title: Conformational analysis of lipophilic antifolates: crystal and molecular structures of three s-triazine dihydrofolate reductase inhibitors.
abstract: The results of crystal structure determinations on a series of protonated N1-phenyl-substituted 1,2-dihydro-2,2-dimethyl-4,6-diamino-s-triazine anti-cancer antifolates show that the s-triazine ring adopts a twist-sofa conformation with C2 nearly 0.5 A above the plane and the N1-phenyl ring is nearly perpendicular to the s-triazine ring, in agreement with minimum energy calculations and with antifolate binding in the active site of chicken liver dihydrofolate reductase. The 2,2-dimethyl groups are equatorial and axial. Comparison of these s-triazines with analogous pyrimidine antifolates reveals that the axial 2-methyl group occupies the same conformational space as the 6-methyl group in active anti-cancer agents.
authors.affiliation: Medical Foundation of Buffalo, Inc., New York 14203.
authors.forename: V
authors.initials: V
authors.lastname: Cody
authors.forename: P A
authors.initials: PA
authors.lastname: Sutton
mesh_terms: D003460:Crystallization; D005493:Folic Acid Antagonists; D008968:Molecular Conformation; D014227:Triazines
chemical_list: D005493:Folic Acid Antagonists; D014227:Triazines