Certain phosphonomethyl-pentanedioic acid derivatives thereof
AssigneeGuilford Pharmaceuticals Inc.
InventorsPaul F. Jackson, Barbara S. Slusher
Life of this patent
Estimating the term…
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.
Claims11
A compound having the formula:
- ##STR8## where R is a C.sub.1 -C.sub.9 straight or branched chain alkyl, C.sub.2 -C.sub.9 straight or branched chain alkenyl group, C.sub.3 -C.sub.8 cycloalkyl, C.sub.5 -C.sub.7 cycloalkenyl, phenyl, 1-naphthyl, 2-naphthyl, or phenyl(C.sub.1 -C.sub.4 alkyl), wherein said alkyl, alkenyl, cycloalkyl, cycloalkenyl, phenyl, 1-naphthyl, 2-napthyl, or phenyl (C.sub.1 -C.sub.4 alkyl) groups are optionally substituted with a 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.1 -C.sub.4 alkenyl, hydroxy, halo, hydroxyl, nitro, trifluoromethyl, C.sub.1 -C.sub.6 straight or branched chain alkyl or alkenyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkenyloxy, phenoxy, benzyloxy, amino, and Ar.sub.1, where Ar.sub.1 is selected from the group consisting of 1-naphthyl, 2-naphthyl, and phenyl, and where Ar.sub.1 has one to three substituents which are independently selected from the group consisting of hydrogen, halo, hydroxyl, nitro, trifluoromethyl, C.sub.1 -C.sub.6 straight or branched alkyl or alkenyl, C.sub.1 -C.sub.4 alkoxy or C.sub.1 -C.sub.4 alkenyloxy, phenoxy, benzyloxy, and amino;
- or a pharmaceutically acceptable salt, hydrate or a mixture thereof.
A compound selected from the group consisting of:
- 2-methylhydroxyphosphinyl!methyl!pentanedioic acid;
- 2-ethylhydroxyphosphinyl!methyl!pentanedioic acid;
- 2-propylhydroxyphosphinyl!methyl!pentanedioic acid;
- 2-butylhydroxyphosphinyl!methyl!pentanedioic acid;
- 2-cyclohexylhydroxyphosphinyl!methyl!pentanedioic acid;
- 2-phenylhydroxyphosphinyl!methyl!pentanedioic acid;
- 2-(phenylmethyl)hydroxyphosphinyl!methyl!pentanedioic acid;
- 2-((2-phenylethyl)methyl)hydroxyphosphinyl!methyl!pentanedioic acid;
- 2-((3-phenylpropyl)methyl)hydroxyphosphinyl!methyl!pentanedioic acid;
- 2-((3-phenylbutyl)methyl)hydroxyphosphinyl!methyl!pentanedioic acid;
- 2-((2-phenylbutyl)methyl)hydroxyphosphinyl!methyl!pentanedioic acid;
- 2-(4-phenylbutyl)hydroxyphosphinyl!methyl!pentanedioic acid;
- 2-(aminomethyl)hydroxyphosphinyl!methyl!pentanedioic acid;
- or a
- pharmaceutically acceptable salt, hydrate or a mixture thereof.
A compound selected from the group consisting of:
- 2-methylhydroxyphosphinyl!methyl!pentanedioic acid;
- 2-ethylhydroxyphosphinyl!methyl!pentanedioic acid;
- 2-propylhydroxyphosphinyl!methyl!pentanedioic acid;
- 2-phenylhydroxyphosphinyl!methyl!pentanedioic acid;
- 2-phenylmethylhydroxyphosphinyl!methyl!pentanedioic acid;
- or a pharmaceutically acceptable salt, hydrate or a mixture thereof.
Dependencies are inferred from the claim text.