Inhibitors of matrix metalloproteinases
View Patent ↗The present invention provides novel compounds of formulas I-IX, as described herein. Also provided are compositions of compounds of formulas I-IX, methods of making compounds of formulas I-IX, and methods of using compounds of formulas I-IX. The compounds of the invention can be used to inhibit matrix metalloproteinases, and are useful to treat conditions and diseases associated therewith.
1. A compound of Formula (30):
wherein
R 3 and R 4 are each independently H, OH, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkanoyloxy, aryl, heteroaryl, carboxy, cyano, nitro, halo, trifluoromethyl, trifluoromethoxy, SR 5 , SO 2 N(R 5 ) 2 , NR 5 R 5 , or COOR 5 ;
each R 5 is independently H, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkanoyl, (C 6 -C 10 )aroyl, aryl, aryl(C 1 -C 6 )alkyl, heteroaryl, heteroaryl(C 1 -C 6 )alkyl, or a nitrogen protecting group;
any alkyl, amino, aryl, or heteroaryl is optionally substituted with 1 to about 5 (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl, heteroaryl(C 1 -C 6 )alkyl, nitro, halo, amino, or hydroxy groups;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 wherein R 3 is H.
3. The compound of claim 1 wherein R 4 is H.
4. The compound of claim 1 wherein both R 3 and R 4 are H.
5. The compound of claim 1 wherein the position of the —NH 2 of Formula (30) is ortho or para to the oxygen linking the two aryl rings in Formula (30).
6. The compound of claim 1 wherein the position of the —NH 2 of Formula (30) is ortho or meta to the oxygen linking the two aryl rings in Formula (30).
7. The compound of claim 4 wherein the position of the —NH 2 of Formula (30) is ortho or para to the oxygen linking the two aryl rings in Formula (30).
8. The compound of claim 4 wherein the position of the —NH 2 of Formula (30) is ortho or meta to the oxygen linking the two aryl rings in Formula (30).
9. The compound of claim 1 wherein the compound is in the form of a pharmaceutically acceptable salt.
10. The compound of claim 4 wherein the compound is in the form of a pharmaceutically acceptable salt.
11. The pharmaceutically acceptable salt of claim 9 wherein the salt is derived from hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid, acetic acid, propionic acid, succinic acid, glycolic acid, stearic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, pamoic acid, maleic acid, hydroxymaleic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, sulfanilic acid, 2-acetoxybenzoic acid, fumaric acid, toluenesulfonic acid, methanesulfonic acid, ethane disulfonic acid, oxalic acid, or isethionic acid.
12. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier or excipient.
13. The composition of claim 12 wherein the compound is present at about 0.075% w/w to 20% w/w.
14. The composition of claim 13 wherein the compound is present at about 0.2% w/w to 15% w/w.
15. The composition of claim 12 wherein the composition is formulated for injection, oral administration, or topical administration.
16. The composition of claim 15 wherein the composition is formulated for injection and the composition comprises a buffer.
17. The composition of claim 15 wherein the composition is formulated for injection and the composition is an isotonic sterile injectable preparation.
18. The composition of claim 15 wherein the composition is formulated for injection and the composition has a pH of about 7 to 10.
19. The composition of claim 15 wherein the composition is formulated for oral administration and the composition is a tablet, troche, capsule, lozenge, emulsion, aqueous or oil suspension, dispersible powder or granule, syrup, or elixir.
20. The composition of claim 15 wherein the composition is formulated for topical administration and composition is an ointment or cream.