Spiro compound and use thereof
The present disclosure relates to a series of tricyclic compounds and the use thereof as receptor agonists of sphingosine-1-phosphate subtype 1 (S1P1), and in particular relates to compounds as shown in formula (I) or pharmaceutically acceptable salts thereof.
1. A compound represented by formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof,
wherein
each R 1 is independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , and CN, or is independently selected from the group consisting of C 1-6 alkyl and C 1-6 heteroalkyl, each of which is optionally substituted by 1, 2 or 3 R;
R 2 is H, or is selected from the group consisting of C 1-6 alkyl, C 1-6 heteroalkyl and C 3-6 cycloalkyl, each of which is optionally substituted by 1, 2 or 3 R;
T is selected from the group consisting of N and CH;
moiety
is selected from the group consisting of
moiety
is selected from the group consisting of
ring B is selected from the group consisting of phenyl and 5- to 6-membered heteroaryl;
m is 1 or 2;
n is 0, 1, 2 or 3;
R is selected from the group consisting of F, Cl, Br, I, OH, NH 2 , CN, and COOH, or is selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, N,N-di(C 1-6 alkyl)amino, and C 3-6 cycloalkyl;
the heteroatom or the heteroatom group of the C 1-6 heteroalkyl and the 5- to 6-membered heteroaryl is each independently selected from the group consisting of N, O, S, NH, —NHC(═O)—, —S(═O)— and —S(═O) 2 —; and
the number of the heteroatom or the heteroatom group is 1, 2, 3 or 4.
2. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R is selected from the group consisting of F, Cl, Br, I, OH, NH 2 , CN, COOH, Me, Et, N(CH 3 ) 2 ,
3. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein each R 1 is independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , and CN, or is independently selected from the group consisting of C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylamino, and C 1-3 alkyl-S(═O) 2 —, each of which is optionally substituted by 1, 2 or 3 R.
4. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 3 , wherein each R 1 is independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , and CN, or is independently selected from the group consisting of Me, Et,
each of which is optionally substituted by 1, 2 or 3 R.
5. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 4 , wherein each R 1 is independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , CN, Me, Et,
6. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2 is selected from the group consisting of C 1-4 alkyl, C 1-3 alkyl-O—C 1-3 alkyl-, C 1-3 alkyl-S(═O) 2 —C 1-3 alkyl-, C 1-3 alkyl-NH—C 1-3 alkyl-, C 1-3 alkyl-NHC(═O)—C 1-3 alkyl- and C 3-6 cycloalkyl, each of which is optionally substituted by 1, 2 or 3 R.
7. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 6 , wherein R 2 is selected from the group consisting of Me, Et,
each of which is optionally substituted by 1, 2 or 3 R.
8. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 7 , wherein R 2 is selected from the group consisting of
9. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the moiety ring
is selected from the group consisting of
10. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein ring B is selected from the group consisting of 1,2,4-oxadiazolyl, 1,2,4-thiadiazolyl, pyrazinyl, thiazolyl, oxazolyl and pyrimidinyl.
11. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein ring B is selected from the group consisting of
12. The compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the moiety
is selected from the group consisting of
13. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 12 , wherein the moiety
is selected from the group consisting of
14. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the moiety
is selected from the group consisting of
15. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the moiety
is selected from the group consisting of
16. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , which is selected from the group consisting of
wherein n, R 1 and R 2 are as defined in claim 1 .
17. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 16 , which is selected from the group consisting of
wherein R 1 and R 2 are as defined in claim 16 .
18. A compound represented by the following formula, an optical isomer thereof or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of
19. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 18 , which is selected from the group consisting of
20. A pharmaceutical composition comprising a therapeutically effective amount of a compound, an optical isomer thereof or a pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient, and pharmaceutically acceptable carriers.
21. A method of treating a disease associated with S1P1 receptor in a subject, comprising administering to the subject claim 1 .
22. A method of treating a disease associated with S1P1 receptor in a subject, comprising administering to the subject a composition according to claim 20 .