1: J Med Chem 1998 Aug 13;41(17):3239-44
Design, synthesis, and anticonvulsant activity of 1-(pyrid-3-ylsulfonamido)-2-nitroethylenes.
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.
bernard.masereel@fundp.ac.be
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.
PMID: 9703469, UI: 98369076