- Novel, broad-spectrum anticonvulsants containing a sulfamide group: Pharmacological properties of (S)- N -[(6-chloro-2,3-dihydrobenzo[1,4]dioxin-2- yl)methyl]sulfamide (JNJ-26489112)
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Broad-spectrum anticonvulsants are of considerable interest as antiepileptic drugs, especially because of their potential for treating refractory patients. Such "neurostabilizers" have also been used to treat other neurological disorders, including migraine, bipolar disorder, and neuropathic pain. We synthesized a series of sulfamide derivatives (4-9, 10a-i, 11a, 11b, 12) and evaluated their anticonvulsant activity. Thus, we identified promising sulfamide 4 (JNJ-26489112) and explored its pharmacological properties. Compound 4 exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures. Mechanistically, 4 inhibited voltage-gated Na+ channels and N-type Ca2+ channels and was effective as a K+ channel opener. The anticonvulsant profile of 4 suggests that it may be useful for treating multiple forms of epilepsy (generalized tonic-clonic, complex partial, absence seizures), including refractory (or pharmacoresistant) epilepsy, at dose levels that confer a good safety margin. On the basis of its pharmacology and other favorable characteristics, 4 was advanced into human clinical studies.
- McComsey, David F.,Smith-Swintosky, Virginia L.,Parker, Michael H.,Brenneman, Douglas E.,Malatynska, Ewa,White, H. Steve,Klein, Brian D.,Wilcox, Karen S.,Milewski, Michael E.,Herb, Mark,Finley, Michael F. A.,Liu, Yi,Lubin, Mary Lou,Qin, Ning,Reitz, Allen B.,Maryanoff, Bruce E.
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p. 9019 - 9030
(2014/01/06)
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- USE OF BENZO-FUSED HETEROCYLE SULFAMIDE DERIVATIVES FOR THE TREATMENT OF ANXIETY
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The present invention is a method for the treatment of anxiety and related disorders comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle sulfamide derivatives of formula (I)
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Page/Page column 15
(2009/10/06)
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- USE OF BENZO-FUSED HETEROCYCLE SULFAMIDE DERIVATIVES FOR THE TREATMENT OF PAIN
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The present invention is a method for the treatment of pain comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle sulfamide derivatives of formula (I) and formula (II) as desc
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Page/Page column 14
(2008/06/13)
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- USE OF BENZO-FUSED HETEROCYCLE SULFAMIDE DERIVATIVES FOR DISEASE MODIFICATION / EPILEPTOGENESIS
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The present invention is a method for treating, preventing, reversing, arresting or inhibiting the occurrence, development and maturation of seizures or seizure-related disorders. More specifically, the present invention is directed to methods for the use
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Page/Page column 20
(2008/06/13)
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- CO-THERAPY FOR THE TREATMENT OF EPILEPSY AND RELATED DISORDERS
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The present invention is directed to co-therapy for the treatment of epilepsy and related disorders comprising administering to a subject in need thereof, co-therapy with a therapeutically effective amount of a benzo-fused heterocycle sulfamide derivative
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Page/Page column 33-34
(2008/06/13)
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- USE OF BENZO-FUSED HETEROCYCLE SULFAMIDE DERIVATIVES FOR LOWERING LIPIDS AND LOWERING BLOOD GLUCOSE LEVELS
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The present invention is a method for the glucose related disorders and lipid related disorders comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle sulfamide derivatives of
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Page/Page column 15
(2010/11/27)
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- USE OF BENZO-FUSED HETEROCYCLE SULFAMIDE DERIVATIVES AS NEUROPROTECTIVE AGENTS
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The present invention is a methods for neuroprotection, for treating an acute neurodegenerative disorder, for treating a chronic neurodegenerative disorder and/or for preventing neuron death or damage following brain, head and/or spinal cord trauma or inj
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Page/Page column 12
(2010/11/27)
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- USE OF BENZO-FUSED HETEROCYCLE SULFAMIDE DERIVATIVES FOR THE TREATMENT OF SUBSTANCE ABUSE AND ADDICTION
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The present invention is a method for the treatment of alcohol abuse and/or addiction comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle sulfamide derivatives of formula (I
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Page/Page column 12-13
(2010/11/27)
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- USE OF BENZO-FUSED HETEROCYLE SULFAMIDE DERIVATIVES FOR THE TREATMENT OF MANIA AND BIPOLAR DISORDER
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The present invention is a method for the treatment of mania and/or bipolar disorder comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle sulfamide derivatives of formula (I)
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Page/Page column 15
(2010/11/27)
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- USE OF BENZO-FUSED HETEROCYCLE SULFAMIDE DERIVATIVES FOR THE TREATMENT OF DEPRESSION
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The present invention is a method for the treatment of depression comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle sulfamide derivatives of formula (I) and formula (II) a
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Page/Page column 14
(2010/11/27)
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- USE OF BENZO-FUSED HETEROCYCLE SULFAMIDE DERIVATIVES FOR THE TREATMENT OF OBESITY
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The present invention is a method for the treatment of obesity, for promoting weight loss and / or suppressing appetite comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle s
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Page/Page column 32-33
(2010/11/27)
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- USE OF BENZO-FUSED HETEROCYLE SULFAMIDE DERIVATIVES FOR THE TREATMENT OF MIGRAINE
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The present invention is a method for the treatment or prevention of migraine comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle sulfamide derivatives of formula (I) and fo
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Page/Page column 15
(2010/11/28)
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- SULFAMATE AND SULFAMIDE DERIVATIVES FOR THE TREATMENT OF EPILEPSY AND RELATED DISORDERS
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The present invention is directed to novel sulfamide and sulfamate derivatives, pharmaceutical composlons containing them and their use in the treatment of epilepsy and related disorders.
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Page/Page column 37
(2010/02/15)
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- Comparison of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II by using topiramate as a structural platform
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This paper examines the relative effectiveness of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II (CA-II). Topiramate (1) and its sulfamide analogue 4, and 4,5-cyclic sulfate 6 and its sulfamide analogue 5, were compared for inhibition of human CA-II. A colorimetric assay, based on the pH shift that accompanies hydration of carbon dioxide, and an esterase assay were used. For these bioisosteric pairs, 1/4 and 6/5, the sulfamate compound was markedly more potent than its sulfamide counterpart. A similar, large difference in potency was also observed for the sulfamate/sulfamide pairs 14/15 and 16/17. These results indicate that the sulfamide moiety is not particularly suitable for obtaining potent carbonic anhydrase inhibition. A discussion of this structure-activity relationship with respect to the interactions of 1 and 6 with CA-II from published X-ray data is presented. A metabolic acidosis study was performed in rats with 1, 4, 6, and 2, and the results are discussed with respect to the degree of inhibition of CA-II in vivo.
- Maryanoff, Bruce E.,McComsey, David F.,Costanzo, Michael J.,Hochman, Coralie,Smith-Swintosky, Virginia,Shank, Richard P.
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p. 1941 - 1947
(2007/10/03)
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- Novel sulfamate and sulfamide derivatives useful for the treatment of epilepsy and related disorders
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The present invention is directed to novel sulfamide and sulfamate derivatives, pharmaceutical compositions containing them and their use in the treatment of epilepsy and related disorders.
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Page/Page column 16
(2010/11/29)
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