl]-4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
119.
6-(2'-((cyclohexyl(methyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid;
120.
(R)-2-methyl-6-(2,3,5,6-tetrafluoro-4'-((2-
hydroxypyrrolidin-1-yl)methyl)-[1,1'-
biphenyl]-4-yl)-1H-benzo[d]imidazole-4-carboxylic acid;
121.
2-methyl-6-(2,3,5,6-tetrafluoro-4'-
((4-methylpiperidin-1-yl)methyl)-[1,1'-
biphenyl]-4-yl)-1H-benzo[d]imidazole-4-
carboxylic acid.2,2,2-trifluoroacetic acid;
122.
6-(4'-(((cyclopropylmethyl)amino)methyl)-
2,3,5,6-tetrafluoro-[1,1'-biphenyl]-4-
yl)-2-methyl-1H-benzo[d]imidazole-4-
carboxylic acid.2,2,2-trifluoroacetic acid;
123.
(R)-2-methyl-6-(2,3,5,6-tetrafluoro-4'-((2-
fluoropyrrolidin-1-yl)methyl)-[1,1'-
biphenyl]-4-yl)-1H-benzo[d]imidazole-4-
carboxylic acid.2,2,2-trifluoroacetic acid;
124.
6-(3'-(((cyclohexylmethyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
125.
6-(3'-(((3-(dimethylamino)propyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-
1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
126.
6-(3'-((diisobutylamino)methyl)-[1,1'-
biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
127.
2-methyl-6-(2,3,5,6-tetrafluoro-4'-((prop-2-
yn-1-ylamino)methyl)-[1,1'-biphenyl]-
4-yl)-1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
128.
6-(4'-((cyclohexylamino)methyl)-2,3,5,6-
tetrafluoro-[1,1'-biphenyl]-4-yl)-2-
methyl-1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
129.
6-(2'-(((cyclohexylmethyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
130.
6-(2'-(((4-hydroxycyclohexyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
131.
2-methyl-6-(2'-((prop-2-yn-1-ylamino)methyl)-
[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
132.
(E)-6-(3'-((methoxyimino)methyl)-[1,1'-
biphenyl]-4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid;
133.
6-(2'-(((3-(dimethylamino)propyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-
1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
134.
6-(2-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl)-
2-methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
135.
2-methyl-6-(3'-(((2,2,2-trifluoroethyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
136.
2-methyl-6-(3'-(((3,3,3-trifluoropropyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
137.
6-(3'-((1,1-dioxidothiomorpholino)methyl)-
2,3,5,6-tetrafluoro-[1,1'-biphenyl]-4-
yl)-2-methyl-1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
138.
6-(4-(3,5-dimethyl-1H-pyrazol-1-yl)phenyl)-
2-methyl-1H-benzo[d]imidazole-4-
carboxylic acid.2,2,2-trifluoroacetic acid;
139.
2-methyl-6-(4-(3-methyl-1H-pyrazol-1-
yl)phenyl)-1H-benzo[d]imidazole-4-
carboxylic acid.2,2,2-trifluoroacetic acid;
140.
6-(2'-((diisobutylamino)methyl)-[1,1'-biphenyl]-
4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid;
141.
2-methyl-6-(2'-(((2-(piperidin-1-yl)ethyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid;
142.
2-methyl-6-(2'-(((3,3,3-trifluoropropyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid;
143.
(E)-6-(3'-((ethoxyimino)methyl)-[1,1'-biphenyl]-
4-yl)-2-methyl-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
144.
6-(4-(4,5-dimethyloxazol-2-yl)phenyl)-
2-methyl-1H-benzo[d]imidazole-4-
carboxylic acid.2,2,2-trifluoroacetic acid;
145.
6-(2',6'-dimethyl-[1,1'-biphenyl]-4-yl)-2-
methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
146.
6-(4'-(((3-(dimethylamino)propyl)amino)methyl)-
2,3,5,6-tetrafluoro-[1,1'-
biphenyl]-4-yl)-2-methyl-1H-benzo[d]imidazole-
4-carboxylic acid.2,2,2-
trifluoroacetic acid;
147.
2-methyl-6-(2,3,5,6-tetrafluoro-4-
(morpholinomethyl)phenyl)-1H-benzo[d]
imidazole-4-carboxylic acid.2,2,2-trifluoroacetic acid;
148.
(R)-2-methyl-6-(2,3,5,6-tetrafluoro-3'-((3-
fluoropyrrolidin-1-yl)methyl)-[1,1'-
biphenyl]-4-yl)-1H-benzo[d]imidazole-4-
carboxylic acid.2,2,2-trifluoroacetic acid;
149.
(R)-2-methyl-6-(2,3,5,6-tetrafluoro-3'-((3-
hydroxypyrrolidin-1-yl)methyl)-[1,1'-
biphenyl]-4-yl)-1H-benzo[d]imidazole-4-
carboxylic acid.2,2,2-trifluoroacetic acid;
150.
6-(2'-fluoro-6'-(pyrrolidin-1-ylmethyl)-
[1,1'-biphenyl]-4-yl)-2-methyl-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
151.
6-(3-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl)-
2-methyl-1H-benzo[d]imidazole-4-
carboxylic acid;
152.
2-methyl-6-(2'-(((3-morpholinopropyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-1H-
benzo[d]imidazole-4-carboxylic acid.2,2,2-
trifluoroacetic acid;
153.
6-(2'-(((2-(dimethylamino)ethyl)(methyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-2-
methyl-1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
154.
6-(2'-((3,3-difluoropiperidin-1-yl)methyl)-
2,3,5,6-tetrafluoro-[1,1'-biphenyl]-4-yl)-
2-methyl-1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
155.
6-(3'-((cyclohexylamino)methyl)-2,3,5,6-
tetrafluoro-[1,1'-biphenyl]-4-yl)-2-
methyl-1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid;
and
156.
2-methyl-6-(2'-(((2-(methylsulfonyl)ethyl)amino)methyl)-
[1,1'-biphenyl]-4-yl)-
1H-benzo[d]imidazole-4-carboxylic
acid.2,2,2-trifluoroacetic acid.

683 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/488,151Filed 23 Feb 2018
Priority: IN 20174100658624 Feb 2017
Published: US 2020/0140395 A17 May 2020
Granted: 8 Jun 2021
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 235/24
Benzimidazoles; Hydrogenated benzimidazoles: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond…
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 19/02
Drugs for skeletal disorders: for joint disorders, e.g. arthritis, arthrosis
C07D 235/08
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2: radicals containing only hydrogen and…

Family

US 2020/0140395 A1Pre-grant publication · published 7 May 2020
US 11,028,054 B2This patent

From the US filing history. Foreign family members aren’t listed.

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