Pro-neuron, Inc.

Wellstat Therapeutics Corporation

Other

Michael K Bamat

Reid W Von Borstel

Reid Warren Von Borstel

Bradley M Hiltbrand

Shalini Sharma

James C Butler

Shyam Shirali

Stephen D Wolpe

Kirvin L Hodge

James Dennen O'Neil

Ramachandran Arudchandran

Reld W Von Borstel

James Dennen O'neil

Borstel Reid W Von

Uric acid in mammalian subjects is reduced and excretion of uric acid is increased by administering a compound of Formula I or a pharmaceutically acceptable salt thereof.  In Formula I m is 0, 1, 2, 3 or 4; n is 0 or 1; m+n is not more than 4; t is 0 or 1; q is 0 or 1; and r is 0, 1 or 2. Ris hydrogen, methyl or ethyl and Ris hydrogen or methyl, or Ris hydroxy and Ris hydrogen, or Ris O and Ris absent, or Rand Rtogether are &#x2014;CHCH&#x2014;. Ris hydrogen or alkyl having from 1 to 3 carbon atoms. One of Rand Ris alkyl having from 1 to 3 carbon atoms, and the other is hydrogen or alkyl having from 1 to 3 carbon atoms. Ris hydrogen, halo, alkyl having from 1 to 3 carbon atoms or alkoxy having from 1 to 3 carbon atoms. X is C(O) and r is 0 and t is 0; or X is NH(R) wherein Ris hydrogen or alkyl having from 1 to 3 carbon atoms. A is phenyl, unsubstituted or substituted by 1 or 2 groups selected from halo, hydroxy, methyl, ethyl, perfluoromethyl, methoxy, ethoxy, and perfluoromethoxy; or a 5 or 6 membered heteroaromatic ring having 1 or 2 ring heteroatoms selected from N, S and O and the heteroaromatic ring is covalently bound to the remainder of the compound of Formula I by a ring carbon; or cycloalkyl having from 3 to 6 ring carbon atoms wherein the cycloalkyl is unsubstituted or one or two ring carbons are independently monosubstituted by methyl or ethyl. The uric acid-lowering effects of the Compounds of Formula I are used to treat or prevent a variety of conditions including gout, hyperuricemia, elevated levels of uric acid that do not meet the levels customarily justifying a diagnosis of hyperuricemia, renal dysfunction, kidney stones, cardiovascular disease, risk for developing cardiovascular disease, tumor-lysis syndrome, and cognitive impairment.

Compounds and method for reducing uric acid

Uric acid in mammalian subjects is reduced and excretion of uric acid is increased by administering a compound of Formula I or a pharmaceutically acceptable salt thereof.  In Formula I m is 0, 1, 2, 3 or 4; n is 0 or 1; t is 0 or 1; q is 0 or 1; and r is 0, 1 or 2. Ris hydrogen, O or hydroxyl. Ris hydrogen or alkyl having from 1 to 3 carbon atoms. One of Rand Ris alkyl having from 1 to 3 carbon atoms, and the other is hydrogen or alkyl having from 1 to 3 carbon atoms. Ris hydrogen, halo, alkyl having from 1 to 3 carbon atoms or alkoxy having from 1 to 3 carbon atoms. X is C(O) and r is 0 and t is 0; or X is NH(R) wherein Ris hydrogen or alkyl having from 1 to 3 carbon atoms. A is phenyl, unsubstituted or substituted by 1 or 2 groups selected from halo, hydroxy, methyl, ethyl, perfluoromethyl, methoxy, ethoxy, and perfluoromethoxy; or a 5 or 6 membered heteroaromatic ring having 1 or 2 ring heteroatoms selected from N, S and O and the heteroaromatic ring is covalently bound to the remainder of the compound of Formula I by a ring carbon; or cycloalkyl having from 3 to 6 ring carbon atoms wherein the cycloalkyl is unsubstituted or one or two ring carbons are independently monosubstituted by methyl or ethyl. The uric acid-lowering effects of the Compounds of Formula I are used to treat or prevent a variety of conditions including gout, hyperuricemia, elevated levels of uric acid that do not meet the levels customarily justifying a diagnosis of hyperuricemia, renal dysfunction, kidney stones, cardiovascular disease, risk for developing cardiovascular disease, tumor-lysis syndrome, and cognitive impairment.

Compounds useful for the treatment of various metabolic disorders, such as insulin resistance syndrome, diabetes, hyperlipidemia, fatty liver disease, cachexia, obesity, atherosclerosis and arteriosclerosis, are disclosed.

Method for the treatment of metabolic disorders

The subject invention discloses compounds, compositions and methods for treatment and prevention of toxicity due to chemotherapeutic agents and antiviral agents. Disclosed are acylated derivatives of non-methylated pyrimidine nucleosides. These compounds are capable of attenuating damage to the hematopoietic system in animals receiving antiviral or antineoplastic chemotherapy.

Treatment of chemotherapeutic agent and antiviral agent toxicity with acylated pyrimidine nucleosides

Pyrimidine nucleotide precursors including acyl derivatives of cytidine, uridine, and orotate, and uridine phosphorylase inhibitors, and their use in enhancing resistance to sepsis or systemic inflammation are disclosed.

Pyrimidine nucleotide precursors for treatment of systemic inflammation and inflammatory hepatitis

The invention relates to certain oxypurine nucleosides, congeners of such oxypurine nucleosides, and acyl derivatives thereof, and compositions which contain at least one of these compounds. The invention also relates to methods of treating or preventing hematopoietic disorders and modifying hematopoiesis, and treating or preventing inflammatory diseases and bacterial infections by administering a compound or composition of the present invention to an animal.

Oxpurine nucleosides and their congeners, and acyl, derivatives thereof, for improvement of hematopoiesis

The invention relates to compositions comprising acyl derivatives of 2'-deoxyribonucleosides. The invention also relates to methods of treating or preventing radiation, mutagen and sunlight-induced biological damage, and methods for improving wound healing and tissue repair, comprising administering the compositions of the present invention to an animal.

Acyl deoxyribonucleoside derivatives and uses thereof

The invention relates to compositions comprising acyl derivatives of cytidine and uridine. The invention also relates to methods of treating hepatopathies, diabetes, heart disease, cerebrovascular disorders, Parkinson's disease, infant respiratory distress syndrome and for enhancement of phospholipid biosynthesis comprising administering the acyl derivatives of the invention to an animal.

Acylated uridine and cytidine and uses thereof

The invention relates to compositions comprising 2'-deoxyribonucleosides. The invention also relates to methods of accelerating the healing of wounds, abrasions, cuts, incisions, and superficial burns induced by heat, sunlight, chemical agents, or infections, and methods for ameliorating the effects of aging of the epidermal tissues comprising administering the compositions of the present invention to an animal.

Pharmaceutical compositions containing deoxyribonucleosides for wound healing

The invention relates to compositions comprising acyl derivates of 2&prime;-deoxyribonucleosides. The invention also relates to methods of treating or preventing radiation, mutagen and sunligth-induced cellular damage, methods for improving wound healing and tissue repair, and methods for ameliorating the effects of aging comprising administering the composition of the present invention to an animal.

The invention relates to compositions comprising acyl derivatives of 2&prime;-deoxyribonucleosides. The invention also relates to methods of treating or preventing radiation, mutagen and sunlight-induced biological damage, and methods for improving wound healing and tissue repair, comprising administering the compositions of the present invention to an animal.

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Potomac, MD, United States of America

Michael K Bamat