Pyrazine derivatives and uses thereof in renal monitoring
View Patent ↗The present invention relates to pyrazine derivatives such as those represented by Formulas (I) and (II) below. X 1 to X 4 of the compounds of Formulas I and II may be characterized as electron withdrawing groups. In contrast, Y 1 to Y 4 of the compounds of Formulas I and II may be characterized as electron donating groups. Pyrazine derivatives of the present invention may be utilized in assessing renal function. In particular, an effective amount of a pyrazine derivative of the invention may be administered into a body of a patient. The pyrazine derivative that is in the body may be exposed to visible and/or infrared light to cause spectral energy to emanate from the pyrazine derivative. This emanating spectral energy may be detected and utilized to determine renal function of the patient.
1. A compound of Formula I, wherein:
X 1 and X 2 are independently —CO(AA);
Y 1 and Y 2 are independently —OR 10 , —SR 11 , —NR 12 R 13 , —N(R 14 )COR 15 , —P(R 16 ) 2 or —P(OR 17 ) 2 ,
R 10 to R 17 are independently —H, —(CH 2 ) a OR 43 , —CH 2 (CHOH) a R 44 , —CH 2 (CHOH) a CO 2 H, —(CHCO 2 H) a CO 2 H, —(CH 2 ) a NR 45 R 46 , —CH[(CH 2 ) b NH 2 ] a CO 2 H, —CH[(CH 2 ) b NH 2 ] a CH 2 OH, —CH 2 (CHNH 2 ) a CH 2 NR 47 R 48 , —(CH 2 CH 2 O) c R 49 , —(CH 2 ) d CO(CH 2 CH 2 O) c R 50 , —(CH 2 ) a SO 3 H, —(CH 2 ) a SO 3 − , —(CH 2 ) a OSO 3 H, —(CH 2 ) a OSO 3 − , —(CH 2 ) a NHSO 3 H, —(CH 2 ) a NHSO 3 − , —(CH 2 ) a PO 3 H 2 , —(CH 2 ) a PO 3 H − , —(CH 2 ) a PO 3 = , —(CH 2 ) a OPO 3 H 2 , —(CH 2 ) a OPO 3 H − and —(CH 2 ) a OPO 3 ;
R 43 to R 50 are independently —H or —CH 3 ;
(AA) is a polypeptide chain comprising one or more natural or unnatural α-amino acids linked together by peptide bonds; and
‘a’, ‘b’, and ‘d’ independently vary from 1 to 10, and ‘c’ varies from 1 to 100.
2. The compound of claim 1 , wherein Y 1 and Y 2 are each independently —NR 12 R 13 .
3. The compound of claim 1 , wherein R 10 to R 17 are independently —H, —(CH 2 ) a OR 43 , —CH 2 (CHOH) a R 44 , —(CH 2 ) a NR 45 R 46 , —(CH 2 CH 2 O) c R 49 , or —(CH 2 ) d CO(CH 2 CH 2 O) d R 50 .
4. The compound of claim 1 , wherein R 10 to R 17 are independently —H, —(CH 2 ) a OR 43 , —CH 2 (CHOH) a R 44 , —(CH 2 ) a NR 45 R 46 , or —(CH 2 ) d CO(CH 2 CH 2 O) d R 50 .
5. The compound of claim 1 , wherein ‘a’, ‘b’, and ‘d’ independently vary from 1 to 6.
6. The compound of claim 1 , wherein ‘c’ varies from 1 to 20.
7. The compound of claim 1 , wherein the one or more α-amino acids of the polypeptide chain (AA) are selected from aspartic acid, asparigine, arginine, histidine, lysine, glutamic acid, glutamine, serine, and homoserine.
8. The compound of claim 1 , wherein the one or more α-amino acids of the polypeptide chain (AA) are selected from aspartic acid, glutamic acid, serine, and homoserine.
9. The compound of claim 1 , wherein the polypeptide chain (AA) is a homopolypeptide chain.
10. The compound of claim 1 , wherein the polypeptide chain (AA) is a heteropolypeptide chain.
11. The compound of claim 1 , wherein the polypeptide chain (AA) is aspartic acid or serine.
12. The compound of claim 2 , wherein each of R 12 and R 13 is —H.
13. The compound of claim 1 , wherein each (AA) is a single natural or unnatural α-amino acid.
14. The compound of claim 2 , wherein each (AA) is a single natural or unnatural α-amino acid.
15. The compound of claim 12 , wherein each (AA) is a single natural or unnatural α-amino acid.
16. The compound of claim 1 , wherein each (AA) is serine.
17. The compound of claim 16 , wherein each of Y 1 and Y 2 is —NR 12 R 13 .
18. The compound of claim 17 , wherein each of R 12 and R 13 is —H.