Phosphate transport inhibitors
View Patent ↗Disclosed are compounds which have been identified as inhibitors of phosphate transport. Many of the compounds are represented by Structural Formula (I): Ar 1 —W—X—Y—Ar 2 ; or a pharmaceutically acceptable salt thereof. Ar 1 and Ar 2 are independently a substituted or unsubstituted aryl group or an optionally substituted five membered or six membered non-aromatic heterocylic group fused to an optionally substituted monocylic aryl group. W and Y are independently a covalent bond or a C1–C3 substituted or unsubstituted alkylene group. X is a heteroatom-containing functional group, an aromatic heterocyclic group, substituted aromatic heterocyclic group, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, an olefin group or a substituted olefin group. Also disclosed are methods of treating a subject with a disease associated with hyperphosphatemia, as well as a disease mediated by phosphate-transport function. The methods comprise the step of administering an effective amount of the one of the compounds described above.
1. A method of inhibiting phosphate transport in a subject in need of phosphate transport inhibition, said method comprising the step of administering an effective amount of a compound represented by the following structural formula:
wherein
R 9 is a halogen,
R 10 is a halogen, a substituted alkyl group, an alkoxy group, a substituted alkoxy group or —NO 2 ; and
Ring C is substituted with one or more substituents independently selected from a halogen, a hydroxy group, an alkoxy group, a lower alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, an aryloxy group, an aralkyl group, a heteroaralkyl group, —C(O)NR 4 R 5 , —C(O)OR 6 , —P(O)(OR 6 ) 2 , —NR 4 R 5 , —NCR 7 (PO 3 ) 2 , —NO 2 , SO 3 , —S(O) 2 R 6 , —C(O)R 7 , —SR 4 , —CR 7 ═NR 4 , —NR 4 SO 2 R 5 , —N═N—R 4 , —CN, —N 3 or —N═C═S,
R 4 , R 5 and R 6 are independently a hydrogen, lower alkyl group, heteroalkyl group, cycloalkyl group, aralkyl group, or heteroaralkyl group; and
R 7 is a hydrogen, lower alkyl group, heteroalkyl group, cycloalkyl group, an aryl group, a heteroaryl group, —OR 6 or —NR 4 R 5 .
2. The method of claim 1 , wherein said subject is in need of treatment for hyperphosphatemia.
3. The method of claim 1 , wherein the subject is in need of treatment for chronic renal failure.
4. The method of claim 1 , wherein the subject is in need of treatment for disorders of phosphate metabolism or impaired phosphate transport function.
5. The method of claim 1 , wherein the subject is in need of treatment for hyperparathyroidism, uremic bone disease, soft tissue calcification or osteoporosis.
6. The method of claim 1 , wherein the method further comprises co-administering one or more phosphate sequestrants to the subject.
7. The method of claim 6 , wherein the method further comprises co-administering sevelamer to the subject.
8. The method of claim 1 , wherein R 10 is a halogen or a substituted alkoxy group.
9. The method of claim 8 , wherein R 10 is a trifluoromethoxy group.
10. A method of inhibiting phosphate transport in a subject in need of phosphate transport inhibition, said method comprising the step of administering an effective amount of a compound represented by the following structural formula: