Description References
ChemicalBook > CAS DataBase List > Pemetrexed Disodium

Pemetrexed Disodium

Description References
Product Name
Pemetrexed Disodium
CAS No.
150399-23-8
Chemical Name
Pemetrexed Disodium
Synonyms
ALIMTA;LY-231514;PEMETREXED SODIUM;Alimt;AliMta disodiuM;LY231514 disodiuM;LY 231514 disodiuM;LY-231514 disodiuM;PeMetexed DisodiuM;PEMETREXED DISODIUM
CBNumber
CB4385473
Molecular Formula
C20H22N5NaO6
Formula Weight
451.41
MOL File
150399-23-8.mol
More
Less

Pemetrexed Disodium Property

Melting point:
254-258°C (dec.)
storage temp. 
Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
solubility 
Methanol, Water
form 
Solid
color 
Off-White
Stability:
Hygroscopic
InChI
InChI=1/C20H21N5O6.Na.H/c21-20-24-16-15(18(29)25-20)12(9-22-16)6-3-10-1-4-11(5-2-10)17(28)23-13(19(30)31)7-8-14(26)27;;/h1-2,4-5,9,13H,3,6-8H2,(H,23,28)(H,26,27)(H,30,31)(H4,21,22,24,25,29);;/t13-;;/s3
InChIKey
UTEALKYVANXUSG-NVZXTOETNA-N
SMILES
C(C1=CNC2NC(N)=NC(=O)C1=2)CC1C=CC(C(=O)N[C@H](C(=O)O)CCC(=O)O)=CC=1.[NaH] |&1:20,r|
CAS DataBase Reference
150399-23-8(CAS DataBase Reference)
More
Less

Safety

Hazard Codes 
T;Xi,Xi,T
Risk Statements 
36/38-60-61-68
Safety Statements 
36/37/39-53
More
Less

Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

More
Less

N-Bromosuccinimide Price

ApexBio Technology
Product number
A4390
Product name
Pemetrexed
Packaging
1unit
Price
$28
Updated
2021/12/16
ApexBio Technology
Product number
A4390
Product name
Pemetrexed
Packaging
100mg
Price
$50
Updated
2021/12/16
ApexBio Technology
Product number
A4390
Product name
Pemetrexed
Packaging
10mM(in 1mL DMSO)
Price
$50
Updated
2021/12/16
Biosynth Carbosynth
Product number
BP164243
Product name
Pemetrexed disodium
Packaging
50mg
Price
$50
Updated
2021/12/16
ApexBio Technology
Product number
A4390
Product name
Pemetrexed
Packaging
200mg
Price
$80
Updated
2021/12/16
More
Less

Pemetrexed Disodium Chemical Properties,Usage,Production

Description

Pemetrexed disodium (marketed as ALIMTA®, “pemetrexed”) is a novel, multi-targeted antifolate. It suppresses tumor growth by impeding both DNA synthesis and folate metabolism. Pemetrexed disodium has demonstrated promising clinical activity in a wide variety of solid tumors, including non-small cell lung, breast, mesothelioma, colorectal, pancreatic, gastric, bladder, cervix, and head and neck.
Pemetrexed disodium is approved to be used alone or with other drugs to treat malignant pleural mesothelioma in patients who cannot be treated with surgery and non-small cell lung cancer (certain types) in patients whose disease is locally advanced or has metastasized (spread to other parts of the body). Pemetrexed disodium is also being studied in the treatment of other types of cancer.

References

[1] https://www.cancer.gov/about-cancer/treatment/drugs/pemetrexeddisodium
[2] Axel-R. Hanauske, V. Chen P. Paoletti, C. Niyikiza (2001) Pemetrexed Disodium: A Novel Antifolate Clinically Active Against Multiple Solid Tumors, The Oncologist, 6, 363-373

