Novel, broad-spectrum anticonvulsants containing a sulfamide group: advancement of N-((benzo[b]thien-3-yl)methyl)sulfamide (JNJ-26990990) into human clinical studies.
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Parker MH, Smith-Swintosky VL, McComsey DF, Huang Y, Brenneman D, Klein B, Malatynska E, White HS, Milewski ME, Herb M, Finley MF, Liu Y, Lubin ML, Qin N, Iannucci R, Leclercq L, Cuyckens F, Reitz AB, Maryanoff BE
Novel, broad-spectrum anticonvulsants containing a sulfamide group: advancement of N-((benzo[b]thien-3-yl)methyl)sulfamide (JNJ-26990990) into human clinical studies.
J Med Chem. 2009 Dec 10;52(23):7528-36. doi: 10.1021/jm801432r.
- PubMed ID
- 19388676 [ View in PubMed]
- Abstract
In seeking broad-spectrum anticonvulsants to treat epilepsy and other neurological disorders, we synthesized and tested a group of sulfamide derivatives (4a-k, 5), which led to the clinical development of 4a (JNJ-26990990). This compound exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures, with very weak inhibition of human carbonic anhydrase-II (IC(50) = 110 microM). The pharmacological profile for 4a supports its potential in the treatment of multiple forms of epilepsy, including pharmacoresistant variants. Mechanistically, 4a inhibited voltage-gated Na(+) channels and N-type Ca(2+) channels but was not effective as a K(+) channel opener. The pharmacokinetics and metabolic properties of 4a are discussed.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Topiramate Carbonic anhydrase 2 Ki (nM) 300 N/A N/A Details Topiramate Carbonic anhydrase 2 IC 50 (nM) 2100 N/A N/A Details