| Identification | Back Directory | [Name]
(2S)-6-chloro-2-[(sulfamoylamino)methyl]-2,3-dihydro-1,4-benzodioxine | [CAS]
871824-55-4 | [Synonyms]
JNJ 26489112,JNJ26489112
(2S)-6-chloro-2-[(sulfamoylamino)methyl]-2,3-dihydro-1,4-benzodioxine
Sulfamide, N-[[(2S)-6-chloro-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]- | [Molecular Formula]
C9H11ClN2O4S | [MDL Number]
MFCD28411396 | [MOL File]
871824-55-4.mol | [Molecular Weight]
278.713 |
| Hazard Information | Back Directory | [Uses]
JNJ-26489112, a CNS-active agent, exhibits broad-spectrum anticonvulsant activity in rodents against audiogenic, electrically-induced, and chemically-induced seizures. JNJ-26489112 inhibits voltage-gated Na+ channels and N-type Ca2+ channels, and is effective as a K+ channel opener. JNJ-26489112 has very weak inhibition of CA-II (IC50=35 μM) and CA-I (18 μM)[1]. | [in vivo]
JNJ-26489112 (i.p.) effectively blocks chemically-induced, forelimb clonic seizures in mice ( male CF-1 albino mice) that are caused by subcutaneous bicuculine (Bic), picrotoxin (Pic), or pentylenetetrazol (PTZ), with 1-h ED50 values of 197, 189, or 109 mg/kg, respectively[1].
In adult male rats, JNJ-26489112 (p.o; 10 mg/kg) treatment shows the Cmax, tmax, F, t1/2, and AUC (total exposure) values in plasma were 9090 ng/mL (33 μM), 53 min, 95%, 8.2 h, and 53,200 ng-h/mL. Linear, dose-related increases in exposure were observed at 10, 30, and 300 mg/kg. JNJ-26489112 (i.v.; 2 mg/kg) treatment shows the Vdss is 390 mL/kg and the CL is 96 mL/h-kg. In female beagle dogs, JNJ-26489112 (p.o; 10 mg/kg) treatment shows the Cmax, tmax, F, t1/2, and AUC values in plasma are 11,500 ng/mL (41 μM), 55 min, 83%, 20 h, and 212,000 ng-h/mL. . JNJ-26489112 (i.v.; 2 mg/kg) treatment shows the the Vdss and CL values are 630 mL/kg and 30 mL/h-kg, respectively[1]. | [References]
[1] McComsey DF, et al. 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). J Med Chem. 2013;56(22):9019-9030. DOI:10.1021/jm400894u |
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