Pyrazine derivatives and uses thereof in renal monitoring

Patent metadata

Field	Value
Publication number	US-9480687-B2
Application number	US-201514805048-A
Country	US
Kind code	B2
Filing date	Jul 21, 2015
Priority date	Dec 23, 2004
Publication date	Nov 1, 2016
Grant date	Nov 1, 2016

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Medibeacon Llc
• Medibeacon Inc

Inventors

• Rajagopalan Raghavan
• Dorshow Richard B
• Neumann William L

Classifications

• A61K31/4965 Primary

  Non-condensed pyrazines · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• C07D241/26

  with nitrogen atoms directly attached to ring carbon atoms · CPC title

• A61K49/0054

  Macromolecular compounds, i.e. oligomers, polymers, dendrimers · CPC title

• A61K49/0021

  the fluorescent group being a small organic molecule · CPC title