Neprilysin inhibitors
In one aspect, the invention relates to compounds having the formula XII: where R a , R b , R 2 , R 7 , and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds described herein are prodrugs of compounds having neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising these compounds; methods of using these compounds; and processes and intermediates for preparing these compounds.
1. A compound selected from a compound of Formula (1), (2), (3) and (4):
or a salt thereof.
2. The compound or salt of claim 1 , wherein the compound is a compound of Formula (1).
3. The compound or salt of claim 1 , wherein the compound is a compound of Formula (2).
4. The compound or salt of claim 1 , wherein the compound is a compound of Formula (3).
5. The compound or salt of claim 1 , wherein the compound is a compound of Formula (4).
6. A method of preparing a compound of Formula (2):
comprising (i) contacting a compound of Formula (1) with trifluoroacetic acid:
7. The method of claim 6 , further comprising (ii) contacting the compound of Formula (2) with pivaloyl chloride, thereby forming a compound of Formula (3):
8. The method of claim 7 , further comprising contacting the compound of Formula (2) with sodium hydride prior to the contacting of (ii).
9. The method of claim 7 , further comprising purifying the compound of Formula (3).
10. The method of claim 7 , further comprising (iii) contacting the compound of Formula (3) with (+)-(8,8-dichlorocamphorylsulfonyl)oxaziridine, thereby forming a compound of Formula (4):
11. The method of claim 10 , further comprising contacting the compound of Formula (3) with sodium hexamethyldisilazide prior to the contacting of (iii).
12. The method of claim 10 , further comprising purifying the compound of Formula (4).
13. The method of claim 10 , further comprising (iv) contacting the compound of Formula (4) with hydrochloric acid, thereby forming a compound of the formula:
14. A method of preparing a compound of Formula (4):
comprising (iii) contacting a compound of Formula (3) with (+)-(8,8-dichlorocamphorylsulfonyl) oxaziridine:
15. The method of claim 14 , further comprising contacting the compound of Formula (3) with sodium hexamethyldisilazide prior to the contacting of (iii).
16. The method of claim 14 , further comprising purifying the compound of Formula (4).
17. The method of claim 14 , further comprising (iv) contacting the compound of Formula (4) with hydrochloric acid, thereby forming a compound of the formula:
18. The method of claim 14 , further comprising (ii) contacting a compound of Formula (2) with pivaloyl chloride:
thereby forming the compound of Formula (3).
19. The method of claim 18 , further comprising contacting the compound of Formula (2) with sodium hydride prior to the contacting of (ii).
20. The method of claim 18 , further comprising purifying the compound of Formula (3).