Trimetrexate: molecular structures and conformational similarities in two crystal forms

The structure of the non-classical quinazoline antifolate trimetrexate (TMQ) has been determined in two crystal forms, TMQ acetate monohydrate, and hydrated TMQ free base. Trimetrexate has an extended conformation in both structures, and the quinazoline and phenyl rings are mutually perpendicular. Protonation occurs at N1 in the acetate salt. The TMQ conformation is similar to corresponding parts of quinespar, the only other quinazoline antifolate structurally determined, and the hydrated strontium salt of methotrexate.