Syntheses and adrenergic activities of ring-fluorinated epinephrines.
The study of chemical and biological effects of fluorine substitution on the aromatic ring of catecholamines has now been extended to epinephrine (Epi). 2- and 6-fluoroepinephrines (2-FEpi and 6-FEpi) have been synthesized. Fluorine substitution on the 2- or 6-carbon of the aromatic ring alters the selectivity of epinephrine toward alpha- and beta-adrenergic receptors, similar in manner to the change in selectivity seen with norepinephrine (NE). Thus, 2-FEpi is a relatively selective beta-adrenergic ligand, while 6-FEpi is a relatively selective alpha-adrenergic ligand. Fluorine substitution of Epi also can markedly increase potency at either alpha- or beta-adrenergic receptors.
Adejare
A
A
Laboratory of Chemistry, National Institute of Diabetes, and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Gusovsky
F
F
Padgett
W
W
Creveling
C R
CR
Daly
J W
JW
Kirk
K L
KL
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D004146:Dioxanes / Q000378:metabolism; D004837:Epinephrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D000242:Cyclic AMP; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D004837:Epinephrine