3-Sphere approach is applied on prediction dihedral angle θHnHn+1[deg] only from vicinal coupling constant 3JHnHn+1[Hz] with Java script, in comparation with angles calculated from the differences between two atoms of carbon chemical shift (ΔδCnCn+1[ppm]) and Karplus equations. The trigonometric equations 1, 2 ensuring the right sign along the D-, L series rule.

Direct iodination of sydnones has been achieved using iodine monochloride, leading to yields in excess of 80%. The products were subjected to 1,3-dipolar cycloaddition reactions affording novel 5-iodopyrazoles, To date, there has been only one report on the direct iodination of the sydnone ring, the reagent used being N-iodosuccinimide and the reported yield rather low (23 %). [l] Previously, two indirect methods had been described, which involved treatment of the GrignardL2] or 4-chloromerc~r y [~I [~l derivatives of the sydnones with iodine. In 1957, Ohta and KatoL21 claimed to have obtained the 4-iodo-3-phenylsydnone (2c) by iodination of the corresponding bromo derivative. However, the procedure was not mentioned in a review article by the same authors[5] published in 1969. The only 4-iodo-substituted sydnones described in literature are those bearing 3-phenyl, L2]L3l 3-(3-pyridyl) ['l and 3-(2-amin0phenyl)[~I groups.We have obtained excellent results in the direct iodination of the sydnone ring by using the mild reagent iodine monochloridelacetic acid. This reagent has been used in the iodination of activated aromatic compounds such as acetanilide, p-nitrophenol, salicylic acid and p-nitroaniline, affording either mono-or diiodo derivatives. c6] More recently, the same method has been used for iodination of 2-and 6-aminopyrimidine derivatives in the 5-position. C7l 8-Hydroxyquinolines were iodinated in the 7-position by using ethanol in place of acetic acid. ['] Sydnones la-j could be readily iodinated with this reagent in the presence of an equivalent amount of sodium acetate added to neutralize the hydrochloric acid formed in the reaction. The products were obtained in a highly pure state and in yields of over 80%. Eight new 4-iodosydnones (2a-b, d-j) were obtained by this method. Yields, melting points, and 'H-and 13C-NMR data are given in Table 1 and elemental analyses in Table 3. 13C-NMR spectra of 4-iodo-and 4-bromosydnones have not previously been measured and there is only one published example of that of a chloro derivative.L9I Upon examination of the 13C-NMR spectra of the 4-iodosydnones a strong negative increment could be observed at C-4 (A6 = 38.5-45.1). A weak influence on the polarization of the carbonyl group could also be observed with bromine and chlorine as substituents. A shielding effect of the 3-phenyl group on C-4 was also apparent, provided that the aromatic

Rings with 7 or more membersRings with 7 or more members Q 0050 3-Substituted Azulene-1-azo(4'-methylbenzenes). Preparation and Study ofSpectral Characteristics. -(RAZUS, A. C.; BIRZAN*, L.; NAE, S.; CRISTIAN, L.; CHIRALEU, F.; MAGANU, M.; CIMPEANU, V.; TARKO, L.; Rev. Roum. Chim. 48 (2003) 6, 455-461; Nenitzescu Inst. Org. Chem., Roum. Acad., RO-77208 Bucharest, Rom.; Eng.) -M. Kowall 15-076

For practical drug design purposes, the proposed method should be applied only if the analyzed database includes a prediction set (a group of a new molecules, not yet synthesized, with unknown values of the dependent property). The characteristics of the proposed method are: a) elimination of some molecules from the initial calibration and prediction sets, according to the result of a specific molecular similarity procedure b) the validation set is identified based on the results of similarity calculations and includes the molecules of the new calibration set most similar to the molecules of the new prediction set c) inclusion of the validation set in the new calibration set, used for model building d) it uses an original mathematical formula as validation function e) the most suitable equation for the description of the molecules in the new calibration set is different from the validated equation; these two equations are identified within the group of the best 1000 QSPRs f) the validated equation is considered the most suitable equation for the description of the molecules in the new prediction set. In five QSPR studies the validated equation made better prediction for molecules in the new prediction set than the most suitable equation for the description of molecules in the new calibration set. In the sixth study the proposed method produced, for the same prediction set, a better result than an external validation method.

This paper presents results of three QSAR (Quantitative Structure Activity Relationship) studies realized with the PRECLAV computer program. The database we used contains initially 100 derivatives of 3-carboxy-4-quinolone. The dependent property is bactericidal activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. A specific criterion identifies the outlier molecules in the calibration set. Two molecules are identified as �possible outliers for lead hopping�. After the elimination of outliers, we obtained: N = 77 / 86 / 84, s = 0.2904 / 0.3583 / 0.2993, r2 = 0.8850 / 0.7943 / 0.8645, F = 91.1 / 37.6 / 82.9 and r2CV = 0.8415 / 0.7337 / 0.8415. The bactericidal activity against the three studied bacteria was favored by the presence of saturated C substituted (hetero)cycles, by the presence of certain groups (-F, unconjugated -NH/-NH2) and by a non-balanced molecular shape. The bactericidal activity was disfavored by the presence of certain chemical groups (-NO2, -C6H4, -CO-) and of the triazole cycle. The lipophilic/hydrophilic feature of quinolones has little impact upon bactericidal activity.