Abstract:
:The free fatty acid receptor 1 (FFA1) and peroxisome proliferator-activated receptor δ (PPARδ) were considered as potential anti-diabetic targets, and the dual FFA1/PPARδ agonists might provide synergistic effect in insulin secretion and sensibility. Herein, we further develop dual agonists by screening 7 series of heterocycles, resulting in the discovery of compound 19 with considerable oral pharmacokinetic profile. Compound 19 exhibited a balanced potency between FFA1 and PPARδ, and high selectivity over PPARα and PPARγ. Moreover, compound 19 exerted improved glucose-lowering effects and insulin sensitivity in a dose-dependent manner, which might be attributed to its dual effects to simultaneously regulate insulin secretion and resistance. Our results extended the existing chemical space, and provided a potent tool compound 19.
journal_name
Bioorg Chemjournal_title
Bioorganic chemistryauthors
Li Z,Hu L,Wang X,Zhou Z,Deng L,Xu Y,Zhang Ldoi
10.1016/j.bioorg.2019.103254subject
Has Abstractpub_date
2019-11-01 00:00:00pages
103254eissn
0045-2068issn
1090-2120pii
S0045-2068(19)30934-4journal_volume
92pub_type
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journal_title:Bioorganic chemistry
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journal_title:Bioorganic chemistry
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pub_type: 杂志文章
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journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2018.06.029
更新日期:2018-10-01 00:00:00
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journal_title:Bioorganic chemistry
pub_type: 杂志文章
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