Pyrazine compounds, their use and methods of preparation
The invention provides compounds according to formula (I) their use and methods for preparation wherein A, X, Y, R1, R2 and R3 are defined herein. The compounds of the invention inhibit specific serine/threonine kinases involved in inflammatory processes and aberrant cell proliferation, and are thus useful for treating associated diseases and pathological conditions such as Pim kinase-mediated diseases and pathological conditions involving inflammation, including Chron's disease, inflammatory bowel disease, rheumatoid arthritis, and chronic inflammatory disease, or aberrant cell proliferation including various cancers.
1. A compound of formula (I)
wherein:
X is C
Y is N
R1 is Hydrogen, C1-C3 alkyl,
R2 is Hydrogen, C1-C5 alkyl, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl, each optionally independently substituted with 1-3 R4, wherein R4 is selected from C1-C5 alkyl, C1-C5 alkoxy, carboxamido, acyl, benzyl, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl, hydroxyl and amino optionally mono or disubstituted with C1-C4 alkyl;
wherein each R4 is optionally independently substituted with 1-3 substituents selected from C1-C5 alkyl C1-C5 alkoxy, acyl, benzyl, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl, hydroxyl and amino optionally mono or disubstituted with C1-C4 alkyl
or;
wherein R1 and R2 together with the nitrogen atom to which they are attached form a C3-C8 ring containing 1-3 heteroatoms and which is optionally substituted by 1-3 R5, wherein R5 is selected from C1-C5 alkyl, C1-C5 alkoxy, carboxamido, acyl, benzyl, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl, hydroxyl, and amino optionally mono or disubstituted with C1-C4 alkyl; wherein each R5 is optionally independently substituted by with substituents selected from hydroxyl, C1-C5 alkoxy, or amino optionally mono or disubstituted with C1-C4 alkyl;
R3 is
or a pharmaceutically acceptable salts thereof.
2. A compound according to formula (I) of claim 1 wherein:
X is C
Y is N
R1 is Hydrogen, C1-C3 alkyl
R2 is C1-C5 alkyl, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl, each optionally independently substituted with 1-3 R4, wherein R4 is selected from C1-C5 alkyl, C1-C5 alkoxy, carboxamido, benzyl, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl, hydroxyl and amino optionally mono or disubstituted with C1-C4 alkyl;
wherein each R4 is optionally independently substituted with 1-3 substituents selected from C1-C5 alkyl, C1-C5 alkoxy, acyl, benzyl, hydroxyl and amino optionally mono or disubstituted with C1-C4 alkyl
or;
wherein R1 and R2 together with the nitrogen atom to which they are attached form a
C3-C8 ring containing 1-3 heteroatoms and which is optionally substituted by 1-3 R5, wherein R5 is selected from C1-C5 alkyl, C1-C5 alkoxy, carboxamido, acyl, benzyl, hydroxyl and amino optionally mono or disubstituted with C1-C4 alkyl; wherein each R5 is optionally independently substituted with substituents selected from hydroxyl, C1-C5 alkoxy, or amino optionally mono or disubstituted with C1-C4 alkyl
R3 is
or a pharmaceutically acceptable salt thereof.
3. A compound according to formula (I) of claim 1 wherein:
X is C
Y is N
R1 is Hydrogen, C1-C3 alkyl
R2 is C1-C5 alkyl, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl, each optionally independently substituted with 1-3 R4, wherein R4 is selected from C1-C5 alkyl, C1-C5 alkoxy, carboxamido, benzyl, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl, hydroxyl and amino optionally mono or disubstituted with C1-C4 alkyl;
wherein each R4 is optionally independently substituted with 1-3 substituents selected from C1-C5 alkyl, C1-C5 alkoxy, benzyl, hydroxyl and amino optionally mono or disubstituted with C1-C4 alkyl
or;
wherein R1 and R2 together with the nitrogen atom to which they are attached form a
C3-C8 ring containing 1-3 heteroatoms and which is optionally substituted by 1-3 R5, wherein R5 is selected from C1-C5 alkyl, C1-C5 alkoxy, carboxamido, benzyl, hydroxyl and amino optionally mono or disubstituted with C1-C4 alkyl; wherein each R5 is optionally independently substituted with substituents selected from hydroxyl, C1-C5 alkoxy, or amino optionally mono or disubstituted with C1-C4 alkyl
R3 is
or a pharmaceutically acceptable salts thereof.
