# US 2020/0399282 A1 · Inhibitors of trpc6

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- Number: US 2020/0399282 A1
- Document ID: US20200399282A1
- Status: Published application
- Kind: A1
- Application number: 16/970,129
- Filed: 2019-02-13
- Published: 2020-12-24
- Earliest claimed: 2018-02-15
- Assignees: Boehringer Ingelheim International GmbH; Hydra Biosciences, Inc.
- Applicants: Boehringer Ingelheim International GmbH; Hydra Biosciences, LLC
- Inventors: Steven Brunette; Jianwen Cui; Michael D. Lowe; Christopher Ronald Sarko; Simon Surprenant; Michael Robert Turner; Xinyuan Wu; Lana Louise Smith Keenan; Thierry Bouyssou; Paul Nicklin
- Web page: https://patentgrep.com/patent/US20200399282A1

## CPC

- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 487/08: Bridged systems
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/14: containing three or more hetero rings
- C07D 405/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention relates to compounds of formula (I) and pharmaceutically acceptable salts therefore, wherein R1 to R6, A, U, V, W, X, Y, and Z are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

## Claims

### Claim 1

A compound of formula (I)
Wherein:
A is CR7 or N;
U is CH or N;
V is CR8 or N;
W is CR9 or N;
X is CH, CC1-6alkyl, COC1-6alkyl, or N;
Y is CH or N;
Z is CH, COH, COC1-6alkyl or N;
R1 is selected from the group consisting of H and halogen;
R2 is selected from the group consisting of H, C1-6alkyl, —CN, —CF3, —OCF3, C3-6cycloalkyl, OC1-6alkyl, and OC3-6cycloalkyl;
when Z is COH, R1 may join with the hydroxyl group attached to the Z ring atom to form a central furanyl ring;
R3 is selected from the group consisting of
H,
C1-6alkyl optionally substituted with one to three groups independently selected from the group consisting of halogen, hydroxy or methoxy, and
C3-6cycloalkyl;
R4 is selected from the group consisting of H, C1-6alkyl optionally substituted with hydroxyl, C3-6cycloalkyl;
R5 is H or C1-6alkyl;
R3 and R5 can together form a bicyclic ring;
R6 is selected from the group consisting of
H,
C1-6alkyl,
—CN,
—CF3,
—OCF3,
C3-6cycloalkyl, and
OC1-6alkyl optionally substituted one to three halogen;
R7 is selected from the group consisting of H, C1-6alkyl, and OC1-6alkyl optionally substituted with one to three halogen;
R8 is selected from the group consisting of
H,
C1-6alkyl optionally substituted with C3-6cycloalkyl or one to three halogen,
halogen,
—CN,
—CF3,
—NH2,
phenyl,
C3-6cycloalkyl,
OC3-6cycloalkyl,
OC1-6alkyl optionally substituted with one to three halogen or C3-6cycloalkyl optionally substituted with one to three halogen; and
1-fluoromethyl-cyclopropylmethoxy;
R9 is selected from the group consisting of
H,
C1-6alkyl optionally substituted with one to three halogen,
halogen,
—CN,
—CF3,
OH,
C3-6cycloalkyl,
OC1-6alkyl optionally substituted with C3-6cycloalkyl or one to three halogen, and
OC3-6cycloalkyl;
when V is CR8 and W is CR9, R8 and R9 can together form a 5- to 6-membered fused heterocyclic ring;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein
R2 is selected from the group consisting of H, C1-6alkyl, and OC1-6alkyl;
R3 is selected from the group consisting of H and C1-6alkyl optionally substituted with one to three groups independently selected from the group consisting of halogen and hydroxyl;
R4 is selected from the group consisting of H and C1-6alkyl optionally substituted with hydroxyl;
R5 is H;
R6 is selected from the group consisting of H, C1-6alkyl, and OC1-6alkyl optionally substituted with one to three halogen;
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein Z is CH or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The compound according to claim 1 wherein:
U is N, V is CR8, and W is CR9,
X is CH or N,
or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein:
A is N,
X is N,
Y is CH,
or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein:
A is N,
X is CH,
Y is CH,
or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 1)

