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Enaminones-Versatile Therapeutic Pharmacophores. Further Advances

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Enaminones, enamines of -dicarbonyl compounds, have been know for many years. In our initial account (Current Med. Chem. 1994, 1, 159-175), we reported on the anticonvulsant activity of a series of enaminones, notably methyl 4-[(p-chlorophenyl)amino]-6-methyl- 2-oxo-cyclohex-3-en-1-oate, 9a (R=CH 3 , R 1 =4-Cl), which, in animal tests, compared favorably to phenytoin and carbamazepine. Since that time, further research in our laboratory and other laboratories have expanded the therapeutic potential of these compounds. In addition to new anticonvulsant derivatives, we have uncovered a novel brain transport mechanism for the enaminones and developed a preliminary regression model for further synthetic direction. These topics will each be presented and elaborated.
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Keywords: bmec model; carbomethoxy; carbomethoxy monochloro analogues; chromatographic retention; congruent spatial relationship; enaminones versatile therapeutic pharmacophores; isoxazoles; multisubstitution; pyrrolidino enaminones; spartan programs; steric interactions; tonic clonic seizures

Document Type: Review Article

Publication date: 2000-04-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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