Synthesis and pharmacological evaluation of hydrophobic esters and ethers of butorphanol at opioid receptors.

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Fulton BS, Knapp BI, Bidlack JM, Neumeyer JL

Synthesis and pharmacological evaluation of hydrophobic esters and ethers of butorphanol at opioid receptors.

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4474-6. doi: 10.1016/j.bmcl.2008.07.054. Epub 2008 Jul 17.

PubMed ID

18674902 [ View in PubMed

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Abstract

We synthesized several hydrophobic esters and ethers of butorphanol and assessed their affinities at opioid receptors in CHO cell membranes. Tested compounds displayed moderate to high affinities to the mu and kappa receptors. The findings accord with previous evidence of a lipophilic binding pocket in the opioid receptors that can be accessed to afford good binding affinity without the need for a phenolic hydrogen-bond donor group. The most potent (K(i)=61 pM at mu and 48 pM at kappa) novel agent was (-)-N-cyclobutylmethylmorphinan-3-yl-14-ol phenoxyacetate (4d).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Butorphanol	Kappa-type opioid receptor	Ki (nM)	0.12	N/A	N/A	Details
Butorphanol	Mu-type opioid receptor	Ki (nM)	0.22	N/A	N/A	Details
Levorphanol	Kappa-type opioid receptor	Ki (nM)	2.3	N/A	N/A	Details
Levorphanol	Mu-type opioid receptor	Ki (nM)	0.21	N/A	N/A	Details