The compound according to claim 1, wherein:
A is CR7,
X is N,
Y is N,
or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 1)

The compound according to claim 1, wherein
A is CR7,
X is N,
Y is CH,
or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 1)

The compound according to claim 1, wherein R8 is selected from the group consisting H, F, CF3, ethyl, methoxy, ethoxy, sec-butoxy, trifluoromethoxy, trifluoroethoxy, cyclopropyl, cyclopropylmethoxy, 1-cyclopropylethoxy, 1-methylcyclopropylmethoxy, 1-fluoromethylcyclopropylmethoxy, 2,2,2-trifluoroethoxy, 2,2,-dimethylcyclopropylmethoxy, 2,2,-diflurocyclopropylmethoxy, cyclopropoxy, and cyclobutoxy,
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1)

The compound according to claim 1, wherein R2 is H or OCH3, or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 1)

The compound according to claim 1, wherein
R3, R4, R5 and R6 are each H,
or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 1)

The compound according to claim 1, wherein R2 is OCH3, or a pharmaceutically acceptable salt thereof.

### Claim at position 13

13-20. (canceled)

### Claim 21 (depends on 1)

The compound according to claim 1, wherein R8 is selected from the group consisting of H, fluoro, chloro, CF3, —CN, methyl, ethyl, isobutyl, tert-butyl, difluoromethyl, methoxy, difluoromethoxy, ethoxy, isopropoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, cyclopropylmethoxy, cyclopropoxy, and cyclopentoxy, or a pharmaceutically acceptable salt thereof.

### Claim 22 (depends on 1)

The compound according to claim 1, wherein R2 is H or OCH3, or a pharmaceutically acceptable salt thereof.

### Claim 23

(canceled)

### Claim 24 (depends on 1)

The compound according to claim 1, wherein R2 is OCH3, or a pharmaceutically acceptable salt thereof.

### Claim 25 (depends on 1)

The compound according to claim 1, wherein R2 is H, or a pharmaceutically acceptable salt thereof.

