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 pharmaceutical composition comprising a compound of Formula I, wherein:
each of X 1 and X 2 is independently —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 —;
R 1 is —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 − , —(CH 2 ) a PO 3 H 2 , —(CH 2 ) a PO 3 H − , or —(CH 2 ) a PO 3 = ;
each of R 44 and R 49 is independently —H or —CH 3 ;
each of R 2 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 − , —(CH 2 ) a PO 3 H 2 , —(CH 2 ) a PO 3 H − , or —(CH 2 ) a PO 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.
2. The pharmaceutical composition as recited in claim 1 further comprising a pharmaceutically acceptable excipient.
3. The pharmaceutical composition as recited in claim 2 wherein the pharmaceutically acceptable excipient is chosen from a diluent, preservative, solubilizer, emulsifier, adjuvant, and carrier.
4. The pharmaceutical composition as recited in claim 2 wherein the pharmaceutical acceptable excipient is phosphate buffered saline.
5. The pharmaceutical composition as recited in claim 2 wherein the pharmaceutical composition is a liquid.