Organic compounds
View Patent ↗The present invention relates to novel aza-thia-benzoazulene derivatives of formula I as defined in the claims, their preparation, the use of these novel compounds for the preparation of pharmaceutical compositions, the use of these novel compounds and compositions for managing arthritis and arthritis-related conditions as well as in the treatment of pain in animals and humans. More particularly, the present invention relates to pharmaceutical, preferably veterinary compositions and methods for reducing inflammation and pain associated with acute inflammation of body parts, particularly joints, due to injury or due to arthritic conditions or other disease conditions.
1. A compound of the formula Ia
wherein R 3 is C 1 -C 6 -alkyl;
R 4 is OH, NH 2 , or C 1 -C 6 -alkyloxy;
R 5 is H, or halogen; and
R 6 is H, halogen, NO 2 , CN or C 1 -C 6 -alkyl;
or a physiologically acceptable ester or a pharmaceutical acceptable salt thereof.
2. A compound of formula Ia according to claim 1 , wherein R 3 is methyl or ethyl; and R 4 is OH, methoxy or ethoxy.
3. A compound according to claim 1 selected from the group consisting of [7-Chloro-10-hydroxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid; [7-Chloro-10-methoxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid; [7-Chloro-10-ethoxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid; [2-Chloro-10-hydroxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid; [2-Chloro-10-methoxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid; [2-Chloro-10-ethoxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid; [2-Chloro-7-fluoro-10-hydroxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid; (2-Chloro-7-fluoro-10-methoxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid; [2-Chloro-7-fluoro-10-ethoxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid; [2,7-Difluoro-10-hydroxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid; [2,7-Difluoro-10-methoxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid; [2,7-Difluoro-10-ethoxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid; [2,7-Dichloro-10-hydroxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid; [2,7-Dichloro-10-ethoxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid; and [2,7-Dichloro-10-methoxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid or a physiologically acceptable ester or a pharmaceutically acceptable salt thereof.
4. A compound according to claim 3 , wherein the compound is cis[2,7-Dichloro-10-methoxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid or a physiologically acceptable ester or a pharmaceutically acceptable salt thereof.
5. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 and a physiologically acceptable adjuvant, diluent or carrier.
6. The pharmaceutical composition according to claim 5 , wherein said composition is an oral or transdermal dosage form.
7. The pharmaceutical composition according to claim 5 wherein said composition is a veterinary composition in a palatable dosage form.
8. A method of treating pain or discomfort of inflammatory ailments in a human or animal in need of such treatment, which method comprises administering to said subject an analgesically effective amount of a compound according to claim 1 .
9. A compound according to claim 3 , wherein the compound is [2,7-Dichloro-10-methoxy-3-thia-9-aza-benzo[f]azulen-4-ylidene]-acetic acid.
10. A pharmaceutical composition comprising the compound of claim 9 and a physiologically acceptable adjuvant, diluent, or carrier.
11. A method of treating pain in a subject in need thereof, comprising administering the compound of claim 9 .
12. A process for preparing a compound of formula Ia according to claim 1 , wherein a compound of formula
wherein R 3 , R 5 and R 6 are defined as given for formula Ia, is reacted with a compound of formula
(MeO) 2 POCH 2 COOMe IX,
optionally in the presence of a basic catalyst to form a compound of formula Ia.
13. The process of claim 12 , wherein said compound of formula Ia is a racemic ester, the process further comprising the step of saponifying said ester and isolating at least one isomer of said compound.
14. A compound of formula Ia according to claim 1 , wherein R 3 is C 1 -C 6 -alkyl, R 4 is OH, NH 2 or C 1 -C 6 -alkyloxy, R 5 is halogen, and R 6 is H or halogen, or a pharmaceutically acceptable salt thereof.
15. A compound of the formula I according to claim 14 , wherein R 3 is methyl or ethyl.