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.
D000374:Aggression / Q000187:drug effects; D000596:Amino Acids; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001570:Benzodiazepinones / Q000138:chemical synthesis* / Q000494:pharmacology; D001577:Benzophenones; D003500:Cyclization; D004597:Electroshock; D005260:Female; D006801:Humans; D007700:Kinetics; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D012640:Seizures / Q000517:prevention & control
D000596:Amino Acids; D001570:Benzodiazepinones; D001577:Benzophenones; D010433:Pentylenetetrazole