Resolution and adrenergic activities of the optical isomers of 4-[1-(1-naphthyl)ethyl]-1H-imidazole.
Recently we synthesized a naphthalene analog of medetomidine, 4-[1-(1-naphthyl)ethyl]-1H-imidazole hydrochloride (1), and found it to be highly potent in adrenergic systems. The separation of optical isomers of this naphthalene analog was achieved by using the isomers of tartaric acid. The optical purities of the isomers were determined by HPLC using a chiral column. Using X-ray analysis the (+)-isomer was determined to have the S absolute configuration. It has been reported that the (+)-isomer of medetomidine (2) is the most potent enantiomer on alpha 2-adrenergic receptors. There were both qualitative and quantitative differences in biological activities of the optical isomers of 1 in alpha 1- and alpha 2-adrenergic receptor systems of guinea pig ileum and human platelets. (+)-(S)-1, but not (-)-(R)-1 was a selective agonist of alpha 2-mediated responses in ileum whereas (-)-(R)-1 was more potent than (+)-(S)-1 as an inhibitor of alpha 2-mediated platelet aggregation.
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University, Columbus 43210.
S S
SS
Hong
K J
KJ
Romstedt
D R
DR
Feller
F L
FL
Hsu
C
C
George
T L
TL
Cupps
R A
RA
Lyon
D D
DD
Miller
D000316:Adrenergic alpha-Agonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D020926:Medetomidine / Q000031:analogs & derivatives; D008968:Molecular Conformation; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D007202:Indicators and Reagents; C073198:4-(1-(1-naphthyl)ethyl)imidazole; D020926:Medetomidine; D004837:Epinephrine