Organic compounds -- part of the class 532-570 series – Organic compounds – Phosphorus esters
Reexamination Certificate
2000-09-20
2002-03-12
Higel, Floyd D. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Phosphorus esters
C558S158000, C558S161000, C558S162000, C558S163000
Reexamination Certificate
active
06355823
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to compounds that are inhibitors of intestinal apical membrane Na/phosphate co-transportation, medications containing these compounds, and methods for inhibiting sodium-mediated phosphate uptake, reducing serum PTH, calcium, calcitriol, and phosphate, and treating renal disease with these compounds and medications containing them.
2. Description of the Related Art
In 1995, 260,000 people with end-stage renal disease were being treated in this country at a Medicare cost of $9 billion. Another 500,000 people were diagnosed with chronic renal failure. Increasing the time for progression from chronic renal failure to end-stage renal failure by control of serum PTH, calcium, calcitriol, and phosphate, while improving patient nutritional status, would drastically reduce the projected cost of the 500,000 patients progressing to end-stage renal failure and improve the survival of those undergoing dialysis.
However, the medications currently available are less than adequate to address these problems. It would be desirable to develop medications capable of controlling serum PTH, calcium, calcitriol, and phosphate.
BRIEF SUMMARY OF THE INVENTION
In a first aspect, this invention provides compounds of formula (I):
where:
A
1
and A
2
are the same or different aryl groups collectively bearing at least one hydrophilic substituent;
E
1
and E
2
are the same or different and are O, S, or NR
2
(where R
2
is a linear or branched C
1
-C
20
carbon containing group);
M is H or a pharmaceutically acceptable monovalent cation;
R
1
is a linear or branched, saturated or unsaturated, C
1
-C
20
carbon containing group;
Z is a single bond, a carbonyl, CE
3
E
4
, or CR
3
E
3
, where
E
3
and E
4
are the same or different and are OR
4
, SR
4
, or NR
4
2
, where
R
3
is a linear or branched C
1
-C
20
carbon containing group, and
R
4
is H or a linear or branched C
1
-C
20
carbon containing group; and
n is 0 or 1,
or a pharmaceutically acceptable salt thereof, provided that the compound is not 4′-phosphophloretin or a pharmaceutically acceptable salt thereof.
These compounds are hydrophilic aryl phosphate, thiophosphate, and aminophosphate intestinal apical membrane Na-mediated phosphate co-transportation inhibitors; and are useful for inhibiting sodium-mediated phosphate uptake, reducing serum PTH, calcium, calcitriol, and phosphate, and treating renal disease.
In a second aspect, this invention provides a medication including a therapeutically effective amount of at least one compound of formula (I) or 4′-phosphophloretin in a suitable carrier.
In a third aspect, this invention provides a method of inhibiting sodium-mediated phosphate uptake, reducing serum PTH, calcium, calcitriol, and phosphate, and treating renal disease in an animal, including a human, by administering to that animal a therapeutically effective amount of at least one compound of formula (I) or 4′-phosphophloretin, or a medication containing it.
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Board of Regents , The University of Texas System
Braman & Rogalskyj LLP
Higel Floyd D.
Sackey Ebenezer
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