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Eribulin Mesylate

CAS No.
441045-17-6
Chemical Name:
Eribulin Mesylate
Synonyms
Halaven;Eribulin Mesilate;E7389 mesylate;B1939 mesylate;Ibrine mesylate;Ezebrine mesylate;Eribulin Mesylate;Irebulin mesylate;Arebrine mesylate;ER-086526 mesylate
CBNumber:
CB32563308
Molecular Formula:
C41H63NO14S
Molecular Weight:
826.01
MDL Number:
MFCD22572760
MOL File:
441045-17-6.mol
Last updated:2024-11-08 16:17:51

Eribulin Mesylate Properties

storage temp. Store at -20°C, protect from light, stored under nitrogen
solubility Soluble in DMSO
form Powder
color White to off-white
InChIKey QAMYWGZHLCQOOJ-PEKQNERQNA-N
NCI Dictionary of Cancer Terms eribulin mesylate; Halaven
FDA UNII AV9U0660CW
NCI Drug Dictionary eribulin mesylate

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictograms
GHS07
Signal word  Warning
Hazard statements  H302-H315-H319-H335
Precautionary statements  P261-P280-P301+P312-P302+P352-P305+P351+P338

Eribulin Mesylate price

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
ChemScene CS-2803 Eribulin(mesylate) 99.52% 441045-17-6 500ug $1020 2021-12-16 Buy
ChemScene CS-2803 Eribulin(mesylate) 99.52% 441045-17-6 1mg $1200 2021-12-16 Buy
ApexBio Technology B3386 Eribulinmesylate 441045-17-6 500ug $1559 2021-12-16 Buy
ApexBio Technology B3386 Eribulinmesylate 441045-17-6 1mg $1969 2021-12-16 Buy
American Custom Chemicals Corporation API0024271 ERIBULIN MESYLATE 95.00% 441045-17-6 1MG $5355 2021-12-16 Buy
Product number Packaging Price Buy
CS-2803 500ug $1020 Buy
CS-2803 1mg $1200 Buy
B3386 500ug $1559 Buy
B3386 1mg $1969 Buy
API0024271 1MG $5355 Buy

Eribulin Mesylate Chemical Properties,Uses,Production

Uses

Eribulin Mesylate is a synthetic analog of the marine natural product halichondrin B.

Definition

ChEBI: Eribulin mesylate is a methanesulfonate salt obtained by reaction of eribulin with one equivalent of methanesulfonic acid. A fully synthetic macrocyclic ketone analogue of marine sponge natural products. Inhibits growth phase of microtubules via tubulin-based antimitotic mechanism, which leads to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. It has a role as an antineoplastic agent and a microtubule-destabilising agent. It contains an eribulin(1+).

Clinical Use

Eribulin is a highly potent cytotoxic agent approved in the U.S. for the treatment of metastatic breast cancer for patients who have received at least two previous chemotherapeutic regimens. Eribulin was discovered and developed by Eisai and it is currently undergoing clinical evaluation for the treatment of sarcoma (PhIII) and non-small cell lung cancer which shows progression after platinumbased chemotherapy and for the treatment of prostate cancer (PhII). Early stage clinical trials are also underway to evaluate eribulin’s efficacy against a number of additional cancers. Eribulin is a structural analog of the marine natural product halichondrin B. Its mechanism of action involves the disruption of mitotic spindle formation and inhibition of tubulin polymerization which results in the induction of cell cycle blockade in the G2/M phase and apoptosis.

Clinical Use

Eribulin mesylate, a nontaxane, completely synthetic microtubule inhibitor, has recently been approved by the U.S. Food and Drug Administration as third-line treatment of metastatic breast cancer refractory to anthracyclines and taxanes.

