title: On the structure selectivity problem in drug design. A comparative study of benzylpyrimidine inhibition of vertebrate and bacterial dihydrofolate reductase via molecular graphics and quantitative structure-activity relationships.
abstract: Quantitative structure-activity relationships (QSAR) have been derived for the action of 68 5-(substituted benzyl)-2,4-diaminopyrimidines on dihydrofolate reductase (DHFR) from Lactobacillus casei and chicken liver. The QSAR are analyzed with respect to the stereographics models of the active sites of the enzymes and found to be in good agreement. Using these QSAR equations, we have attempted to design new trimethoprim-type antifolates having higher selectivity for the bacterial enzyme. The general problem of developing selective inhibitors is discussed.
authors.affiliation: Department of Chemistry, Pomona College, Claremont, California 91711.
authors.forename: C D
authors.initials: CD
authors.lastname: Selassie
authors.forename: Z X
authors.initials: ZX
authors.lastname: Fang
authors.forename: R L
authors.initials: RL
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Hansch
authors.forename: G
authors.initials: G
authors.lastname: Debnath
authors.forename: T E
authors.initials: TE
authors.lastname: Klein
authors.forename: R
authors.initials: R
authors.lastname: Langridge
authors.forename: B T
authors.initials: BT
authors.lastname: Kaufman
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002645:Chickens; D015195:Drug Design; D005493:Folic Acid Antagonists; D007780:Lacticaseibacillus casei / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D011743:Pyrimidines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
chemical_list: D005493:Folic Acid Antagonists; D011743:Pyrimidines