Anthelmintic compounds comprising a pyridine structure
The present invention relates to new anthelmintic compounds. These compounds can for example be used in the treatment of the kind of worm disease caused by helminths such as Dirofilaria , in particular Dirofilaria immitis.
1 . A Compound of Formula (I)
wherein
L is independently selected from
being absent, —CH 2 —, —NR L —, —O—, —S—, —S(O)— and —S(O) 2 —, with R L being independently selected from hydrogen and C 1-3 -alkyl,
R 1 is independently selected from the group consisting of
hydrogen, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclyl, C 6-10 aryl, 5 to 10-membered heteroaryl, C 1-6 -alkoxy, C 1-6 -alkylmercapto, halogen, cyano, nitro, hydroxy, mercapto, NR 2 R 3 , COOH, C(═O)OR 4 , SR 4 , S(O)R 4 , S(O) 2 R 4 , S(O) 2 NR 5 R 6 and C(═O)NR 5 R 6 ,
wherein each C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclyl, C 6-10 aryl, 5 to 10-membered heteroaryl, C 1-6 -alkoxy or C 1-6 -alkylmercapto, is optionally substituted with one or more substituent(s) independently selected from the group consisting of
C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclyl, C 6-10 -aryl, 5 to 10-membered heteroaryl, C 1-6 -alkoxy, C 1-6 -alkylmercapto, halogen, cyano, nitro, hydroxy, mercapto, NR 2′ R 3′ , C(═O)OR 4′ , SR 4′ , S(O)R 4′ , S(O) 2 R 4′ , S(O) 2 NR 5′ R 6′ and C(═O)NR 5′ R 6′ ,
R 2 and R 3 are independently selected from the group consisting of
hydrogen, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclyl, C 6-10 -aryl, 5 to 10-membered heteroaryl, C 1-6 -alkoxy-C 1-6 -alkyl, C 1-6 -alkyl substituted with C 3-10 -cycloalkyl, C 1-6 -alkyl substituted with 4 to 10-membered heterocyclyl, C 1-6 -alkyl substituted with C 6-10 -aryl and C 1-6 -alkyl substituted with 5 to 10-membered heteroaryl, or
R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 further ring atoms are selected from N, S and O,
wherein each C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclyl, C 6-10 -aryl, 5 to 10-membered heteroaryl, C 1-6 -alkoxy-C 1-6 -alkyl, C 1-6 -alkyl substituted with C 3-10 -cycloalkyl, C 1-6 -alkyl substituted with 4 to 10-membered heterocyclyl, C 1-6 -alkyl substituted with C 6-10 -aryl, C 1-6 -alkyl substituted with 5 to 10-membered heteroaryl or the heterocyclic ring formed by R 2 and R 3 together with the N atom to which they are attached is optionally substituted with one or more substituent(s) independently selected from the group consisting of
C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclyl, C 6-10 -aryl, 5 to 10-membered heteroaryl, C 1-6 -alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, NR 2″ R 3″ , C(═O)OR 4″ , SR 4″ , S(O)R 4″ , S(O) 2 R 4″ , S(O) 2 NR 5″ R 6″ and C(═O)NR 5″ R 6″ ,
R 4 , R 5 and R 6 are independently selected from hydrogen and C 1-6 -alkyl,
R 2′ , R 3′ , R 4′ , R 5′ and R 6′ are independently selected from hydrogen and C 1-6 -alkyl,
R 2″ , R 3″ , R 4″ , R 5″ and R 6″ are independently selected from hydrogen and C 1-6 -alkyl,
R 7 is independently selected from the group consisting of
methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methyl sulfoxyl, methyl sulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidin-1-yl and 3,3-difluoroazetidin-1-yl,
R 8 and R 9 are independently selected from the group consisting of
hydrogen, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclyl, C 6-10 -aryl, 5 to 10-membered heteroaryl, C 1-6 -alkoxy-C 1-6 -alkyl, C 1-6 -alkyl substituted with C 3-10 -cycloalkyl, C 1-6 -alkyl substituted with 4 to 10-membered heterocyclyl, C 1-6 -alkyl substituted with C 6-10 -aryl and C 1-6 -alkyl substituted with 5 to 10-membered heteroaryl, or
R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 further ring atoms are selected from N, S and O,
