Vorinostat

Base Information

• Chemical Name: Vorinostat
• CAS No.: 149647-78-9
• Molecular Formula: C14H20N2O3
• Molecular Weight: 264.324
• Hs Code.: 29280000
• European Community (EC) Number: 682-505-1
• NSC Number: 759852,748799,701852
• UNII: 58IFB293JI
• DSSTox Substance ID: DTXSID6041133
• Nikkaji Number: J653.349C
• Wikipedia: Vorinostat
• Wikidata: Q905901
• NCI Thesaurus Code: C1796
• RXCUI: 194337
• Pharos Ligand ID: 3A6WF2F4D5BG
• Metabolomics Workbench ID: 43614
• ChEMBL ID: CHEMBL98
• Mol file: 149647-78-9.mol

Synonyms:18F Suberoylanilide Hydroxamic Acid;18F-SAHA;18F-suberoylanilide hydroxamic acid;M344;MK 0683;MK-0683;MK0683;N Hydroxy N' phenyloctanediamide;N-hydroxy-N'-phenyloctanediamide;N1 Hydroxy N8 phenyloctanediamide;N1-hydroxy-N8-phenyloctanediamide;NHNPODA;suberanilohydroxamic acid;suberoyl anilide hydroxamic acid;suberoylanilide hydroxamic acid;Vorinostat;zolinza

Chemical Property of Vorinostat

Chemical Property:

• Appearance/Colour: white crystalline solid
• Melting Point: 161-162 °C
• Refractive Index: 1.566
• PKA: 9.48±0.20(Predicted)
• PSA: 78.43000
• Density: 1.174 g/cm³
• LogP: 2.93500
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO: ≥15mg/mL
• XLogP3: 1.9
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 8
• Exact Mass: 264.14739250
• Heavy Atom Count: 19
• Complexity: 276

Purity/Quality:

99% ^*data from raw suppliers

Suberoylanilide Hydroxamic Acid ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 61-68
• Safety Statements: 53-36/37-45

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: C1=CC=C(C=C1)NC(=O)CCCCCCC(=O)NO
• Recent ClinicalTrials: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial
• Recent EU Clinical Trials: Phase II basket trial evaluating the efficacy of a combination of pembrolizumab and vorinostat in patients with recurrent and/or metastatic squamous cell carcinoma
• Recent NIPH Clinical Trials: Study of KW-0761 Versus Vorinostat In Relapsed/Refractory CTCL.
• Description: Vorinostat is the first drug in a new class of anti-cancer agents that inhibit histone deacetylases (HDAC). It was launched as an oral treatment for cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent, or recurrent disease on or following two systemic therapies. HDACs are enzymes that catalyze the removal of the acetyl modification on lysine residues of proteins, including the core nucleosomal histones. Together with their counterpart histone acetyltransferases (HATs), HDACs regulate the acetylation level of the histones, which plays an important role in the regulation of chromatin plasticity and gene transcription. Hypoacetylation of histones is associated with a condensed chromatin structure resulting in the repression of gene transcription, whereas acetylated histones are associated with a more open chromatin structure and activation of transcription. In some cancer cells, there is an overexpression of HDACs, resulting in hypoacetylation of histones. Inhibitors of HDAC are thought to transcriptionally reactivate dormant tumor-suppressor genes by allowing for the accumulation of acetyl groups on histones and an open chromatin structure. Vorinostat inhibits the enzymatic activity of HDAC1, HDAC2, HDAC3, and HDAC6 at nanomolar concentrations (IC50 ＜86 nM). In vitro, it induces growth arrest, differentiation or apoptosis in a variety of tumor cells. In addition, vorinostat inhibits tumor growth in animal models bearing solid tumors, including breast, prostate, lung and gastric cancers, as well as hematologic malignancies such as multiple myeloma and leukemias.
• Uses: A potent, selective, cell permeable histone deacetylase inhibitor (HDAC). Displays anti-angiogenic activity by interfering with VEGF signaling in human umbilical vein endothelial cells (HUVECs). Induces differentiation in uman breast cancer cells. antineoplastic, histone deacetylase inhibitor Suberoylanilide Hydroxamic Acid is a potent, selective, cell permeable histone deacetylase inhibitor (HDAC). Suberoylanilide Hydroxamic Acid displays anti-angiogenic activity by interfering with VEGF signaling in human umbilical vein endothelial cells (HUVECs). Suberoylanilide Hydroxamic Acid induces differentiation in uman breast cancer cells. A potent HDAC inhibitor; also causes cell cycle arrest at G1 Vorinostat, a histone deacetylase (HDAC) inhibitor from Merck, was approved for the treatment of cutaneous T-cell lymphoma (CTCL), a type of non-Hodgkin’s lymphoma. Vorinostat was shown to inhibit HDAC1, HDAC2, HDAC3 and HDAC6 at nanomolar concentrations. HDAC inhibitors are potent differentiating agents toward a variety of neoplasms, including leukemia and breast and prostate cancers.

