Characterization of Orally Active Nonpeptide Vasopressin V₂ 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.

Asymmetric Synthesis of 1-Benzazepine Derivatives via Copper-Catalyzed Intramolecular Reductive Cyclization

“…1 While asymmetric synthetic methods for chiral 1-benzazepine derivatives with single stereogenic centers have been extensively explored, 2 1-benzazepine skeletons containing two adjacent stereogenic centers are less available due to limited synthetic methodologies despite their potential bioactivities. 3 Moreover, examples of 1-benzazepine derivatives carrying a cyclic tertiary amine moiety are especially rare with only one known report on their synthesis. This report involved Mo-catalyzed asymmetric ring-closing metathesis (ARCM) based on desymmetrization of polyenes (Figure 1).…”

“…In the past decade, several elegant methods for in situ generation of chiral allylcopper nucleophiles through copper-catalyzed borylcupration 8 or hydrocupration 9 of allenes and 1,3-dienes have been established, circumventing the prior preparation of reactive allylic organometallic reagents. In 2017, Hoveyda and coworkers reported an asymmetric allylation of ketimines with allenes using N-heterocyclic carbene (NHC)−Cu−Bpin catalyst (Bpin = 4,4,5,3,. 8d Other related copper-catalyzed asymmetric allylations of ketones, using conjugated dienes for generation of allylcopper intermediates, afforded chiral homoallylic tertiary alcohols.…”

Chemoselective and Enantioselective Hydrogenation of 2,4‐Diaryl‐3H‐benzo[b]azepines Catalyzed by Dendritic Phosphinooxazoline Iridium Complexes

“…Seven‐membered nitrogen heterocycles are important compounds in organic synthesis given their wide potential in pharmaceutical applications . Exhibiting biological activities towards several enzymes, G‐protein‐coupled receptors and anti‐HIV‐1 agents, benzazepine derivatives have attracted much attention –. Over the past decades, many efforts have been devoted to the synthesis of benzazepine derivatives .…”

Readily Available Highly Active [Ti]-Adamantyl-BINOL Catalysts for the Enantioselective Alkylation of Aldehydes

“…1 These alcohols are key compounds serving as both starting materials and resolving agents, which are used in the preparation of pharmaceuticals or intermediates. 1,2…”

“…The synthesis of optically active pure secondary alcohols via the enantioselective addition of diethylzinc to various aldehydes is a successful method for testing the effectiveness of chiral ligands . These alcohols are key compounds serving as both starting materials and resolving agents, which are used in the preparation of pharmaceuticals or intermediates. , …”