Patents by Inventor Valentin K. Gribkoff
Valentin K. Gribkoff has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20090005304Abstract: 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.Type: ApplicationFiled: June 28, 2007Publication date: January 1, 2009Inventors: Steven I. Dworetzky, Chandra S. Ramanathan, Joanne T. Trojnacki, Christopher G. Boissard, Valentin K. Gribkoff
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Patent number: 7041496Abstract: 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.Type: GrantFiled: April 24, 2002Date of Patent: May 9, 2006Assignee: Bristol-Myers SquibbInventors: Michael A. Blanar, Steven Dworetzky, Wen-Pin Yang, Paul C. Levesque, Valentin K. Gribkoff, Michael G. Neubauer, Wayne A. Little
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Patent number: 6893858Abstract: 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.Type: GrantFiled: May 24, 2001Date of Patent: May 17, 2005Assignee: Bristol-Myers Squibb CompanyInventors: Steven I. Dworetzky, Chandra S. Ramanathan, Joanne T. Trojnacki, Valentin K. Gribkoff
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Patent number: 6855829Abstract: 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.Type: GrantFiled: February 14, 2002Date of Patent: February 15, 2005Assignee: Bristol-Myers Squibb CompanyInventors: Steven I. Dworetzky, Valentin K. Gribkoff, Gene G. Kinney, Piyasena Hewawasam
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Publication number: 20020183335Abstract: There is provided a method of treatment for disorders responsive to the modulation of KCNQ potassium channels by administering to a mammal in need thereof a therapeutically effective amount of a 2,4-disubstituted pyrimidine-5-carboxamide derivative of the Formula I 1Type: ApplicationFiled: February 14, 2002Publication date: December 5, 2002Inventors: Piyasena Hewawasam, Dharmpal S. Dodd, Charles D. Weaver, Pierre Dextraze, Valentin K. Gribkoff, Gene G. Kinney, Steven I. Dworetzky
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Publication number: 20020168724Abstract: 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.Type: ApplicationFiled: April 24, 2002Publication date: November 14, 2002Inventors: Michael A. Blanar, Steven Dworetzky, Wen-Pin Yang, Paul C. Levesque, Valentin K. Gribkoff, Michael G. Neubauer, Wayne A. Little
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Publication number: 20020156120Abstract: There is provided novel 3-fluoro-3-phenyl oxindole derivatives of Formula I 1Type: ApplicationFiled: February 14, 2002Publication date: October 24, 2002Inventors: Piyasena Hewawasam, Pierre Dextraze, Valentin K. Gribkoff, Gene G. Kinney, Steven I. Dworetzky
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Patent number: 6469042Abstract: There is provided novel 3-fluoro-3-phenyl oxindole derivatives of Formula I wherein R1, R2, R3 and R4 each are independently hydrogen, C1-4 alkyl, halogen, fluoromethyl, trifluoromethyl, phenyl, 4-methylphenyl or 4-trifluoromethylphenyl; R5 is C1-6 alkyl optionally substituted with one to three same or different groups selected from fluoro and chloro, provided R5 is not C1-6 alkyl when Y is O; Y is O or S; and R6 and R7 each are independently hydrogen, chloro, bromo or trifluoromethy; which are openers of the KCNQ potassium channels and are useful in the treatment of disorders which are responsive to the opening of the KCNQ potassium channels.Type: GrantFiled: February 14, 2002Date of Patent: October 22, 2002Assignee: Bristol-Myers Squibb CompanyInventors: Piyasena Hewawasam, Pierre Dextraze, Valentin K. Gribkoff, Gene G. Kinney, Steven I. Dworetzky
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Publication number: 20020128277Abstract: 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.Type: ApplicationFiled: February 14, 2002Publication date: September 12, 2002Inventors: Steven I. Dworetzky, Valentin K. Gribkoff, Gene G. Kinney, Piyasena Hewawasam
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Publication number: 20020045566Abstract: The present invention describes calcium sensitive and selective maxi-K potassium channel opener/activator compounds that function to open maxi-K channels under conditions of high intracellular calcium concentrations, and which do not significantly affect the opening of maxi-K channel proteins under conditions of low or physiologically normal intracellular calcium concentrations. Methods of assaying for and using such compounds are also provided. According to the invention, whole cell voltage patch-clamp studies newly demonstrated that the ability of opener compounds, e.g., fluoro-oxindoles and chloro-oxindoles, to open maxi-K channels was sensitive to the intracellular Ca2+ concentration ([Ca2+])i, i.e., more channels opened at more negative potentials.Type: ApplicationFiled: October 12, 2001Publication date: April 18, 2002Inventors: Valentin K. Gribkoff, Debra J. Post-Munson, Sarita W. Yeola, Christopher G. Boissard, Piyasena Hewawasam, John E. Starrett
