Pralatrexate

Base Information

• Chemical Name: Pralatrexate
• CAS No.: 146464-95-1
• Molecular Formula: C₂₃H₂₃N₇O₅
• Molecular Weight: 477.48
• European Community (EC) Number: 680-662-0
• NSC Number: 754230
• UNII: A8Q8I19Q20
• DSSTox Substance ID: DTXSID3048578
• Nikkaji Number: J557.257F
• Wikipedia: Pralatrexate
• Wikidata: Q637059
• NCI Thesaurus Code: C2250
• RXCUI: 662019
• Pharos Ligand ID: SPPQGS51D4V2
• Metabolomics Workbench ID: 65528
• ChEMBL ID: CHEMBL1201746
• Mol file: 146464-95-1.mol

Synonyms:10-propargyl-10-deazaaminopterin;pralatrexate

Chemical Property of Pralatrexate

Chemical Property:

• Melting Point: 215 °C(dec.)
• Refractive Index: 1.703
• PKA: 3.53±0.10(Predicted)
• PSA: 207.30000
• Density: 1.471 g/cm³
• LogP: 2.53490
• Storage Temp.: 2-8°C
• Solubility.: ≥23.85 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
• Water Solubility.: Insoluble in water
• XLogP3: -0.9
• Hydrogen Bond Donor Count: 5
• Hydrogen Bond Acceptor Count: 11
• Rotatable Bond Count: 10
• Exact Mass: 477.17606686
• Heavy Atom Count: 35
• Complexity: 809

Purity/Quality:

98.0%Min ^*data from raw suppliers

Pralatrexate ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: C#CCC(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O
• Isomeric SMILES: C#CCC(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(=O)O)C(=O)O
• Recent ClinicalTrials: Study of Pembrolizumab Combined With Decitabine and Pralatrexate in PTCL and CTCL
• Recent EU Clinical Trials: A Phase 3, Randomized, Two-Arm, Open-Label, Multicenter, International Trial of Alisertib (MLN8237) or Investigator’s Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma
• Description: Pralatrexate, an injectable DHFR inhibitor, was launched for the treatment of patients with relapsed or refractory PTCL. PTCL is an aggressive form of non-Hodgkin’s lymphoma (NHL) characterized by the proliferation of abnormal T-lymphocytes that circulate in the peripheral bloodstream. The inhibition of the folate enzymes DHFR and thymidylate synthase is a well-validated method of cancer treatment. In vitro, pralatrexate is slightly less potent than MTX in inhibiting DHFR derived from murine leukemia L1210 cells (Ki = 18.2 pM vs. 5.75 pM) and human leukemia CCRF-CEM cells (Ki = 13.4 pM vs. 5.4 pM). However, it is transported into both types of cells with 10-fold higher efficiency than MTX, thereby providing a more potent inhibition of cell growth as compared with MTX. In vivo, intraperitonally administered pralatrexate at 60 mg/ kg twice weekly for three or four doses caused complete lymphoma regressions in 89, 56, and 30% of HT, RL, and SKI-DLBCL-1 xenografted mice, respectively, whereas a similar dosing of MTX at 40 mg/kg twice weekly did not produce complete regression. The posttreatment tumor diameter was also smaller in pralatrexate-treated animals. Pralatrexate is a dihydrofolate reductase (DHFR) inhibitor (Ki = 13.4 pM) and antifolate. It inhibits growth of CCRF-CEM acute lymphocytic leukemia cells (IC50 = 0.04 μM), MDA-468, SK-BR-3, and ZR-75-1 breast cancer cells (IC50s = 0.11, 0.28, and 0.26 μM, respectively), and SK-LC8 and SK-LC16 non-small cell lung cancer cells (NSCLC; IC50s = 0.42 and 0.11 μM, respectively). In vivo, pralatrexate increases median survival from 21 to 40 days when administered in 4 doses of 15 mg/kg over 11 days in an H9 T cell lymphoma mouse xenograft model. Pralatrexate is transported into cells via the reduced folate carrier (RFC) and undergoes polyglutamation by folylpolyglutamate synthetase (FPGS) to a greater extent than methotrexate or pemetrexed . Formulations containing pralatrexate have been used in the treatment of relapsed or refractory peripheral T cell lymphoma.
• Uses: An antifolate with high affinity for the reduced folate carrier-type 1, produces marked complete and durable remissions in a diversity of chemotherapy refractory cases of T-cell lymphoma.
• Clinical Use: Pralatrexate, an injectable dihydrofolate reductase (DHFR) inhibitor, has a superior potency and toxicity profile compared to other DHFR inhibitors. In 2009, the compound was launched by Allos and approved in the U.S. for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) as a single agent. It is the first drug approved for this indication.70 In 2010, orphan drug designation was received in the E.U. for the treatment of cutaneous T-cell lymphoma (CTCL).

Technology Process of Pralatrexate

There total 33 articles about Pralatrexate 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: 90.5%

10-propargyl-10-deazaaminopterin dimethyl ester (374777-77-2) → pralatrexate (146464-95-1)

Guidance literature:

With water; sodium hydroxide; In acetone; at 10 - 13 ℃; Reagent/catalyst; Temperature; Solvent;

Reference yield: 81.0%

(2S)-2-[[4-[(1RS)-1-[(2,4-diaminopteridin-6-yl)methyl]but-3-ynyl]benzoyl]amino]pentanedioic acid disodium salt → pralatrexate (146464-95-1)

Guidance literature:

With hydrogenchloride; In water; pH=4.5;

Reference yield: 80.0%

C27H31N7O5 → 10-propargyl-10-deazaaminopterin (146464-95-1)

Guidance literature:

With sodium hydroxide; In methanol; at 0 - 20 ℃; for 10.5h;

upstream raw materials:

10-propargyl-10-deazaaminopterin diethyl ester

methyl 4-(2-methoxy-2-oxoethyl)benzoate

diethyl-L-glutamate hydrochloride

α-propargylhomoterephthalic acid dimethyl ester

Refernces

• 1、 -. "A suitable industrial production pula Qu Sha method for the preparation of". Paragraph 0051-0052. . Retrieved 2017/01/23.
• 2、 -. "PROCESS FOR PRALATREXATE". Page/Page column 8. . Retrieved 2014/05/24.