PMID: 11504641Aug 16, 2001Paper

Novel (4-piperidin-1-yl)-phenyl sulfonamides as potent and selective human beta(3) agonists

Bioorganic & Medicinal Chemistry
B HuV Wong

Abstract

A series of novel (4-piperidin-1-yl)-phenyl sulfonamides was prepared and evaluated for their biological activity on the human beta(3)-adrenergic receptor (AR). Replacement of the 3,4-dihydroxyl group of the catechol moiety with 4-hydroxyl-3-methyl sulfonamide on the left-hand side of the compounds resulted in a number of potent full agonists at the beta(3) receptor. Modification of the right-hand side of the compounds by incorporation of a free carboxylic acid resulted in a few potent human beta(3) agonists with low affinities for beta(1)- and beta(2)-ARs. N-Alkyl substitution on the 4-piperidin-1-yl-phenylamine further increased the beta(3) potency while maintaining the selectivity. For example, sulfonamide 48 is a potent full beta(3) agonist (EC(50)=0.004 microM, IA=1.0) with > 500-fold selectivity over beta(1)- and beta(2)-ARs.

References

Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·T FrielleB K Kobilka
Jan 1, 1999·Bioorganic & Medicinal Chemistry Letters·E R ParmeeA E Weber
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Mar 30, 2001·Bioorganic & Medicinal Chemistry Letters·B HuV Wong
Apr 20, 2001·Journal of Medicinal Chemistry·B HuJ Tillett

Citations

Dec 21, 2010·Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents·P Senthil Kumar, Prasad V Bharatam
May 1, 2001·Bioorganic & Medicinal Chemistry Letters·B HuJ Tillett
Dec 1, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tomáš GoněcAidan Coffey

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