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Publication number: 20020040000Abstract: 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.Type: ApplicationFiled: May 24, 2001Publication date: April 4, 2002Inventors: Steven I. Dworetzky, Chandra S. Ramanathan, Joanne T. Trojnacki, Christopher G. Boissard, Valentin K. Gribkoff
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Patent number: 6326526Abstract: 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.Type: GrantFiled: January 7, 2000Date of Patent: December 4, 2001Assignees: Bristol-Myers Squibb Company, The General Hospital CorporationInventors: Steven M. Reppert, Valentin K. Gribkoff
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Patent number: 6271249Abstract: Novel compounds of Formula 1 are useful to treat disorders responsive to openers of the large conductance calcium-activated potassium channels: wherein “Het” is one of a select group of heterocyclic moieties; Z is independently for each occurrence selected from O or S; Ra, Rb and Rc each are independently selected from hydrogen, halogen, OH, CF3, NO2, or provided Rc is not hydrogen; and when Ra and Rb are hydrogen, Rc may be a heterocyclic moiety selected from the group consisting of imidazol-1-yl, morpholinomethyl, N-methylimidazol-2-yl, and pyridin-2-yl; Rd and Re each are independently selected from hydrogen, halogen, CF3, NO2 or imidazol-1-yl; m, n and p each are independently selected from an integer of 0 or 1; and Rf and Rg each are independently hydrogen; C1-4 alkyl; or Rf and Rg, 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,Type: GrantFiled: March 29, 2000Date of Patent: August 7, 2001Assignee: Bristol-Myers Squibb CompanyInventors: Jeffrey L. Romine, Scott W. Martin, Piyasena Hewawasam, Nicholas A. Meanwell, Valentin K. Gribkoff, John E. Starrett, Jr.
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Patent number: 6077861Abstract: 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.Type: GrantFiled: November 23, 1998Date of Patent: June 20, 2000Assignee: Bristol-Myers Squibb CompanyInventors: Jeffrey L. Romine, Scott W. Martin, Piyasena Hewawasam, Nicholas A. Meanwell, Valentin K. Gribkoff, John E. Starrett, Jr.
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Patent number: 5869509Abstract: 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.Type: GrantFiled: July 30, 1997Date of Patent: February 9, 1999Assignee: Bristol-Myers Squibb CompanyInventors: Jeffrey L. Romine, Scott W. Martin, Piyasena Hewawasam, Nicholas A. Meanwell, Valentin K. Gribkoff, John E. Starrett, Jr.
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Patent number: 5621007Abstract: 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.Type: GrantFiled: April 28, 1995Date of Patent: April 15, 1997Assignee: Bristol-Myers Squibb CompanyInventors: Valentin K. Gribkoff, Steven I. Dworetzky, Davis L. Temple
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Patent number: 5602169Abstract: There is provided novel substituted 3-phenyl oxindole derivatives of the formula ##STR1## whereinR is hydrogen, hydroxy or fluoro;R.sup.1, R.sup.2, R.sup.3 and R.sup.4 each are independently hydrogen, C.sub.1-4 alkyl, halogen, trifluoromethyl, phenyl, p-methylphenyl or p-trifluoromethylphenyl; or R.sup.1 and R.sup.2, R.sup.2 and R.sup.3 or R.sup.3 and R.sup.4 are joined together to form a benzo fused ring;R.sup.5 is hydrogen or C.sub.1-4 alkyl; andR.sup.6 is chlorine or trifluoromethyl; or a nontoxic pharmaceutically acceptable salt, solvate or hydrate thereof, which are openers of the large-conductance calcium-activated potassium channels and are useful in the treatment of disorders which are responsive to the opening of the potassium channels.Type: GrantFiled: April 19, 1996Date of Patent: February 11, 1997Assignee: Bristol-Myers Squibb CompanyInventors: Piyasena Hewawasam, Nicholas A. Meanwell, Valentin K. Gribkoff
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Patent number: 5565483Abstract: There is provided novel substituted 3-phenyl oxindole derivatives of the formula ##STR1## wherein R is hydrogen, hydroxy or fluoro; R.sup.1, R.sup.2, R.sup.3and R.sup.4 each are independently hydrogen, C.sub.1-4 alkyl, halogen, trifluoromethyl, phenyl, p-methylphenyl or p-trifluoromethylphenyl; or R.sup.1 and R.sup.2, R.sup.2 and R.sup.3 or R.sup.3 and R.sup.4 are joined together to form a benzo fused ring;R.sup.5 is hydrogen or C.sub.1-4 alkyl; andR.sup.6 is chlorine or trifluoromethyl;or a nontoxic pharmaceutically acceptable salt, solvate or hydrate thereof, which are openers of the large-conductance calcium-activated potassium channels and are useful in the treatment of disorders which are responsive to the opening of the potassium channels.Type: GrantFiled: June 7, 1995Date of Patent: October 15, 1996Assignee: Bristol-Myers Squibb CompanyInventors: Piyasena Hewawasam, Nicholas A. Meanwell, Valentin K. Gribkoff