title: 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.
abstract: 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.
authors.affiliation: Second Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Company, 463-10 Kagasuno Kawauchi-cho, Tokushima 771-0192, Japan. k_kondo@research.otsuka.co.jp
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kondo
authors.forename: Keizo
authors.initials: K
authors.lastname: Kan
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Tanada
authors.forename: Masahiko
authors.initials: M
authors.lastname: Bando
authors.forename: Tomoichi
authors.initials: T
authors.lastname: Shinohara
authors.forename: Muneaki
authors.initials: M
authors.lastname: Kurimura
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ogawa
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nakamura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hirano
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yamamura
authors.forename: Masaru
authors.initials: M
authors.lastname: Kido
authors.forename: Toyoki
authors.initials: T
authors.lastname: Mori
authors.forename: Michiaki
authors.initials: M
authors.lastname: Tominaga
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018360:Crystallography, X-Ray; D000242:Cyclic AMP / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D011869:Radioligand Assay; D051381:Rats; D011910:Rats, Brattleboro; D017483:Receptors, Vasopressin / Q000819:agonists*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D017483:Receptors, Vasopressin; D000242:Cyclic AMP