wherein each C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclyl, C 6-10 -aryl, 5 to 10-membered heteroaryl, C 1-6 -alkoxy-C 1-6 -alkyl, C 1-6 -alkyl substituted with C 3-10 -cycloalkyl, C 1-6 -alkyl substituted with 4 to 10-membered heterocyclyl, C 1-6 -alkyl substituted with C 6-10 -aryl, C 1-6 -alkyl substituted with 5 to 10-membered heteroaryl or the heterocyclic ring formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted with one or more substituent(s) independently selected from the group consisting of
C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclyl, C 6-10 -aryl, 5 to 10-membered heteroaryl, C 1-6 -alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, NR 8″ R 9″ , C(═O)OR 10″ , SR 10″ , S(O)R 10″ , S(O) 2 R 10″ , S(O) 2 NR 11″ R 12″ and C(═O)NR 11″ R 12″ ,
R 10 , R 11 and R 12 are independently selected from hydrogen and C 1-6 -alkyl,
R 8′ , R 9′ , R 10′ , R 11′ and R 12′ are independently selected from hydrogen and C 1-6 -alkyl,
R 8″ , R 9″ , R 10″ , R 11″ and R 12″ are independently selected from hydrogen and C 1-6 -alkyl,
R 13 and R 14 together with the atoms to which they are attached form a 5 or 6-carbon atoms containing saturated ring, wherein the saturated ring is optionally substituted with one or more C 1-3 -alkyl or ═O, and/or wherein one or more of the ring-forming carbon atoms are optionally replaced by —NH—, —O—, —S(O)—, —S(O) 2 — or —S—, or
R 13 and R 14 together with the atoms to which they are attached form a 5 or 6-carbon atoms containing unsaturated ring, wherein the unsaturated ring is optionally substituted with one or more C 1-3 -alkyl, and/or wherein one or more of the ring-forming carbon atoms are optionally replaced by —NH—, —N═, =N—, —O— or —S—,
A1 is N or CR 15 , wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 15′ R 15″ , wherein R 15′ and R 15″ are independently C 1-3 -alkyl,
A2 is N or CR 16 , wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 16′ R 16″ , wherein R 16′ and R 16″ are independently C 1-3 -alkyl,
A3 is N or CR 17 , wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 17′ R 17″ , wherein R 17′ and R 17″ are independently C 1-3 -alkyl,
A4 is N or CR 18 , wherein R 18 is independently hydrogen, halogen C 1-3 alkyl, C 1-3 alkoxy, or NR 18′ R 18″ , wherein R 18′ and R 18″ are independently C 1-3 -alkyl,
R 19 is independently selected from the group consisting of
C 6-10 -aryl and 5 to 10-membered heteroaryl,
wherein each C 6-10 -aryl or 5 to 10-membered heteroaryl is optionally substituted with one or more substituent(s) independently selected from the group consisting of
C 1-6 -alkyl, C 2-6 -alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclyl, C 6-10 -aryl, 5 to 10-membered heteroaryl, C 1-6 -alkoxy, C 1-6 -alkylmercapto, halogen, cyano, nitro, hydroxy, mercapto, NR 20 R 21 , C(═O)OR 22 , SR 22 , S(O)R 22 , S(O) 2 R 22 , S(O) 2 NR 23 R 24 and C(═O)NR 23 R 24 ,
R 20 and R 21 are independently selected from the group consisting of
hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heteroaryl, C 1-6 -alkoxy-C 1-6 -alkyl, C 1 -C 6 -alkyl substituted with C 6-10 -aryl and C 1-6 -alkyl substituted with 5 to 10-membered heteroaryl, or
R 20 and R 21 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 further ring atoms are selected from N, S and O,
wherein each C 1-6 -alkyl, C 2-6 -alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclyl, C 6-10 -aryl, 5 to 10-membered heteroaryl, C 1-6 -alkoxy, C 1-6 -alkylmercapto or the heterocyclic ring formed by R 20 and R 21 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from the group consisting of
C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclyl, C 6-10 -aryl, 5 to 10-membered heteroaryl, C 1-6 -alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, NR 20′ R 21′ , C(═O)OR 22′ , SR 22′ , S(O)R 22′ , S(O) 2 R 22′ , S(O) 2 NR 23′ R 24′ and C(═O)NR 23′ R 24′ ,
R 22 , R 23 and R 24 are independently selected from hydrogen and C 1-6 -alkyl,
R 20′ , R 21′ , R 22′ , R 23′ and R 24′ are independently selected from hydrogen and C 1-6 -alkyl,
R 25 is independently selected from hydrogen and C 1-6 -alkyl,
or a stereoisomer, physiologically acceptable salt, ester, solvate, polymorph, prodrug and mixtures thereof.
