Naaladase inhibitors
AssigneeGuilford Pharmaceuticals Inc.
InventorsPaul F. Jackson, Barbara S. Slusher
Life of this patent
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Abstract
The present disclosure relates to dipeptidase inhibitors, and more particularly, to N-Acetylated .alpha.-Linked Acidic Dipeptidase (NAALADase) enzyme inhibitors which are proposed as novel agents for the treatment of prostate cancer. NAALADase is enzyme which is a membrane-bound metalloprotease which hydrolyzes the dipeptide, N-acetyl-L-aspartate-L-glutamate (NAAG) to yield glutamate and N-acetylaspartate. The compounds of the present invention include phosphinic acid derivatives that inhibit NAALADase enzyme activity and which have been found useful for inhibiting the growth of prostate cancer cells.
Claims14
A compound having the formula:
- ##STR8## where R is Ar.sub.1, where Ar.sub.1 is selected from the group consisting of 2-indolyl, 3-indolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, and 4-pyridyl, wherein Ar.sub.1 is optionally substituted with at least one substituent selected from the group consisting of C.sub.3 -C.sub.8 cycloalkyl, C.sub.5 -C.sub.7 cycloalkenyl, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, hydroxy, halo, nitro, trifluoromethyl, C.sub.1 -C.sub.6 straight or branched chain alkyl, C.sub.2 -C.sub.6 straight or branched chain alkenyl, C.sub.1 -C.sub.4 alkoxy, C.sub.2 -C.sub.4 alkenyloxy, phenoxy, benzyloxy, 1-naphthyl, 2-naphthyl, phenyl, and Ar.sub.1, or a pharmaceutically acceptable salt, hydrate, or a mixture thereof.
A compound selected from the group consisting of:
- [2-[[2-(tetrahydrofuranyl)hydroxyphosphinyl]methyl]pentanedioic acid]
- 2-[[(2-tetrahydrofuranyl)hydroxyphosphinyl]methyl]pentanedioic acid;
- 2-[[(2-tetrahydropyranyl)hydroxyphosphinyl]methyl]pentanedioic acid;
- [2-[[((4-pyridyl)methyl)hydroxyphosphinyl]methyl]pentanedioic acid]
- 2-[[((4-pyridyl)methyl)hydroxyphosphinyl]methyl]pentanedioic acid;
- [2-[[((2-pyridyl)methyl)hydroxyphosphinyl]methyl]pentanedioic acid]
- 2-[[((2-pyridyl)methyl)hydroxyphosphinyl]methyl]pentanedioic acid;
- and a pharmaceutically acceptable salt, hydrate, or a mixture thereof.
Dependencies are inferred from the claim text.