Aza spiro alkane derivatives as inhibitors of metalloproteases
The present invention provides a compound of Formula I or Formula II: enantiomer, diastereomer, prodrug, solvate, metabolite, or pharmaceutically acceptable salt thereof, wherein constituent variables are provided herein. The compounds of Formula I and II are modulators of metalloproteases and are useful in treating diseases associated with metalloprotease activity such as arthritis, cancer, cardiovascular disorders, skin disorders, inflammation and allergic conditions.
1. A method for treating a disease associated with unwanted ADAM10, ADAM15, or ADAM17 activity in a mammalian subject, the method comprising administering to said mammal in need thereof a therapeutically effective amount of a compound which is methyl (6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate, or a pharmaceutically acceptable salt thereof, wherein the disease is selected from breast cancer, ovarian cancer, prostate cancer, non-small cell lung cancer, colon cancer, gastric cancer, pancreatic cancer, and glioma.
2. The method of claim 1 , wherein the disease is associated with unwanted ADAM10 activity.
3. The method of claim 1 , wherein the disease is associated with unwanted ADAM15 activity.
4. The method of claim 1 , wherein the disease is associated with unwanted ADAM17 activity.
5. The method of claim 1 , wherein the disease is glioma.
6. The method of claim 1 , wherein the compound methyl (6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate is administered.
7. The method of claim 2 , wherein the compound methyl (6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate is administered.
8. The method of claim 3 , wherein the compound methyl (6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate is administered.
9. The method of claim 4 , wherein the compound methyl (6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate is administered.
10. The method of claim 5 , wherein the compound methyl (6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate is administered.