Pseudosaccharin amines as potent and selective KV1.5 blockers

https://doi.org/10.1016/j.bmcl.2015.02.066Get rights and content

Abstract

Phenethyl aminoheterocycles like compound 1 were known to be potent IKur blockers although they lacked potency in vivo. Modification of the heterocycle led to the design and synthesis of pseudosaccharin amines. Compounds such as 14, 17d and 21c were found to be potent KV1.5 blockers and selective over other cardiac ion channels. These compounds had potent pharmacodynamic activity, however, they also showed off-target activities such as hemodynamic effects.

Graphical abstract

Synthesis of pseudosaccharin amines as KV1.5 blockers led to the discovery of potent antagonists such as 17d. These compounds had potent pharmacodynamic activity, however, showed off-target activities such as hemodynamic effects.

  1. Download : Download high-res image (31KB)
  2. Download : Download full-size image

References and notes (12)

  • D.J. Snyders et al.

    J. Gen. Physiol.

    (1993)
  • H. Sun et al.

    Heart Rhythm.

    (2008)
  • E. Anter et al.

    Circulation

    (2009)
    M.W. Rich

    J. Interventional Card Electrophysiol.

    (2009)
  • W.M. Feinberg et al.

    Arch. Intern. Med.

    (1995)
    A.S. Go et al.

    JAMA

    (2001)
  • Circulation

    (2006)
    R.G. Hart et al.

    Ann. Intern. Med.

    (1999)
  • D.M. Roden

    Br. J. Pharmacol.

    (2008)
There are more references available in the full text version of this article.

Cited by (0)

View full text