Evofosfamide

Base Information

• Chemical Name: Evofosfamide
• CAS No.: 918633-87-1
• Molecular Formula: C₉H₁₆Br₂N₅O₄P
• Molecular Weight: 449.039
• UNII: 8A9RZ3HN8W
• ChEMBL ID: CHEMBL260046
• DSSTox Substance ID: DTXSID60238721
• Metabolomics Workbench ID: 149625
• NCI Thesaurus Code: C71722
• Nikkaji Number: J3.504.735B
• Wikidata: Q7670203
• Wikipedia: Evofosfamide
• Mol file: 918633-87-1.mol

Synonyms:evofosfamide;TH 302;TH-302;TH302 cpd

Chemical Property of Evofosfamide

Chemical Property:

• Boiling Point: 565.4±60.0 °C(Predicted)
• PKA: 0.34±0.70(Predicted)
• PSA: 123.81000
• Density: 1.97
• LogP: 3.22700
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 0.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 9
• Exact Mass: 448.92862
• Heavy Atom Count: 21
• Complexity: 374

Purity/Quality:

98%Min ^*data from raw suppliers

TH-302 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN1C(=CN=C1[N+](=O)[O-])COP(=O)(NCCBr)NCCBr
• Recent ClinicalTrials: A Phase 2 Biomarker - Enriched Study of TH-302 in Subjects With Advanced Melanoma
• Recent EU Clinical Trials: A phase II trial to assess the activity and safety of TH-302 in combination with sunitinib in patients with well- and moderately-differentiated metastatic pancreatic neuroendocrine tumors (pNET) previously untreated
• Recent NIPH Clinical Trials: A Phase II, Single-arm, Japanese Multicenter Trial of TH-302 in Combination with Doxorubicin in Subjects with Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma(EMR 200592-008)
• Description: TH-302 is a hypoxia-activated prodrug and DNA alkylating agent with anticancer activity. It is selectively cytotoxic to H460 human non-small cell lung cancer (NSCLC) cells grown under hypoxic over normoxic conditions (IC50s = 0.019 and 5.1 μM, respectively). Under hypoxic conditions, TH-302 undergoes a one-electron reduction to form an active radical intermediate that is then further reduced to form a DNA-intercalating hydroxylamine. Under normoxic conditions, the radical intermediate is quenched and induces reformation of the inactive nitroazole prodrug. TH-302 reduces survival of H460 and HT-29 cells in a clonogenic assay (IC50s = 0.2 and 0.2 μM, respectively). In vivo, TH-302 (33 mg/kg per day) inhibits primary tumor growth by 41% in an MIA PaCa-2-RFP mouse orthotopic xenograft model. It inhibits tumor growth by greater than 40% in Calu-6 NSCLC, H82 small cell lung, A375 melanoma, PC-3 prostate, and BxPC-3 pancreatic cancer mouse xenograft models when administered at 50 mg/kg.
• Uses: TH-302 is a 2-nitroimidazole triggered hypoxia-activated prodrug (HAP) of bromo-isophosphoramide mustard. Studies have shown that TH-302 treatment exhibited hypoxia-selective cytotoxicity and DNA dama ge in human cancer cell TH-302 is a 2-nitroimidazole triggered hypoxia-activated prodrug (HAP) of bromo-isophosphoramide mustard. Studies have shown that TH-302 treatment exhibited hypoxia-selective cytotoxicity and DNA damage in human cancer cell

Technology Process of Evofosfamide

There total 6 articles about Evofosfamide 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: 47.6%

N,N'-bis(2-bromoethyl)phosphorodiamidic acid (141025-16-3) + 1-methyl-2-nitro-5-hydroxymethylimidazole (39070-14-9) → evofosfamide (918633-87-1)

Guidance literature:

With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20 ℃;

DOI:10.1021/jm701028q

Reference yield: 35.0%

2-bromoethylamine hydrobromide (2576-47-8) + 1-methyl-2-nitro-5-hydroxymethylimidazole (39070-14-9) → evofosfamide (918633-87-1)

Guidance literature:

1-methyl-2-nitro-5-hydroxymethylimidazole; With triethylamine; trichlorophosphate; In dichloromethane; for 1h;

2-bromoethylamine hydrobromide; With triethylamine; In dichloromethane; at 20 ℃; for 2h;

Reference yield:

C4H10Br2ClN2OP + 1-methyl-2-nitro-5-hydroxymethylimidazole (39070-14-9) → evofosfamide (918633-87-1)

Guidance literature:

With triethylamine; In dichloromethane; at 0 ℃;

DOI:10.1021/acsmedchemlett.7b00355

upstream raw materials:

N,N'-bis(2-bromoethyl)phosphorodiamidic acid

1-methyl-2-nitro-5-hydroxymethylimidazole

ethyl 1-N-methyl-2-nitro-1H-imidazole-5-carboxylate

2-bromoethylamine hydrobromide

Refernces

• 1、 Zhang, Wenting,Fan, Wei,Zhou, Zhengyuan,Garrison, Jered. "Synthesis and Evaluation of Radiolabeled Phosphoramide Mustard with Selectivity for Hypoxic Cancer Cells". supporting information. p. 1269 - 1274. Retrieved 2017/12/26.
• 2、 Duan, Jian-Xin,Jiao, Hailong,Kaizerman, Jacob,Stanton, Timothy,Evans, James W.,Lan, Leslie,Lorente, Gustavo,Banica, Monica,Jung, Don,Wang, Jinwei,Ma, Huaiyu,Li, Xiaoming,Yang, Zhijian,Hoffman, Robert M.,Ammons, W. Steve,Hart, Charles P.,Matteucci, Mark. "Potent and highly selective hypoxia-activated achiral phosphoramidate mustards as anticancer drugs". . p. 2412 - 2420. Retrieved 2008/12/22.