Fourteen 8-hydroxyquinolines were tested for antiplaque activity by measuring their minimum inhibitory concentrations [MIC (M)] against Streptococcus mutans No. 6715. Linear regression analysis was conducted with the MIC (M) values and hydrophobic (log P), electronic (beta, pKaOH, pKaN), and steric [molar refractivity (MR), molecular weight (mol wt)] parameters. The best correlation (r2 = 0.90) was obtained with MR, log P, and beta. The smaller the steric contribution of the 5-substituent, the more active the compound. The parent 8-hydroxyquinoline was the most active. The negative contribution toward activity by 5-substituents larger than hydrogen can be overcome by the positive contributions of groups that are lipophilic and electron withdrawing; for example, the 5-chloro derivative is as active as the parent 8-hydroxyquinolines.

b) Compound 11 (220 mg, 0.414 mmole) was dissolved in DMF (10 ml) containing , (0.5 ml), Li,CO, (0.55 g), and Li Cl (0.35 g), and the mixt was brought quickly to reflux and kept refluxing vigorously for 10 min. After diln with EtOAc, the soln was filtered, and the filtrate washed ( , , 2 A HQ, and NaHCO, soln), dried, and evapd to give 100 mg of 6 (54%) (from C6H14), identical with 6 prepared from 9 in all respects.

No abstract

Notes E(His) 0.83 (pH 1.95), E(His) 1.10 (pH 8.6). Anal. (C47H73N13On.lAcOH.lH2O) C, , . Amino acid ratio in the acid hydrolysate was Asp 1.00, Arg 1.04, Val 1.00, Phe 1.00, lie 2.01, His 1.00, Pro 1.01, and after incubation with l-amino acid oxidase His 0.07, Pro 1.00.

A series of 5- and 7-substituted 8-hydroxyquinolines was evaluated as inhibitors of catechol O-methyltransferase (COMT, E.C. 2.1.1.6). The electronic character of the substituents in the 5 position appeared to have only a small effect if any on the inhibitory activity of these compounds. A significant factor which contributes to the inhibitory activity of these compounds appears to be the nature of the 7-substituent. The structure-activity relationship for this series of inhibitors is discussed relative to the nature of the enzymatic binding site.