4. A compound according to formula (I) of claim 1 wherein:
X is C
Y is N
R1 is Hydrogen, C1-C3 alkyl
R2 is C1-C5 alkyl, C3-C8 cycloalkyl, each optionally independently substituted with 1-3 R4, wherein R4 is selected from carboxamido, C3-C8 heterocycloalkyl, hydroxyl and amino optionally mono or disubstituted with C1-C4 alkyl;
or;
wherein R1 and R2 together with the nitrogen atom to which they are attached form a
C3-C8 ring containing 1-3 heteroatoms and which is optionally substituted by 1-3 R5, wherein R5 is selected from C1-C3 alkyl, benzyl and amino optionally mono or disubstituted with C1-C4 alkyl; wherein each R5 is optionally independently substituted with amino optionally mono or disubstituted with C1-C4 alkyl
R3 is
5. A method of treating cancer said method comprised of the step of administering to a patient in need thereof a therapeutic amount of a compound according to claim 1 of a pharmaceutically acceptable salt thereof, wherein the cancer is selected from the list consisting of prostate, chronic lymphocytic leukemia and non-Hodgkin's lymphoma and multiple myeloma.
6. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 .
7. A process for preparing a compound according to claim 1 wherein said process is comprised of the steps of
combining a 2,6-dichloropyrazine or 2,6-dichloropyridine (II) with an amine in a suitable solvent to form a product (IV);
b) treating product (IV) with a reagent (V) and additional reagents required for Suzuki coupling to provide product (I)
c) modifying R 1 or R 2 , such as by protection/deprotection;
wherein (X=C, Y=N, C).
8. A compound chosen from:
Cpd
#
Structure
name
1
(E)-3-{3-[6-(4-Amino-cyclohexylamino)-pyrazin-2- yl]-phenyl}-acrylic acid
2
(E)-3-{3-[6-(4-Amino-cyclohexylamino)-pyrazin-2- yl]-phenyl}-acrylic acid
3
(E)-3-{3-[6-(4-Hydroxy-cyclohexylamino)-pyrazin- 2-yl]-phenyl}-acrylic acid
4
(E)-3-(3-{6-[(Piperidin-4-ylmethyl)-amino]-pyrazin- 2-yl}-phenyl)-acrylic acid
5
(E)-3-{3-[6-(4-Amino-butylamino)-pyrazin-2-yl]- phenyl}-acrylic acid
6
(E)-3-{3-[6-(3-Amino-propylamino)-pyrazin-2-yl]- phenyl}-acrylic acid
7
(E)-3-{3-[6-(3-Amino-2,2-dimethyl-propylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
8
(E)-3-{3-[6-(3-Dimethylamino-propylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
9
(E)-3-{3-[6-(2-Dimethylamino-ethylamino)-pyrazin- 2-yl]-phenyl}-acrylic acid
10
(E)-3-(3-{6-[Methyl-(3-methylamino-propyl)- amino]-pyrazin-2-yl}-phenyl)-acrylic acid
11
(E)-3-{3-[6-(3-Ethylamino-propylamino)-pyrazin-2- yl]-phenyl}-acrylic acid
12
(E)-3-{3-[6-(2-Amino-ethylamino)-pyrazin-2-yl]- phenyl}-acrylic acid
