- IMPROVED PROCESS FOR THE PREPARATION OF PRALATREXATE
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An improved process for the preparation of Pralatrexate which is less hazardous. The invention further relates to novel intermediates and process thereof useful for the preparation of Pralatrexate. The present invention also relates to a substantially pure Pralatrexate and a process for obtaining the same in high yield.
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Paragraph 0166; 0167; 0168; 0169; 0170
(2015/07/15)
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- PROCESS FOR PRALATREXATE
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The present invention provides a novel process for the purification of alpha-propargylhomoterephthalic acid dimethyl ester substantially free of homoterephthalic acid dimethyl ester. The present invention also provides a novel process for the purification of pralatrexate.
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- A PROCESS FOR PREPARING INTERMEDIATES OF 10-PROPARGYL-10-DEAZAAMINOPTERIN (PRALATREXATE) SYNTHESIS AND THE INTERMEDIATES THEREOF
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A process for preparation of 4-(1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl)benzoic acid and other key intermediates in synthesis of 10-propargyl-10-deazaaminopterin (Pralatrexate) and the intermediates thereof. The 10-propargyl-10-deazaaminopterin (Pralatrexate) is obtained by peptide formation and ester hydrolysis of the intermediate compound 4-(1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl)benzoic acid by methods known in the art.
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- PROCESSES AND INTERMEDIATES FOR PREPARING PRALATREXATE
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Processes for preparing and purifying Pralatrexate are described in the present application, as well as intermediates in these processes, and salts and solid state forms of the Pralatrexate intermediates.
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- PROCESS FOR PREPARATION OF AN ANTIFOLATE AGENT
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The specification relates to a process for preparation of an antifolate compound of formula 7, such as Pralatrexate. Also, disclosed are intermediates and processes for preparation of intermediates useful in the preparation of the antifolate compound. The substituents Y, Z, R, R1 and R2 are as described herein. The processes and intermediates can provide an alternate route to the synthesis of the antifolate compound. Further, the processes can help to avoid distillation or evaporation of high boiling point solvents, chromatographic purification and use of hazardous combination of solvents; and can also provide a product having high purity, all of which are desirable for synthesis on a large scale.
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Paragraph 0073
(2014/01/07)
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- Optically Pure Diastereomers of 10-Propargyl-10-Deazaaminopterin and Methods of Using Same
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The present invention relates to diastereomers of 10-propargyl-10-deazaminopterin, compositions comprising optically pure diastereomers of 10-propargyl-10-deazaminopterin, in particular the two (R,S) diastereomers about the C10 position. Methods of preparation of these diastereomers, compositions containing them, and their use for the treatment of conditions related to inflammatory disorders and cancer are also disclosed.
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- Treatment of T-cell lymphoma using 10-propargyl-10-deazaaminopterin
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T cell lymphoma is treated by administering to a patient suffering from T cell lymphoma a therapeutically effective amount of 10-propargyl-10-deazaaminopterin. Remission is observed in human patients, even with drug resistant T cell lymphoma at weekly dosages levels as low as 30 mg/m2. In general, the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m2 per dose.
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Page/Page column 3; 4; Sheet 2
(2008/06/13)
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- Synthesis and in vitro antitumor activity of new deaza analogues of the nonpolyglutamatable antifolate Nα-(4-amino-4-deoxypteroyl)-Nδ- hemiphthaloyl-L-ornithine (PT523)
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Details are disclosed for the synthesis of Nα-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-N δ-hemiphthaloyl-L-ornithine (2) and Nα-[4-[5-(2,4-diaminoteridin-6-yl)pent-1-yn-4-yl]benzoyl]-N δ-hemiphthaloyl-L-
- Vaidya, Chitra M.,Wright, Joel E.,Rosowsky, Andre
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p. 1690 - 1696
(2007/10/03)
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- Combinations of 10-propargyl-10-deazaaminopterin and taxols and methods of using same in the treatment of tumors
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Preliminary clinical studies in humans have now been done which show both the efficacy of 10-propargyl-10dAM and a preferred dosage schedule for such treatments. In addition, it has now been determined that combinations of 10-propargyl-10-deazaaminopterin
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- Purified compositions of 10-propargyl-10-deazaaminopterin and methods of using same in the treatment of tumors
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PCT No. PCT/US97/11982 Sec. 371 Date Mar. 8, 1999 Sec. 102(e) Date Mar. 8, 1999 PCT Filed Jul. 16, 1997 PCT Pub. No. WO98/02163 PCT Pub. Date Jan. 22, 1998Highly purified 10-propargyl-10-deazaaminopterin (10-propargyl-10dAM) compositions tested in xenogra
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- Synthesis and antitumor activity of 10-propargyl-10-deazaaminopterin
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Successive alkylation of dimethyl homoterephthalate with propargyl bromide and 2,4-diamino-6-(bromomethyl)pteridine followed by ester saponification at room temperature afforded 2,4-diamino-4-deoxy-10-carboxy-10-propargyl-10- deazapteroic acid. The 10-COOH was readily decarboxylated by heating in DMSO at a temperature of only 120 °C to yield the diamino-10-propargyl-10- deazapteroic acid intermediate. Coupling with diethyl L-glutamate and ester hydrolysis gave the title compound. The 10-propargyl analogue was about 5 times more potent than MTX as an inhibitor of growth in L1210 cells, but was only one-third as potent as an inhibitor of DHFR from L1210. The analogue was transported inward very effectively in L1210 cells showing a 10-fold advantage over MTX. At a dose of 36 mg/kg the 10-propargyl compound caused shrinkage of the E0771 solid murine mammary tumor to only 1% of untreated controls.
- DeGraw,Colwell,Piper,Sirotnak
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p. 2228 - 2231
(2007/10/02)
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