Guilford Pharmaceuticals, Inc.

Keith M Maclin

Paul F Jackson

Barbara S Slusher

Kevin L Tays

Jie Zhang

Jia-He Li

Eric Yanjun Wang

Rena S Lapidus

Pavel Majer

Takashi Tsukamoto

Weixing Li

The present invention relates to PARP inhibitors, pharmaceutical compositions comprising the same, and methods of using the same to treat tissue damage resulting from cell damage or death due to necrosis or apoptosis, effect neuronal activities not mediated by NMDA toxicity; to treat neural tissue damage resulting from ischemia and reperfusion injury, neurological disorders and neurodegenerative diseases; to prevent or treat vascular stroke; to treat or prevent cardiovascular disorders; to treat other conditions and/or disorders such as age-related macular degeneration, AIDS and other immune senescence diseases, arthritis, atherosclerosis, cachexia, cancer, degenerative diseases of skeletal muscle involving replicative senescence, diabetes, head trauma, immune senescence, inflammatory bowel disorders (such as colitis and Crohn's disease), muscular dystrophy, osteoarthritis, osteoporosis, chronic and/or acute pain (such as neuropathic pain), renal failure, retinal ischemia, septic shock (such as endotoxic shock), organ damage due to transplantation, and skin aging; to extend the lifespan and proliferative capacity of cells; to alter gene expression of senescent cells; or to radiosensitize hypoxic tumor cells.

PARP inhibitors, pharmaceutical compositions comprising same, and methods of using same

Compounds, methods and pharmaceutical compositions for treating neural or cardiovascular tissue damage

The present disclosure relates to dipeptidase inhibitors, and more particularly, to novel phosphonate derivatives, hydroxyphosphinyl derivatives, and phosphoramidate derivatives that inhibit N-Acetylated &agr;-Linked Acidic Dipeptidase (NAALADase) enzyme activity, pharmaceutical compositions comprising such derivatives, and methods of using such derivatives to inhibit NAALADase activity, and to treat prostate diseases, especially using the compounds of the present invention for the inhibition of the growth of prostate cancer cells.

NAALADase inhibitors

The present invention relates to N-Acetylated &agr;-Linked Acidic Dipeptidase (NAALADase) inhibitors enzyme activity, pharmaceutical compositions comprising such inhibitors, and methods of their use to inhibit NAALADase enzyme activity, thereby effecting neuronal activities, inhibiting angiogenesis, and treating glutamate abnormalities, compulsive disorders, prostate diseases, pain and diabetic neuropathy.

NAALADase inhibitors useful as pharmaceutical compounds and compositions

Alkoxy-substituted compounds, methods and compositions for inhibiting parp activity

The present invention relates to a method of treating a glutamate abnormality and a method of effecting a neuronal activity in an animal using a NAALADase inhibitor, and a pharmaceutical composition comprising an effective amount of a NAALADase inhibitor for treating a glutamate abnormality and effecting a neuronal activity in an animal.

Pharmaceutical compositions and methods of effecting a neuronal activity in an animal using naaladase inhibitors

Alkoxy-substituted compounds, methods, and compositions for inhibiting PARP activity

The present disclosure relates to dipeptidase inhibitors, and more particularly, to novel methods of using phosphonate derivatives, hydroxyphosphinyl derivatives, and phosphoramidate derivatives to inhibit N-Acetylated &agr;-Linked Acidic Dipeptidase (NAALADase) enzyme activity, and to treat prostate diseases, especially using the compounds of the present invention for the inhibition of the growth of prostate cancer cells.

Methods of cancer treatment using NAALADase inhibitors

Poly(ADP-ribose) polymerase (&ldquo;PARP&rdquo;) inhibitors and methods for treating neurodegenerative diseases, neural tissue damage related to cerebral ischemia and reperfusion injury, and cardiovascular in an animal.

Poly(ADP-ribose) polymerase inhibitors and method for treating neural or cardiovascular tissue damage using the same

This invention relates to compounds, pharmaceutical compositions, and methods for the treatment or prevention of neural or cardiovascular tissue damage related to cerebral ischemia and reperfusion injury in an animal by administering Poly(ADP-ribose) polymerase (&ldquo;PARP&rdquo;) inhibitors.

The present invention relates to phosphonic acid derivatives that inhibit N-Acetylated &agr;-Linked Acidic Dipeptidase (NAALADase) enzyme activity, pharmaceutical compositions comprising such derivatives, and methods of using such derivatives to inhibit NAALADase activity, to treat a glutamate abnormality and to treat a prostate disease in an animal.

Phosphonic acid derivatives

The present invention relates to hydroxamic acid derivatives that inhibit N-Acetylated &agr;-Linked Acidic Dipeptidase (NAALADase) enzyme activity, pharmaceutical compositions comprising such derivatives, and methods of using such derivatives to inhibit NAALADase activity, to treat a glutamate abnormality and to treat a prostate disease in an animal.

Hydroxamic acid derivatives

The present invention relate to thio-substituted pentanedioic acid derivatives that inhibit N-Acetylated &agr;-Linked Acidic Dipeptidase (NAALADase) enzyme activity, pharmaceutical compositions comprising the same, and methods of using the same to inhibit NAALADase enzyme activity, to effect neuronal activities, to inhibit angiogenesis, and to treat glutamate abnormalities, compulsive disorders and prostate diseases.

Thio-substituted pentanedioic acid derivatives

A compound, compositions, methods of use, and processes of making formula I:

A compound of formula I: ##STR1## or a pharmaceutically acceptable salt, hydrate, ester, solvate, prodrug, metabolite, stereoisomer, or mixtures thereof, wherein: Y represents the atoms necessary to form a fused 5- to 6-membered, aromatic or non-aromatic, heterocyclic ring containing at least one nitrogen heteroatom in a 1,3-relationship with the nitrogen atom depicted in formula I, wherein Y may be unsubstituted or substituted with at least one alkyl, alkenyl, cycloalkyl, cycloalkenyl, aralkyl, aryl, double bonded oxygen, or --COOR.sup.5 group, or a moiety selected from the group consisting of: ##STR2## wherein R.sup.5 and R.sup.7 are independently hydrogen or alkyl, alkenyl, cycloalkyl, cycloalkenyl, aralkyl, or aryl.

Growing community of inventors

Baltimore, MD, United States of America

Keith M Maclin