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(1976). A RAPID, CONVENIENT, HIGH YIELD PROCEDURE FOR THE REGENERATION OF 2,3-DICHLORO-5,6-DICYANOBENZOQUINONE (DDQ) FROM THE CORRESPONDING HYDROQUINONE (DDHQ) Organic Preparations and Procedures International: Vol. 8, No. 3, pp. 141-143.

Thirty-seven compounds, including 17 biguanides, 6 carbamimidates, and 14 bisbiguanides, were evaluated for potential antiplaque activity by measuring their minimum inhibitory concentrations [MIC (M)] against Streptococcus mutans no. 6715. Linear regression analysis was conducted with the log 1/MIC (M) values and log P, pi, sigma, and MR. The best correlation for the biguanides (r2 = 0.92) was obtained with log P and (log P)2. When the biguanides were included with the carbamimidates, essentially the same correlation (r2 = 0.91) was obtained with log P and (log P)2. The best correlation for the bisbiguanides (r2 = 0.70) was also obtained with log P and (log P)2. Use of an indicator variable (I) for the bisgiguanides allowed all three groups to be included in one equation, which accounted for over 87% of the variance in the data for inhibition of bacterial growth. These results from the classical parabolic model were also compared with those from the recently developed bilinear model.

Continued structural evaluation of the [(aminomethyl)aryloxy]acetic ester diuretics has produced a series of compounds in which the functional group that bridges the two aromatic rings has been varied. Diuretic screening of these analogues in rats indicates that the keto group can be effectively replaced with an ether or thio ether function with a slight increase in potency, whereas the methylene and sulfoxide linking groups lead to diminished saluretic potency. Replacement with either -SO2-, -COCO-, -CH2O-, -CONH- or direct bond results in a loss of activity. Although the series was designed according to QSAR criteria, the traditional linear free-energy properties of these compounds do not correlate with diuretic potency. However, conformational analysis of the series by potential energy calculations indicates that all active compounds have an accessible conformation that matches the bridge atom-carboxylate distance of the very potent dihydrobenzofuran analogue 56. Conformational calculations of several compounds in which the aminomethyl group was varied suggests that the active conformation is probably a low-energy conformation. Consideration of rotation about the bridge could not distinguish between two possible orientations of the aminomethyl ring in the active conformation. However, there is a quantitative negative linear correlation between diuretic potency and the protrusion into space of the group that bridges the two aromatic rings.

A quantitative structure-activity relationship has been formulated for 646 antimalarials acting against P. berghei in mice. The equation developed has 14 terms, 9 of which are indicator variables. The correlation coefficient for the QSAR is 0.898 and the standard deviation is 0.309. The antimalarials are all arylcarbinols of the type X-ArCHOHCH2NR1R2. Sixty different aryl structures, including a variety of heterocyles, are contained in the study. The most important determinate of activity is found to be the electron-withdrawing ability of the substituents X; the hydrophobic character of X and R plays less important roles. Suggestions for more potent analogues are made and the lack of activity of about 100 additional analogues is also considered.