Wu, Xing-De published the artcileDesign, synthesis and structural-activity relationship studies of phanginin A derivatives for regulating SIK1-cAMP/CREB signaling to suppress hepatic gluconeogenesis, Name: Pentane-1,5-diol, the publication is European Journal of Medicinal Chemistry (2022), 114171, database is CAplus and MEDLINE.
Persistent activation of hepatic gluconeogenesis is a main cause of fasting hyperglycemia in patients with type 2 diabetes (T2D), and the salt-induced kinase 1 (SIK1) acts as a key modulator in regulating hepatic gluconeogenesis. Recently, we first reported phanginin A (PA, 1), a natural cassane diterpenoid isolated from the seeds of Caesalpinia sappan, exhibited potent anti-diabetic effect through activation of SIK1 and increasing PDE4 activity to inhibit hepatic gluconeogenesis pathway by suppressing the cAMP/PKA/CREB pathway in the liver. In present study, we designed and prepared 25 PA derivatives and their structure-activity relationship (SAR) for gluconeogenesis inhibitory activity were established. Among them, compound I exhibited remarkable inhibitory activity on hepatic gluconeogenesis by enhancing the SIK1 phosphorylation and ameliorated the hyperglycemia of type 2 diabetic mice. Our results supported that compound I could be served as a potential candidate for the treatment of T2D.
European Journal of Medicinal Chemistry published new progress about 111-29-5. 111-29-5 belongs to alcohols-buliding-blocks, auxiliary class Aliphatic hydrocarbon chain,Alcohol,Ploymers, name is Pentane-1,5-diol, and the molecular formula is C16H24BF4Ir, Name: Pentane-1,5-diol.
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