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Discovery of benzamides as potent human β3 adrenergic receptor agonists.

Abstract：

:The paper will describe the synthesis and SAR studies that led to the discovery of benzamide (reverse amide) as potent and selective human β3-adrenergic receptor agonist. Based on conformationally restricted pyrrolidine scaffold we discovered earlier, pyrrolidine benzoic acid intermediate 22 was synthesized. From library synthesis and further optimization efforts, several structurally diverse reverse amides such as 24c and 24i were found to have excellent human β3-adrenergic potency and good selectivity over the β1 and β2 receptors. In addition to human β1, β2, β3 and hERG data, PK of selected compounds will be described.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Zhu C,Kar NF,Li B,Costa M,Dingley KH,Di Salvo J,Ha SN,Hurley AL,Li X,Miller RR,Salituro GM,Struthers M,Weber AE,Hale JJ,Edmondson SD

doi

10.1016/j.bmcl.2015.11.030

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

55-9

issue

1

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(15)30238-9

journal_volume

26

pub_type

杂志文章

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