Design, Synthesis, and Anticonvulsant Activity of 1-(Pyrid-3-ylsulfonamido)-2-nitroethylenes
- 24 July 1998
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 41 (17), 3239-3244
- https://doi.org/10.1021/jm981022n
Abstract
The lipophilic 1-cycloalkylamino-1-(pyrid-3-yl-sulfonamido)-2-nitroethylenes 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.Keywords
This publication has 15 references indexed in Scilit:
- Synthesis and biological evaluation of sulfonylcyanoguanidines and sulfonamidonitroethylenes as bioisosteres of hypoglycemic sulfonylureasEuropean Journal of Medicinal Chemistry, 1997
- Anticonvulsant Activity of Pyrid‐3‐yl‐Sulfonyl Ureas and ThioureasEpilepsia, 1997
- Update on the Mechanism of Action of Antiepileptic DrugsEpilepsia, 1996
- Bioavailability and Anticonvulsant Activity of 2-Cyanoguanidinophenytoin, a Structural Analogue of PhenytoinJournal of Pharmaceutical Sciences, 1996
- First synthesis of 4-substituted benzenesulfonylcyanoguanidinesTetrahedron Letters, 1996
- Synthesis and pharmacology of pyrid-3-ylsulfonylcyanoguanidines as diureticEuropean Journal of Medicinal Chemistry, 1995
- Antiepileptic Drug Mechanisms of ActionEpilepsia, 1995
- TorasemideDrugs, 1991
- Isosterism and molecular modification in drug designChemical Society Reviews, 1979
- Ketenderivate, XII. Beiträge zur Chemie der Dithiocarbonsäureester und KetenmercaptaleEuropean Journal of Inorganic Chemistry, 1967