GSK 2334470

Base Information

• Chemical Name: GSK 2334470
• CAS No.: 1227911-45-6
• Molecular Formula: C25H34N8O
• Molecular Weight: 462.598
• Mol file: 1227911-45-6.mol

Synonyms:CS-0917;(3S,6R)-1-[6-(3-amino-1H-indazol-6-yl)-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide;QC-8425;

Chemical Property of GSK 2334470

Chemical Property:

• PKA: 12.84±0.40(Predicted)
• PSA: 132.30000
• Density: 1.30±0.1 g/cm3(Predicted)
• LogP: 3.95490
• Storage Temp.: 2-8°C
• Solubility.: DMSO: ≥10mg/mL

Purity/Quality:

98%,99%, ^*data from raw suppliers

GSK2334470 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: GSK2334470 (1227911-45-6)?is a potent (IC50?= 10 nM) and selective inhibitor of 3-Phosphoinositide-dependent kinase 1 (PDK1), which phosphorylates and activates a group of protein kinases in the AGC/PKG/PKC family.1?It is more effective at inhibiting PDK1 substrates that are activated in the cytosol rather than at the plasma membrane.1?GSK2334470 delayed melanogenesis and metastasis in Braf(V600E)::Pten(-/-)?mice.2?It also displays antitumor activity against multiple myeloma synergistically with mTORC1/2 inhibitor PP2423?and proteasome inhibitor MG-1324.
• Uses: GSK2334470 has been used as an inhibitor of 3-phosphoinositide dependent protein kinase-1 (PDK-1) in: Treg cells, to identify regulators of interleukin 2 (IL-2)– signal transducer and activator of transcription 5 (STAT5) signalingglycodelin-transfected HEC-1B human endometrial adenocarcinoma cells. HeLa and Hs578T cells to test its effect on formylglycinamidine ribonucleotide synthase?(FGAMS) assembly

Technology Process of GSK 2334470

There total 9 articles about GSK 2334470 which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield:

(3S,6R)-1-[6-(4-cyano-3-fluorophenyl)-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide (1227911-44-5) → GKS2334470 (1227911-45-6)

Guidance literature:

With hydrazine hydrate; In ethanol; at 100 ℃; for 48h; Sealed tube; Microwave irradiation;

Reference yield:

Methyl 6-methylnicotinate (5470-70-2) → GKS2334470 (1227911-45-6)

Guidance literature:

Multi-step reaction with 7 steps

1.1: hydrogenchloride; platinum(IV) oxide; hydrogen / methanol; water / 4.5 h / 20 °C / 3102.97 Torr

1.2: 15 - 25 °C

2.1: palladium 10% on activated carbon; hydrogen / ethanol; ethyl acetate / 20 °C / 3361.55 Torr

3.1: water; isopropyl alcohol / 60 °C

4.1: lithium hydroxide monohydrate / water / 20 h / 20 °C

4.2: 24 h / 100 °C

4.3: pH 3

5.1: N-ethyl-N,N-diisopropylamine; HATU / dichloromethane / 0.5 h / 0 °C

6.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium hydrogencarbonate / 1,4-dioxane; water / 95 °C

7.1: hydrazine hydrate / ethanol / 80 - 100 °C

With hydrogenchloride; platinum(IV) oxide; tetrakis(triphenylphosphine) palladium⁽⁰⁾; lithium hydroxide monohydrate; palladium 10% on activated carbon; hydrogen; sodium hydrogencarbonate; hydrazine hydrate; N-ethyl-N,N-diisopropylamine; HATU; In 1,4-dioxane; methanol; ethanol; dichloromethane; water; ethyl acetate; isopropyl alcohol; 6.1: Suzuki coupling;

DOI:10.1021/jm101527u

Reference yield:

4,6-dichloro-N-methyl-2-pyrimidinamine (10397-15-6) → GKS2334470 (1227911-45-6)

Guidance literature:

Multi-step reaction with 4 steps

1.1: lithium hydroxide monohydrate / water / 20 h / 20 °C

1.2: 24 h / 100 °C

1.3: pH 3

2.1: N-ethyl-N,N-diisopropylamine; HATU / dichloromethane / 0.5 h / 0 °C

3.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium hydrogencarbonate / 1,4-dioxane; water / 95 °C

4.1: hydrazine hydrate / ethanol / 80 - 100 °C

With tetrakis(triphenylphosphine) palladium⁽⁰⁾; lithium hydroxide monohydrate; sodium hydrogencarbonate; hydrazine hydrate; N-ethyl-N,N-diisopropylamine; HATU; In 1,4-dioxane; ethanol; dichloromethane; water; 3.1: Suzuki coupling;

DOI:10.1021/jm101527u

upstream raw materials:

(3S,6R)-1-[6-(4-cyano-3-fluorophenyl)-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide

Methyl 6-methylnicotinate

4,6-dichloro-N-methyl-2-pyrimidinamine

methyl (3R*,6S*)-6-methylpiperidine-3-carboxylate

Refernces

• 1、 -. "CHEMICAL COMPOUNDS". Page/Page column 196. . Retrieved 2010/07/10.