Xanthurenic acid derivative pharmaceutical compositions and methods related thereto
OwnerNeal Bricker, Stewart Shankel +3inventors
InventorsNeal Bricker, Stewart Shankel, Christopher Cain, Mark Mitchnick, Michael Schmertzler
Life of this patent
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Abstract
The present invention relates to diuretic pharmaceutical compositions and methods and in particular to certain derivatives of the formula I: or a prodrug or pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
Claims37
A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I:
- wherein R1, R2, R3, R5, R6 and R7 are independently X3R where R is selected from the group consisting of H, halo;
- optionally substituted saccharide, aliphatic, cycloalkyl, heterocycloalkyl, aryl and heteroaryl;
- —P(O)(ORa)(ORb) and —NRaRb, where Ra and Rb are independently H, optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;
- X1, X2 and X3 are independently —C(O)O—, —OC(O)—, —C(O)NH—, —NHC(O)—, —OC(O)NH—, —NHC(O)O—, —OS(O)y—, —S(O)y—, —O—, —NHC(O)—, —NHC(O)O—, —S(O)2NH—, a bond or absent;
- where y is an integer from 0 to 3;
- and
- R4 and R8 are independently H, (═O);
- hydroxy;
- or optionally substituted saccharide, aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;
- or
- —P(O)(ORa)(ORb) or —NRaRb, where Ra and Rb are independently H, or optionally substituted aliphatic, cycloalkyl or heterocycloalkyl, aryl or heteroaryl;
- or
- a prodrug or pharmaceutically acceptable salt thereof;
- and
- a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising:
- (1) a therapeutically effective amount of a compound of formula I:
- wherein R1, R2, R3, R5, R6 and R7 are independently X3R where R is selected from the group consisting of H, halo;
- optionally substituted saccharide, aliphatic, cycloalkyl, heterocycloalkyl, aryl and heteroaryl;
- —P(O)(ORa)(ORb) and —NRaRb, where Ra and Rb are independently H, optionally substituted aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;
- X1, X2 and X3 are independently —C(O)O—, —OC(O)—, —C(O)NH—, —NHC(O)—, —OC(O)NH—, —NHC(O)O—, —OS(O)y—, —S(O)y—, —O—, —NHC(O)—, —NHC(O)O—, —S(O)2NH—, a bond or absent;
- where y is an integer from 0 to 3;
- and
- R4 and R8 are independently H, (═O);
- hydroxy;
- or optionally substituted saccharide, aliphatic, cycloalkyl, heterocycloalkyl, aryl or heteroaryl;
- or —P(O)(ORa)(ORb) or —NRaRb, where Ra and Rb are independently H, or optionally substituted aliphatic, cycloalkyl or heterocycloalkyl, aryl or heteroaryl;
- or
- a prodrug or pharmaceutically acceptable salt thereof;
- and
- (2) one or more additional diuretic compounds or cardiovascular compounds;
- and
- a pharmaceutically acceptable carrier.
An isolated antibody that specifically binds to xanthurenic acid-8-O-β-D-glucoside.
A diagnostic kit for assaying xanthurenic acid-8-O-β-D-glucoside in a serum sample, comprising one or more monoclonal antibodies directed against xanthurenic acid-8-O-β-D-glucoside.
A method for determining xanthurenic acid-8-O-β-D-glucoside present in a human serum sample, comprising:
- a. obtaining a human serum sample;
- b. exposing the human serum sample to one or more antibodies that specifically recognizes xanthurenic acid-8-O-β-D-glucoside, the one or more antibodies being present in a predetermined amount so that a portion of the one or more antibodies remain uncomplexed to the human xanthurenic acid-8-O-β-D-glucoside present in the sample;
- and
- c. measuring the amount of uncomplexed one or more antibodies so as to determine the xanthurenic acid-8-O-β-D-glucoside in the human serum sample.
A process for monitoring or detecting a disease associated with an abnormal level of xanthurenic acid-8-O-β-D-glucoside;
- the process comprising:
- a. exposing a biological sample to a monoclonal antibody directed against xanthurenic acid-8-O-β-D-glucoside;
- and
- b. detecting a level of xanthurenic acid-8-O-β-D-glucoside in said biological sample using the monoclonal antibody, wherein an elevated level of xanthurenic acid-8-O-β-D-glucoside in said biological sample is associated with the disease.
A method for the chromatographic quantification of xanthurenic acid-8-O-β-D-glucoside in a biological sample, the method comprising:
- a. obtaining a biological sample;
- b. injecting a known volume of the biological sample into the column of an HPLC unit;
- and
- c. determining the quantity of xanthurenic acid-8-O-β-D-glucoside in the biological sample relative to a standard of xanthurenic acid-8-O-β-D-glucoside.
A method of treatment of a disease or condition associated with decreased sodium reabsorption, the method comprising administering a therapeutically effective amount of a xanthurenic acid-8-O-β-D-glucoside antagonist.
Dependencies are inferred from the claim text.