Masereel B, Wouters J, Pochet L, Lambert D
Department of Pharmacy and Laboratory of Molecular Structures, University of Namur, FUNDP, 61, rue de Bruxelles, 5000 Namur, Belgium.
J Med Chem. 1998 Aug 13;41(17):3239-44. doi: 10.1021/jm981022n.
The lipophilic 1-cycloalkylamino-1-(pyrid-3-yl-sulfonamido)-2-nitr oethylenes were synthesized as bioisosteres of BM-34, an anticonvulsant sulfonylthiourea. Compound 17 (ip) emerged from the maximal electroshock seizure (MES) test with a 50% effective dose (ED50) of 8.25 mg/kg. Its anticonvulsant profile was similar to that of phenytoin (ED50 = 9.51 mg/kg) and of BM-34 (ED50 = 1.19 mg/kg): active in the MES test and inactive in seizures induced by subcutaneous injection of pentetrazole, strychnine, bicuculline, picrotoxin, or N-methyl-D,L-aspartate. The neurotoxicity of 17 (TD50 = 113.8 mg/kg) was lower than that of phenytoin (TD50 = 65.5 mg/kg) but higher than that of BM-34 (TD50 = 147.2 mg/kg). Crystallographic study revealed that BM-401 (17) was a zwitterionic structure. Its sulfonamido nitroethylene side chain adopted a conformation which placed the two cycloalkyl rings face to face to form a single hydrophobic area.
合成了亲脂性的1-环烷基氨基-1-(吡啶-3-基-磺酰胺基)-2-硝基乙烯，作为抗惊厥磺酰硫脲BM-34的生物电子等排体。化合物17（腹腔注射）在最大电休克惊厥（MES）试验中出现，半数有效剂量（ED50）为8.25 mg/kg。其抗惊厥谱与苯妥英（ED50 = 9.51 mg/kg）和BM-34（ED50 = 1.19 mg/kg）相似：在MES试验中具有活性，而在皮下注射戊四氮、士的宁、荷包牡丹碱、印防己毒素或N-甲基-D，L-天冬氨酸诱导的惊厥中无活性。17的神经毒性（TD50 = 113.8 mg/kg）低于苯妥英（TD50 = 65.5 mg/kg），但高于BM-
