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Additional info for Quantitative Structure–Activity Relationships of Drugs
764). It may be that the terms in π appear be cause the culture medium utilized in this study contained proteins, which were excluded from the later study of Seydel (120). A similar approach to ionization has been followed by Yamazaki et al. (135) w h o related optimal pK of a series of heterocyclic sulfonamides against E. coli to changes in pH of the culture medium. 22, respectively. This work has relevance to the choice of sulfonamide drug for clinical use in that the pK should apparently be close to the pH of the body fluid in which maximal activity is desirable.
Tute molar concentration that is effective in killing bacteria following 10 min exposure, expressed relative to phenol. It is clearly a blunderbuss tech nique for compounds that have a multiplicity of effects, and one cannot expect very precise structural information to accrue by analysis of such results. Lien et al. (92) applied QSAR to Klarmann's data on alkyl halophenols. For the lethal effect of alkyl bromophenols on S. aureus they derived the linear Eq. (7), and for that of alkyl chlorophenols on S.
S. Tute synthase and charge derealization from the substituent to the S 0 group thus enhances activity. Activity of dapsone is high but not exceptional; clearly the action of dapsone against M. leprae must be qualitatively dif ferent from other sulfones or from sulfonamides. 2 B. Trimethoprim After incorporation of PAB into dihydropteroic acid, folate bio synthesis proceeds (Scheme 2) by addition of a glutamic acid unit to give dihydrofolic acid. This is then reduced by N A D P H to yield the essential cofactor, tetrahydrofolic acid, a reaction catalyzed by the enzyme dihy drofolate reductase (DHFR).