Design, synthesis, and anticonvulsant activity of 1-(pyrid-3-ylsulfonamido)-2-nitroethylenes.

Abstract

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.

• Authors: B Masereel, J Wouters, L Pochet, D Lambert
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 41 Issue 17 Pg. 3239-44 (Aug 13 1998) ISSN: 0022-2623 [Print] United States
• PMID: 9703469 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Convulsants
• Neurotoxins
• BM 34
• Phenytoin
• Thiourea

Topics

• Animals
• Anticonvulsants (chemical synthesis, chemistry, pharmacology)
• Convulsants
• Crystallography, X-Ray
• Drug Design
• Electroshock
• Male
• Mice
• Mice, Inbred Strains
• Models, Molecular
• Molecular Conformation
• Molecular Structure
• Neurotoxins (chemistry, pharmacology)
• Phenytoin (pharmacology)
• Seizures (chemically induced, drug therapy)
• Stereoisomerism
• Structure-Activity Relationship
• Thiourea (analogs & derivatives, chemical synthesis, chemistry, pharmacology)