Description

Pemetrexed, a pyrrolo[2,3-d]pyrimidine-based antifolate that disrupts cell replication by inhibiting multiple folate-dependent metabolic processes, was initially developed and launched in the US for the treatment of malignant pleural mesothelioma in conjunction with cisplatin. Patients who are not candidates for surgery may benefit from this combination therapy. Clinical data demonstrated that the median overall survival time increased to 12.1 months, compared with 9.3 months for patients receiving cisplatin alone. In August of 2004, the FDA also approved pemetrexed as a second-line treatment of non-small-cell lung cancer (NSCLC). While median survival is comparable to the standard second-line treatment docetaxel, the improved toxicity profile (significant reduction in neutropenia) accelerated the approval for NSCLC. Its effectiveness as an anticancer drug is derived from its ability to gain internal cell access via the reduced folate carrier and membrane folate binding protein transport systems. Once inside, pemetrexed undergoes polyglutamation, and the resultant polyglutamate forms (predominantly the pentaglutamate) inhibit the folate-dependent enzymes thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). Against recombinant human TS, pemetrexed has a Ki of 109nM while the triglutamate and pentaglutamate forms have Ki values of 1.6nM and 1.3 nM, respectively. All forms of pemetrexed display similar potency against recombinant human DHFR (7 nM), but the pentaglutamate form is significantly more potent against recombinant murine GARFT than the parent (Ki=65nM versus 9.3μM). The selectivity of pemetrexed may be explained by the fact that polyglutamation is more likely to occur in cancer cells compared to normal cells while its prolonged duration of action may be attributed to decreased cellular efflux of the polyglutamate forms. While several different routes have provided pemetrexed, one of the most efficient exploits the propensity of 2,6-diamino-3Hpyrimidin- 4-one to undergo Michael additions at its unsubstituted C-5 position. Using ethyl 4-(4-nitrobut-3-enyl)benzoate as the Michael acceptor, the resulting adduct is then converted to the ultimate precursor for glutamyl coupling via a onepot, three-step process (Nef reaction to transform the nitro to the aldehyde, intramolecular condensation to afford the pyrrole, and saponification of the ethyl ester). A typical treatment regimen involves intravenous administration of pemetrexed, infused over ten minutes, at a dose of 500mg/m2 followed by a thirty minute wash-out period and then cisplatin intravenously over two hours at a dose of 75mg/m2. Both drugs are given on Day 1 of a 21-day cycle. In order to reduce treatment-related hematological and GI toxicity, patients are instructed to take folic acid and vitamin B12 as a prophylactic measure. Pretreatment with a corticosteroid is also recommended to prevent possible skin rashes. Pemetrexed is primarily excreted intact in the urine, with 70–90% of the dose being recovered within 24 hours of administration. The half-life of pemetrexed is 3.5 hours in patients with normal renal function, and the total systemic clearance is 91.8mL/min. As expected, clearance decreases as renal impairment increases. The drug’s plasma protein binding is 81%, and it has a steady state volume of distribution of 16.1 L. The pharmacokinetics of pemetrexed is linear with dose and remains unchanged over multiple treatment cycles. While in vitro studies suggest that pemetrexed would not interfere with drugs metabolized by CYP3A4, CYP2D6, CYP2C9, and CYP1A2, ibuprofen (400mg q.d.) does reduce pemetrexed clearance by 20%. Caution should, therefore, be taken when administering pemetrexed concurrently with ibuprofen to patients with renal insufficiency and should not be given at all to patients whose creatinine clearance is <45mL/min. .

Chemical Properties

Crystalline Solid

Originator

Eli Lilly (US)

Uses

Multitargeted antifolate; inhibits thymidylate synthase as well as other folate dependent enzymes. Antineoplastic.

Uses

Pemetrexed is a novel antifolate and antimetabolite for TS, DHFR and GARFT with Ki of 1.3 nM, 7.2 nM and 65 nM, respectively

Definition

ChEBI: An organic sodium salt that is the disodium salt of N-{4-[2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acid. Inhibits thymidylate synthase (TS), 4 1 dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT).

brand name

Alimta (Lilly).

General Description

The drug is available in a 100-mg sterile vial for IV use. Thedrug appears to be effective against a range of tumors includingmesothelioma, NSCLC, colorectal cancer, bladdercancer, and lung cancer. The mechanism of action involvesinhibition of TS resulting in inhibition of thymidylate andDNA synthesis. This drug is a pyrrolopyrimidine analog offolate with antifolate activity. Resistance can occur by increasedexpression of TS, decreased binding affinity for TS,or decreased drug transport into cells. The drug is administeredonly via the IV route and distributes to all tissues.Cellular activation to the more potent polyglutamated formsoccurs, and the majority of the dose is excreted unchangedin the urine. The drug interaction and toxicity profiles aresimilar to that of methotrexate.

Mechanism of action

Like methotrexate, it is actively transported into tumor cells through reduced folate carriers and, in polyglutamated form, inhibits the synthesis of pyrimidine and purine-based nucletotides by disrupting folatedependent metabolic processes . In addition to DHFR, this pyrrolopyrimidine-based inhibitor binds tightly to thymidylate synthase and GAR transformylase.

