Indole analogs as 5-oxo-ETE receptor antagonists and method of use thereof
This invention relates to novel pharmaceutically-useful compounds, to methods for their preparation, and to pharmaceutical compositions and therapeutic methods for treating certain conditions.
1. A compound of formula
or a pharmaceutically acceptable salt or solvate thereof; wherein
R 1 is H, a straight or branched alkyl, or lower cycloalkyl;
R 2 is a lower straight or branched alkyl or lower cycloalkyl;
L is an alkylene chain of 4-7 members, an alkenylene chain of 4-7 members, a CH(OH)-alkylene chain wherein said alkylene chain in CH(OH)-alkylene chain has 4-6 members or an alkylene-O-alkylene chain wherein the two alkylene chains together in alkylene-O-alkylene chain have a total of 4-6 members;
Rb is H or F;
m is an integer of 0 to 5;
X is a substituent;
n is an integer of 0 to 4; and
Ra is a substituent.
2. The compound as defined in claim 1 , having the formula
or a pharmaceutically acceptable salt or solvate thereof; wherein R 2 , Ra, L, X, m and n are as defined in claim 1 .
3. The compound as defined in claim 1 , having the formula
or a pharmaceutically acceptable salt or solvate thereof; wherein R 2 , Ra, L, X, m and n are as defined in claim 1 .
4. The compound as defined in claim 1 , wherein R 1 is a lower straight or branched alkyl; R 2 is a lower straight or branched alkyl; L is an alkylene chain of 4-6 members or a CH(OH)-alkylene chain wherein said alkylene chain in CH(OH)-alkylene chain has 4-6 members; is an integer of 0 to 3 and X is halogen, C1-6alkyl, C1-6 alkoxy, —NR40R41, —C(O)NR40R41, —NR40COR41, carboxy, hydroxyl, —S(O) 0-2 R40, —C(O)R40, —C(O)OR40 or —SO 2 NR40R41; wherein R40 and R41 are each independently H, or C1-6alkyl; n is an integer of 0 to 3 and Ra is halogen, C1-6alkyl, C1-6 alkoxy, —NR40R41, —C(O)NR40R41, —NR40COR41, carboxy, hydroxyl, —S(O) 0-2 R40, —C(O)R40, —C(O)OR40 or —SO 2 NR40R41; wherein R40 and R41 are each independently H, or C1-6alkyl; and Rb is H.
5. The compound as defined in claim 1 , wherein R 1 is a methyl, ethyl, n-propyl or isopropyl; R 2 is a methyl, ethyl, n-propyl or isopropyl; L is —CH(OH)—(CH 2 ) 6 —, —(CH 2 ) 7 —, —(CH 2 ) 6 —, —CH(OH)—(CH 2 ) 5 —, —CH 2 —O—(CH 2 ) 3 —, —(CH 2 ) 2 —O—(CH 2 ) 2 —, —(CH 2 ) 3 —O—(CH 2 )—, —CH═CH—(CH 2 ) 4 —, —CH 2 —CH═CH—(CH 2 ) 3 —, —(CH 2 ) 2 —CH═CH—(CH 2 ) 2 —, or —(CH 2 ) 3 —CH═CH—CH 2 —; m is an integer of 0 to 2 and X is F, Cl, C1-3alkyl, C1-3 alkoxy, or hydroxyl; n is an integer of 0 to 2 and Ra is F, Cl, C1-3alkyl, C1-3 alkoxy, or hydroxyl; and Rb is H.
6. The compound as defined in claim 1 , wherein R 1 is a lower straight or branched alkyl.
7. The compound as defined in claim 1 , wherein R 2 is a lower straight or branched alkyl.
8. The compound as defined in claim 1 , wherein
9. The compound as defined in claim 1 , wherein L is —CH(OH)—(CH 2 ) 6 —, —(CH 2 ) 7 —, —(CH 2 ) 6 —, —CH(OH)—(CH 2 ) 5 —, —(CH 2 ) 5 —, or —(CH 2 ) 4 —.
10. The compound as defined in claim 1 , wherein
is any one of X1-X14:
11. The compound as defined in claim 1 having the formula
or a pharmaceutically acceptable salt or solvate thereof; wherein Ra, L, X and m are as defined in claim 1 .
12. A compound as defined in table 2 or table 3:
TABLE 2
Compounds
Formula
15
13
14
17
18
19
20
21
22
23
24
25
39
37
38
46
47
48
49
50
51
52
53
54
55
61
62
63
64
65
66
67
68
69
70
83
85
94
95
96
97
159
or
TABLE 3
Com-
pounds
Formula
46M
50M
54M
or
49M
13. A pharmaceutical composition comprising the compound as defined in claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and one or more pharmaceutically acceptable carrier and/or excipient.
14. A method for treating a disease or condition selected from asthma, allergic rhinitis, chronic obstructive pulmonary disorder, atopic dermatitis, psoriasis and acne, the method comprising administering a therapeutically effective amount of the compound as defined in claim 1 , or a pharmaceutically acceptable salt or solvate thereof, to a subject in need thereof.