Side effects

Eribulin Mesylate (Halaven) may cause serious side effects including:hives; difficulty breathing; swelling of your face, lips, tongue, or throat; chest pain; severe dizziness; fast or pounding heartbeats, numbness, tingling, or burning pain in your hands or feet; pain or burning when you urinate; confusion; uneven heart rate; extreme thirst; increased urination; leg discomfort; muscle weakness; limp feeling; fever; chill; painful mouth sores; pain when swallowing; cough; trouble breathing; pale skin; easy bruising; sore throat; skin pain followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Toxicology

Peripheral neuropathy was the most common toxicity leading to discontinuation of eribulin (5 percent). Single doses of 0.75 mg/kg were lethal to rats and two doses of 0.075 mg/kg were lethal to dogs. The no-observed-adverse-effect level (NOAEL) in rats and dogs were 0.015 and 0.0045 mg/kg/day, respectively.

Synthesis

Several synthetic routes for the preparation of eribulin have been disclosed, each of which utilizes the same strategy described by Kishi and co-workers for the total synthesis of halichondrin B. Although the scales of these routes were not disclosed in all cases, this review attempts to highlight what appears to be the production-scale route based on patent literature. Nonetheless, the synthesis of eribulin represents a significant accomplishment in the field of total synthesis and brings a novel chemotherapeutic option to cancer patients.
The strategy to prepare eribulin mesylate (V) employs a convergent synthesis featuring the following: the late stage coupling of sulfone 22 and aldehylde 23 followed by macrocyclization under Nozaki-Hiyami-Kishi coupling conditions, formation of a challenging cyclic ketal, and installation of the primary amine. Sulfone 22 was further simplified to aldehyde 24 and vinyl triflate 25 which were coupled through a Nozaki-Hiyami-Kishi reaction.

Synthesis_441045-17-6


With the three key fragments 23, 24 and 25 along with the entire molecule completed, the next step was to assemble them and complete the synthesis of eribulin. Aldehyde 24 was coupled to vinyl triflate 25 using an asymmetric Nozaki- Hiyami-Kishi reaction using CrCl2, NiCl2, Et3N and chiral ligand 67 (the Scheme) to give alcohol 83 (Scheme 11). Formation of the THP ring was accomplished by reaction with KHMDS which allowed for displacement of the mesylate with the secondary alcohol and provided the THP containing product in 72% yield for the three steps. The pivalate ester group was removed with DIBAL-H to give the western fragment 22 in 92% yield.
The completion of the synthesis of eribulin is illustrated in Scheme 12. The lithium anion of sulfone 22 generated upon reaction with nBuLi was coupled to aldehyde 23 to give diol 84 in 84% yield. Both of the alcohol functional groups of 84 were oxidized using a Dess-Martin oxidation in 90% yield and the resulting sulfone was removed via a reductive cleavage upon reaction with SmI2 to give ketoaldehyde 85 in 85% yield. Macrocyclization of 85 was accomplished via an asymmetric Nozaki Hiyami-Kishi reaction using CrCl2, NiCl2, Et3N and chiral ligand 67 to give alcohol 86 in 70% yield.
Modified Swern oxidation of the alcohol provided the corresponding ketone in 91% yield and this was followed by removal of the five silyl ether protecting groups upon reaction with TBAF and subsequent cyclization to provide ketone 87. Compound 87 was treated with PPTS to provide the ?°caged?± cyclic ketal 88 in 79% over two steps. The vicinal diol of 88 was reacted with Ts2O in collidine to affect selective tosylation of the primary alcohol and this crude product was reacted with ammonium hydroxide to install the primary amine to give eribulin which was treated with methanesulfonic acid in aqueous ammonium hydroxide to give eribulin mesylate (V) in 84% yield over the final 3 steps.

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Mode of action

Eribulin Mesylate is the mesylate salt of a synthetic analogue of halichondrin B, a substance derived from a marine sponge (Lissodendoryx sp.) with antineoplastic activity. Eribulin binds to the vinca domain of tubulin and inhibits the polymerization of tubulin and the assembly of microtubules, resulting in inhibition of mitotic spindle assembly, induction of cell cycle arrest at G2/M phase, and, potentially, tumor regression.

