Characterization of orally active nonpeptide vasopressin V(2) receptor agonist. Synthesis and biological evaluation of both the (5R)- and (5S)-enantioisomers of 2-[1-(2-Chloro-4-pyrrolidin-1-yl-benzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepin- 5-yl]-N-isopropylacetamide.

The synthesis and evaluation of both the (R)- and (S)-enantioisomers about the 5-position on a tetrahydro-1H-1-benzazepine derivative were described. The absolute configuration of the (R,R)-isomer (10) was determined by X-ray crystallographic analysis. After evaluation of both enantiomers (compounds R-2, S-2) for binding affinity, cAMP accumulation, and an in vivo study using Brattleboro rats, R-2 showed more potent activity as a V(2) receptor agonist than S-2.