13
(E)-3-(3-{6-[Methyl-(2-methylamino-ethyl)-amino]- pyrazin-2-yl}-phenyl)-acrylic acid
14
(E)-3-(3-{6-[(3-Dimethylamino-propyl)-methyl- amino]-pyrazin-2-yl}-phenyl)-acrylic acid
15
(E)-3-{3-[6-(Carbamoylmethyl-amino)-pyrazin-2- yl]-phenyl}-acrylic acid
16
(E)-3-{3-[6-(2-Carbamoyl-ethylamino)-pyrazin-2- yl]-phenyl}-acrylic acid; MS, electrospray
17
(E)-3-{3-[6-(2-Hydroxy-ethylamino)-pyrazin-2-yl]- phenyl}-acrylic acid
18
E)-3-{3-[6-(3-Hydroxy-propylamino)-pyrazin-2-yl]- phenyl}-acrylic acid
19
(E)-3-{3-[6-(3-Methoxy-propylamino)-pyrazin-2-yl]- phenyl}-acrylic acid
20
(E)-3-{3-[6-(2-Methoxy-ethylamino)-pyrazin-2-yl]- phenyl}-acrylic acid
21
(E)-3-{3-[6-(2-Acetylamino-ethylamino)-pyrazin-2- yl]-phenyl}-acrylic acid
22
(E)-3-{3-[6-(4-Aminomethyl-piperidin-1-yl)-pyrazin- 2-yl]-phenyl}-acrylic acid
23
(E)-3-{3-[6-(4-Methyl-[1,4]diazepan-1-yl)-pyrazin- 2-yl]-phenyl}-acrylic acid
24
(E)-3-{3-[6-(4-Dimethylamino-piperidin-1-yl)- pyrazin-2-yl]-phenyl}-acrylic acid
25
Preparation of 14 (E)-3-{3-[6-(4-Amino-piperidin- 1-yl)-pyrazin-2-yl]-phenyl}-acrylic acid
26
(E)-3-[3-(4-Methyl-3,4,5,6-tetrahydro-2H- [1,2′]bipyrazinyl-6′-yl)-phenyl]-acrylic acid
27
(E)-3-[3-(6-[1,4]Diazepan-1-yl-pyrazin-2-yl)- phenyl]-acrylic acid
28
(E)-3-[3-(3,4,5,6-Tetrahydro-2H-[1,2′]bipyrazinyl- 6′-yl)-phenyl]-acrylic acid
29
(E)-3-{3-[6-(4-Benzyl-[1,4]diazepan-1-yl)-pyrazin- 2-yl]-phenyl}-acrylic acid
30
(E)-3-{3-[6-(3-Dimethylamino-pyrrolidin-1-yl)- pyrazin-2-yl]-phenyl}-acrylic acid
31
(E)-3-{3-[6-(4-Acetyl-[1,4]diazepan-1-yl)-pyrazin-2- yl]-phenyl}-acrylic acid
32
(E)-3-{3-[6-(4-Hydroxy-piperidin-1-yl)-pyrazin-2- yl]-phenyl}-acrylic acid
33
(E)-3-{3-[6-(4-Hydroxymethyl-piperidin-1-yl)- pyrazin-2-yl]-phenyl}-acrylic acid
34
(E)-3-[3-(6-Morpholin-4-yl-pyrazin-2-yl)-phenyl]- acrylic acid
35
(E)-3-[3-(6-Azepan-1-yl-pyrazin-2-yl)-phenyl]- acrylic acid
36
37
38
3-{3-[6-(4-Methyl-[1,4]diazepam-1-yl)-pyrazin-2- yl]-phenyl}-propionic acid
39
(E)-3-{3-[6-(4-Methyl-[1,4]diazepan-1-yl)-pyrazin- 2-yl]-phenyl}-acrylic acid methyl ester
40
(E)-3-{3-[6-(4-Methyl-[1,4]diazepan-1-yl)-pyrazin- 2-yl]-phenyl}-acrylamide
41
(E)-3-{3-[6-(4-Methyl-[1,4]diazepan-1-yl)-pyrazin- 2-yl]-phenyl}-prop-2-en-1-ol
42
(E)-3-{3-[6-(4-Methyl-[1,4]diazepan-1-yl)-pyrazin- 2-yl]-phenyl}-acrylonitrile
43
1-Methyl-4-(6-{3-[(E)-2-(1H-tetrazol-5-yl)-vinyl]- phenyl}-pyrazin-2-yl)-[1,4]diazepane
44
N-((E)-3-{3-[6-(4-Methyl-perhydro-1,4-diazepin-1- yl)-pyrazin-2-yl]-phenyl}-acryloyl)- methanesulfonamide
45
(E)-N-(2-Hydroxy-ethyl)-3-{3-[6-(4-methyl- perhydro-1,4-diazepin-1-yl)-pyrazin-2-yl]-phenyl}- acrylamide
