Bristol-myers Squibb Compnay

Knopp Neurosciences, Inc.

Other

Bristol-myers Squibb

Knopp Biosciences, LLC

Valentin K Gribkoff

Piyasena Hewawasam

Nicholas A Meanwell

Michael E Bozik

Thomas Petzinger, Jr

Steven Dworetzky

John E Starrett, Jr

Jeffrey Lee Romine

Scott W Martin

Gene G Kinney

Chandra S Ramanathan

Vivekananda M Vrudhula

Bireshwar Dasgupta

Wen-Pin Yang

Michael A Blanar

Pierre Dextraze

Paul Charles Levesque

Michael G Neubauer

Steven M Reppert

Davis L Temple

Wayne A Little

Christopher G Boissard

Joanne T Trojnacki

Steven I Dworetzky

Thomas Petzinger

Pharmaceutical compositions of (R)-pramipexole and one or more secondary therapeutic agents such as, for example, dopamine agonists, dopaminergic agonists, COMT inhibitors, MOA inhibitors, excitatory amino acid antagonists, growth factors, neurotrophic factors, antioxidants, anti-inflammatory agents, immunomodulators, anti-glutamatergics, ion channel blockers, &#x3b1;-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, heat shock protein inducers/protein disaggregators and downregulators, monoamine oxidase type B (MOAB) inhibitors, multi-target agents, kinase inhibitors, Bcl inducers, histone deacetylase (HDAC) mediators, glial modulators, mitochondrial energy promoting agents, myostatin inhibitors, caspase inhibitors and combinations thereof or those related to mitochondrial dysfunction or increased oxidative stress are disclosed.

Compositions and methods of using (R)-pramipexole

Modified release pharmaceutical compositions (controlled release, sustained release, and/or extended release) of the R-(+) enantiomer of pramipexole (RPPX) and methods of using such compositions for the treatment of neurodegenerative diseases, or those related to mitochondrial dysfunction or increased oxidative stress are disclosed.

Modified release formulations of (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine and methods of using the same

Pharmaceutical compositions of (R)-pramipexole and methods and kits of using such compositions for the treatment of neurodegenerative diseases, or those related to mitochondrial dysfunction or increased oxidative stress are disclosed.

Compositions of predetermined amounts of R(+) pramipexole and S(&#x2212;) pramipexole and methods of using the same, including for the treatment and prevention of Parkinson's disease, are provided.

Compositions of R(+) and S(&#x2212;) pramipexole and methods of using the same

The present invention relates to KCNQ proteins defining potassium channels. In particular, the invention concerns the human KCNQ2, human KCNQ3, murine KCNQ2, and rat KCNQ2 proteins reported herein. KCNQ2 and KCNQ3 proteins are nervous system-selective and may be involved in neurotransmission and neuroprotection. The KCNQ2 and KCNQ3 of the present invention can be used to assay for modulators of the proteins, which would be useful in treatment of such disorders as ataxia, myokymia, seizures, Alzheimer's disease, Parkinson's disease, age-associated memory loss, learning deficiencies, motor neuron diseases, epilepsy, stroke, and the like.

DNA encoding rodent KCNQ2 potassium channel

Atropisomers of 3-substituted-4-arylquinolin-2-one derivatives having the general formulawherein R, R, R, R, Rand R, are as defined herein, or a non-toxic pharmaceutically acceptable salt, solvate or prodrug thereof. The atropisomers can modulate the large conductance calcium-activated Kchannels and are useful in the treatment of disorders which are responsive to the opening of the potassium channels. In addition, the atropisomers can be stable, i.e., do not interconvert, for periods of up to one month, or more.

Atropisomers of 3-substituted-4-arylquinolin-2-one derivatives

An isolated polynucleotide encoding a novel potassium channel polypeptide, KCNQ5, that is expressed primarily in brain and skeletal muscle is described. The new polypeptide has been cloned and isolated from a human brain cDNA library and is a member the KCNQ family of potassium channels. The provided human KCNQ5 nucleic acid sequence and encoded polypeptide can be employed for diagnostic, screening and therapeutic uses. Moreover, the hKCNQ5 polypeptide can be used to assay for KCNQ5 potassium channel modulators, which can be utilized in the treatment of neurological, neurophysiological, neuropsychological and neuroaffective diseases, conditions and disorders, including, but not limited to, acute and chronic pain, migraine, acute stroke, dementia, vascular dementia, trauma, epilepsy, amyelotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's Disease, learning and cognitive disorders, and neurophysiological disorders including anxiety disorders, depression, bipolar disorders, sleep disorders, addiction, and eating disorders.

