1109276-89-2

Basic information

• Product Name: PF-04620110
• Synonyms: Cyclohexaneacetic acid, 4-[4-(4-amino-7,8-dihydro-5-oxopyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]-, trans-;2-[4-[4-(4-Amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6-yl)phenyl]cyclohexyl]acetic acid;2-(trans-4-(4-(4-Amino-5-oxo-7,8-dihydropyrimido[5,4-f]-[1,4]oxazepin-6(5H)-yl)phenyl)cyclohex;PF-04620110;trans-4-[4-(4-Amino-7,8-dihydro-5-oxopyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexaneacetic acid;2-((1r,4r)-4-(4-(4-aMino-5-oxo-7,8-dihydropyriMido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)cyclohexyl)acetic acid;2-(4-(4-(4-aMiNA-5-oxo-7,8-dihydropyriMido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl)cyclohexyl)acetic acid;2-(trans-4-(4-(4-Amino-5-oxo-7,8-dihydropyrimido[5,4-f]-[1,4]oxazepin-6(5H)-yl)phenyl)cyclohexyl)
• CAS NO: 1109276-89-2
• Molecular Formula: C₂₁H₂₄N₄O₄
• Molecular Weight: 396
• Product Categories: Inhibitors
• Mol File: 1109276-89-2.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 701.9±60.0 °C(Predicted)
• Appearance: white to beige/
• Density: 1.326
• Storage Temp.: room temp
• Solubility: DMSO: soluble10mg/mL (clear solution)
• PKA: 4.72±0.10(Predicted)
• CAS DataBase Reference: PF-04620110(CAS DataBase Reference)
• NIST Chemistry Reference: PF-04620110(1109276-89-2)
• EPA Substance Registry System: PF-04620110(1109276-89-2)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• Hazardous Substances Data: 1109276-89-2(Hazardous Substances Data)

Usage

Description

PF-04620110 is a pharmaceutical compound that functions as an orally-active inhibitor with selectivity towards neutral-diglyceride acyltransferase-1 (DGAT-1). This enzyme plays a crucial role in the final step of triglyceride synthesis, making PF-04620110 a potential candidate for the treatment of conditions related to lipid metabolism.

Uses

Used in Pharmaceutical Industry:
PF-04620110 is used as a therapeutic agent for the treatment of dyslipidemia and other related metabolic disorders. By inhibiting DGAT-1, it can potentially reduce the synthesis of triglycerides and improve lipid profiles in patients, thus managing and preventing the progression of these conditions.
Additionally, PF-04620110 may also be used as a research tool to study the role of DGAT-1 in lipid metabolism and its potential implications in various diseases, further expanding its applications in the pharmaceutical and biotechnology sectors.

Biological Activity

pf-04620110 is a potent, selective and orally-bioavailable inhibitor of diacylglycerol acyltransferase 1 (dgat-1), an enzyme catalyzing the final committed step in the biosynthesis of triglycerides, that inhibits dgat-1 with values of 50% inhibition concentration ic50 of 19 nm and 8 nm in human and ht-29 cells respectively. pf-04620110 displays a highly selective, more than 100 fold, inhibition against dgat-1 rather than a range of lipid processing enzymes, including human dgat-2, human acyl-coa:cholesterol acyltransferase 1, human acyl-coa:wax alcohol acyltransferase 1, human acyl-coa:wax alcohol acyltransferase 2, human acyl-coa:monacylglycerol acyltransferase 2, human acyl-coa:monacylglycerol acyltransferase 3 and mouse mgat 1.lee kr, choi sh, song js, seo h, chae yj, cho he, ahn jh, ahn sh, bae ma. determination of pf-04620110, a novel inhibitor of diacylglycerol acyltransferase-1, in rat plasma using liquid chromatography-tandem mass spectrometry and its application in pharmacokinetic studies. biomed chromatogr. 2013; 27(7):846-852.robert l. dow *, jian-cheng li , michael p. pence , e. michael gibbs , jennifer l. laperle , john litchfield , david w. piotrowski , michael j. munchhof , tara b. manion , william j. zavadoski , gregory s. walker , r. kirk mcpherson , susan tapley , eliot sugarman , angel guzman-perez , and paul dasilva-jardine discovery of pf-04620110, a potent, selective, and orally bioavailable inhibitor of dgat-1. acs med. chem. lett., 2011, 2 (5), pp 407–412

Biochem/physiol Actions

PF-04620110 is known to regulate gut hormones. Inhibition of DGAT1 might serve as a good approach for the treatment of obesity and type 2 diabetes. DGAT1 inhibition might increase the oxidation of fatty acids, thus it is found to be protective against hepatic steatosis.

Upstream product

• 1109276-87-0 methyl {trans-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6-(5H)-yl)phenyl]cyclohexyl}acetate 

Downstream Products

• 1109277-18-0 2-{trans-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl}-N-(methylsulfonyl)acetamide 
• 1236356-66-3 4-amino-6-(4-{trans-4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]cyclohexyl}phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one 
• 1236356-58-3 4-amino-6-(4-{trans-4-[2-(4-methoxypiperidin-1-yl)-2-oxoethyl]cyclohexyl}phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one 
• 1236357-13-3 4-amino-6-(4-{trans-4-[2-(4-methyl-3-oxopiperazin-1-yl)-2-oxoethyl]cyclohexyl}phenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one 
• 1450727-77-1 4-amino-6-{4-[trans-4-(2-morpholin-4-yl-2-oxoethyl)cyclohexyl]phenyl}-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one 
• 1236356-83-4 4-amino-6-[4-(trans-4-{2-[(3R)-3-hydroxypyrrolidin-1-yl]-2-oxoethyl}cyclohexyl)phenyl]-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one 
• 1450727-76-0 2-{trans-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl}-N-[(1R)-1-(hydroxymethyl)-2-methylpropyl]acetamide 
• 1109277-25-9 2-{trans-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl}-N-cyclopentylacetamide 
• 1109277-23-7 2-{trans-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl}-N-ethylacetamide 
• 1109277-21-5 2-trans-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexylacetamide 
• 1236356-57-2 N-({trans-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl}acetyl)-N-methylglycine 
• 1109277-42-0 6-(4-(trans-4-((2H-tetrazol-5-yl)methyl)cyclohexyl)phenyl)-4-amino-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one 
• 1109277-38-4 {trans-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl}acetonitrile 
• 1236357-71-3 trans-2-{4-[4-(4-amino-5-oxo-7,8-dihydro-5H-9-oxa-1,3,6-triaza-benzocyclohepten-6-yl)-phenyl]-cyclohexyl}-N-methylthioacetamide 

Relevant articles and documents

LACTAM DERIVATIVES AS DGAT-1 INHIBITORS

Described herein are compounds of formula I The compounds of formula I act as DGAT1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for hyperlipidemia, diabetes mellitus and obesity.

4-AMINO-5-OXO-7, 8-DIHYDROPYRIMIDO [5,4-F] [1,4] OXAZEPIN-6 (5H) -YL) PHENYL DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF

The invention provides compounds of Formula (I), wherein R1, R2a, R2b, R3, m and A are as defined herein, as well as compositions thereof and methods for treating a disease, condition or disorder that is modulated by the inhibition of the diacylglycerol O-acyltransferase 1 (DGAT-1) enzyme by administering the compounds of the present invention and/or compositions thereof.