Azaindole acetic acid derivatives and their use as prostaglandin D2 receptor modulators
The present invention relates to azaindole acetic acid derivatives of formula (I), wherein R 1 and R 2 are as described in the description, and their use as prostaglandin receptor modulators, most particularly as prostaglandin D 2 receptor modulators, in the treatment of various prostaglandin-mediated diseases and disorders, to pharmaceutical compositions containing these compounds and to processes for their preparation.
1. A method for treating nasal polyposis comprising administering to a subject in need thereof a compound of formula (I):
wherein
R 1 represents hydrogen, (C 1-4 )alkyl, (C 1-2 )fluoroalkyl, (C 1-4 )alkoxy, or halogen; and
R 2 represents hydrogen or methyl;
or a salt thereof.
2. The method according to claim 1 , comprising administering to a subject in need thereof the compound of formula (I), wherein R 1 represents hydrogen, methyl, trifluoromethyl, methoxy, or fluoro; or a salt thereof.
3. The method according to claim 1 , comprising administering to a subject in need thereof the compound of formula (I), wherein R 1 represents hydrogen, (C 1-4 )alkyl, or (C 1-4 )alkoxy; or a salt thereof.
4. The method according to claim 1 , comprising administering to a subject in need thereof the compound of formula (I), wherein R 1 represents hydrogen, methyl, or methoxy; or a salt thereof.
5. The method according to claim 1 , comprising administering to a subject in need thereof the compound of formula (I), wherein R 1 represents fluoro; or a salt thereof.
6. The method according to claim 1 , comprising administering to a subject in need thereof the compound of formula (I), wherein R 2 represents methyl; or a salt thereof.
7. The method according to claim 2 , comprising administering to a subject in need thereof the compound of formula (I), wherein R 2 represents methyl; or a salt thereof.
8. The method according to claim 1 , comprising administering to a subject in need thereof the compound of formula (I), wherein the absolute configuration of the stereogenic center is a compound of formula (I St1 )
or a salt thereof.
9. The method according to claim 7 , comprising administering to a subject in need thereof the compound of formula (I), wherein the absolute configuration of the stereogenic center is a compound of formula (I St1 )
or a salt thereof.
10. The method according to claim 1 , comprising administering to a subject in need thereof the compound of formula (I), wherein the compound is:
2-(8-((5-chloropyrimidin-2-yl)amino)-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid;
2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid;
2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-methyl-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid;
2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid;
2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-methoxy-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid; or
2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-(trifluoromethyl)-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid;
or a salt thereof.
11. The method according to claim 1 , comprising administering to a subject in need thereof the compound of formula (I), wherein the compound is:
(S)-2-(8-((5-chloropyrimidin-2-yl)amino)-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid;
(S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid;
(S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-methyl-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid;
(S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid;
(S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-methoxy-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid; or
(S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-(trifluoromethyl)-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid;
or a salt thereof.
12. The method according to claim 1 , comprising administering to a subject in need thereof the compound of formula (I), wherein the compound is
(S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid; or a pharmaceutically acceptable salt thereof.
13. The method according to claim 1 , comprising administering to a subject in need thereof the compound of formula (I), wherein the compound is
(S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid; or a pharmaceutically acceptable salt thereof.
14. The method according to claim 1 , comprising administering to a subject in need thereof the compound of formula (I), wherein the compound is
(S)-2-(8-((5-chloropyrimidin-2-yl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid; or a pharmaceutically acceptable salt thereof.