### Claim 26 (depends on 1)

The compound according to claim 1, selected from the group consisting of:
Cpd No.
Structure
Structure Name
1
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-biphenyl-4-yl- methanone
2
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(4′-ethyl- biphenyl-4-yl)-methanone
3
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(4′-methyl- biphenyl-4-yl)-methanone
4
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(4′-chloro- biphenyl-4-yl)-methanone
5
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(4′-methoxy- biphenyl-4-yl)-methanone
6
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(3′-chloro- biphenyl-4-yl)-methanone
7
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(4′-fluoro- biphenyl-4-yl)-methanone
8
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(3′-fluoro- biphenyl-4-yl)-methanone
9
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(3′-methoxy- biphenyl-4-yl)-methanone
10
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(4′-tert-butyl- biphenyl-4-yl)-methanone
11
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-dibenzofuran- 3-yl-methanone
12
[4-(6-Amino-pyridin-3-yl)- piperazin-1-yl]-(4′- trifluoromethyl-biphenyl-4-yl)- methanone
13
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-4-methoxy-5- (3-methoxy-4- trifluoromethoxy-phenyl)- pyridin-2-yl]-methanone
14
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(4-fluoro-3- methoxy-phenyl)-4-methoxy- pyridin-2-yl]-methanone
15
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-{5-[4-fluoro- 3-(2,2,2-trifluoro-ethoxy)- phenyl]-4-methoxy-pyridin-2- yl}-methanone
16
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(2,3- dihydro-benzofuran-6-yl)-4- methoxy-pyridin-2-yl]- methanone
17
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(4- cyclopropylmethoxy-phenyl)- 4-methoxy-pyridin-2-yl]- methanone
18
Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(3-chloro-4- cyclopropylmethoxy-phenyl)- 4-methoxy-pyridin-2-yl]- methanone
19
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(3-chloro-4- isopropoxy-phenyl)-4- methoxy-pyridin-2-yl]- methanone
20
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(3-fluoro-4- isopropoxy-phenyl)-4- methoxy-pyridin-2-yl]- methanone
21
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(3- cyclopropylmethoxy-phenyl)- 4-methoxy-pyridin-2-yl]- methanone
22
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(2,3- dihydro-benzo[1,4]dioxin-6- yl)-4-methoxy-pyridin-2-yl]- methanone
23
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(4- cyclopentyloxy-phenyl)-4- methoxy-pyridin-2-yl]- methanone
24
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(2-chloro-4- trifluoromethyl-phenyl)-4- methoxy-pyridin-2-yl]- methanone
25
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[4-methoxy-5- (3-methoxy-4-trifluoromethyl- phenyl)-pyridin-2-yl]- methanone
26
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(3-fluoro-4- trifluoromethyl-phenyl)-4- methoxy-pyridin-2-yl]- methanone
27
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[4-methoxy-5- (4-trifluoromethyl-phenyl)- pyridin-2-yl]-methanone
28
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[4-methoxy-5- (4-methoxy-phenyl)-pyridin- 2-yl]-methanone
29
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-{4-methoxy-5- [4-(2,2,2-trifluoro-ethoxy)- phenyl]-pyridin-2-yl}- methanone
30
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5- (4-isopropoxy-phenyl)-4- methoxy-pyridin-2-yl]- methanone
31
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[4-methoxy-5- (4-trifluoromethoxy-phenyl)- pyridin-2-yl]-methanone
32
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(4-methoxy-5- phenyl-pyridin-2-yl)- methanone
33
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(3,4- difluoro-phenyl)-4-methoxy- pyridin-2-yl]-methanone
34
