5-HT
The present invention relates to compounds of formula I: wherein one of R 1 and R 4 is selected from the group consisting of H, and optionally substituted C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl-C 1-4 alkyl, and phenyl-C 1-4 alkyl; and the other of R 1 and R 4 is an optionally substituted C 9-14 aryl group; R 2 and R 3 are either: (i) independently selected from H, R, R′, SO 2 R, C(═O)R, (CH 2 ) n NR 5 R 6 , where n is from 1 to 4 and R 5 and R 6 are independently selected from H and R, where R is optionally substituted C 1-4 alkyl, and R′ is optionally substituted phenyl-C 1-4 alkyl, or (ii) together with the nitrogen atom to which they are attached, form an optionally substituted C 5-7 heterocyclic group; and their use as pharmaceuticals, in particular for treating conditions alleviated by the antagonism of a 5-HT 2B receptor.
1. A pharmaceutical composition comprising a compound of formula I:
or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or diluent, wherein
R 4 is selected from the group consisting of H, and optionally substituted C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl-C 1-4 alkyl, and phenyl-C 1-4 alkyl;
R 1 is an optionally substituted C 9-14 aryl group comprising at least two fused rings;
R 2 and R 3 are either:
(i) independently selected from H, R, R′, SO 2 R, C(═O)R, (CH 2 ) n NR 5 R 6 , where n is from 1 to 4 and R 5 and R 6 are independently selected from H and R, where R is optionally substituted C 1-4 alkyl, and R′ is optionally substituted phenyl-C 1-4 alkyl, or
(ii) together with the nitrogen atom to which they are attached, form an optionally substituted C 5-7 heterocyclic group.
2. A pharmaceutical composition according to claim 1 , wherein R 4 is selected from H and optionally substituted C 1-6 alkyl and C 3-7 cycloalkyl.
3. A pharmaceutical composition according to claim 1 , wherein R 2 and R 3 independently selected from H, R and R′.
4. A pharmaceutical composition according to claim 1 , wherein R 1 is an optionally substituted C 9-14 carboaryl group.
5. A pharmaceutical composition according to claim 1 , wherein the optional substituent groups for the C 9-14 aryl group are selected from halo, hydroxy, C 1-4 alkoxy, cyano, amino, amido and C 1-4 alkyl.
6. A pharmaceutical composition according to claim 1 , wherein the C 9-14 aryl group bears no oxo substituents.
7. A pharmaceutical composition according to claim 1 , wherein the optional substituents for R 1 , R 2 , R 3 and R 4 are independently selected from halo, hydroxy, alkoxy, amino, and amido.
8. A compound of formula I:
or a salt, solvate and chemically protected form thereof, wherein
R 4 is selected from the group consisting of H, and optionally substituted C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl-C 1-4 alkyl, and phenyl-C 1-4 alkyl;
R 1 is an optionally substituted C 9-14 aryl group comprising at least two fused rings;
R 2 and R 3 are either:
(i) independently selected from H, R, R′, SO 2 R, C(═O)R, (CH 2 ) n NR 5 R 6 , where n is from 1 to 4 and R 5 and R 6 are independently selected from H and R, where R is optionally substituted C 1-4 alkyl, and R′ is optionally substituted phenyl-C 1-4 alkyl, or
(ii) together with the nitrogen atom to which they are attached, form an optionally substituted C 5-7 heterocyclic group.
9. A compound according to claim 8 , wherein R 4 is selected from H and optionally substituted C 1-6 alkyl and C 3-7 cycloalkyl.
10. A compound according to claim 8 , wherein R 2 and R 3 independently selected from H, R and R′.
11. A compound according to claim 8 , wherein R 1 is an optionally substituted C 9-14 carboaryl group.
12. A compound according to claim 8 , wherein the optional substituent groups for the C 9-14 aryl group are selected from halo, hydroxy, C 1-4 alkoxy, cyano, amino, amido and C 1-4 alkyl.
13. A compound according to claim 8 , wherein the C 9-14 aryl group bears no oxo substituents.
14. A compound according to claim 8 , wherein the optional substituents for R 1 , R 2 , R 3 and R 4 are independently selected from halo, hydroxy, alkoxy, amino, and amido.
15. A pharmaceutical composition comprising 5-(2-methoxy-naphthalen-1-yl)-oxazol-2-ylamine, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or diluent.
16. The compound 5-(2-methoxy-naphthalen-1-yl)-oxazol-2-ylamine, or a pharmaceutically acceptable salt thereof.