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.
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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)
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Chemical References |
- Anticonvulsants
- Convulsants
- Neurotoxins
- BM 34
- Phenytoin
- Thiourea
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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)
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