2 . The compound according to claim 1 , wherein the compound is the(S)-enantiomer.
3 . A process for preparing the compound of Formula (I) according to claim 1 comprising the step of
reacting a compound of Formula (A)
with a compound of Formula (B)
wherein L, R 1 , R 7 , R 13 , R 14 , A1, A2, A3, A4, R 19 and R 25 are defined as in claim 1 , to obtain the compound according to Formula (I).
4 . A Veterinary composition comprising
compound according to Formula (I) according to claim 1 , and
one or more physiologically acceptable excipient(s).
5 . A method of treating a disorder or disease in an animal wherein the disorder or disease is caused by helmiths comprising administering to the animal the compound according to claim 1 .
6 . A method of treating a disorder or disease in an animal wherein the disorder or disease is caused by helmiths comprising administering to the animal the composition of claim 4 .
7 . The compound according to claim 1 , wherein A1 to A4 are CH and R 1 is hydrogen and L R 7 , R 13 , R 14 , R 19 , R 25 and the chirality are defined below
No
L
R 7
R 13
R 14
R/S
R 19
R 25
1
S
isopropylamino
CH 3
H
S
H
H
2
S
morpholin-4-yl
CH 3
H
S
H
H
3
S
morpholin-4-yl
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
4
O
morpholin-4-yl
CH 3
H
S
H
H
5
O
morpholin-4-yl
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
6
O
morpholin-4-yl
—CH 2 —CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
7
O
morpholin-4-yl
—CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
8
O
morpholin-4-yl
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
9
S
morpholin-4-yl
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
10
S
morpholin-4-yl
═CH—CH═CH—
3,5-dichlorophenyl
H
11
S
morpholin-4-yl
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
12
O
morpholin-4-yl
—CH 2 —CH 2 —O—
S
2,3-dichlorophenyl
H
13
S
dimethylamino
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
14
S
dimethylamino
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
15
S
dimethylamino
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
16
S
dimethylamino
═CH—CH═CH—
3,5-dichlorophenyl
H
17
S
morpholin-4-yl
—CH 2 —CH 2 —O—
R
3,5-dichlorophenyl
H
18
S
dimethylamino
—CH 2 —CH 2 —O—
R
3,5-dichlorophenyl
H
19
S
dimethylamino
—CH 2 —CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
20
S
dimethylamino
—CH 2 —CH 2 —O—
S
2,3-dichlorophenyl
H
21
S
morpholin-4-yl
—CH 2 —CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
22
S
morpholin-4-yl
—CH 2 —CH 2 —O—
S
2,3-dichlorophenyl
H
23
S
morpholin-4-yl
—CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
24
O
morpholin-4-yl
—CH 2 —CH 2 —O—
R
3,5-dichlorophenyl
H
25
O
morpholin-4-yl
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
26
O
morpholin-4-yl
═CH—CH═CH—
3,5-dichlorophenyl
H
27
S
morpholin-4-yl
═CH—S—
3,5-dichlorophenyl
H
28
O
dimethylamino
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
29
O
dimethylamino
—CH 2 —CH 2 —O—
R
3,5-dichlorophenyl
H
30
O
dimethylamino
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
31
O
dimethylamino
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
32
O
dimethylamino
═CH—CH═CH—
3,5-dichlorophenyl
H
33
S
dimethylamino
═CH—S—
3,5-dichlorophenyl
H
34
O
dimethylamino
—CH 2 —CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
35
O
dimethylamino
—CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
36
O
dimethylamino
═CH—CH═CH—
2,3-dichlorophenyl
H
37
O
dimethylamino
═CH—S—
2,3-dichlorophenyl
H
38
O
dimethylamino
═CH—S—
3,5-dichlorophenyl
H
39
S
dimethylamino
—CH 2 —CH 2 —O—
R
2,3-dichlorophenyl
H
40
O
dimethylamino
—CH 2 —CH 2 —O—
S
2,3-dichlorophenyl
H
41
O
dimethylamino
—CH 2 —CH 2 —O—
S
2,3-dichlorophenyl
H
42
S
dimethylamino
—CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
43
S
dimethylamino
═CH—CH═CH—
2,3-dichlorophenyl
H
44
S
dimethylamino
═CH—S—
2,3-dichlorophenyl
H
45
O
morpholin-4-yl
═CH—CH═CH—
2,3-dichlorophenyl
H
46
O
morpholin-4-yl
═CH—S—
2,3-dichlorophenyl
H
47
O
morpholin-4-yl
═CH—S—
3,5-dichlorophenyl
H
48
S
morpholin-4-yl
═CH—S—
2,3-dichlorophenyl
H
49
S
morpholin-4-yl
═CH—CH═CH—
2,3-dichlorophenyl
H
50
S
morpholin-4-yl
—CH 2 —CH 2 —O—
R
2,3-dichlorophenyl
H
51
O
morpholin-4-yl
—CH 2 —CH 2 —O—
R
2,3-dichlorophenyl
H
52
S
—SCH 3
—CH 2 —CH 2 —O—
S
2,3-dichlorophenyl
H
53
S
—SCH 3
—CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
54
S
—SCH 3
—CH 2 —CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
55
S
—SCH 3
—CH 2 —CH 2 —O—
R
3,5-dichlorophenyl
H
56
O
—SCH 3
