Inhibitors of intestinal apical membrane Na/phosphate co-transportation
AssigneeBoard of Regents, The University of Texas System
InventorBrian E. Peerce
Life of this patent
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Abstract
The compounds of formula (I) are hydrophilic aryl phosphate, thiophosphate, and aminophosphate intestinal apical membrane Na-mediated phosphate co-transportation inhibitors. The compounds can be administered orally, where they act to inhibit Na-dependent phosphate uptake in the intestines, or internally, where they interact with the phosphate control functions of the kidneys and parathyroid. They are therefore useful for inhibiting sodium-mediated phosphate uptake, reducing serum PTH, calcium, calcitriol, and phosphate, and treating renal disease in an animal, including a human.
Claims57
A method for inhibiting activity of an alkaline phosphatase, said method comprising contacting the alkaline phosphatase with a compound of formula (I):
- where:
- A1 and A2 are the same or different aryl groups collectively bearing at least one hydrophilic substituent;
- E1 and E2 are the same or different and are O, S, or NR2 (where R2 is a linear or branched C1-C20 carbon containing group);
- M is H or a pharmaceutically acceptable monovalent cation;
- R1 is a linear or branched, saturated or unsaturated, C1-C20 carbon containing group;
- Z is a single bond, a carbonyl, CE3E4, or CR3E3, where
- E3 and E4 are the same or different and are OR4, SR4, or NR42, where
- R3 is a linear or branched C1-C20 carbon containing group, and
- R4 is H or a linear or branched C1-C20 carbon containing group;
- and
- n is 0 or 1,
- or a pharmaceutically acceptable salt thereof.
A method for inhibiting activity of an alkaline phosphatase in a subject, said method comprising administering to the subject a compound of formula (I):
- where
- A1 and A2 are the same or different aryl groups collectively bearing at least one hydrophilic substituent;
- E1 and E2 are the same or different and are O, S, or NR (where R2 is H or a linear or branched C1-C20 carbon containing group);
- M is H or a pharmaceutically acceptable monovalent cation;
- R1 is a linear or branched, saturated or unsaturated, C1-C20 carbon containing group;
- Z2 is a single bond, a carbonyl, CE3E4, or CR3E4, where
- E3 and E4 are the same or different and are OR4, SR4, and NR42, where
- R3 is a linear or branched C1-C20 carbon containing group;
- and
- R4 is H or a linear or branched C1-C20 carbon containing group;
- and
- n is 0 or 1,
- or a pharmaceutically acceptable salt thereof.
A method for inhibiting sodium-mediated phosphate uptake, said method comprising contacting a compound of formula (I):
- where:
- A1 and A3 are the same or different aryl groups collectively bearing at least one hydrophilic substituent;
- E1 and E3 are the same or different and are O, S, or NR2 (where R3 is H or a linear or branched C1-C20 carbon containing group);
- M is H or a pharmaceutically acceptable monovalent cation;
- R1 is a linear or branched, saturated or unsaturated, C1-C20 carbon containing group;
- Z is a single bond, a carbonyl, CE3E4, or CR3E4, where
- E3 and E4 are the same or different and are OR4, SR4, and NR43, where
- R3 is a linear or branched C1-C20 carbon containing group, and
- R4 is H or a linear or branched C1-C20, carbon containing group;
- and
- n is 0 or 1,
- or a pharmaceutically acceptable salt thereof;
- with intestinal brush border membrane under conditions effective to inhibit sodium-mediated phosphate uptake.
Dependencies are inferred from the claim text.