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
3-{3-[6-(4-Amino-cyclohexylamino)-pyrazin-2-yl]- phenyl}-propionic acid
81
3-{3-[6-(4-Amino-cyclohexylamino)-pyrazin-2-yl]- phenyl}-propionic acid
82
3-(3-{6-[(Piperidin-4-ylmethyl)-amino]-pyrazin-2- yl}-phenyl)-propionic acid
83
3-{3-[6-(4-Dimethylamino-piperidin-1-yl)-pyrazin-2- yl]-phenyl}-propionic acid
84
(E)-3-{3-[6-(4-Carbamoyl-piperidin-1-yl)-pyrazin-2- yl]-phenyl}-acrylic acid
85
(E)-3-{3-[6-(4-Methoxy-piperidin-1-yl)-pyrazin-2- yl]-phenyl}-acrylic acid
86
(E)-3-(3-{6-[(1-Methyl-piperidin-4-ylmethyl)- amino]-pyrazin-2-yl}-phenyl)-acrylic acid
87
(E)-3-{3-[6-(Piperidin-4-ylamino)-pyrazin-2-yl]- phenyl}-acrylic acid
88
(E)-3-{3-[6-(1-Methyl-piperidin-4-ylamino)-pyrazin- 2-yl]-phenyl}-acrylic acid
89
(E)-3-{3-[6-(1-Benzyl-piperidin-4-ylamino)-pyrazin- 2-yl]-phenyl}-acrylic acid
90
(E)-3-{3-[6-(1-Acetyl-piperidin-4-ylamino)-pyrazin- 2-yl]-phenyl}-acrylic acid
91
(E)-3-{3-[6-(4-Acetylamino-cyclohexylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
92
N-(6-{3-[(E)-2-(1H-Tetrazol-5-yl)-vinyl]-phenyl}- pyrazin-2-yl)-cyclohexane-1,4-diamine
93
4-(6-{3-[(E)-2-(1H-tetrazol-5-yl)-vinyl]-phenyl}- pyrazin-2-yl)-[1,4]diazepane
94
N,N,N′-Trimethyl-N′-(6-{3-[(E)-2-(1H-tetrazol-5-yl)- vinyl]-phenyl}-pyrazin-2-yl)-propane-1,3-diamine
95
N 1 -(6-{3-[(E)-2-(1H-Tetrazol-5-yl)-vinyl]-phenyl}- pyrazin-2-yl)-propane-1,3-diamine
96
97
98
or the pharmaceutically acceptable salts thereof.
9. A compound of claim 8 chosen from
Cpd
#
Structure
name
1
(E)-3-{3-[6-(4-Amino-cyclohexylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
2
(E)-3-{3-[6-(4-Amino-cyclohexylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
3
(E)-3-{3-[6-(4-Hydroxy-cyclohexylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
4
(E)-3-(3-{6-[(Piperidin-4-ylmethyl)-amino]- pyrazin-2-yl}-phenyl)-acrylic acid
5
(E)-3-{3-[6-(4-Amino-butylamino)-pyrazin- 2-yl]-phenyl}-acrylic acid
6
(E)-3-{3-[6-(3-Amino-propylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
7
(E)-3-{3-[6-(3-Amino-2,2-dimethyl- propylamino)-pyrazin-2-yl]-phenyl}-acrylic acid
8
(E)-3-{3-[6-(3-Dimethylamino- propylamino)-pyrazin-2-yl]-phenyl}-acrylic acid
9
(E)-3-{3-[6-(2-Dimethylamino-ethylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
10
(E)-3-(3-{6-[Methyl-(3-methylamino- propyl)-amino]-pyrazin-2-yl}-phenyl)- acrylic acid
11
(E)-3-{3-[6-(3-Ethylamino-propylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
12
(E)-3-{3-[6-(2-Amino-ethylamino)-pyrazin- 2-yl]-phenyl}-acrylic acid
13
(E)-3-(3-{6-[Methyl-(2-methylamino-ethyl)- amino]-pyrazin-2-yl}-phenyl)-acrylic acid
14
