1453848-26-4

Basic information

• Product Name: GDC-0994
• Synonyms: GDC-0994;(S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one GDC-0994;(S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one;1-[(1S)-1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl]-4-[2-[(1-methyl-1H-pyrazol-5-yl)amino]-4-pyrimidinyl]-2(1H)-pyridinone;Ravoxertinib;EOS-60648
• CAS NO: 1453848-26-4
• Molecular Formula: C₂₁H₁₈ClFN₆O₂
• Molecular Weight: 440.8580232
• Product Categories: Inhibitors
• Mol File: 1453848-26-4.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 734.6±70.0 °C(Predicted)
• Appearance: /
• Density: 1.45±0.1 g/cm3(Predicted)
• Solubility: ≥44.1 mg/mL in DMSO; insoluble in H2O; ≥19.2 mg/mL in EtOH
• PKA: 14.03±0.10(Predicted)
• CAS DataBase Reference: GDC-0994(CAS DataBase Reference)
• NIST Chemistry Reference: GDC-0994(1453848-26-4)
• EPA Substance Registry System: GDC-0994(1453848-26-4)

Safety Data

• Hazardous Substances Data: 1453848-26-4(Hazardous Substances Data)

Usage

Description

GDC-0994 is a potent and selective ERK1 and ERK2 inhibitor with IC50 values of 6.1 and 4.1 nM, respectively. It inhibits ERK-dependent p90RSK serine 380 phosphorylation in PMA-stimulated HepG2 cells with an IC50 value of 12 nM. GDC-0994 inhibited growth of HCT116 human colorectal cancer xenograft tumors by 49%, 57%, and 80% at 30, 60, and 100 mg/kg, respectively, when administered orally once daily for 21 days.

Uses

GDC-0994 is a potent and orally available ERK12 inhibitor shown to prevent ERK-dependant tumor cell proliferation and survival.

references

[1]. robarge k, schwarz j, blake j, et al. abstract ddt02-03: discovery of gdc-0994, a potent and selective erk1/2 inhibitor in early clinical development. aacr annual meeting, 2014, san diego, ca.

Upstream product

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• 1453851-69-8 (S)-1-(2-((tert-butyldimethylsilyl)oxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(methylsulfonyl)pyrimidin-4-yl)-pyridin-2(1H)-one 
• 1453851-79-0 (S)-1-(2-((tert-butyldimethylsilyl)oxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(methylthio)pyrimidin-4-yl)pyridin-2(1H)-one 
• 1453851-57-4 4-(2-(methylthio)pyrimidin-4-yl)pyridin-2(1H)-one 

Relevant articles and documents

Development of a Practical Synthesis of ERK Inhibitor GDC-0994

The process development of a synthetic route to manufacture ERK inhibitor GDC-0994 on multikilogram scale is reported herein. The API was prepared as the corresponding benzenesulfonate salt in 7 steps and 41% overall yield. The synthetic route features a biocatalytic asymmetric ketone reduction, a regioselective pyridone SN2 reaction, and a safe and scalable tungstate-catalyzed sulfide oxidation. The end-game process involves a telescoped SNAr/desilylation/benzenesulfonate salt formation sequence. Finally, the development of the API crystallization allowed purging of process-related impurities, obtaining >99.5A% HPLC and >99% ee of the target molecule.

Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development

The extracellular signal-regulated kinases ERK1/2 represent an essential node within the RAS/RAF/MEK/ERK signaling cascade that is commonly activated by oncogenic mutations in BRAF or RAS or by upstream oncogenic signaling. While targeting upstream nodes