—CH 2 —CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
57
O
—SCH 3
—CH 2 —CH 2 —O—
S
2,3-dichlorophenyl
H
58
O
—SCH 3
—CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
59
O
—SCH 3
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
60
O
—SCH 3
—CH 2 —CH 2 —O—
R
3,5-dichlorophenyl
H
61
O
—SCH 3
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
62
S
—SCH 2 CH 3
—CH 2 —CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
63
S
—SCH 2 CH 3
—CH 2 —CH 2 —O—
S
2,3-dichlorophenyl
H
64
S
—SCH 2 CH 3
—CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
65
S
—SCH 3
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
66
S
methoxy
—CH 2 —CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
67
S
methoxy
—CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
68
S
methoxy
—CH 2 —CH 2 —O—
S
2,3-dichlorophenyl
H
69
S
—SCH 3
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
70
S
ethoxy
—CH 2 —CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
71
S
ethoxy
—CH 2 —CH 2 —O—
S
2,3-dichlorophenyl
H
72
S
ethoxy
—CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
73
S
—SCH 2 CH 3
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
74
S
—SCH 2 CH 3
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
75
S
—SCH 2 CH 3
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
76
O
—SCH 2 CH 3
—CH 2 —CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
77
O
—SCH 2 CH 3
—CH 2 —CH 2 —O—
S
2,3-dichlorophenyl
H
78
O
—SCH 2 CH 3
—CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
79
O
—SCH 2 CH 3
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
80
O
—SCH 2 CH 3
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
81
O
—SCH 2 CH 3
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
82
S
methoxy
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
83
S
methoxy
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
84
S
methoxy
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
85
O
methoxy
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
86
O
methoxy
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
87
O
methoxy
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
88
S
ethoxy
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
89
O
ethoxy
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
90
O
ethoxy
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
91
O
ethoxy
—CH 2 —CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
92
O
ethoxy
—CH 2 —CH 2 —O—
S
2,3-dichlorophenyl
H
93
O
ethoxy
—CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
94
O
methoxy
—CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
95
O
methoxy
—CH 2 —CH 2 —O—
S
2,3-dichlorophenyl
H
96
O
methoxy
—CH 2 —CH 2 —CH 2 —
S
2,3-dichlorophenyl
H
97
S
ethoxy
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
98
O
ethoxy
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
99
S
ethoxy
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
100
SO 2
dimethylamino
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
101
SO
dimethylamino
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
102
SO 2
dimethylamino
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
103
SO
dimethylamino
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
104
SO
dimethylamino
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
105
SO 2
dimethylamino
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
106
NH
morpholin-4-yl
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
107
NH
morpholin-4-yl
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
108
NH
dimethylamino
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
109
NH
morpholin-4-yl
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
110
CH 2
dimethylamino
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
111
CH 2
dimethylamino
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
112
CH 2
morpholin-4-yl
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
113
CH 2
morpholin-4-yl
—CH 2 —CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
114
CH 2
morpholin-4-yl
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
115
NH
dimethylamino
—CH 2 —CH 2 —O—
S
3,5-dichlorophenyl
H
116
NH
dimethylamino
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
117
CH 2
morpholin-4-yl
—CH 2 —CH 2 —
S
3,5-dichlorophenyl
H
8 . The compound according to claim 1 , wherein A1 to A4 are each CH, R 1 is hydrogen, L is 5, R 7 is morpholin-4-yl, R 13 and R 14 is —CH 2 —CH 2 —O—, R 19 is 3,5-dichlorophenyl, R 25 is H.
9 . The compound according to claim 8 , wherein the compound is the(S)-enantiomer.