Aminomethylpiperazines as selective urotensin antagonists.

Abstract

Aminomethylpiperazines, reported previously as being kappa-opioid receptor agonists, were identified as lead compounds in the development of selective urotensin receptor antagonists. Optimized substitution of the piperazine moiety has provided high affinity urotensin receptor antagonists with greater than 100-fold selectivity over the kappa-opioid receptor. Select compounds were found to inhibit urotensin-induced vasoconstriction in isolated rat aortic rings consistent with the hypothesis that an urotensin antagonist may be useful for the treatment of hypertension.

• Authors: Mark A Hilfiker, Daohua Zhang, Sarah E Dowdell, Krista B Goodman, John J McAtee, Jason W Dodson, Andrew Q Viet, Gren Z Wang, Clark A Sehon, David J Behm, Zining Wu, Luz H Carballo, Stephen A Douglas, Michael J Neeb
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 18 Issue 16 Pg. 4470-3 (Aug 15 2008) ISSN: 1464-3405 [Electronic] England
• PMID: 18674898 (Publication Type: Journal Article)

Chemical References

• Piperazines
• Receptors, Opioid, kappa
• Urotensins
• Taurine
• Acamprosate

Topics

• Acamprosate
• Animals
• Aorta (metabolism)
• Chemistry, Pharmaceutical (methods)
• Drug Design
• Humans
• Hypertension (drug therapy)
• Models, Chemical
• Piperazines (chemistry, pharmacology)
• Rats
• Receptors, Opioid, kappa (antagonists & inhibitors)
• Structure-Activity Relationship
• Taurine (analogs & derivatives, drug effects)
• Urotensins (antagonists & inhibitors)