Hypnotics ureide

Acylated derivatives of urea are referred to as ureides. Acylation of urea with a monoacid produces acyclic ureides, whereas diacylation with malonic acid (a diacid) yields the cyclic structure of barbiturates. The acyclic ureides carbromal and bromisoval, now outdated hypnotics, can be considered ring-opened analogues of the barbiturates to be examined in the next subsection. 

The barbiturates are substituted pyrimidine derivatives with an ureide configuration (Fig. 20.4). They are lipophilic weak acids (pKa 7-8) that are weii distributed into brain (see Appendix A for the respective pKa values). Although many barbiturates dispiay sedative-hypnotic activity (see Chapter 19), oniy a few have antiseizure properties. Paradoxically, many barbiturates cause convulsions at larger doses. The barbiturates clinically useful as AEDs are phenobarbital, mephobarbital, and primidone (Fig. 20.8). In laboratory animals, phenobarbital is effective by several tests in nontoxic doses. It is active against electrically induced seizures (MES), and it elevates the threshold for pentylenetetrazole stimulation. The mechanism of antiseizure action for the barbiturates... 

A Simple Gas Chromatographic Analysis for Commonly Used Hypnotics (Bromo-ureides, Novonal, and Barbiturates) Aerztl. Lab. 25(8) 189-194 (1979) CA 91 117076z... 

This interpretation shed a new and unfavourable light on the one-group one-action hypothesis that had dominated the thoughts of many workers in this field, especially in the drug industry (e.g. I. G. Farben, 1933-8 Dyson, 1928). This hypothesis had been born with the Crum Brown and Fraser correlation and was nurtured by Ehrlich s successes in the cure of trypanosomiasis and syphilis with the aromatic arsenicals, and by the wide range of barbiturates (and other ureides) that had shown hypnotic action. 

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