An Efficient Synthesis of Pemetrexed Disodium

Qi, Hongzhao; Wen, Jianxun; Li, L.; Bai, Rui; Chen, L.; Wang, D.

doi:10.1002/jhet.2164

Cited by 9 publications

(4 citation statements)

References 12 publications

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“…Conjugation with diethyl glutamate to furnish 72 and a final second saponification gave pemetrexed disodium (Scheme 30). A synthesis of the anticancer drug pemetrexed disodium [74] is based on a Hantzsch pyrrole synthesis starting from 2,6-diaminopyrimidin-4(3H)-one 69 and α-bromoaldehyde 70. In the presence of sodium acetate, these starting materials afforded compound 71 after saponification of the ester group.…”

Section: Hantzsch Pyrrole Synthesismentioning

confidence: 99%

Multicomponent Reactions for the Synthesis of Active Pharmaceutical Ingredients

et al. 2022

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Multicomponent reactions 9i.e., those that engage three or more starting materials to form a product that contains significant fragments of all of them), have been widely employed in the construction of compound libraries, especially in the context of diversity-oriented synthesis. While relatively less exploited, their use in target-oriented synthesis offers significant advantages in terms of synthetic efficiency. This review provides a critical summary of the use of multicomponent reactions for the preparation of active pharmaceutical principles.

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Section: Hantzsch Pyrrole Synthesismentioning

confidence: 99%

Multicomponent Reactions for the Synthesis of Active Pharmaceutical Ingredients

et al. 2022

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“…The anticancer drug pemetrexed (LY231514, Alimta ® ) and related compounds provide a good example of the application of the Hantzsch reaction to the synthesis of complex heterocyclic systems containing a pyrrole fragment. A synthesis of pemetrexed 33 starts from 2,6-diaminopyrimidin-4(3H)-one 40 and an α-bromoaldehyde 41, which is the suitable kind of reaction partner to obtain a β-substituted pyrrole moiety. The Hantzsch reaction was achieved by exposure of these starting materials to sodium acetate and afforded compound 42 after saponification of the ester group.…”

Section: Short Review Syn Thesis 4 Applications Of the Hantzsch Pyrromentioning

confidence: 99%

The Hantzsch Pyrrole Synthesis: Non-conventional Variations and Applications of a Neglected Classical Reaction

Leonardi¹,

Estévez²,

Villacampa³

et al. 2018

Synthesis

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Pyrrole is one of the most important one-ring heterocycles because of its widespread presence in natural products and unnatural bioactive compounds and drugs in clinical use. The preparation of pyrroles by reaction between primary amines, β-dicarbonyl compounds, and α-halo ketones, known as the Hantzsch pyrrole synthesis, is reviewed here for the first time. In spite of its age and its named reaction status, this method has received little attention in the literature. Recent work involving the use of non-conventional conditions has rejuvenated this classical reaction and this is emphasized in this review. Some applications of the Hantzsch reaction in target-oriented synthesis are also discussed.1 Introduction2 The Conventional Hantzsch Pyrrole Synthesis3 Hantzsch Pyrrole Synthesis under Non-conventional Conditions4 Applications of the Hantzsch Pyrrole Synthesis5 Conclusions

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“…The folate metabolism inhibitors have antineoplastic activity especially in treating haematologic and solid tumours [ 43 , 44 ]. The synthetic pathway was mainly developed to enhance the efficiency and yield of the total synthesis starting from 2,6-diamino-4(3 H )-pyrimidinone through different condensation steps to the last peptide coupling with chiral glutamate [ 45 , 46 , 47 , 48 ]. Different structure-activity relationship modifications have been implemented either on substituted pyrrolo [2,3- d ] pyrimidine [ 49 , 50 , 51 ] or in the bridge between this substance and the benzoyl ring in the side chain [ 52 ].…”

Section: Pemetrexedmentioning

confidence: 99%

Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery

et al. 2017

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Mesenchymal stromal cells are a population of undifferentiated multipotent adult cells possessing extensive self-renewal properties and the potential to differentiate into a variety of mesenchymal lineage cells. They express broad anti-inflammatory and immunomodulatory activity on the immune system and after transplantation can interact with the surrounding microenvironment, promoting tissue healing and regeneration. For this reason, mesenchymal stromal cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Another clinical application of mesenchymal stromal cells is the targeted delivery of chemotherapeutic agents to neoplastic cells, maximizing the cytotoxic activity against cancer cells and minimizing collateral damage to non-neoplastic tissues. Mesenchymal stem cells are home to the stroma of several primary and metastatic neoplasms and hence can be used as vectors for targeted delivery of antineoplastic drugs to the tumour microenvironment, thereby reducing systemic toxicity and maximizing antitumour effects. Paclitaxel and gemcitabine are the chemotherapeutic drugs best loaded by mesenchymal stromal cells and delivered to neoplastic cells, whereas other agents, like pemetrexed, are not internalized by mesenchymal stromal cells and therefore are not suitable for advanced antineoplastic therapy. This review focuses on the state of the art of advanced antineoplastic cell therapy and its future perspectives, emphasizing in vitro and in vivo preclinical results and future clinical applications.

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An Efficient Synthesis of Pemetrexed Disodium

Cited by 9 publications

References 12 publications

Multicomponent Reactions for the Synthesis of Active Pharmaceutical Ingredients

Multicomponent Reactions for the Synthesis of Active Pharmaceutical Ingredients

The Hantzsch Pyrrole Synthesis: Non-conventional Variations and Applications of a Neglected Classical Reaction

Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery

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