Clinical Use

Pemetrexed is a novel multitarget antifolate used by the IV route for the treatment of advanced or metastatic nonsmall cell lung cancer and in combination with cisplatin in malignant pleural mesothelioma.

Side effects

Patients on pemetrexed must take folate and vitamin B12 supplements to reduce the risk of bone marrow suppression (neutropenia, thrombocytopenia, and anemia) and GI side effects. Pretreatment with corticosteroids can reduce the risk of drug-induced skin rash. Pemetrexed has a half-life of 3.5 hours and is excreted primarily unchanged via the kidneys. Significant cross-resistance has been noted between pemetrexed and other pyrimidine and folate antagonists.

Synthesis

A number of papers outlining the syntheses of pemetrexed and related analogs have appeared. A practical and scalable synthetic route is depicted in Scheme 9. Palladium (0) coupling of methyl 4-bromobenzoate (57) with 3-butyn-1-ol (58) gave crystalline 59, which was then reduced over palladium on carbon in DCM to give alcohol 60. Filtration of the catalyst afforded a DCM solution of alcohol 60, which was utilized directly in a TEMPO-catalyzed sodium hypochlorite oxidation, providing known aldehyde 61 without isolation. Addition of 5,5-dibromobarbituric acid (DBBA) and catalytic amount of HBr in acetic acid to the DCM solution of 61 effected the conversion to a-bromoaldehyde 62. After aqueous work-up, the solution was concentrated and diluted with acetonitrile to exchange solvents. Addition of commercially available 2,4-diamino-6-hydroxypyrimidine (63), aqueous sodium acetate and heating to 45??C resulted in cyclic condensation and precipitation of pyrrolo[2,3- d]pyrimidine 64 from the reaction mixture in 67% yield based on 60. Saponification of 64 with aqueous sodium hydroxide followed by acidification afforded the carboxylic acid derivative 65, which was elaborated to 66 by chlorodimethoxytriazine active ester coupling method. Reaction of 65 with 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) in the presence of N-methylmorpholine in DMF solution followed by reaction of the resulting dimethoxy-s-triazinyl ester with diethyl L-glutamate afforded crude 66, which was isolated via crystallization as pTSA salt 67. Saponification of 67 with aqueous sodium hydroxide followed by acidification with HCl gave pemetrexed as the free acid, which was crystallized as disodium salt form.

target

MEK | ERK

Drug interactions

Potentially hazardous interactions with other drugs
Antimalarials: antifolate effect increased by pyrimethamine.
Antipsychotics: avoid with clozapine, increased risk of agranulocytosis.
Nephrotoxic agents: may reduce clearance of pemetrexed - use with caution.
Live vaccines: avoid use; YELLOW FEVER VACCINE ABSOLUTELY CONTRAINDICATED.

Metabolism

Pemetrexed undergoes minimal hepatic metabolism, and about 70-90% of a dose is eliminated unchanged in the urine within 24 hours. In vitro studies indicate that pemetrexed is actively secreted by OAT3 (organic anion transporter).

Pemetrexed Disodium Preparation Products And Raw materials

Raw materials

Preparation Products

More
Less

Pemetrexed Disodium Suppliers

Jinan Baozhao Pharmaceutical Technology Co., Ltd.
Tel
0531-82371868 13210529039
Fax
0531-82371858
Email
baozhaopharm@163.com
Country
China
ProdList
141
Advantage
58
Nanjing Yunzhi Xinhe Biotechnology Co., Ltd
Tel
19852363252 13151442052
Email
2634809846@qq.com
Country
China
ProdList
51
Advantage
58
Jiangsu Simcere Pharmaceutical CO.,Ltd
Tel
025-85566666-7321 15195996671
Email
API@simcere.com
Country
China
ProdList
19
Advantage
58
Nanjing Dasf Biotechnology Co., Ltd.
Tel
025-+86-02585846866 +86-18094231287
Fax
025-83144123
Email
eric@dasfbio.com
Country
China
ProdList
1987
Advantage
58
J & K SCIENTIFIC LTD.
Tel
010-82848833 400-666-7788
Fax
86-10-82849933
Email
jkinfo@jkchemical.com
Country
China
ProdList
96815
Advantage
76
Chembest Research Laboratories Limited
Tel
021-20908456
Fax
021-58180499
Email
sales@BioChemBest.com
Country
China
ProdList
6013
Advantage
61
BeiJing Hwrk Chemicals Limted
Tel
0757-86329057 18501085097
Fax
010-89508210
Email
sales3.gd@hwrkchemical.com
Country
China
ProdList
7508
Advantage
55
Beijing Ouhe Technology Co., Ltd
Tel
010-82967028 13552068683
Fax
+86-10-82967029
Email
2355560935@qq.com
Country
China
ProdList
12426
Advantage
60
Pure Chemistry Scientific Inc.
Tel
001-857-928-2050 or 1-888-588-9418
Fax
001-617-206-9595
Email
sales@chemreagents.com
Country
United States
ProdList
10194
Advantage
62
LGM Pharma
Tel
1-(800)-881-8210
Fax
615-250-9817
Email
inquiries@lgmpharma.com
Country
United States
ProdList
2127
Advantage
70
More
Less

