Three series of amidoxime derivatives including nitrous derivatives of a-chloro-a-isonitrosoacetone and hydrochlorides of O-aroyl-b-aminopropioamidoximes and 3-[b-(piperidin-1-yl)]ethyl-5-aryl-1,2,4-oxadiazoles were tested for conduction, infiltration, and terminal anesthesia. There are four interesting "hit" compounds, i.e., the hydrochloride of O-m-chlorophenyl-b-(benzimidazol-1-yl)propioamidoxime (VII), the hydrochlo-, which exhibit higher activity than the reference drugs (trimecaine, lidocaine, novocaine, kazcaine). As a whole, all tested compounds were active in conduction and infiltration anesthesia (at the level of the reference drugs) and did not show activity in terminal anesthesia. Compounds VII -X are of interest for further testing under condition and infiltration anesthesia conditions. Amidoximes are an attractive class of compounds with respect to their versatile reactivity at the imine and amine N atoms and the oxime O atom. As a result, various heterocyclic and linear derivatives containing pharmacophores that exhibit a broad spectrum of biological activity can be prepared [1]. These include antituberculosis, antimicrobial, antiviral, insecticidal, fungicidal, herbicidal, antidepressant, antihistamine, anti-inflammatory, local anesthetic, pyretic, etc. Several amidoximes are already used as drugs or are being tested in various phases of incorporation into medical 468 0091-150X/11/4508-0468 Note: p 1 , correlation coefficient relative to trimecaine; p 2 , relative to lidocaine; p 3 , relative to novocaine; p 4 , relative to kazcaine.

Synthesis of 2-[2-(5-Phenyl-1,2,4,oxadiazol-3-yl)ethyl]benzimidazole and ItsX-Ray Analysis. -The biologically active substrate (I) is dehydrated to the title compound (II) for further activity studies. -(KAYUKOVA*, L. A.; BEKETOV, K. M.; AKHELOVA, A. L.; PRALIEV, K. D.; Chem. Heterocycl. Compd. (N. Y.) 42 (2006) 7, 914-917; Bekturov Inst. Chem. Sci., Min. Educ. Sci., Almaty 480100, Kazakhstan; Eng.) -C. Cyrus

Keywords: O-benzoyl-2-(benzimidazol-1-yl)propioamidoxime, 2-[2-(5-phenyl-1,2,4-oxadiazol-3-yl)-ethyl]benzimidazole, dehydration, X-ray analysis.We have previously shown [1, 2] that heating O-aroyl-2-piperidino(morpholino)propioamidoximes in DMF solution at 60°C for 1-2.5 h (method A) causes cyclization to the corresponding oxadiazoles whereas heating in the solid phase for 30 seconds (method B) is sufficient to bring about the reaction.Since the O-benzoyl-2-(benzimidazol-1-yl)propioamidoxime hydrochloride (1) prepared by us [3, 4] shows antitubercular and neuropharmacological activity we have carried out the dehydration of its base in order to study further the biological activity of the 2-[2-(5-phenyl-1,2,4-oxadiazol-3-yl)ethyl]benzimidazole (2) formed. It was found that the cyclodehydration of base 1 using method A needs a much longer time (4 days) (yield 42%) than a simple melting of crystalline 1 (method B) when compound 2 was obtained in 58% yield after only 7 minutes. The structure of the compound obtained was confirmed from its 1 H NMR spectrum and elemental analysis and by X-ray analysis which showed it to be 2-[2-(5-phenyl-1,2,4-oxadiazol-3-yl)ethyl]benzimidazole (2) (Figs. 1 and 2). N N NOCOPh NH 2 N N O N N Ph (CH 2 ) 2 C A. DMF, 60-65°C, 4 days B. ∆, mp, 7 min (CH 2 ) 2 1 2The values of the valence bonds of oxadiazole 2 (Fig. 1) are close to standard. As might be expected, the six-membered ring of the benzimidazole substituent in the molecule 2 is planar to within 0.001 and the fivemembered ring to 0.002 Å respectively. The angle between the mean square planes of these rings is 0.8(3)°. The oxadiazole and phenyl rings (planar to within 0.004 and 0.002 Å respectively) lie in a single plane. The dihedral angle between them is 1.4(4)°.