Bendamustine hydrochloride

Base Information

• Chemical Name: Bendamustine hydrochloride
• CAS No.: 3543-75-7
• Molecular Formula: C16H22Cl3N3O2
• Molecular Weight: 394.729
• Hs Code.: 29339900
• European Community (EC) Number: 631-540-0
• NSC Number: 138783
• UNII: 981Y8SX18M
• DSSTox Substance ID: DTXSID40188912
• Wikidata: Q27272066
• NCI Thesaurus Code: C61565
• RXCUI: 1114693
• ChEMBL ID: CHEMBL1201734
• Mol file: 3543-75-7.mol

Synonyms:bendamustin;bendamustine;bendamustine hydrochloride;Cytostasan;Hydrochloride, Bendamustine;IMET 3393;Ribomustin;Treanda;Zimet 3393

Chemical Property of Bendamustine hydrochloride

Chemical Property:

• Appearance/Colour: pale brown crystals
• Vapor Pressure: 1.55E-14mmHg at 25°C
• Melting Point: 149-151 °C
• Boiling Point: 585.2 °C at 760 mmHg
• Flash Point: 307.7 °C
• PSA: 58.36000
• LogP: 4.06660
• Storage Temp.: Desiccate at RT
• Solubility.: H2O: >30mg/mL
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 9
• Exact Mass: 393.077760
• Heavy Atom Count: 24
• Complexity: 380

Purity/Quality:

99% ^*data from raw suppliers

Bendamustine Hydrochloride ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,Xn
• Hazard Codes: T,Xn
• Statements: 60-61-22-40
• Safety Statements: 36-37

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: CN1C2=C(C=C(C=C2)N(CCCl)CCCl)N=C1CCCC(=O)O.Cl
• Recent ClinicalTrials: Obinutuzumab With or Without Umbralisib, Lenalidomide, or Combination Chemotherapy in Treating Patients With Relapsed or Refractory Grade I-IIIa Follicular Lymphoma
• Recent EU Clinical Trials: A Phase 3 Randomized, Open-Label, Multicenter Study Evaluating the Efficacy of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Subjects with Relapsed/Refractory Follicular Lymphoma
• Recent NIPH Clinical Trials: Clinical trials for HDC / ASCT indication rrDLBCL
• Indications: In March 2008, the US Food and Drug Authority (briefly called FDA) first approved bendamustine hydrochloride for the treatment of chronic lymphocytic leukemia (CLL). In October of the same year, FDA had approved for the second indication of the drug: the indolent B-cell non-Hodgkin's lymphoma (NHL) patients who have their symptoms still be in progress during the treatment with either rituximab or rituximab-containing regimen or within 6 months of the treatment.
• Drug Interactions: When used in combination with the CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin), it may increase blood concentrations of bendamustine while causing the decrease of the concentration of its metabolites M3 and M4. When used in combination with CYP1A2 inducers (such as omeprazole, smoking, etc.), it may reduce the blood concentration of bendamustine while increasing the concentration of it metabolites M3 and M4.
• Description: Bendamustine is a purine analog and DNA alkylating agent. It inhibits growth of SKW-3, Reh, CML-T1, BV-173, and HL-60 leukemia cell lines (IC50s = 27.0, 28.6, 15.6, 20.8, and 57.7 μM, respectively) but not MCF-7 and MDA-MB-231 breast cancer cell lines (IC50s = >200 and >200 μM, respectively). It kills B cell-chronic lymphocytic leukemia (B-CLL) cells derived from na?ve and bendamustine-pretreated patients (LD50s = 6.8-8.3 and 3.8-4.9 mg/ml, respectively). Bendamustine (50 mg/kg) inhibits tumor growth by 9% and 96% alone and in combination with ofatumumab, respectively, in a JVM-3 CLL mouse xenograft model. It activates the DNA-damage stress response, the base excision DNA repair pathway, and apoptosis, as well as inhibits mitotic checkpoints and induces mitotic catastrophe. Formulations containing bendamustine have been used to treat CLL and non-Hodgkin lymphoma.
• Uses: Used as an anticancer drug Bendamustine HCL is a DNA-damaging agent with IC50 of 50 μM. alkylating agent recently approved by the FDA for treatment of Chronic Lymphocytic Leukemia Bendamustine hydrochloride hydrate has been used as: a chemotherapy agent for chronic lymphocytic leukemia (CLL) samples to monitor spliced and unspliced gene expression an inhibitor to E3 ubiquitin-protein ligase RNF3 (HOIP) in?matrix-assisted laser desorption ionization time-of-flight mass spectrometry?(MALDI-TOF) assaya cytotoxic chemotherapeutic drug in high-throughput screening to test interaction with BAY87-2243
• Clinical Use: Alkylating agent: CLL, NHL and multiple myeloma

Technology Process of Bendamustine hydrochloride

There total 23 articles about Bendamustine hydrochloride 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: 83.0%

4-{5-[bis-(2-chloro-ethyl)amino]-1-methyl-1H-benzoimidazol-2-yl}butyric acid ethyl ester → bendamustine hydrochloride (3543-75-7,97832-05-8)

Guidance literature:

With hydrogenchloride; In water; for 4h; Reflux;

Reference yield: 76.2%

4-{5-[bis-(2-hydroxyl-ethyl)-amino]-1-methyl-1H-benzoimidazol-2yl}-butyric acid ethyl ester (3543-74-6) → bendamustine hydrochloride (3543-75-7,97832-05-8)

Guidance literature:

4-{5-[bis-(2-hydroxyl-ethyl)-amino]-1-methyl-1H-benzoimidazol-2yl}-butyric acid ethyl ester; With thionyl chloride; In dichloromethane; at -1 - 22 ℃; for 17h;

With hydrogenchloride; In water; at 75 ℃;

Reference yield: 76.0%

4-{5-[bis-(2-chloro-ethyl)amino]-1-methyl-1H-benzoimidazol-2-yl}butyric acid methyl ester (109882-25-9) → bendamustine hydrochloride (3543-75-7,97832-05-8)

Guidance literature:

With hydrogenchloride; for 4h; Reflux; Large scale reaction;

DOI:10.1021/op200176f

upstream raw materials:

4-{5-[bis-(2-chloro-ethyl)amino]-1-methyl-1H-benzoimidazol-2-yl}butyric acid methyl ester

4-{5-[bis-(2-hydroxyl-ethyl)-amino]-1-methyl-1H-benzoimidazol-2yl}-butyric acid ethyl ester

isopropyl 4-(5-amino-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate

bendamustine isopropyl ester

Downstream raw materials:

4-(6-((2-chloroethyl)(2-hydroxyethyl)amino)-3-methylbenzimidazolyl(2))butyric acid hydrochloride

4-{5-[bis-(2-chloro-ethyl)amino]-1-methyl-1H-benzoimidazol-2-yl}butyric acid methyl ester

4-{5-[bis-(2-chloro-ethyl)amino]-1-methyl-1H-benzoimidazol-2-yl}butyric acid cyclohexyl ester

bendamustine isopropyl ester

Refernces

• 1、 -. "Purification method of bendamustine hydrochloride". Paragraph 0043-0046. . Retrieved 2020/11/23.
• 2、 -. "Novel Solid Forms Of Bendamustine Hydrochloride". Paragraph 0099; 0100; 0101; 0102. . Retrieved 2016/07/05.