Chiral 1,4-benzodiazepine. VII. Cyclization rates of 2-(n-alpha-ammoniumacyl)-amino-5-chloro-benzophenones in the chiral 1,4-benzodiazepin-2-ones.

Cyclisation rates of some S-alpha-amino acid derivatives (I--VII) into chiral 1,4-benzodiazepin-2-ones were determined under physiological-like conditions (pH, temperature) and plotted against pKa values of the corresponding alpha-amino acids. No correlation between k, i.e. t1/2 values, of the acidic precursors, and pharmacodynamic activity, as determined by some standard tests, were observed, however. Unambiguity of cyclisation, and its t1/2 values reveal benefit for physico-chemical properties of the investigated acyclic precursors as transport-forms of the chiral 1,4-benzodiazepin-2-ones with prolonged pharmacological activity.