844499-71-4

Usage

Uses

Used in Pharmaceutical and Biomedical Research:
A 769662 is used as a research tool for stimulating CYP450-mediated fatty acid oxidation, which helps in understanding the role of AMPK in metabolic regulation and energy homeostasis.
Used in Cell Biology and Metabolic Studies:
A 769662 is used as an inhibitor of adipocyte differentiation, providing insights into the molecular mechanisms underlying adipogenesis and its potential as a therapeutic target for obesity and related metabolic disorders.
Used in Skeletal Muscle Research:
A 769662 is used to explore glucose uptake in skeletal muscle, aiding in the investigation of AMPK's role in glucose metabolism and its potential implications for diabetes and other metabolic diseases.
Used in Vascular Biology and Angiogenesis:
A 769662 is used to promote endothelial cell survival during metabolic stress, contributing to the study of AMPK's protective effects on the vascular system and its potential role in angiogenesis and tissue repair.
Used in Cardiology:
A 769662 is used as a selective activator of cardiac AMPK heterotrimeric complexes containing α2/β1-subunits, enabling researchers to investigate the specific functions and therapeutic potential of this AMPK complex in the context of heart health and disease.

Biological Activity

Potent, reversible AMP-activated protein kinase (AMPK) activator (EC 50 = 0.8 μ M) that displays selectivity towards β 1 subunit-containing heterotrimers. Inhibits fatty acid synthesis (IC 50 = 3.2 μ M) and decreases plasma glucose and triglyceride levels in vivo .

References

1) Scott et al. (2008), Thienopyridone drugs are selective activators of AMP-activated protein kinase beta1-containing complexes; Cell Biol., 15 1220 2) Cool et al. (2006), Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome; Cell Metab., 3 403 3) Zhou et al. (2009), Inhibitory effects of A-769662, a novel activator of AMP-activated protein kinase on 3T3-L1 adipogenesis; Biol. Pharm. Bull., 32?993 4) Vazquez-Martin et al. (2012) Activation of AMP-activated protein kinase (AMPK) provides a metabolic barrier to reprogramming somatic cells into stem cells; Cell Cycle, 11 974 5) Ducommun et al. (2014) Enhanced activation of cellular AMPK by dual-small molecule treatment: AICAR and A769662; Am. J. Physiol. Endocrinol. Metab., 306 E688

Synthetic route

4-hydroxy-3-(2′-hydroxy-[1,1′-biphenyl]-4-yl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carbonitrile (844499-71-4) + methylmagnesium bromide (75-16-1) → 5-ethanimidoyl-4-hydroxy-3-(2'-hydroxy-1,1'-biphenyl-4-yl)thieno[2,3-b]pyridin-6(7H)-one

Conditions	Yield
In tetrahydrofuran at 0 - 20℃; for 4h;

4-hydroxy-3-(2′-hydroxy-[1,1′-biphenyl]-4-yl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carbonitrile (844499-71-4) → 4-hydroxy-3-(2'-hydroxy-1,1'-biphenyl-4-yl)thieno[2,3-b]pyridin-6(7H)-one

Conditions	Yield
Stage #1: 4-hydroxy-3-(2′-hydroxy-[1,1′-biphenyl]-4-yl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carbonitrile With sulfuric acid for 16h; Heating / reflux; Stage #2: With sodium hydroxide pH=2;

4-hydroxy-3-(2′-hydroxy-[1,1′-biphenyl]-4-yl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carbonitrile (844499-71-4) → 3-[4-(2-hydroxyphenyl)-phenyl]-4-hydroxy-5-iminomethyl-6-oxo-7H-thieno[2,3-b]-pyridine-6-one (844501-29-7)

Conditions	Yield
aluminum nickel In formic acid for 24h; Heating / reflux;

4-hydroxy-3-(2′-hydroxy-[1,1′-biphenyl]-4-yl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carbonitrile (844499-71-4) + ethyl bromoacetate (105-36-2) → {[4'-(5-cyano-4-hydroxy-6-oxo-6,7-dihydrothieno[2,3-b]pyridin-3-yl)-1,1'-biphenyl-2-yl]oxy}acetic acid

Conditions	Yield
Stage #1: 4-hydroxy-3-(2′-hydroxy-[1,1′-biphenyl]-4-yl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carbonitrile With tetra-(n-butyl)ammonium iodide; potassium carbonate In acetone at 20℃; for 0.5h; Stage #2: ethyl bromoacetate In acetone at 20℃; for 16h;

Downstream Products

• 844501-29-7 3-[4-(2-hydroxyphenyl)-phenyl]-4-hydroxy-5-iminomethyl-6-oxo-7H-thieno[2,3-b]-pyridine-6-one 

Relevant academic research and scientific papers

Thienopyridones as AMPK activators for the treatment of diabetes and obesity

The present invention relates to compounds that activate AMP-activated protein kinase (AMPK), including the preparation of the compounds, compositions containing the compounds and the use of the compounds in the prevention or treatment of disorders such as diabetes, metabolic syndrome, and obesity.