2. Academic Validation
  3. 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

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

  • J Med Chem. 2002 Aug 15;45(17):3805-8. doi: 10.1021/jm020133q.
Kazumi Kondo 1,  Keizo Kan,  Yoshihisa Tanada,  Masahiko Bando,  Tomoichi Shinohara,  Muneaki Kurimura,  Hidenori Ogawa,  Shigeki Nakamura,  Takahiro Hirano,  Yoshitaka Yamamura,  Masaru Kido,  Toyoki Mori,  Michiaki Tominaga
Affiliations

Affiliation

  • 1 Second Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Company, 463-10 Kagasuno Kawauchi-cho, Tokushima 771-0192, Japan. [email protected]
PMID: 12166952 DOI: 10.1021/jm020133q
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.

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