(E)-3-(3-{6-[(3-Dimethylamino-propyl)- methyl-amino]-pyrazin-2-yl}-phenyl)- acrylic acid
15
(E)-3-{3-[6-(Carbamoylmethyl-amino)- pyrazin-2-yl]-phenyl}-acrylic acid
16
(E)-3-{3-[6-(2-Carbamoyl-ethylamino)- pyrazin-2-yl]-phenyl}-acrylic acid; MS, electrospray
17
(E)-3-{3-[6-(2-Hydroxy-ethylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
18
E)-3-{3-[6-(3-Hydroxy-propylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
19
(E)-3-{3-[6-(3-Methoxy-propylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
20
(E)-3-{3-[6-(2-Methoxy-ethylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
21
(E)-3-{3-[6-(2-Acetylamino-ethylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
22
(E)-3-{3-[6-(4-Aminomethyl-piperidin-1-yl)- pyrazin-2-yl]-phenyl}-acrylic acid
23
(E)-3-{3-[6-(4-Methyl-[1,4]diazepan-1-yl)- pyrazin-2-yl]-phenyl}-acrylic acid
24
(E)-3-{3-[6-(4-Dimethylamino-piperidin-1- yl)-pyrazin-2-yl]-phenyl}-acrylic acid
25
Preparation of 14 (E)-3-{3-[6-(4-Amino- piperidin-1-yl)-pyrazin-2-yl]-phenyl}-acrylic acid
26
(E)-3-[3-(4-Methyl-3,4,5,6-tetrahydro-2H- [1,2′]bipyrazinyl-6′-yl)-phenyl]-acrylic acid
27
(E)-3-[3-(6-[1,4]Diazepan-1-yl-pyrazin-2- yl)-phenyl]-acrylic acid
28
(E)-3-[3-(3,4,5,6-Tetrahydro-2H- [1,2′]bipyrazinyl-6′-yl)-phenyl]-acrylic acid
29
(E)-3-{3-[6-(4-Benzyl-[1,4]diazepan-1-yl)- pyrazin-2-yl]-phenyl}-acrylic acid
30
(E)-3-{3-[6-(3-Dimethylamino-pyrrolidin-1- yl)-pyrazin-2-yl]-phenyl}-acrylic acid
31
(E)-3-{3-[6-(4-Acetyl-[1,4]diazepan-1-yl)- pyrazin-2-yl]-phenyl}-acrylic acid
32
(E)-3-{3-[6-(4-Hydroxy-piperidin-1-yl)- pyrazin-2-yl]-phenyl}-acrylic acid
33
(E)-3-{3-[6-(4-Hydroxymethyl-piperidin-1- yl)-pyrazin-2-yl]-phenyl}-acrylic acid
34
(E)-3-[3-(6-Morpholin-4-yl-pyrazin-2-yl)- phenyl]-acrylic acid
35
(E)-3-[3-(6-Azepan-1-yl-pyrazin-2-yl)- phenyl]-acrylic acid
36
37
38
3-{3-[6-(4-Methyl-[1,4]diazepam-1-yl)- pyrazin-2-yl]-phenyl}-propionic acid
39
(E)-3-{3-[6-(4-Methyl-[1,4]diazepan-1-yl)- pyrazin-2-yl]-phenyl}-acrylic acid methyl ester
40
(E)-3-{3-[6-(4-Methyl-[1,4]diazepan-1-yl)- pyrazin-2-yl]-phenyl}-acrylamide
41
(E)-3-{3-[6-(4-Methyl-[1,4]diazepan-1-yl)- pyrazin-2-yl]-phenyl}-prop-2-en-1-ol
42
(E)-3-{3-[6-(4-Methyl-[1,4]diazepan-1-yl)- pyrazin-2-yl]-phenyl}-acrylonitrile
43
1-Methyl-4-(6-{3-[(E)-2-(1H-tetrazol-5-yl)- vinyl]-phenyl}-pyrazin-2-yl)-[1,4]diazepane
44
N-((E)-3-{3-[6-(4-Methyl-perhydro-1,4- diazepin-1-yl)-pyrazin-2-yl]-phenyl}- acryloyl)-methanesulfonamide
45
(E)-N-(2-Hydroxy-ethyl)-3-{3-[6-(4-methyl- perhydro-1,4-diazepin-1-yl)-pyrazin-2-yl]- phenyl}-acrylamide
or the pharmaceutically acceptable salts thereof.
