2. Academic Validation
  3. Cyclobutane derivatives as novel nonpeptidic small molecule agonists of glucagon-like peptide-1 receptor

Cyclobutane derivatives as novel nonpeptidic small molecule agonists of glucagon-like peptide-1 receptor

  • J Med Chem. 2012 Jan 12;55(1):250-67. doi: 10.1021/jm201150j.
Qing Liu 1,  Na Li,  Yunyun Yuan,  Huili Lu,  Xiaoyan Wu,  Caihong Zhou,  Min He,  Haoran Su,  Meng Zhang,  Jia Wang,  Bao Wang,  You Wang,  Dawei Ma,  Yang Ye,  Hans-Christoph Weiss,  Ernst R F Gesing,  Jiayu Liao,  Ming-Wei Wang
Affiliations

Affiliation

  • 1 The National Center for Drug Screening, 189 Guo Shou Jing Road, Shanghai 201203, China.
PMID: 22103243 DOI: 10.1021/jm201150j
Abstract

A novel cyclobutane class of nonpeptidic glucagon-like peptide-1 (GLP-1) receptor agonists, exemplified by 3, was identified using receptor binding and multiple response element/cAMP response element (MRE/CRE)-driven reporter gene assays. The structures of 3 and its three isomers were elucidated by NMR, HRESIMS, and X-ray crystallography. A series of structural modifications were also made based on the core structure of 3 with different substitution groups at the west and east ends. Among these analogues, compound 16 was found to be 4- to 5-fold more potent than 3 both in vitro and in vivo.

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