2-(3,4-Di-chloro-phen-yl)-N-methyl-N-[2-(pyrrolidin-1-yl)cyclo-hex-yl]acetamide hydro-chloride: (±)-U50,488H

Area of Science:

• Crystallography
• Medicinal Chemistry
• Pharmacology

Background:

• U50,488 is a selective kappa-opioid receptor agonist with significant pharmacological applications.
• The hydrochloride salt form is widely used but lacks detailed structural characterization.

Purpose of the Study:

• To determine the crystal structure of the methanol-solvated hydrochloride salt of (±)-U50,488.
• To provide the first structural insights into this widely used pharmacological compound's salt form.

Main Methods:

• Single-crystal X-ray diffraction was employed to analyze the crystal structure.
• The compound crystallized as a racemate of (S,S) and (R,R) enantiomers.

Main Results:

• The crystal structure revealed a chair conformation of the cyclohexane ring with equatorial-equatorial substituents.
• Protonation occurred at the pyrrolidine nitrogen, which adopted a twisted half-chair conformation.
• The crystal packing involved hydrogen bonding, C-H...O interactions, pi-stacking, and Cl...O halogen bonding.

Conclusions:

• This study presents the first structural characterization of the U50,488 hydrochloride salt.
• The findings elucidate the molecular interactions and conformation within the crystal lattice.
• This structural information can aid in understanding the compound's properties and guiding future drug design.