1030612-90-8

Basic information

• Product Name: MK8245
• Synonyms: 5-[3-[4-(2-Bromo-5-fluorophenoxy)-1-piperidinyl]-5-isoxazolyl]-2H-tetrazole-2-acetic acid;2-(5-(3-(4-(2-broMo-5-fluorophenoxy)piperidin-1-yl)isoxazol-5-yl)-2H-tetrazol-2-yl)acetic acid
• CAS NO: 1030612-90-8
• Molecular Formula: C₁₇H₁₆BrFN₆O₄
• Molecular Weight: 467.2491432
• Product Categories: Inhibitor;Inhibitors
• Mol File: 1030612-90-8.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 698.3±65.0 °C(Predicted)
• Appearance: /
• Density: 1.82
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility: ≥23.35 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O
• PKA: 2.85±0.10(Predicted)
• CAS DataBase Reference: MK8245(CAS DataBase Reference)
• NIST Chemistry Reference: MK8245(1030612-90-8)
• EPA Substance Registry System: MK8245(1030612-90-8)

Safety Data

• Hazardous Substances Data: 1030612-90-8(Hazardous Substances Data)

Usage

Description

MK-8245, also known as a liver-targeted inhibitor of stearoyl-CoA desaturase (SCD), is a compound developed by chemists at Merck & Co., Inc. It selectively inhibits SCD1 over other desaturases, making it a potential candidate for various pharmaceutical applications. MK-8245 is also part of the Aryl Halide Chemistry Informer Library, which aids in comparing and analyzing new reactions in complex synthesis.

Uses

Used in Pharmaceutical Applications:
MK-8245 is used as a liver-targeted inhibitor for stearoyl-CoA desaturase (SCD), particularly SCD1, to reduce the hepatic ratio of oleic acid to stearic acid, a marker of chronic SCD activity. This inhibition can help lower blood glucose levels without causing side effects such as skin lesions or eye squinting behavior in a mouse model of high-fat diet-induced obesity.
Used in Antiviral Applications:
MK-8245 is used as an inhibitor of hepatitis C virus (HCV) replication, demonstrating its effectiveness without inducing cytotoxicity in LucNeo2 cells.
Used in Chemical Synthesis:
MK-8245 is used as an Informer compound X9 in the Aryl Halide Chemistry Informer Library, allowing chemists to directly compare and analyze a reaction's successes and shortcomings among different methods and various research teams. It also facilitates deeper method development for performance or utility in complex synthesis.

references

[1] oballa rm, belair l, black wc, bleasby k, chan cc, desroches c, du x, gordon r, guay j, guiral s, hafey mj, hamelin e, huang z, kennedy b, lachance n, landry f, li cs, mancini j, normandin d, pocai a, powell da, ramtohul yk, skorey k, srensen d, sturkenboom w, styhler a, waddleton dm, wang h, wong s, xu l, zhang l. development of a liver-targeted stearoyl-coa desaturase (scd) inhibitor (mk-8245) to establish a therapeutic window for the treatment of diabetes and dyslipidemia. j med chem. 2011 jul 28;54(14):5082-96.[2] lachance n, guiral s, huang z, leclerc jp, li cs, oballa rm, ramtohul yk, wang h, wu j, zhang l. discovery of potent and liver-selective stearoyl-coa desaturase (scd) inhibitors in an acyclic linker series. bioorg med chem lett. 2012 jan 1;22(1):623-7.

Upstream product

• 1030613-41-2 ethyl (5-{3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]isoxazol-5-yl}-2H-tetrazol-2-yl)acetate 
• 1329632-66-7 (5-{3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-isoxazol-5-yl}tetrazol-2-yl)-acetic acid tert-butyl ester 
• 1030613-34-3 3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-4,5-dihydroisoxazole-5-carboxylic acid amide 
• 1030613-38-7 3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]isoxazole-5-carbonitrile 
• 1030613-36-5 3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]isoxazole-5-carboxylic acid amide 
• 147460-41-1 2-bromo-5-fluorophenol 
• 109384-19-2 t-butyl 4-hydroxy piperidine-1-carboxylate 
• 1030613-40-1 4-(2-bromo-5-fluorophenoxy)-1-[5-(1H-tetrazol-5-yl)isoxazol-3-yl]-piperidine 
• 105-36-2 ethyl bromoacetate 
• 1313515-96-6 ethyl 3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]isoxazole-5-carboxylate 
• 916971-27-2 4-(2-bromo-5-fluorophenoxy)piperidine 

Relevant articles and documents

Development of a liver-targeted stearoyl-CoA desaturase (SCD) inhibitor (MK-8245) to establish a therapeutic window for the treatment of diabetes and dyslipidemia

The potential use of SCD inhibitors for the chronic treatment of diabetes and dyslipidemia has been limited by preclinical adverse events associated with inhibition of SCD in skin and eye tissues. To establish a therapeutic window, we embarked on designing liver-targeted SCD inhibitors by utilizing molecular recognition by liver-specific organic anion transporting polypeptides (OATPs). In doing so, we set out to target the SCD inhibitor to the organ believed to be responsible for the therapeutic efficacy (liver) while minimizing its exposure in the tissues associated with mechanism-based SCD depletion of essential lubricating lipids (skin and eye). These efforts led to the discovery of MK-8245 (7), a potent, liver-targeted SCD inhibitor with preclinical antidiabetic and antidyslipidemic efficacy with a significantly improved therapeutic window.