Technology Process of Vorinostat

There total 34 articles about Vorinostat 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: 95.6%

8-oxo-8-(phenylamino)octanoic acid methyl ester (162853-41-0) → vorinostat (149647-78-9)

Guidance literature:

8-oxo-8-(phenylamino)octanoic acid methyl ester; With hydroxylamine hydrochloride; sodium methylate; In methanol; water; for 16.1667h;

With water; acetic acid; In methanol; for 0.166667h; pH=8.7 - 12.02;

Reference yield: 91.0%

C21H24N2O3 → vorinostat (149647-78-9)

Guidance literature:

With 10 wt% Pd(OH)2 on carbon; hydrogen; trifluoroacetic acid; In methanol; at 20 ℃; for 2h;

DOI:10.3762/bjoc.15.245

Reference yield: 88.5%

N-phenylhexanamide (6998-10-3) → vorinostat (149647-78-9)

Guidance literature:

With hydroxylamine hydrochloride; In N,N-dimethyl-formamide; at 40 ℃; for 1h; Reagent/catalyst;

upstream raw materials:

8-oxo-8-(phenylamino)octanoic acid methyl ester

suberic acid monomethyl ester

aniline

octane-1,8-dioic acid

Downstream raw materials:

methyl 2,3,4-tri-O-acetyl-1-O-7-(phenylcarbamoyl)hepthydroxamoyl-β-D-glucopyranosyluronate

2,3,4,6-tetra-O-acetyl-1-O-7-(phenylcarbamoyl)hepthydroxamoyl-β-D-galactopyranose

N-[(8-anilino-8-oxooctanoyl)oxy]-N'-phenyloctanediamide

N¹-phenyl-N⁸-(4-(3-thioxo-3H-1,2-dithiol-4-yl)benzoyloxy)octanediamide

Refernces

• 1、 Chattopadhyay, Shital K.,Ghosh, Subhankar,Sarkar, Sarita,Bhadra, Kakali. "α,?-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA". . p. 2524 - 2533. Retrieved 2019.
• 2、 Riva, Elena,Gagliardi, Stefania,Mazzoni, Caterina,Passarella, Daniele,Rencurosi, Anna,Vigo, Daniele,Martinelli, Marisa. "Efficient continuous flow synthesis of hydroxamic acids and suberoylanilide hydroxamic acid preparation". . p. 3540 - 3543. Retrieved 2009.
• 3、 Gediya, Lalji K.,Chopra, Pankaj,Purushottamachar, Puranik,Maheshwari, Neha,Njar, Vincent C. O.. "A new simple and high-yield synthesis of suberoylanilide hydroxamic acid and its inhibitory effect alone or in combination with retinoids on proliferation of human prostate cancer cells". . p. 5047 - 5051. Retrieved 2005.
• 4、 Kavianpour, Poya,Gemmell, Madeleine C. M.,Kahlert, Jan U.,Rendina, Louis M.. "Histone Deacetylase 2 (HDAC2) Inhibitors Containing Boron". . p. 2786 - 2791. Retrieved 2020/06/25.