¹H NMR Studies of Drugs with Achiral and Chiral Lanthanide Shift Reagents. CGP29953: Analog of the Aromatase Inhibitor, Aminoglutethimide

Abstract

1-(4-Aminophenyl)-3-n-propyl-3-azabicyclo[3.1.0]hexane-2, 4-dione, compound 1 (CGP29953), is an analog of the aromatase inhibitor aminoglutethimide (AG); AG has applications in cancer treatment. We have studied the ¹H NMR spectra of racemic compound 1 (in CDC1₃, ambient temperatures, 300-MHz) with the added achiral LSR, tris(6, 6, 7, 7, 8, 8, 8-heptafluoro-2, 2-dimethyl-3, 5-octanedionato) europium (III), compound 2, and the chiral LSR, tris[3-(heptafluoropropylhydroxymethylene)-(+) - camphorato]europium (III), compound 3. Use of compound 3 produced substantial enantiomeric shift differences for several nuclei of compound 1. ¹H-¹H COSY spectra were used to determine the relative sense of magnetic nonequivalence for selected nuclei of compound 1 with added compound 3. Relative lanthanide induced shift (LIS) magnitudes for compound 1. with added LSR are discussed.

Key Words:

• Anti-cancer agent
• Stereoisomers
• Enantiomers
• Eu(FOD)₃
• Eu(HFC)₃
• 1-(4-Aminophenyl)-3-n-propyl-3-azabicyclo[3.1.0]hexane-2, 4-dione
• One- and two-dimensional ¹H NMR