View Lastest Price from Pemetrexed Disodium manufacturers

WUHAN FORTUNA CHEMICAL CO., LTD
Product
Pemetrexed disodium 150399-23-8
Price
US $0.00/g/Bag
Min. Order
1g
Purity
99%min
Supply Ability
10kg
Release date
2021-10-18
Hebei Lingding Biotechnology Co., Ltd.
Product
Pemetrexed disodium 150399-23-8
Price
US $72.00-32.00/KG
Min. Order
1KG
Purity
99%
Supply Ability
9000kg/per week
Release date
2021-11-04
Honest Joy Holdings Limited
Product
Pemetrexed disodium 150399-23-8
Price
US $0.00/KG
Min. Order
1KG
Purity
98.1%
Supply Ability
100 tons
Release date
2022-02-08

150399-23-8, Pemetrexed DisodiumRelated Search:


  • n-[4-[2-(2-amino-4,7-dihydro-4-oxo-1h-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-l-glutamic acid disodium salt
  • PEMETREXED DISODIUM
  • PEMETREXED DISODIUM(ALIMTA)
  • PEMETREXED SODIUM
  • PEMETREXED DISODIUM 99%
  • PEMETREXED DISODIUM 2.5H2O
  • PEMETREXED DISODIUM FOR INJECTION
  • PEMETREXED DISODIUM FOR INJECTION BK-A-01
  • Pemetrexed Dinatrium
  • ALIMTA
  • Alimt
  • LY-231514
  • N-[4-[(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium
  • Pemwtrexed Disodium
  • 2-[4-[2-(4-Amino-2-oxo-3,5,7-triazabicyclo[4.3.0]nona-3,8,10-trien-9-yl)ethyl]benzoyl]aminopentanedioic acid disodium salt
  • PeMetrexed disodiuM (LY-231514)
  • PEMETREXED DISODIUM 7 H2O
  • PeMetrexed (AliMta)
  • N-[4-[2-(2-AMino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyriMidin-5-yl)ethyl]benzoyl]-L-glutaMic Acid SodiuM Salt
  • AliMta disodiuM
  • LY 231514 disodiuM
  • LY231514 disodiuM
  • LY-231514 disodiuM
  • PeMetexed DisodiuM
  • Pemetrexed Disodium Salt
  • disodiuM (2S)-2-{[4-(2-{2-aMino-4-oxo-3H,4H,7H-pyrrolo[2,3-d]pyriMidin-5-yl}ethyl)phenyl]forMaMido}pentanedioic acid
  • Sodium (S)-2-(4-(2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)
  • Two sodium for the United States and the United States
  • Pemetrexed phosphate
  • sodium (S)-2-(4-(2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)pentanedioate
  • N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid disodium salt Pemetrexed
  • Pemetrexed Disodium ,≥99%
  • Pemetrexed disodium, a novel antifolate
  • Pemetrexed disodium USP/EP/BP
  • Pemetrexed Disodium(USFDA)
  • Sodium (4-(2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzoyl)-L-glutamate
  • Pemetrexed disodium
  • L-Glutamic acid, N-[4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-, sodium salt (1:2)
  • N-4-2-(2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo2,3-dpyrimidin-5-yl)ethylbenzoyl-L-glutamic acid disodium salt
  • 150399-23-8
  • 357166-90-4
  • 150339-23-8
  • C20H21N5O62Na
  • C20H19N5Na2O6
  • C20H33N5Na2O13
  • C20H19N5O62Na
  • LY-231514
  • Molecular Targeted Antineoplastic
  • All Inhibitors
  • Inhibitors
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • Chiral Reagents