Discovery of novel thiourea derivatives as potent and selective beta3-adrenergic receptor agonists.

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Maruyama T, Seki N, Onda K, Suzuki T, Kawazoe S, Hayakawa M, Matsui T, Takasu T, Ohta M

Discovery of novel thiourea derivatives as potent and selective beta3-adrenergic receptor agonists.

Bioorg Med Chem. 2009 Aug 1;17(15):5510-9. doi: 10.1016/j.bmc.2009.06.031. Epub 2009 Jun 21.

PubMed ID
19581100 [ View in PubMed
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Abstract

In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, we prepared a novel series of phenoxypropanolamine derivatives containing the thiourea moiety and evaluated their biological activities at human beta3-, beta2-, and beta1-ARs. Among these compounds, 4-nitrophenylthiourea (18i) and 3-methoxyphenylthiourea (18k) derivatives were found to exhibit potent agonistic activity at the beta3-AR, with EC(50) values of 0.10 and 0.16 microM, respectively, and no agonistic activity for either the beta1- or beta2-AR. In addition, they showed significant hypoglycemic activity in a rodent diabetic model.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
IsoprenalineBeta-1 adrenergic receptorEC 50 (nM)12N/AN/ADetails
IsoprenalineBeta-1 adrenergic receptorEC 50 (nM)1000N/AN/ADetails
IsoprenalineBeta-3 adrenergic receptorEC 50 (nM)100N/AN/ADetails
IsoprenalineBeta-3 adrenergic receptorEC 50 (nM)1000N/AN/ADetails