10. A compound according to claim 9 chosen from:
Cpd
#
Structure
name
1
(E)-3-{3-[6-(4-Amino-cyclohexylamino)-pyrazin-2- yl]-phenyl}-acrylic acid
2
(E)-3-{3-[6-(4-Amino-cyclohexylamino)-pyrazin-2- yl]-phenyl}-acrylic acid
3
(E)-3-{3-[6-(4-Hydroxy-cyclohexylamino)-pyrazin- 2-yl]-phenyl}-acrylic acid
4
(E)-3-(3-{6-[(Piperidin-4-ylmethyl)-amino]-pyrazin- 2-yl}-phenyl)-acrylic acid
5
(E)-3-{3-[6-(4-Amino-butylamino)-pyrazin-2-yl]- phenyl}-acrylic acid
6
(E)-3-{3-[6-(3-Amino-propylamino)-pyrazin-2-yl]- phenyl}-acrylic acid
7
(E)-3-{3-[6-(3-Amino-2,2-dimethyl-propylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
8
(E)-3-{3-[6-(3-Dimethylamino-propylamino)- pyrazin-2-yl]-phenyl}-acrylic acid
9
(E)-3-{3-[6-(2-Dimethylamino-ethylamino)-pyrazin- 2-yl]-phenyl}-acrylic acid
10
(E)-3-(3-{6-[Methyl-(3-methylamino-propyl)- amino]-pyrazin-2-yl}-phenyl)-acrylic acid
11
(E)-3-{3-[6-(3-Ethylamino-propylamino)-pyrazin-2- yl]-phenyl}-acrylic acid
12
(E)-3-{3-[6-(2-Amino-ethylamino)-pyrazin-2-yl]- phenyl}-acrylic acid
13
(E)-3-(3-{6-[Methyl-(2-methylamino-ethyl)-amino]- pyrazin-2-yl}-phenyl)-acrylic acid
15
(E)-3-{3-[6-(Carbamoylmethyl-amino)-pyrazin-2- yl]-phenyl}-acrylic acid
16
(E)-3-{3-[6-(2-Carbamoyl-ethylamino)-pyrazin-2- yl]-phenyl}-acrylic acid; MS, electrospray
22
(E)-3-{3-[6-(4-Aminomethyl-piperidin-1-yl)-pyrazin- 2-yl]-phenyl}-acrylic acid
23
(E)-3-{3-[6-(4-Methyl-[1,4]diazepan-1-yl)-pyrazin- 2-yl]-phenyl}-acrylic acid
24
(E)-3-{3-[6-(4-Dimethylamino-piperidin-1-yl)- pyrazin-2-yl]-phenyl}-acrylic acid
25
Preparation of 14 (E)-3-{3-[6-(4-Amino-piperidin- 1-yl)-pyrazin-2-yl]-phenyl}-acrylic acid
26
(E)-3-[3-(4-Methyl-3,4,5,6-tetrahydro-2H- [1,2′]bipyrazinyl-6′-yl)-phenyl]-acrylic acid
27
(E)-3-[3-(6-[1,4]Diazepan-1-yl-pyrazin-2-yl)- phenyl]-acrylic acid
28
(E)-3-[3-(3,4,5,6-Tetrahydro-2H-[1,2′]bipyrazinyl- 6′-yl)-phenyl]-acrylic acid
29
(E)-3-{3-[6-(4-Benzyl-[1,4]diazepan-1-yl)-pyrazin- 2-yl]-phenyl}-acrylic acid
30
(E)-3-{3-[6-(3-Dimethylamino-pyrrolidin-1-yl)- pyrazin-2-yl]-phenyl}-acrylic acid
36
43
1-Methyl-4-(6-{3-[(E)-2-(1H-tetrazol-5-yl)-vinyl]- phenyl}-pyrazin-2-yl)-[1,4]diazepane
or a pharmaceutically acceptable salt thereof.