844499-71-4

Basic information

• Product Name: A 769662
• Synonyms: A 769662;4-Hydroxy-3-(2'-hydroxy-1,1'-biphenyl-4-yl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carbonitrile;6,7-Dihydro-4-hydroxy-3-(2'-hydroxy[1,1'-biphenyl]-4-yl)-6-oxo-thieno[2,3-b]pyridine-5-carbonitrile;Thieno[2,3-b]pyridine-5-carbonitrile, 6,7-dihydro-4-hydroxy-3-(2'-hydroxy[1,1'-biphenyl]-4-yl)-6-oxo-;A-769662/A769662;4-Hydroxy-3-(2'-hydroxy-[1,1'-biphenyl]-4-yl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carbonitri;A-769622;A-769662 4-Hydroxy-3-(2'-hydroxy-1,1'-biphenyl-4-yl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carbonitrile
• CAS NO: 844499-71-4
• Molecular Formula: C₂₀H₁₂N₂O₃S
• Molecular Weight: 360.38588
• Product Categories: Signalling;APIs;Inhibitors;Akt;mTOR;PI3K
• Mol File: 844499-71-4.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 556.6 °C at 760 mmHg
• Flash Point: 334.9℃
• Appearance: /
• Density: 1.56
• Storage Temp.: Store at +4°C
• Solubility: Soluble in DMSO (up to 30 mg/ml) or in Ethanol (up to 5 mg/ml),
• PKA: 4.50±1.00(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: A 769662(CAS DataBase Reference)
• NIST Chemistry Reference: A 769662(844499-71-4)
• EPA Substance Registry System: A 769662(844499-71-4)

Safety Data

• Safety Statements: 24/25
• Hazardous Substances Data: 844499-71-4(Hazardous Substances Data)

Usage

Description

A-769662 is a small molecule thienopyridone that activates AMPK directly in cell-free assays (EC50 = 116 nM) and intact cells by allosterically activating AMPK and inhibiting its dephosphorylation on Thr172. A-769662 specifically activates β1 subunit-containing AMPK heterotrimers, and its effects are independent of kinases upstream of AMPK. A-769662 has been used to stimulate CYP450-mediated fatty acid oxidation, inhibit adipocyte differentiation, explore glucose uptake in skeletal muscle, and promote endothelial cell survival during metabolic stress.

Uses

A 769662 is an AMP-activated protein kinase (AMPK) activiator. A 769662 selectively activates cardiac AMPK heterotrimeric complexes contg. α2/β1-subunits.

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 articles and documents

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.