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

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.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

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

doi

10.1016/j.bmc.2009.06.031

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

5510-9

issue

15

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(09)00594-X

journal_volume

17

pub_type

杂志文章

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