2. Academic Validation
  3. Use of receptor chimeras to identify small molecules with high affinity for the dynorphin A binding domain of the kappa opioid receptor

Use of receptor chimeras to identify small molecules with high affinity for the dynorphin A binding domain of the kappa opioid receptor

  • Bioorg Med Chem Lett. 2008 Jun 15;18(12):3667-71. doi: 10.1016/j.bmcl.2007.11.116.
Virendra Kumar 1,  Deqi Guo,  Michael Marella,  Joel A Cassel,  Robert N Dehaven,  Jeffrey D Daubert,  Erik Mansson
Affiliations

Affiliation

  • 1 Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA. vkumar@adolor.com
PMID: 18487043 DOI: 10.1016/j.bmcl.2007.11.116
Abstract

A series of 2-substituted sulfamoyl arylacetamides of general structure 2 were prepared as potent kappa Opioid Receptor agonists and the affinities of these compounds for opioid and chimeric receptors were compared with those of dynorphin A. Compounds 2e and 2i were identified as non-peptide small molecules that bound to chimeras 3 and 4 with high affinities similar to dynorphin A, resulting in K(i) values of 1.5 and 1.2 nM and 1.3 and 2.2 nM, respectively.

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