Yogeeswari P, Ragavendran J V, Thirumurugan R, Induja S, Sriram D, Stables J P
Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani-333031, India.
Med Chem. 2006 Jan;2(1):55-62. doi: 10.2174/157340606775197778.
Seven series of various substituted aryl semicarbazones were synthesized and evaluated for anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure threshold tests. A comprehensive structure-activity relationship was derived comparing the substituents on the aryl ring and in the carbimino terminal. Generally the order of activity was 4-F > 2-Br = 3-Br = 4-Cl > 4-CH(3) > 4-Br > 3-Cl > 3-CH(3) with respect to the primary aryl group. Most of the compounds exhibited activity both in the MES and scPTZ screens. The 4-fluorophenyl substituted semicarbazones (5a-5y) emerged as the most potent compounds exhibiting anticonvulsant activity in mouse intraperitoneal (i.p.) and rat per oral (p.o.) MES, scPTZ and psychomotor seizure (6 Hz) screens.
合成了七组各种取代的芳基氨基脲，并在最大电休克惊厥（MES）和皮下注射戊四氮（scPTZ）诱导的惊厥阈值试验中评估其抗惊厥活性。通过比较芳环和氨基末端的取代基，得出了全面的构效关系。一般来说，就主要芳基而言，活性顺序为4-F > 2-Br = 3-Br = 4-Cl > 4-CH(3) > 4-Br > 3-Cl > 3-CH(3)。大多数化合物在MES和scPTZ筛选中均表现出活性。4-氟苯基取代的氨基脲（5a-5y）在小鼠腹腔注射（i.p.）和大鼠口服（p.o.）的MES、scPTZ和精神运动性惊厥（6 Hz）筛选中成为表现出抗惊厥活性的最有效化合物。
