Entinostat

Base Information

• Chemical Name: Entinostat
• CAS No.: 209783-80-2
• Deprecated CAS: 442532-99-2
• Molecular Formula: C21H20N4O3
• Molecular Weight: 376.415
• Hs Code.: 29333990
• European Community (EC) Number: 630-693-0
• NSC Number: 706995
• UNII: 1ZNY4FKK9H
• DSSTox Substance ID: DTXSID0041068
• Nikkaji Number: J1.120.280B
• Wikipedia: Entinostat
• Wikidata: Q1281020
• NCI Thesaurus Code: C1863
• Pharos Ligand ID: 9CWDQBBBJD9A
• Metabolomics Workbench ID: 152933
• ChEMBL ID: CHEMBL27759
• Mol file: 209783-80-2.mol

Synonyms:entinostat;MS 27-275;MS 275;MS-27-275;MS-275;N-(2-aminophenyl)-4-(N-(pyridin-3-ylmethoxycarbonyl)aminomethyl)benzamide;SNDX-275

Chemical Property of Entinostat

Chemical Property:

• Vapor Pressure: 7.31E-13mmHg at 25°C
• Melting Point: 159-160 °C
• Refractive Index: 1.672
• Boiling Point: 566.7 °C at 760 mmHg
• Flash Point: 296.6 °C
• PSA: 106.34000
• Density: 1.315 g/cm³
• LogP: 4.38760
• Storage Temp.: −20°C
• Solubility.: DMSO: 38 mg/mL, soluble
• XLogP3: 2
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 7
• Exact Mass: 376.15354051
• Heavy Atom Count: 28
• Complexity: 508

Purity/Quality:

99% ^*data from raw suppliers

Entinostat(MS-27-275) ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi,T
• Statements: 36/37/38-62-48/25-25-61
• Safety Statements: 26-36-45

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1=CC=C(C(=C1)N)NC(=O)C2=CC=C(C=C2)CNC(=O)OCC3=CN=CC=C3
• Recent ClinicalTrials: Entinostat in Combination With Aldesleukin in Treating Patients With Metastatic Kidney Cancer
• Recent EU Clinical Trials: A multicenter phase II open label study to evaluate efficacy of concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma
• Recent NIPH Clinical Trials: 2375-002
• Description: Entinostat (SNDX-275, MS-275) belongs to benzamide class HDACi and inhibits HDAC1 and 2, 3 and 9 and has low effect against HDAC4, 6, 7 and 8 (Khan et al. 2007). Entinostat is in phase II clinical trial for treatment of Hodgkin's lymphoma and advanced breast cancer (in combination with aromatase inhibitors) and metastatic lung cancer (in combination with erlotinib).
• Uses: Entinostat is an emerging HDACi (histone deacetylase inhibitor). Entinostat is used for treatment of solid tumors and hematologic malignancies. Entinostat is an emerging HDACi (histone deacetylase inhibitor). Entinostat is used for treatment of solid tumors and hematologic malignancies. Potent Histone deacetylase inhibitor.
• Clinical Use: Entinostat is an HDAC inhibitor with a relatively long half-life (averaging between 33 and 52 hours). Trials have shown significant biological activity in patients with hematological malignancies receiving entinostat treatments. However, the efficacy of entinostat as a single-agent therapy remains limited. Reported dose-limiting toxicities associated with entinostat include neurotoxicity, fatigue, hypophosphatemia, anorexia, and vomiting. The large number of clinical trials using HDAC inhibitors for the treatment of patients with hematological malignancies has demonstrated that these drugs are relatively well tolerated. Although the responses with the currently-available HDAC inhibitors are still limited, there are significant responses in some patients with advanced disease, where options are limited. With better patient selection and the development of more potent HDAC inhibitors, targeting HDACs for the treatment of hematological malignancies remains promising. Furthermore, a growing body of literature suggests that HDAC inhibitors may potentiate some of the currently used cytotoxic or biologic therapies based on their mechanism of action, with multiple trials currently ongoing. Promising combination partners include proteosome inhibitors, DNA demethylating agents, and anthracyclines.

Technology Process of Entinostat

There total 17 articles about Entinostat 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: 88.0%

C21H18N6O3 (1379471-51-8) → Entinostat (209783-80-2,442532-99-2)

Guidance literature:

With [Fe(TPP)Cl]; 2-hydroxyethanethiol; In methanol; dichloromethane; at 30 ℃; for 0.5h; Under air;

DOI:10.1002/cbic.201100719

Reference yield: 80.0%

1,2-diamino-benzene (95-54-5) + 4-benzoic acid (241809-79-0) → Entinostat (209783-80-2,442532-99-2)

Guidance literature:

4-benzoic acid; With 1,1'-carbonyldiimidazole; In tetrahydrofuran; at 60 ℃; for 3h;

1,2-diamino-benzene; With trifluoroacetic acid; In tetrahydrofuran; at 20 ℃; for 16h;

Reference yield: 72.0%

1,3-dimethyl-2-imidazolidinone (80-73-9) + 1,2-diamino-benzene (95-54-5) + 4-benzoic acid (241809-79-0) → Entinostat (209783-80-2,442532-99-2)

Guidance literature:

With methanesulfonic acid; In water; 1,1'-carbonyldiimidazole;

upstream raw materials:

1,2-diamino-benzene

1-{4-[N-(pyridin-3-ylmethoxycarbonyl)-aminomethyl]benzoyl}imidazole

3-hydroxymethylpyridin

pyridin-3-ylmethyl 1H-imidazole-1-carboxylate

Downstream raw materials:

2-[(tert-butoxy)carbonylamino]-N-{2-[(4-{[(3-pyridylmethoxy)-carbonylamino]methyl}phenyl)carbonylamino]phenyl}acetamide

4-{[N-(2-{[4-{[3-pyridylmethoxycarbonylamino]methyl}phenyl]carbonylamino}phenyl)carbamoyloxy]methyl}phenyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetraenoate

C₆₆H₆₁N₇O₂₇

2-amino-N-{2-[(4-{[(3-pyridylmethoxy)-carbonylamino]methyl}phenyl)carbonylamino]phenyl}acetamide

Refernces

• 1、 -. "SOLID FORMS OF ENTINOSTAT". Page/Page column 20. . Retrieved 2018/01/20.
• 2、 Sasmal, Pijus K.,Carregal-Romero, Susana,Han, Alice A.,Streu, Craig N.,Lin, Zhijie,Namikawa, Kazuhiko,Elliott, Samantha L.,Koester, Reinhard W.,Parak, Wolfgang J.,Meggers, Eric. "Catalytic Azide Reduction in Biological Environments". experimental part. p. 1116 - 1120. Retrieved 2012/08/13.