Selective hypoxia inducible factor prolyl-hydroxylase inhibitors
Synthesis and characterization of organoselenium-based triazolo pyrimidines and their use in treating hypoxia and inhibiting prolyl-hydroxylase domain (PHD) activity. The organoselenium-based triazolo pyrimidines have the formula: wherein R is selected from the group consisting of —SeCH 3 , —SePhenyl, —CH 2 SeCH 3 , and —CH 2 SePhenyl.
1. An organoselenium-based triazolo pyrimidine compound having the formula I:
wherein R is selected from the group consisting of —SeCH 3 , —SePhenyl, —CH 2 SeCH 3 , and —CH 2 SePhenyl.
2. The organoselenium-based triazolo pyrimidine compound of claim 1 , wherein the compound is selected from the group consisting of:
3. A pharmaceutically acceptable composition comprising a therapeutically effective amount of the organoselenium-based triazolo pyrimidine compound of claim 1 and a pharmaceutically acceptable carrier.
4. A method of treating hypoxia in a subject comprising administering to a subject in need thereof a therapeutically effective amount of the organoselenium-based triazolo pyrimidine compound of claim 1 .
5. A method of selectively inhibiting prolyl-hydroxylase domain (PHD) activity in a subject comprising administering to a subject in need thereof a therapeutically effective amount of the organoselenium-based triazolo pyrimidine compound of claim 1 .
6. The method of selectively inhibiting prolyl-hydroxylase domain (PHD) activity of claim 5 , wherein the inhibition of the PHD activity is effective for treating one or more of a cancer, renal anemia, and other chronic kidney diseases in the patient.
7. A method of making the organoselenium-based triazolo pyrimidine compound of claim 1 , the method comprising:
refluxing a first mixture of 3-amino-1,2,4,-triazole, acetyl acetone, and an organoselenium based aldehyde in DMF;
cooling the first mixture;
adding ethanol to the first mixture to obtain a second mixture;
refluxing the second mixture;
collecting a precipitate by filtration; and
obtaining the organoselenium-based triazolo pyrimidine compound.
8. The method of making the organoselenium-based triazolo pyrimidine compound of claim 7 , wherein the organoselenium based aldehyde is selected from the group consisting of
9. The method of making the organoselenium-based triazolo pyrimidine compound of claim 7 , wherein the 3-amino-1,2,4,-triazole, acetyl acetone, and organoselenium based aldehyde are present in the first mixture in a 1:1:1.1 equivalent ratio.
10. The method of making the organoselenium-based triazolo pyrimidine compound of claim 7 , wherein the first mixture is refluxed for about 6 hours.
11. The method of making the organoselenium-based triazolo pyrimidine compound of claim 7 , wherein the second mixture is refluxed for about 30 minutes.
12. The method of making the platinum (II) amino acid Schiff base complex of claim 7 , wherein, after refluxing, the second mixture is kept in the dark overnight.