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Despite the optimal use of the currently available antiepileptic drugs, 30 to 40% of the epileptic population fails to experience seizure control, and others do so only at the expense of significant toxic effects that range in severity from minimal brain impairment to death from aplastic anemia or hepatic failure.1-3) These facts provoked the need for new anticonvulsant drugs with higher potency and fewer side effects. Several studies reported that chromone derivatives are promising anticonvulsant candidates that perform their activity through a g-aminobutyric acid (GABA)-mediated mechanism. [4][5][6][7][8][9][10][11][12][13][14][15][16][17] Likewise, flavones (2-phenylbenzopyrons) are with a well known positive GABA-modulating ability; their central activity was attributed to their potential to penetrate the blood-brain barrier which is strongly correlated to their lipophilicity.18) Semicarbazones and their bioisosteres thiosemicarbazones, have a documented essential role in the design of novel anticonvulsant agents that performing their anticonvulsant activity also through a GABA-mediated mechanism.19-41) Extensive structure-activity relationship studies proposed certain pharmacophoric requirements for (thio)-semicarbazones interaction at the binding site which are a hydrophobic binding area represented by aryl or heteroaryl group and a hydrogen bonding domain represented by the NH-CO(S)-NH system. [24][25][26]33,38) It was suggested that (thio)semicarbazones anticonvulsant activity is mediated through GABA-mediated mechanism. 19,22,29,32,37,41) In the present investigation the two anticonvulsant candidates, chromones or flavones and thiosemicarbazones, were amalgamated to obtain more potent anticonvulsants compounds of series 1 and 2. In the synthesized hybrid compounds the chromone or the furochromone ring acts as the hydrophobic aryl ring required for binding which itself possesses anticonvulsant tendency. On the other hand, various bicyclic heterocycles containing thiosemicarbazono group showed significant anticonvulsant activity. 33,34,[42][43][44] Herein the tricyclic furochromone moiety was simplified to the bicyclic benzofuran system, which was reported to possess anticonvulsant activity [42][43][44] to give compounds of series 3. Obviously, the compounds of this series are the bicyclic analogs of the reported phenyl congener 4 synthesized by Dimmock et al. which showed marked anticonvulsant activity. 20) Replacement of the phenyl ring in 4 by the bicyclic benzofuran structure is thought to increase the hydrophobic aryl area which binds to the binding site and thus may enhance the binding. Moreover, the effect of the hydrophobic group on the terminal amino group of the thiosemicarbazono moiety was studied in the synthesized compounds of series 1, 2 and 3.Due to certain limitations associated with the (thio)semicarbazone functionality, mainly the poor solubility and liability to metabolism 45) ; improvement of the molecule, pharmacologically and pharmaceutically, was carried out by replacement of the th...

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Some new tetrahydropyrimidine-2-thione, octahydroquinazoline-2-thione and thiazolo[3,2-a]pyrimidine derivatives have been synthesized and tested for their antihypertensive activity. Among them, compounds 1 and 2b can be considered more potent than the reference, nifedipine (CAS 21829-25-4), while compounds 3b and 10a are equipotent to it. In addition, compound 6 showed significant antihypertensive activity.

Synthesis, Antiinflammatory and Ulcerogenicity Studies of Some Substituted Pyrimido[1,6-a]azepine Derivatives. -The amino group in key compound (Ia) is functionalized using common substitution or condensation reactions. All compounds are screened for their anti-inflammatory activity. Compounds (I) and (II) show activity similar to or higher than diclofenac sodium with no or minimal gastric ulceration. The most active compound with no ulcerogenic effect is (Ia). -(EL-SAYED, N. A.; AWADALLAH*, F. M.; IBRAHIM, N. A.; EL-SAADI, M. T.; Eur.