Discovery of highly potent and selective biphenylacylsulfonamide-based beta3-adrenergic receptor agonists and molecular modeling based on the solved X-ray structure of the beta2-adrenergic receptor: part 6.

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Hattori K, Orita M, Toda S, Imanishi M, Itou S, Nakajima Y, Tanabe D, Washizuka K, Araki T, Sakurai M, Matsui S, Imamura E, Ueshima K, Yamamoto T, Yamamoto N, Ishikawa H, Nakano K, Unami N, Hamada K, Matsumura Y, Takamura F

Discovery of highly potent and selective biphenylacylsulfonamide-based beta3-adrenergic receptor agonists and molecular modeling based on the solved X-ray structure of the beta2-adrenergic receptor: part 6.

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4679-83. doi: 10.1016/j.bmcl.2009.06.083. Epub 2009 Jun 25.

PubMed ID

19608416 [ View in PubMed

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Abstract

As an extension of research, we have investigated modification of left-hand side (LHS) of biphenyl analogues containing an acylsulfonamide moiety in the development of potent and selective human beta(3)-adrenergic receptor (AR) agonists. Result of structure-activity relationships (SAR) and cassette-dosing evaluation in dogs showed that the hydroxynorephedrine analogue 16 had an excellent balance of in vitro and in vivo potency with pharmacokinetic profiles. In addition, to facilitate structure-based drug design (SBDD), we also have performed a docking study of biphenyl analogues based on the X-ray structure of the beta(2)-adrenergic receptor.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Isoprenaline	Beta-3 adrenergic receptor	EC 50 (nM)	2	N/A	N/A	Details