Synthesis of new pyridazinone derivatives and their affinity towards alpha1-alpha2-adrenoceptors

Bioorg Med Chem. 1999 May;7(5):933-41. doi: 10.1016/s0968-0896(99)00046-2.

Abstract

A series of 3(2H)-pyridazinone derivatives was evaluated for their affinity in vitro towards alpha1-alpha2-adrenoceptors by radioligand receptor binding assays. All target compounds showed good affinities for the alpha1-adrenoceptor (with Ki values in the subnanomolar range), and a gradual increase in affinity was observed by increasing the polymethylene chain length of this series up to a maximum of six and seven carbon atoms, when the fragment 4-[2-(2-methoxyphenoxy)-ethyl]-1-piperazinyl is linked in 5 position of the 3(2H)-pyridazinone ring, while a slight decrease was found for the higher homologues. Increasing the chain length when the 4-[2-(2-methoxyphenoxy)-ethyl]-1-piperazinyl group is linked in 6 position of the 3(2H)-pyridazinone ring, had a different effect: there is the highest affinity when the polymethylene chain is of four carbon atoms. The alkylic chain, a spacer between the two major constituents of the molecule, can influence the affinity and the selectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / drug effects
  • In Vitro Techniques
  • Kinetics
  • Models, Chemical
  • Pyridazines / chemical synthesis*
  • Pyridazines / pharmacology*
  • Rats
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Receptors, Adrenergic, alpha-2 / metabolism*

Substances

  • Pyridazines
  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, alpha-2