MK-0752

Base Information

• Chemical Name: MK-0752
• CAS No.: 471905-41-6
• Molecular Formula: C21H21ClF2O4S
• Molecular Weight: 442.911
• Hs Code.: 29163990
• UNII: 9JD9B4S53T
• DSSTox Substance ID: DTXSID101026086,DTXSID70915051
• Nikkaji Number: J2.479.928J
• Wikidata: Q27272627
• NCI Thesaurus Code: C49175
• ChEMBL ID: CHEMBL3392635,CHEMBL4744852,CHEMBL4205422
• Mol file: 471905-41-6.mol

Synonyms:3-(4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acid;MK 0752;MK-0752;MK0752

Chemical Property of MK-0752

Chemical Property:

• PSA: 79.82000
• Density: 1.361
• LogP: 6.42320
• Solubility.: ≥22.15 mg/mL in DMSO; insoluble in H2O; ≥48.8 mg/mL in EtOH with ultrasonic
• XLogP3: 4.7
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 6
• Exact Mass: 442.0817143
• Heavy Atom Count: 29
• Complexity: 665

Purity/Quality:

97% ^*data from raw suppliers

MK-0752 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CC(CCC1CCC(=O)O)(C2=C(C=CC(=C2)F)F)S(=O)(=O)C3=CC=C(C=C3)Cl
• Recent ClinicalTrials: Study Of MK-0752 In Combination With Tamoxifen Or Letrozole to Treat Early Stage Breast Cancer
• Uses: γ-Secretase is a protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors and β-amyloid precursor protein (APP), within the transmembrane domain. MK-0752 is a potent, reversible inhibitor of γ-secretase, reducing the cleavage of APP to Aβ40 in human neuroblastoma SH-SY5Y cells with an IC50 value of 5 nM. It is orally bioavailable and crosses the blood-brain barrier, as orally administered MK-0752 dose-dependently reduces the generation of new amyloid β protein in the brain of rhesus monkeys. Through its effects on the Notch pathway, MK-0752 reduces the number of breast cancer stem cells in tumorgrafts, enhancing the efficacy of the chemotherapy drug docetaxel in mice with breast cancer tumors.[Cayman Chemical] MK-0752 is a gamma secretase inhibitor in clinical development.

Technology Process of MK-0752

There total 22 articles about MK-0752 which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 94.0%

3-[4-[(4-chlorophenyl)sulfanyl]-4-(2,5-difluorophenyl)cyclohexyl]propanoic acid (863605-38-3) → 3-((1S,4R)-4-((4-chlorophenyl)sulfonyl)-4-(2,5- difluorophenyl)cyclohexyl)propanoic acid (471905-41-6)

Guidance literature:

With dihydrogen peroxide; acetic acid; at 50 ℃;

DOI:10.1021/jo0705925

Reference yield: 74.0%

cis-1-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-3-propanal (656810-86-5) + sodium chlorite (7758-19-2) + aminosulfonic acid (5329-14-6) → 3-((1S,4R)-4-((4-chlorophenyl)sulfonyl)-4-(2,5- difluorophenyl)cyclohexyl)propanoic acid (471905-41-6)

Guidance literature:

In dichloromethane; water;

Reference yield: 74.0%

cis-1-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-3-propanal (656810-86-5) → 3-((1S,4R)-4-((4-chlorophenyl)sulfonyl)-4-(2,5- difluorophenyl)cyclohexyl)propanoic acid (471905-41-6)

Guidance literature:

With sodium chlorite; aminosulfonic acid; In dichloromethane; water; for 0.5h;

DOI:10.1021/jo070407n

upstream raw materials:

cis-1-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-3-propanal

3-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohex-1-enyl]propanoic acid

3-[4-[(4-chlorophenyl)sulfanyl]-4-(2,5-difluorophenyl)cyclohexyl]propanoic acid

2-[[(4-chlorophenyl)thio]methyl]-1,4-difluorobenzene

Downstream raw materials:

C₂₃H₂₆ClF₂NO₃S

Refernces

• 1、 Davies, Antony J.,Scott, Jeremy P.,Bishop, Brian C.,Brands, Karel M. J.,Brewer, Sarah E.,DaSilva, Jimmy O.,Dormer, Peter G.,Dolling, Ulf-H.,Gibb, Andrew D.,Hammond, Deborah C.,Lieberman, David R.,Palucki, Michael,Payack, Joseph F.. "A novel crystallization-induced diastereomeric transformation based on a reversible carbon-sulfur bond formation. Application to the synthesis of a γ-secretase inhibitor". . p. 4864 - 4871. Retrieved 2008/02/05.
• 2、 -. "The new cyclohexylpropionic sulfone". Page/Page column 23. . Retrieved 2008/06/13.