Dimerization of sumatriptan as an efficient way to design a potent, centrally and orally active 5-HT1B agonist.
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Perez M, Pauwels PJ, Fourrier C, Chopin P, Valentin JP, John GW, Marien M, Halazy S
Dimerization of sumatriptan as an efficient way to design a potent, centrally and orally active 5-HT1B agonist.
Bioorg Med Chem Lett. 1998 Mar 17;8(6):675-80.
- PubMed ID
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9871581 [View in PubMed]
- Abstract
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A new bivalent ligand of formula 3 which results from the covalent coupling of two sumatriptan molecules with a p-xylyl spacer at the level of the sulfonamide nitrogen has been prepared and evaluated as a 5-HT1B/1D receptors agonist. In vitro experiments at 5-HT1B human cloned receptors (Ki = 0.64 nM; EC50 = 0.58 nM) and at the level of the contraction of the New Zealand white rabbit saphenous vein (pD2 = 6.6) demonstrate the superior potency of dimer 3 as a 5-HT1B receptor agonist when compared to sumatriptan or zolmitriptan. Interestingly enough, the new bivalent agonist 3 was found to induce hypothermia in the guineapig upon oral administration suggesting good oral activity and access to the brain.
DrugBank Data that Cites this Article
- Binding Properties
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Drug Target Property Measurement pH Temperature (°C) Sumatriptan 5-hydroxytryptamine receptor 1A Ki (nM) 407.1 N/A N/A Details Sumatriptan 5-hydroxytryptamine receptor 1B EC 50 (nM) 38.3 N/A N/A Details Sumatriptan 5-hydroxytryptamine receptor 1B Ki (nM) 19.1 N/A N/A Details Sumatriptan 5-hydroxytryptamine receptor 1D Ki (nM) 8.6 N/A N/A Details Zolmitriptan 5-hydroxytryptamine receptor 1A Ki (nM) 124 N/A N/A Details Zolmitriptan 5-hydroxytryptamine receptor 1B EC 50 (nM) 15.7 N/A N/A Details Zolmitriptan 5-hydroxytryptamine receptor 1B Ki (nM) 4.2 N/A N/A Details Zolmitriptan 5-hydroxytryptamine receptor 1D Ki (nM) 0.76 N/A N/A Details