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(3-fluoro-4- methyl-phenyl)-4-methoxy- pyridin-2-yl]-methanone
35
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(3-fluoro- phenyl)-4-methoxy-pyridin-2- yl]-methanone
36
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(4-fluoro- phenyl)-4-methoxy-pyridin-2- yl]-methanone
37
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(4-ethoxy- phenyl)-4-methoxy-pyridin-2- yl]-methanone
38
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(4- difluoromethyl-phenyl)-4- methoxy-pyridin-2-yl]- methanone
39
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(4- difluoromethoxy-phenyl)-4- methoxy-pyridin-2-yl]- methanone
40
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(4-chloro- phenyl)-4-methoxy-pyridin-2- yl]-methanone
41
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(4- cyclopropoxy-phenyl)-4- methoxy-pyridin-2-yl]- methanone
42
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(4-methoxy-6′- trifluoromethyl- [3,3′]bipyridinyl-6-yl)- methanone
43
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(6′- cyclopropyl-4-methoxy- [3,3′]bipyridinyl-6-yl)- methanone
44
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(6′-ethyl-4- methoxy-[3,3′]bipyridinyl-6- yl)-methanone
45
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(6′-ethoxy-4- methoxy-[3,3′]bipyridinyl-6- yl)-methanone
46
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(4,6′- dimethoxy-[3,3′]bipyridinyl-6- yl)-methanone
47
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[4-methoxy-6′- (2,2,2-trifluoro-ethoxy)- [3,3′]bipyridinyl-6-yl]- methanone
48
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(4-methoxy-6′- trifluoromethoxy- [3,3′]bipyridinyl-6-yl)- methanone
49
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(6′- cyclobutoxy-4-methoxy- [3,3′]bipyridinyl-6-yl)- methanone
50
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(6′- cyclopropylmethoxy-4- methoxy-[3,3′]bipyridinyl-6- yl)-methanone
51
5-{6-[4-(6-Amino-pyridazin-3- yl)-piperidine-1-carbonyl]-4- methoxy-pyridin-3-yl}-2- methyl-benzonitrile
52
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(3- isobutoxy-phenyl)-4- methoxy-pyridin-2-yl]- methanone
53
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-(2- isopropoxy-pyrimidin-5-yl)-4- methoxy-pyridin-2-yl]- methanone
54
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-{4-methoxy-5- [2-(2,2,2-trifluoro-ethoxy)- pyrimidin-5-yl]-pyridin-2-yl}- methanone
55
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(2-methoxy-4′- trifluoromethyl-biphenyl-4-yl)- methanone
56
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(2-methoxy-4′- trifluoromethoxy-biphenyl-4- yl)-methanone
57
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(4′-isopropoxy- 2-methoxy-biphenyl-4-yl)- methanone
58
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[2-methoxy-4′- (2,2,2-trifluoro-ethoxy)- biphenyl-4-yl]-methanone
59
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[3-methoxy-4- (6-trifluoromethyl-pyridin-3- yl)-phenyl]-methanone
60
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(2-methoxy- biphenyl-4-yl)-methanone
61
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[3-methoxy-4- (2-trifluoromethyl-pyridin-4- yl)-phenyl]-methanone
62
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[4-(2- isopropoxy-pyrimidin-5-yl)-3- methoxy-phenyl]-methanone
63
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(2-methyl-4′- trifluoromethyl-biphenyl-4-yl)- methanone
64
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[6-methoxy-5- (4-trifluoromethyl-phenyl)- pyridin-2-yl]-methanone
65
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[5-methoxy-6- (4-trifluoromethyl-phenyl)- pyridin-3-yl]-methanone
66
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(3-methoxy-4′- trifluoromethyl-biphenyl-4-yl)- methanone
67
[4-(6-Amino-pyridin-3-yl)- piperazin-1-yl]-(4-methoxy-6′- trifluoromethyl- [3,3′]bipyridinyl-6-yl)- methanone
