4-[2-(4-Amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[(3S)-3-piperidinylmethoxy]-1H-imidazo[4,5-c]pyridin-4-yl]-2-methyl-3-butyn-2-ol Chemical Properties

Boiling point:

683.8±65.0 °C(Predicted)

Density 

1.41

storage temp. 

2-8°C

solubility 

DMSO: soluble5mg/mL (clear solution)

pka

13.11±0.29(Predicted)

form 

powder

color 

white to beige

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO or distilled water may be stored at -20° for up to 1 month.

InChIKey

KGPGFQWBCSZGEL-ZDUSSCGKSA-N

SMILES

CC(C)(O)C#CC1=NC=C(OC[C@H]2CCCNC2)C2N(CC)C(C3C(N)=NON=3)=NC1=2

Safety Information

Hazard Codes 

T

Risk Statements 

25

Safety Statements 

45

RIDADR 

UN 2811 6.1 / PGIII

WGK Germany 

3

4-[2-(4-Amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[(3S)-3-piperidinylmethoxy]-1H-imidazo[4,5-c]pyridin-4-yl]-2-methyl-3-butyn-2-ol Usage And Synthesis

Description

GSK690693 is an ATP-competitive, pan-Akt kinase inhibitor with IC₅₀ values of 2, 13, and 9 nM for Akt1, 2, and 3, respectively. It also inhibits other members of the AGC kinase family, including AMPK, DAPK3, PAKs, PKA, PKC, PKG, and PrkX (IC₅₀ values range from 2-81 nM). By preventing the phosphorylation of downstream Akt substrates, GSK690693 has been shown to inhibit proliferation and to induce apoptosis in various human tumor cells in vitro and in xenografts in immunocompromised mice.

Uses

GSK690693 is a pan-Akt inhibitor targeting Akt1, Akt2 and Akt3 with IC50 of 2 nM, 13 nM, and 9 nM, respectively

Uses

GSK690693 has been used in western blotting and immunoprecipitations.

Definition

ChEBI: A member of the class of imidazopyridines that is 4-(1-ethylimidazo[4,5-c]pyridin-4-yl)-2-methylbut-3-yn-2-ol carrying additional 2-(4-amino-1,2,5-oxadiazol-3-yl and [(3S)-piperidin-3-yl]methoxy substituents at positions 4 and 7 respectively.

Biochem/physiol Actions

GSK690693 is an ATP competitive, potent pan-AKT kinase inhibitor with IC50 values of 2, 13, and 9 nM against AKT1, 2, and 3, respectively.

Synthesis

The compound of Example 1 (c) (35.0 g, 66.6 mmol) and trifluoroacetic acid (TFA, 350 mL of 20% dichloromethane solution, 808 mmol) were stirred at room temperature for 2.5 hours. Upon completion of the reaction, the reaction solution was slowly poured into a rapidly stirred mixture of water, sodium hydroxide (NaOH, 36 g, 900 mmol), ethyl acetate (200 mL) and tetrahydrofuran (THF, 1000 mL). The organic layer was separated and the aqueous layer was extracted with additional ethyl acetate/THF (1:5 v/v, 150 mL). The organic extracts were combined and washed sequentially with saturated sodium bicarbonate (NaHCO3) solution and sodium chloride (NaCl) solution, and then dried over anhydrous sodium sulfate (Na2SO4). The solvent was removed by concentration under reduced pressure and the resulting solid was recrystallized from hot ethanol (1200 mL) to give 26.3 g (93% yield) of (S)-4-(2-(4-amino-1 ,2,5-oxadiazol-3-yl)-1-ethyl-7-(piperidin-3-ylmethoxy)-1H-imidazo[4,5-c]pyridin-4-yl)-2-methylbut-3-yn-2-ol as a white crystalline solid. Mass spectrum (ES+) m/z: 426 [M+H]+.

storage

Store at -20°C

References

[1] NELSON RHODES. Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity.[J]. Cancer research, 2008: 2366-2374. DOI:10.1158/0008-5472.can-07-5783
[2] MING-CHIH CROUTHAMEL. Mechanism and management of AKT inhibitor-induced hyperglycemia.[J]. Clinical Cancer Research, 2009, 15 1: 217-225. DOI:10.1158/1078-0432.ccr-08-1253

4-[2-(4-Amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[(3S)-3-piperidinylmethoxy]-1H-imidazo[4,5-c]pyridin-4-yl]-2-methyl-3-butyn-2-ol(937174-76-0)Related Product Information

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