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:
each of X 1 and X 2 is independently —CN, —CO 2 R 1 , —CONR 2 R 3 , or —CONH(PS);
each of Y 1 and Y 2 is independently —NR 4 R 5 or
Z 1 is a single bond, —CR 18 R 19 —, —O—, —NR 20 —, —NCOR 21 —, —S—, —SO—, or —SO 2 —;
each of R 1 to R 5 and R 18 to R 21 is independently —H, —CH 2 (CHOH) a R 44 , —CH 2 (CHOH) a CO 2 H, —(CHCO 2 H) a CO 2 H, —(CH 2 CH 2 O) c R 49 , —(CH 2 ) a SO 3 H, —(CH 2 ) a SO 3 − , —(CH 2 ) a NHSO 3 H, —(CH 2 ) a NHSO 3 − ,
each of R 44 and R 49 is independently —H or —CH 3 ;
(PS) is a sulfated or non-sulfated polysaccharide chain comprising one or more monosaccharide units connected by glycosidic linkages; and
‘a’ is an integer from 1 to 10, ‘c’ is an integer from 1 to 100, and each of ‘m’ and ‘n’ independently is an integer from 1 to 3;
with the proviso that if:
each of X 1 and X 2 is independently —CN, —CO 2 R 1 or —CONR 2 R 3 ;
each of Y 1 and Y 2 is independently —NR 4 R 5 or
and
Z 1 is a direct bond, then:
each of R 1 , R 2 , R 3 , R 4 and R 5 is not simultaneously —H; and
m, n, N and Z 1 together do not form a 5- or 6-membered ring.
2. The compound of claim 1 , wherein each of X 1 and X 2 is independently —CONR 2 R 3 , and each of Y 1 and Y 2 is independently —NR 4 R 5 .
3. The compound of claim 2 , wherein each of R 2 and R 4 is —H, and R 3 is —CH 2 (CHOH) a R 44 or —(CH 2 CH 2 O) c R 49 , and R 5 is —H or —(CH 2 CH 2 O) c R 49 .
4. The compound of claim 3 , wherein R 3 is —(CH 2 CH 2 O) c R 49 , and R 5 is —H.
5. The compound of claim 4 , wherein R 49 is —CH 3 , and ‘c’ is an integer from 1 to 20.
6. The compound of claim 1 , wherein each of X 1 and X 2 is independently —CO 2 R 1 , and each of Y 1 and Y 2 is independently —NR 4 R 5 .
7. The compound of claim 6 , wherein each of R 1 and R 4 is —H, and R 5 is —CH 2 (CHOH) a R 44 or —(CH 2 CH 2 O) c R 49 .
8. The compound of claim 7 , wherein R 44 is —H, R 49 is —CH 3 , ‘a’ is an integer from 1 to 6, and ‘c’ is an integer from 1 to 20.
9. The compound of claim 1 , wherein each of X 1 and X 2 is —CN, and each of Y 1 and Y 2 is
—NR 4 R 5 .
10. The compound of claim 9 , wherein R 4 is —H, and R 5 is —CH 2 (CHOH) a R 44 or —(CH 2 CH 2 O) c R 49 .
11. The compound of claim 10 , wherein R 44 is —H, R 49 is —CH 3 , ‘a’ is an integer from 1 to 6, and ‘c’ is an integer from 1 to 20.
12. The compound of claim 1 , wherein each of X 1 and X 2 is —CONH(PS), and each of Y 1 and Y 2 is —NR 4 R 5 .
13. The compound of claim 12 , wherein each of R 4 and R 5 is independently —H or —CH 2 (CHOH) a R 44 .
14. The compound of claim 13 , wherein each of R 4 and R 5 is —H.
15. The compound of claim 12 , wherein the one or more monosaccharide units of the polysaccharide chain (PS) are selected from the group consisting of glucose, fructose, mannose, xylose, and ribose.