Two stereoisomeric imidazoline derivatives: synthesis and optical and alpha 2-adrenoceptor activities.

Abstract

Two eight-step pathways for synthesizing the stereoisomeric compounds (-)-2-[1-(2,6-dichlorophenoxy)ethyl]-2-imidazoline hydrochloride ("levlofexidine" hydrochloride; (-)-lofexidine hydrochloride) and (+)-2-[1-(2,6-dichlorophenoxy)ethyl]-2-imidazoline hydrochloride ("dexlofexidine" hydrochloride; (+)-lofexidine hydrochloride) and the optical resolution of (+/-)-lofexidine are described. (-)-Lofexidine, a stereoselective alpha 2-adrenoceptor agonist, due to its center of asymmetry, is demonstrated to be a potent drug for the treatment of hypertension (doses 0.561 microgram/kg) and to have the highest affinity and a concentration dependency for alpha 2-adrenoceptors in direct binding studies (0.36 nmol/L). (+)-Lofexidine is 10 times less potent.

• Authors: J Biedermann, A León-Lomelí, H O Borbe, G Prop
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 29 Issue 7 Pg. 1183-8 (Jul 1986) ISSN: 0022-2623 [Print] United States
• PMID: 2879913 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Adrenergic alpha-Agonists
• Imidazoles
• Indicators and Reagents
• Receptors, Adrenergic, alpha
• Clonidine
• lofexidine

Topics

• Adrenergic alpha-Agonists (chemical synthesis)
• Animals
• Blood Pressure (drug effects)
• Brain (metabolism)
• Clonidine (analogs & derivatives, chemical synthesis, pharmacology)
• Drug Evaluation, Preclinical
• Imidazoles (chemical synthesis, pharmacology)
• Indicators and Reagents
• Male
• Optical Rotation
• Rats
• Rats, Inbred Strains
• Receptors, Adrenergic, alpha (drug effects, metabolism)
• Stereoisomerism
• Structure-Activity Relationship