Synthesis and alpha 2-adrenoceptor effects of substituted catecholimidazoline and catecholimidazole analogues in human platelets

J Med Chem. 1990 Apr;33(4):1138-44. doi: 10.1021/jm00166a009.


It is known that the steric requirements for the interactions of catecholamines and catecholimidazolines with alpha 1- and alpha 2-adrenoceptors are different. New analogues of desoxycatecholimidazoline (1), desoxycatecholimidazole (3), benzylic hydroxyl substituted imidazole (4), and the aromatic fluorine substitution analogues of 1 at the 2 (5), 5 (6), and 6 (7) positions, and a set of asymmetric 4-substituted catecholimidazolines, S-8 and R-8, were prepared and tested for interaction with alpha 2-adrenoceptors in human platelets. With the exception of 3, all compounds were selective for alpha-adrenoceptor-mediated responses in human platelets. Introduction of a double bond in imidazoline 1 to give an imidazole 3 or the introduction of a benzylic hydroxyl group to 3, as in 4, reduced the inhibition of platelet aggregation with a rank order potency of 1 greater than 3 greater than 4. Fluorine atom substitution at the 2-, 5-, or 6-positions only slightly modified the inhibitory activity of 1. Each analogue (1, 3-7) produced alpha 2-mediated inhibition of platelet adenylate cyclase and can be classified as a partial agonist. The inhibition potency of S-8 and R-8 against epinephrine-induced aggregatory responses were greatly different, and only R-8 and 4 were alpha 2-agonists on human platelet function. Our studies provide further evidence for the differential interaction of catecholamines and catecholimidazolines in alpha 1- and alpha 2-adrenoceptor systems.

MeSH terms

  • Blood Platelets / drug effects*
  • Catecholamines / chemical synthesis*
  • Catecholamines / pharmacology
  • Chemical Phenomena
  • Chemistry
  • Epinephrine / antagonists & inhibitors
  • Epinephrine / pharmacology
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology
  • Platelet Aggregation / drug effects
  • Receptors, Adrenergic, alpha / drug effects*
  • Structure-Activity Relationship


  • Catecholamines
  • Imidazoles
  • Receptors, Adrenergic, alpha
  • Epinephrine