Thiazole and thiadiazole inhibitors of tyrosine phosphatases
View Patent ↗Compounds and compositions are provided for modulating the activity of protein tyrosine phosphatases. In one embodiment, the compounds and compositions are thiazoles and thiadiazoles that inhibit the activity of protein tyrosine phosphatase 1B.
1. A compound that has formula II:
or a pharmaceutically acceptable salt, ester, enol ether, enol ester, solvate or hydrate thereof, wherein:
D is
E is CH 2 ;
s is 0;
R 8 and R 9 are H;
R 10 is halo;
R 11 is halo;
R 12 is H;
R 13 is CF 2 PO 3 H 2 ;
R 14 is halo;
R 15 is H;
R 16 is NHC(O)COOH or COOH;
and
R 17 is COO-alkyl.
2. The compound of claim 1 , wherein D is
E is CH 2 ;
s is 0;
R 8 and R 9 are H;
R 10 Cl;
R 11 is Cl;
R 12 is H;
R 13 is CF 2 PO 3 H 2 ;
R 14 is Cl or Br;
R 15 is H;
R 16 NHC(O)COOH or COOH; and
R 17 is COOMe.
3. The compound of claim 1 , wherein R 10 is Cl.
4. The compound of claim 1 , wherein R 11 is Cl.
5. The compound of claim 1 , wherein R 13 is CF 2 PO 3 H 2 .
6. The compound of claim 1 , wherein R 14 is Br.
7. The compound of claim 1 , wherein R 15 is H.
8. The compound of claim 1 , wherein R 16 is NHC(O)COOH or COOH.
9. The compound of claim 1 , wherein R 17 is COOMe.
10. The compound of claim 1 , wherein the compound is:
N-(4-{2-[[3-Bromo-4-(difluoro-phosphono-methyl)-benzyl]-(3 ,4-dichloro-phenyl)-amino]-thiazol-4-yl}-phenyl)-oxalamic acid.
11. The compound of claim 1 , wherein R 8 is H, R 9 is H, R 10 is Cl, R 11 is Cl, R 12 is H, R 13 is CF 2 PO 3 H 2 , R 14 is Br, R 15 is H, R 16 is NHC(O)COOH, R 17 is COOMe and s is zero (0).
12. A compound that has formula II:
or a pharmaceutically acceptable salt, ester, enol ether, enol ester, solvate or hydrate thereof, wherein:
D is
E is CH 2 ;
s is 0;
R 8 and R 9 are H;
R 10 is halo;
R 11 is halo;
R 12 is H;
R 13 is CF 2 PO 3 H 2 ;
R 13 is CF 2 PO 3 H 2 ;
R 14 is halo;
R 15 is H;
R 16 is NHC(O)COOH; and
R 17 is H or, COO-alkyl.
13. The compound of claim 12 , wherein D is
E is CH 2 ;
s is 0;
R 8 and R 9 are H;
R 10 is Cl;
R 11 is Cl;
R 12 is H;
R 13 is CF 2 PO 3 H 2 ;
R 14 is Cl or Br;
R 15 is H;
R 16 is NHC(O)COOH; and
R 17 is H or COOMe.
14. The compound of claim 12 , wherein R 10 is Cl.
15. The compound of claim 12 , wherein R 11 is Cl.
16. The compound of claim 12 , wherein R 14 is Br.
17. The compound of claim 12 , wherein R 17 is H or COOMe.
18. The compound of claim 17 , wherein R 17 is H.
19. The compound of claim 17 , wherein R 17 is COOMe.