936350-00-4

Basic information

• Product Name: GSK2190915
• Synonyms: GSK2190915;GSK2190915 (AM803);fiboflapon;AM 803;3-[(1,1-Dimethylethyl)thio]-1-[[4-(6-ethoxy-3-pyridinyl)phenyl]methyl]-alpha,alpha-dimethyl-5-[(5-methyl-2-pyridinyl)methoxy]-1H-indole-2-propanoic acid
• CAS NO: 936350-00-4
• Molecular Formula: C38H43N3O4S
• Molecular Weight: 637.83072
• Mol File: 936350-00-4.mol

Chemical Properties

• Boiling Point: 796.3±60.0 °C(Predicted)
• Appearance: /
• Density: 1.16±0.1 g/cm3(Predicted)
• PKA: 4.70±0.10(Predicted)
• CAS DataBase Reference: GSK2190915(CAS DataBase Reference)
• NIST Chemistry Reference: GSK2190915(936350-00-4)
• EPA Substance Registry System: GSK2190915(936350-00-4)

Safety Data

• Hazardous Substances Data: 936350-00-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
GSK2190915 is used as a therapeutic agent for the treatment of non-alcoholic fatty liver disease, obesity, and certain types of cancer. Its ability to inhibit acetyl-CoA carboxylase (ACC) helps reduce lipid accumulation and promote lipid oxidation, making it a promising candidate for managing diseases associated with abnormal lipid metabolism.
Used in Cancer Therapy:
GSK2190915 is used as an anticancer agent, particularly for cancers that depend on lipid metabolism for growth and survival. By inhibiting acetyl-CoA carboxylase (ACC), it can disrupt the lipid synthesis and metabolism required by cancer cells, potentially leading to reduced tumor growth and improved treatment outcomes.
Used in Metabolic Disorders:
GSK2190915 is used as a treatment for metabolic disorders such as obesity, where its inhibition of acetyl-CoA carboxylase (ACC) can help regulate lipid metabolism and reduce lipid accumulation, potentially contributing to weight loss and improved metabolic health.
Preclinical studies have shown promising results for GSK2190915, and ongoing research is focused on evaluating its safety and efficacy for various therapeutic indications.

Upstream product

• 1300640-25-8 5-[4-(chloromethyl)phenyl]-2-(ethyloxy)pyridine 
• 1300640-30-5 2-(ethyloxy)-5-(4-{[1-(4-{[(5-methylpyridin-2-yl)methyl]oxy}phenyl)hydrazino]methyl}phenyl)pyridine 
• 1300640-24-7 5-[4-(bromomethyl)phenyl]-2-(ethyloxy)pyridine hydrobromide 
• 1300640-23-6 5-[4-(bromomethyl)phenyl]-2-(ethyloxy)pyridine 
• 1300640-22-5 5-[4-(hydroxymethyl)phenyl]-2-(ethyloxy)pyridine 
• 55849-30-4 5-bromo-2-ethoxypyridine 
• 59016-93-2 p-hydroxymethylphenylboronic acid 
• 136558-13-9 ethyl 5-t-butylthio-2,2-dimethyl-4-oxo-pentanoate 
• 71670-70-7 2-(chloromethyl)-5-methyl-pyridine monohydrochloride 
• 589-93-5 2,5-dimethylpyridine 
• 1346434-77-2 (5-methylpyridin-2-yl)methanol hydrochloride 
• 1196965-14-6 3-{3-tert-butylsulfanyl-1-[4-(6-ethoxy-pyridin-3-yl)-benzyl]-5-hydroxy-1H-indol-2-yl}-2,2-dimethyl-propionic acid ethyl ester 
• 772-71-4 2-acetoxymethyl-5-methyl pyridine 
• 936351-54-1 3-[1-(4-bromo-benzyl)-3-tert-butylsulfanyl-5-hydroxy-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester 

Relevant articles and documents

Novel Processes

The present invention provides processes useful for preparing 5-lipoxygenase activating protein (FLAP) inhibitors and their intermediates. In particular, processes for preparing 3-[3-(tert-butylsulfanyl)-1-[4-(6-ethoxy-pyridin-3-yl)benzyl]-5-(5-methyl-pyridin-2-yl-methoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid, the anhydrous Form C polymorph of sodium 3-[3-(tert-butylsulfanyl)-1-[4-(6-ethoxy-pyridin-3-yl)benzyl]-5-(5-methyl-pyridin-2-yl-methoxy)-1H-indol-2-yl]-2,2-dimethyl-propionate, and intermediates useful in said processes are provided.

5-lipoxygenase-activating protein (FLAP) inhibitors. Part 4: Development of 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin- 2-ylmethoxy)-1 H -indol-2-yl]-2,2-dimethylpropionic acid (AM803), a potent, oral, once daily FLAP inhibitor

The potent 5-lipoxygenase-activating protein (FLAP) inhibitor 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2- ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic acid 11cc is described (AM803, now GSK2190915). Building upon AM103 (1) (Hutchinson et al. J. Med Chem.2009, 52, 5803-5815; Stock et al. Bioorg. Med. Chem. Lett. 2010, 20, 213-217; Stock et al. Bioorg. Med. Chem. Lett.2010, 20, 4598-4601), SAR studies centering around the pyridine moiety led to the discovery of compounds that exhibit significantly increased potency in a human whole blood assay measuring LTB4 inhibition with longer drug preincubation times (15 min vs 5 h). Further studies identified 11cc with a potency of 2.9 nM in FLAP binding, an IC50 of 76 nM for inhibition of LTB4 in human blood (5 h incubation) and excellent preclinical toxicology and pharmacokinetics in rat and dog. 11cc also demonstrated an extended pharmacodynamic effect in a rodent bronchoalveolar lavage (BAL) model. This compound has successfully completed phase 1 clinical studies in healthy volunteers and is currently undergoing phase 2 trials in asthmatic patients.

5-Lipoxygenase-Activating Protein Inhibitor

Described herein is the FLAP inhibitor 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxy-pyridin-3-yl)-benzyl]-5-(5-methyl-pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid, or a pharmaceutically acceptable salt thereof. Also described are methods of p

5-LIPOXYGENASE-ACTIVATING PROTEIN (FLAP) INHIBITORS

Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of 5-lipoxygenase-activating protein (FLAP). Also described herein are methods of using such FLAP modulators, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions or diseases.