68
[4-(6-Amino-pyridin-3-yl)- piperazin-1-yl]-(4-methoxy-5- phenyl-pyridin-2-yl)- methanone
69
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(3-methyl-4′- trifluoromethyl-biphenyl-4-yl)- methanone
70
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(2-ethyl-4′- trifluoromethyl-biphenyl-4-yl)- methanone
71
(6-Amino-3′,4′,5′,6′- tetrahydro-2′H- [3,4′]bipyridinyl-1′-yl)-(4- methoxy-5-phenyl-pyridin-2- yl)-methanone
72
(6-Amino-3′,4′,5′,6′- tetrahydro-2′H- [3,4′]bipyridinyl-1′-yl)-[5-(4- fluoro-phenyl)-4-methoxy- pyridin-2-yl]-methanone
73
[4-(6-Amino-pyridazin-3-yl)- pipendin-1-yl]-[4-(6- cyclopropoxy-pyridin-3-yl)-3- methoxy-phenyl]-methanone
74
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-{4-[6-((R)-sec- butoxy)-pyridin-3-yl]-3- methoxy-phenyl}-methanone
75
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-{4-[6-((S)-sec- butoxy)-pyridin-3-yl]-3- methoxy-phenyl}-methanone
76
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-{4-[6-(2,2- difluoro-cyclopropylmethoxy)- pyridin-3-yl]-3-methoxy- phenyl}-methanone
77
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-{4-[6-(2,2- dimethyl- cyclopropylmethoxy)-pyridin- 3-yl]-3-methoxy-phenyl}- methanone
78
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-{4-[6-((S)-1- cyclopropyl-ethoxy)-pyridin- 3-yl]-3-methoxy-phenyl}- methanone
79
[4-(6-Amino-pyridazin-3-yl)- piperidin-1- yl]-{3-methoxy-4- [6-(1-methyl- cyclopropylmethoxy)-pyridin- 3-yl]-phenyl}-methanone
80
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-{4-[6-(1- fluoromethyl- cyclopropylmethoxy)-pyridin- 3-yl]-3-methoxy-phenyl}- methanone
81
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-{4-[6-((R)-1- cyclopropyl-ethoxy)-pyridin- 3-yl]-3-methoxy-phenyl}- methanone
82
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[4-(6- cyclopropylmethoxy-pyridin- 3-yl)-3-methoxy-phenyl]- methanone
83
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(4′-isobutyl- biphenyl-4-yl)-methanone
84
(6-Amino-4-methoxy- 3′,4′,5′,6′-tetrahydro-2′H- [3,4]bipyridinyl-1′-yl)-[4- methoxy-5-(4-trifluoromethyl- phenyl)-pyridin-2-yl]- methanone
85
[4-(6-Amino-4-methoxy- pyridazin-3-yl)-piperidin-1-yl]- [4-methoxy-5-(4- trifluoromethyl-phenyl)- pyridin-2-yl]-methanone
86
[4-(6-Amino-4-methoxy- pyridazin-3-yl)-piperidin-1-yl]- (4-methoxy-6′-trifluoromethyl- [3,3′]bipyridinyl-6-yl)- methanone
87
[4-(6-Amino-4-methoxy-pyridazin- 3-yl)-piperidin-1-yl]- (4-methoxy-5-phenyl-pyridin- 2-yl)-methanone
88
[4-(6-Amino-4-methyl- pyridazin-3-yl)-piperidin-1-yl]- [4-methoxy-5-(4- trifluoromethyl-phenyl)- pyridin-2-yl]-methanone
89
[(S)-4-(6-Amino-4-methoxy- pyridin-3-yl)-2- hydroxymethyl-piperazin-1- yl]-(4-methoxy-5-phenyl- pyridin-2-yl)-methanone
90
[(R)-4-(6-Amino-pyridin-3-yl)- 2-hydroxymethyl-piperazin-1- yl]-[5-(4-fluoro-phenyl)-4- methoxy-pyridin-2-yl]- methanone
91
[(R)-4-(6-Amino-pyridin-3-yl)- 2-hydroxymethyl-piperazin-1- yl]-(4-methoxy-5-phenyl- pyridin-2-yl)-methanone
92
[(R)-4-(6-Amino-4-methyl- pyridin-3-yl)-2- hydroxymethyl-piperazin-1- yl]-[4-methoxy-5-(4- trifluoromethyl-phenyl)- pyridin-2-yl]-methanone
93
[(R)-4-(6-Amino-4-methyl- pyridin-3-yl)-2- hydroxymethyl-piperazin-1- yl]-[5-(4-fluoro-phenyl)-4- methoxy-pyridin-2-yl]- methanone
94
[(R)-4-(6-Amino-4-methyl- pyridin-3-yl)-2- hydroxymethyl-piperazin-1- yl]-(4-methoxy-5-phenyl- pyridin-2-yl)-methanone
95
[(R)-4-(6-Amino-4-methoxy- pyridin-3-yl)-2- hydroxymethyl-piperazin-1- yl]-[4-methoxy-5-(4- trifluoromethyl-phenyl)- pyridin-2-yl]-methanone
96
[(R)-4-(6-Amino-4-methoxy- pyridin-3-yl)-2- hydroxymethyl-piperazin-1- yl]-(4-methoxy-5-phenyl- pyridin-2-yl)-methanone
97
(6-Amino-3′,4′,5′,6′- tetrahydro-2′H- [3,4′]bipyridinyl-1′-yl)-(4- methoxy-6′-trifluoromethyl- [3,3′]bipyridinyl-6-yl)- methanone
98
[(R)-4-(6-Amino-4-methoxy- pyridin-3-yl)-2- methoxymethyl-piperazin-1- yl]-[5-(4-fluoro-phenyl)-4- methoxy-pyridin-2-yl]- methanone
