701232-20-4

Basic information

• Product Name: DGAT-3
• Synonyms: DGAT-3;Cyclohexaneacetic acid, 4-[4-(4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)phenyl]-, trans-;trans-4-[4-(4-Amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)phenyl]cyclohexaneacetic acid;Mino-7,7-diMethyl-2-((1r,4r)-4-(4-(4-a7H-pyriMido[4,5-b][1,4]oxazin-6-yl)phenyl)cyclohexyl)acetic acid;trans-2-(4-(4-(4-aMino-7,7-diMethyl-7H-pyriMido[4,5-b][1,4]oxazin-6-yl)phenyl)cyclohexyl)acetic acid;2-((1,4-trans)-4-(4-(4-Amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)- phenyl)cyclohexyl)acetic acid
• CAS NO: 701232-20-4
• Molecular Formula: C22H26N4O3
• Molecular Weight: 394.472
• Mol File: 701232-20-4.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 616.6±55.0 °C(Predicted)
• Appearance: white to beige/
• Density: 1.36±0.1 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble15mg/mL (clear solution)
• PKA: 4.72±0.10(Predicted)
• CAS DataBase Reference: DGAT-3(CAS DataBase Reference)
• NIST Chemistry Reference: DGAT-3(701232-20-4)
• EPA Substance Registry System: DGAT-3(701232-20-4)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 701232-20-4(Hazardous Substances Data)

Usage

Uses

T863 has been used as a diglyceride acyltransferase (DGAT1) inhibitor:to provide the opportunity to precisely control the DGAT inhibitionto treat mouse embryonic fibroblasts (MEFs) to analyse lipid droplet biogenesisto specifically block neutral?lipid synthesis?and lipid droplet formation in HT-1080 cellsto block lipid droplet (LD) formation

Biological Activity

diacylglycerol acyltransferase (dgat1) inhibitor

Biochem/physiol Actions

T863 is an orally active, selective and potent DGAT1 (Acyl-CoA:diacylglycerol acyltransferase 1) inhibitor that interacts with the acyl-CoA binding site of DGAT1, and inhibits triacylglycerol synthesis in cells. T863 causes weight loss, reduction in serum and liver triglycerides, and improved insulin sensitivity in obese mice.

Upstream product

• 701232-18-0 ethyl 2-(4-(4-(2-bromo-2-methylpropanoyl)phenyl)cyclohexyl)acetate 
• 1672-50-0 4,5-diamino-6-hydroxypyrimidine 
• 4894-75-1 1-phenyl-4-cyclohexanone 
• 701232-19-1 C₂₄H₃₀N₄O₃ 
• 411238-92-1 ethyl 2-(4-phenylcyclohexyl)acetate 
• 115880-04-1 ethyl 2-(4-phenylcyclohexylidene)acetate 

Downstream Products

• 1593076-96-0 C₂₂H₂₅N₅O 

Relevant articles and documents

Discovery of 6-phenylpyrimido[4,5- B ][1,4]oxazines as potent and selective Acyl CoA: Diacylglycerol acyltransferase 1 (DGAT1) inhibitors with in vivo efficacy in rodents

The discovery and optimization of a series of acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) inhibitors based on a pyrimido[4,5-b][1,4]oxazine scaffold is described. The SAR of a moderately potent HTS hit was investigated resulting in the discovery of phenylcyclohexylacetic acid 1, which displayed good DGAT1 inhibitory activity, selectivity, and PK properties. During preclinical toxicity studies a metabolite of 1 was observed that was responsible for elevating the levels of liver enzymes ALT and AST. Subsequently, analogues were synthesized to preclude the formation of the toxic metabolite. This effort resulted in the discovery of spiroindane 42, which displayed significantly improved DGAT1 inhibition compared to 1. Spiroindane 42 was well tolerated in rodents in vivo, demonstrated efficacy in an oral triglyceride uptake study in mice, and had an acceptable safety profile in preclinical toxicity studies.