| Identification | Back Directory | [Name]
10-Propargyl-10-deazaaminopterin | [CAS]
146464-95-1 | [Synonyms]
Pdx
Folotyn
CS-2172
Pralatrexat
Prelatrexate
Pralatrexate
Unii-A8Q8I19Q20
Pralatrexate, >=98%
FOLOTYN PRALATREXATE
Pralatrexate(Folotyn)
Pralatrexate Impurity
10-Propargyl-10-deazaaMinopteri
10-Propargyl-10-deazaaminopterin
10-Propargyl-10-deazaaminopterin USP/EP/BP
N-(4-(1-((2,4-Diamino-6-pteridinyl)methyl)-3-butynyl)benzoyl)-L-glutamic acid
L-Glutamic acid, N-(4-(1-((2,4-diamino-6-pteridinyl)methyl)-3-butynyl)benzoyl)-
N-(4-{1-[(2,4-diaMinopteridin-6-yl)Methyl]but-3-yn-1-yl}benzoyl)-L-glutaMic acid
N-[4-[1-[(2,4-DiaMino-6-pteridinyl)Methyl]-3-butyn-1-yl]benzoyl]-L-glutaMic Acid
(2S)-2-(4-(1-(2,4-diaMinopteridin-6-yl)pent-4-yn-2-yl)benzaMido)pentanedioic acid
L-Glutamic acid, N-[4-[1-[(2,4-diamino-6-pteridinyl)methyl]-3-butyn-1-yl]benzoyl]-
10-Propargyl-10-deazaaminopterin
N-(4-(1-((2,4-Diamino-6-pteridinyl)methyl)-3-butynyl)benzoyl)-L-glutamic acid
N-(4-(1-((2,4-Diamino-6-pteridinyl)methyl)-3-butynyl)benzoyl)-L-glutamic acid Pralatrexate | [Molecular Formula]
C23H23N7O5 | [MDL Number]
MFCD00920897 | [MOL File]
146464-95-1.mol | [Molecular Weight]
477.47 |
| Chemical Properties | Back Directory | [Melting point ]
215 °C(dec.) | [density ]
1.471±0.06 g/cm3(Predicted) | [storage temp. ]
Sealed in dry,2-8°C | [solubility ]
≥23.85 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH | [Water Solubility ]
Insoluble in water | [form ]
powder to crystal | [pka]
3.53±0.10(Predicted) | [color ]
White to Light yellow | [InChIKey]
OGSBUKJUDHAQEA-WMCAAGNKSA-N | [SMILES]
C(O)(=O)[C@H](CCC(O)=O)NC(=O)C1=CC=C(C(CC2C=NC3C(N=2)=C(N)N=C(N)N=3)CC#C)C=C1 |
| Hazard Information | Back Directory | [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. | [Originator]
SRI International/ Southern Research Institute/Sloan-Kettering (US) | [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. | [Definition]
ChEBI: A pteridine that is the N-4-[1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl]benzoyl derivative of L-glutamic acid. Used for treatment of Peripheral T-Cell Lymphoma, an aggressive form of non-Hodgkins lymphoma. | [Brand name]
Folotyn | [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). | [Side effects]
The most common adverse reactions associated with pralatrexate are mucositis, thrombocytopenia, nausea, and fatigue. Folic acid and vitamin B12 supplements are administered as adjunct therapies to potentially reduce pralatrexate-related hematological toxicity and mucositis. | [Synthesis]
The chemical synthesis of pralatrexate starts with the alkylation of the anion of dimethyl homoterephthalate with propargyl bromide, promoted by potassium hydride in dimethylformamide, to afford the corresponding a-propargyl diester. Further alkylation of the potassium salt of a-propargyl diester with 2,4-diamino-6-(bromomethyl)pteridine followed by saponification with sodium hydroxide yields a diacid intermediate (2,4diamino- 4-deoxy-10-propargyl-10-deazapteroic acid). Mono-decarboxylation of the diacid intermediate by heating in dimethylsulfoxide at 120 C, followed by coupling with diethyl L-glutamate, and subsequent ester hydrolysis with sodium hydroxide yields pralatrexate. | [storage]
Store at -20°C,protect from light | [References]
[1]. izbicka e, diaz a, streeper r, et al. distinct mechanistic activity profile of pralatrexate in comparison to other antifolates in in vitro and in vivo models of human cancers. cancer chemother pharmacol, 2009, 64(5): 993-999.
[2]. serova m, bieche i, sablin mp, et al. single agent and combination studies of pralatrexate and molecular correlates of sensitivity. br j cancer, 2011, 104(2): 272-280. |
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