99
[(R)-4-(6-Amino-4-methoxy- pyridin-3-yl)-2- methoxymethyl-piperazin-1- yl]-[4-methoxy-5-(4- trifluoromethyl-phenyl)- pyridin-2-yl]-methanone
100
[(R)-4-(6-Amino-4-methoxy- pyridin-3-yl)-2- methoxymethyl-piperazin-1- yl]-(4-methoxy-5-phenyl- pyridin-2-yl)-methanone
101
[(S)-4-(6-Amino-4-methoxy- pyridin-3-yl)-2- hydroxymethyl-piperazin-1- yl]-[4-methoxy-5-(4- trifluoromethyl-phenyl)- pyridin-2-yl]-methanone
102
[(S)-4-(6-Amino-4-methoxy- pyridin-3-yl)-2- hydroxymethyl-piperazin-1- yl]-[5-(4-fluoro-phenyl)-4- methoxy-pyridin-2-yl]- methanone
103
[4-(6-Amino-4-methoxy- pyridin-3-yl)-piperazin-1-yl]- [4-methoxy-5-(4- trifluoromethyl-phenyl)- pyridin-2-yl]-methanone
104
[4-(6-Amino-4-methoxy- pyridin-3-yl)-piperazin-1-yl]- [5-(4-fluoro-phenyl)-4- methoxy-pyridin-2-yl]-methanone
105
[4-(6-Amino-4-methoxy- pyridin-3-yl)-piperazin-1-yl]- (4-methoxy-5-phenyl-pyridin- 2-yl)-methanone
106
[(R)-4-(6-Amino-4-methoxy- pyridin-3-yl)-2-((R)-1- hydroxy-ethyl)-piperazin-1- yl]-[4-methoxy-5-(4- trifluoromethyl-phenyl)- pyridin-2-yl]-methanone
107
[(R)-4-(6-Amino-4-methoxy- pyridin-3-yl)-2-((S)-1- hydroxy-ethyl)-piperazin-1- yl]-[4-methoxy-5-(4- trifluoromethyl-phenyl)- pyridin-2-yl]-methanone
108
[4-(6-Amino-4-methoxy- pyridin-3-yl)-2-(2,2-difluoro- ethyl)-piperazin-1-yl]-[4- methoxy-5-(4-trifluoromethyl- phenyl)-pyridin-2-yl]- methanone
109
[(S)-4-(6-Amino-4-methoxy- pyridin-3-yl)-2-(2,2-difluoro- ethyl)-piperazin-1-yl]-[4- methoxy-5-(4-trifluoromethyl- phenyl)-pyridin-2-yl]- methanone
110
[(R)-4-(6-Amino-4-methoxy- pyridin-3-yl)-2-(2,2-difluoro- ethyl)-piperazin-1-yl]-[4- methoxy-5-(4-trifluoromethyl- phenyl)-pyridin-2-yl]- methanone
111
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-[6′-(2,2- difluoro-cyclopropylmethoxy)- 4-methoxy-[3,3′]bipyridinyl-6- yl]-methanone
112
[4-(6-Amino-pyridazin-3-yl)- piperidin-1-yl]-(6′- cyclopropoxy-4-methoxy- [3,3′]bipyridinyl-6-yl)- methanone
113
[(R)-4-(6-Amino-pyridin-3-yl)- 3-methyl-piperazin-1-yl]-(4′- trifluoromethyl-biphenyl-4-yl)- methanone
114
[(R)-4-(6-Amino-pyridin-3-yl)- 3-methyl-piperazin-1-yl]-(2- methoxy-4′-trifluoromethyl- biphenyl-4-yl)-methanone
115
[(1S,4S)-5-(6-Amino- pyridazin-3-yl)-2,5-diaza- bicyclo[2.2.1]hept-2-yl]-(2- methoxy-4′-trifluoromethyl- biphenyl-4-yl)-methanone
116
[(1S,4S)-5-(6-Amino- pyridazin-3-yl)-2,5-diaza- bicyclo[2.2.1]hept-2-yl]-[4- methoxy-5-(4-trifluoromethyl- phenyl)-pyridin-2-yl]- methanone,
or a pharmaceutically acceptable salt thereof.

### Claim 27

(canceled)

### Claim 28 (depends on 1)

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

### Claim 29 (depends on 1)

A method of treating a disease or disorder that can be alleviated by TRPC6 inhibition comprising administering a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, to a patient in need thereof.

### Claim 30 (depends on 29)

The method according to claim 29, wherein the disease or disorder is selected from sepsis, severe sepsis, septic shock, cardiac hypertrophy, ischemia, ischemic reperfusion injury, hypertension, pulmonary arterial hypertension, idiopathic pulmonary arterial hypertension, restenosis, chronic obstructive pulmonary disease, cystic fibrosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), trauma induced brain disorders, asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, multiple sclerosis, muscular dystrophy, Duchenne's muscular dystrophy, preeclampsia and pregnancy-induced hypertension, non-alcoholic steatohepatitis (NASH), minimal change disease, focal segmental glomerulosclerosis (FSGS), nephrotic syndrome, diabetic nephropathy or diabetic kidney disease (DKD), chronic kidney disease (CKD), renal insufficiency, end stage renal disease, ischemia or an ischemic reperfusion injury, cancer, diabetes, lung fibrosis, idiopathic pulmonary fibrosis (IPF), emphysema and acute respiratory disease syndrome (ARDS).