References

Eribulin mesylate: a novel halichondrin B analogue for the treatment of metastatic breast cancer DOI: 10.2146/ajhp110237
From micrograms to grams: scale-up synthesis of eribulin mesylate DOI: 10.1039/c3np70051h
Eribulin mesylate: mechanism of action of a unique microtubule-targeting agent DOI: 10.1158/1078-0432.CCR-14-3252

Eribulin Mesylate Preparation Products And Raw materials

Raw materials

Preparation Products

Global( 172)Suppliers
Supplier Tel Email Country ProdList Advantage
AFINE CHEMICALS LIMITED
+86-0571-85134551 sales@afinechem.com China 15352 58
ChemExpress
+86-021-58950125 +86-021-58950125; info@chemexpress.com China 781 58
Hebei Yanxi Chemical Co., Ltd.
+8617531190177 peter@yan-xi.com China 5857 58
Changzhou Rokechem Technology Co., Ltd.
18758118018 sales001@rokechem.com China 255 58
Beijing Cooperate Pharmaceutical Co.,Ltd
010-60279497 sales01@cooperate-pharm.com CHINA 1803 55
Henan Tianfu Chemical Co.,Ltd.
+86-0371-55170693 +86-19937530512 info@tianfuchem.com China 21634 55
ATK CHEMICAL COMPANY LIMITED
+undefined-21-51877795 ivan@atkchemical.com China 32957 60
BOC Sciences
+1-631-485-4226 inquiry@bocsci.com United States 19553 58
career henan chemical co
+86-0371-86658258 +8613203830695 factory@coreychem.com China 29811 58
TargetMol Chemicals Inc.
+1-781-999-5354 +1-00000000000 marketing@targetmol.com United States 32161 58

Related Qustion

View Lastest Price from Eribulin Mesylate manufacturers

Image Update time Product Price Min. Order Purity Supply Ability Manufacturer
Eribulin Mesylate pictures 2024-12-13 Eribulin Mesylate
441045-17-6
US $0.00 / g 1g 99%min 100g WUHAN FORTUNA CHEMICAL CO., LTD
Eribulin Mesylate pictures 2024-10-25 Eribulin Mesylate
441045-17-6
US $25.00-10.00 / kg 1kg 0.99 10 tons Hebei Yanxi Chemical Co., Ltd.
Eribulin Mesylate pictures 2023-06-28 Eribulin Mesylate
441045-17-6
US $0.00-0.00 / Kg 1Kg 99%;USP/EP/CP 1-10000kgs Changzhou Rokechem Technology Co., Ltd.
  • Eribulin Mesylate pictures
  • Eribulin Mesylate
    441045-17-6
  • US $0.00-0.00 / Kg
  • 99%;USP/EP/CP
  • Changzhou Rokechem Technology Co., Ltd.
Eribulin Mesylate Eribulin mesylate Halaven ER-086526 mesylate B1939 mesylate E7389 mesylate EribulinMesylate USP/EP/BP Eribulin Mesylate (E7389) Halaven Eribulin Mesilate Ibrine mesylate Ezebrine mesylate ER 086526,E-7389,Eribulin,metastatic,B1939,Inhibitor,Eribulin mesylate,inhibit,breast,Microtubule/Tubulin,cancer,Apoptosis,E7389,B 1939,B-1939,microtubule,E 7389,ER-086526,ER086526 Irebulin mesylate (2R,3R,3aS,7R,8aS,9S,10aR,11S,12R,13aR,13bS,15S,18S,21S,24S,26R,28R,29aS)-2-[(2S)-3-Amino-2-hydroxypropyl]hexacosahydro-3-methoxy-26-methyl-20,27-bis(methylene)-11,15:18,21:24,28-triepoxy-7,9-ethano-12,15-methano-9H,15H-furo[3,2-i]furo[2′,3′:5,6]pyrano[4,3-b][1,4]dioxacyclopentacosin-5(4H)-one methanesulfonate N,N'-diallyl-6-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-1,3,5-triazine-2,4-diamine dimethanesulphonate Eribulin Mesylate iMpurity Arebrine mesylate 441045-17-6 C40H59NO11CH4O3S C41H63NO14S API API 441045-17-6