Human kcnq5 potassium channel, methods and compositions thereof

Compounds which function as modulators, particularly, openers, of human KCNQ potassium channel proteins or polypeptides, particularly, central nervous system (CNS)-located KCNQ potassium channels, and heteromultimers thereof, and their use in the treatment of migraine are provided by the present invention. One novel type of potassium channel polypeptide openers provided by the present invention is the fluorooxindole compounds, described for the first time as therapeutics for the treatment of migraine by preventing the asynchronous firing of neurons. Other KCNQ potassium channel opener compounds that are also useful in the treatments of the invention include 2,4-disubstituted pyrimidine-5-carboxamide derivatives. One or more of the compounds according to the present invention may be utilized alone, in combination, or in conjunction with other treatment modalities for reducing, ameliorating and/or alleviating migraine or diseases similar to, or mechanistically related to, migraine, e.g., cluster headache.

3-fluoro-2-oxindole modulators of KCNQ potassium channels and use thereof in treating migraine and mechanistically related disease

Fluoro oxindole derivatives as modulators if KCNQ potassium channels

Disclosed are mice containing a targeted disruption of various melatonin receptor subtypes, and methods of using the mice to identify agonists and antagonists of melatonin.

Melatonin receptor-deficient mice and uses thereof

Novel compounds of Formula 1 are useful to treat disorders responsive to openers of the large conductance calcium-activated potassium channels:

Diphenyl imidazoles as potassium channel modulators

Novel compounds of Formula 1 are useful to treat disorders responsive to openers of the large conductance calcium-activated potassium channels: ##STR1## wherein 'Het' is one of a select group of heterocyclic moieties; Z is independently for each occurrence selected from O or S; R.sup.a, R.sup.b and R.sup.c each are independently selected from hydrogen, halogen, OH, CF.sub.3, NO.sub.2, or ##STR2## provided R.sup.c is not hydrogen; and when R.sup.a and R.sup.b are hydrogen, R.sup.c may be a heterocyclic moiety selected from the group consisting of imidazol-1-yl, morpholinomethyl, N-methylimidazol-2-yl, and pyridin-2-yl; R.sup.d and R.sup.e each are independently selected from hydrogen, halogen, CF.sub.3, NO.sub.2 or imidazol-1-yl; m, n and p each are independently selected from an integer of O or 1; and R.sup.f and R.sup.g each are independently hydrogen; C.sub.1-4 alkyl; or R.sup.f and R.sup.g, taken together with the nitrogen atom to which they are attached, is a heterocyclic moiety selected from the group consisting of N-methylpiperazine, morpholine, thiomorpholine, N-benzylpiperazine and imidazolinone.

Diphenyl triazoles as potassium channel modulators

Novel compounds of Formula 1 are useful to treat disorders responsive to openers of the large conductance calcium-activated potassium channels: ##STR1## wherein 'Het' is one of a select group of heterocyclic moieties; Z is independently for each occurrence selected from O or S; R.sup.a, R.sup.b and R.sup.c each are independently selected from hydrogen, halogen, OH, CF.sub.3, ##STR2## provided R.sup.c is not hydrogen; and when R.sup.a and R.sup.b are hydrogen, R.sup.c may be a heterocyclic moiety selected from the group consisting of imidazol-1-yl, morpholinomethyl, N-methylimidazol- 2-yl, and pyridinyl; R.sup.d and R.sup.e each are independently selected from hydrogen, halogen, CF.sub.3, NO.sub.2 or imidazol-1-yl; m, n and p each are independently selected from an integer of O or 1; and R.sup.f and R.sup.g each are independently hydrogen; C.sub.1-4 alkyl; or R.sup.f and R.sup.g, taken together with the nitrogen atom to which they are attached, is a heterocyclic moiety selected from the group consisting of N-methylpiperazine, morpholine, thiomorpholine, N-benzylpiperazine and imidazolinone.

Diphenyl oxadiazolones as potassium channel modulators

Methods for the therapy of cystic fibrosis and multi-drug resistance in cancer chemotherapy by administering to a patient in need thereof 5-trifluoroethyl-1-(5-chloro-2-hydroxyphenyl)-1,3-dehydro-2H-benzimidazol- 2-one (NSOO4) or a pharmaceutically acceptable salt thereof.

Growing community of inventors

Wallingford, CT, United States of America

Valentin K Gribkoff