2. Academic Validation
  3. Novel, broad-spectrum anticonvulsants containing a sulfamide group: advancement of N-((benzo[b]thien-3-yl)methyl)sulfamide (JNJ-26990990) into human clinical studies

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.
Michael H Parker 1,  Virginia L Smith-Swintosky,  David F McComsey,  Yifang Huang,  Douglas Brenneman,  Brian Klein,  Ewa Malatynska,  H Steve White,  Michael E Milewski,  Mark Herb,  Michael F A Finley,  Yi Liu,  Mary Lou Lubin,  Ning Qin,  Robert Iannucci,  Laurent Leclercq,  Filip Cuyckens,  Allen B Reitz,  Bruce E Maryanoff
Affiliations

Affiliation

  • 1 Research and Early Development, Johnson & Johnson Pharmaceutical Research & Development, Spring House, Pennsylvania 19477-0776, USA.
PMID: 19388676 DOI: 10.1021/jm801432r
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.

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