The chemistry of methotrexate and its analogues

Rahman, Loay K. A.; Chhabra, Siri Ram

doi:10.1002/med.2610080106

Cited by 55 publications

(21 citation statements)

References 112 publications

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“…Following our recent studies in developing benign methods for the synthesis of biologically important heterocycles [25][26][27][28] and potential biological activities of pyrido [2,3-d] pyrimidines as diazaanlogues of petridines [29,30], propeled us to combine two concepts together, synthesis of the heterocyclic compounds based on pyrido [2,3-d]pyrimidine structure for medical purposes and use of multicomponent reactions (MCRs) methodology to achieve the efficient and productive process with high final yields. The project aimed to synthesize novel derivatives of pyrido [2,3-d] Table I.…”

Section: Resultsmentioning

confidence: 99%

One-pot, three-component, catalyst-free synthesis of novel derivatives of pyrido-[2,3-d]pyrimidines under ultrasonic irradiations

Barghi-Lish

Farzaneh

Mamaghani

2016

Synthetic Communications

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Novel derivatives of pyrido-[2,3-d] pyrimidines were synthesized via an efficient and catalyst-free one-pot three-component reaction of 3-(1-methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile, 6-amino-(ethylthio)pyrimidine-4(3H)-one and arylaldehydes under ultrasonic irradiations. This practical method furnished the desired pyridopyrimidines in high yields (79-89%) and shorter reaction times (25-40 min). GRAPHICAL ABSTRACT

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Section: Resultsmentioning

confidence: 99%

One-pot, three-component, catalyst-free synthesis of novel derivatives of pyrido-[2,3-d]pyrimidines under ultrasonic irradiations

Barghi-Lish

Farzaneh

Mamaghani

2016

Synthetic Communications

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“…As extensively reported, an increase in the overall lipophilicity of MTX can be achieved by a substitution at one or both the carboxyl groups present in its glutamate moiety [Piper et al, 1982;Antonjuk et al, 1984Antonjuk et al, , 1989Rosowsky et al, 1986;Pignatello et al, 1996Pignatello et al, , 1998Pignatello et al, , 1999Rahman and Cchabra, 1988]. LAA conjugation of anticancer drugs was shown to maintain or even increase the activity against different cell lines in vitro [Wood et al, 1992;Pignatello et al, 1998Pignatello et al, , 2000.…”

Section: Introductionmentioning

confidence: 92%

Lipophilic methotrexate conjugates with glucose‐lipoamino acid moieties: Synthesis and in vitro antitumor activity

Pignatello

Vicari

Sorrenti

et al. 2001

Drug Development Research

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To obtain methotrexate (MTX) derivatives with a balanced hydrolipophilic character, we synthesized a series of conjugates in which the drug was linked to lipoamino acid (LAA)-glucose residues (LAAG-MTX). These conjugates displayed increased solubility in polar media compared with the corresponding LAA-MTX conjugates previously described. In vitro biological testing of LAAG-MTX indicated that the introduction of the sugar moiety decreased the biological activity of these MTX conjugates. The tetradecyl derivative 6b, however, was effective in inhibiting the dihydrofolate reductase activity in vitro and showed an inhibitory effect on human lymphoblastoid cell growth. Drug Dev. Res. 52:454-461, 2001.

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“…Efforts to improve the therapeutic significance of these agents have resulted in identification of more potent compounds. Pyrido [2,3-d]pyrimidine and some of its derivatives display several potentially useful biological activities [1,2]. They show dihydrofolate reductase inhibition and antitumor [3,4] as well as diuretic properties [5].…”

Section: Introductionmentioning

confidence: 99%

Pyrido [2, 3-d]pyrimidines and Pyrimido[5′, 4′:5, 6]pyrido[2, 3-d]pyrimidines as New Antiviral Agents: Synthesis and Biological Activity

Nasr

Gineinah

2002

Arch. Pharm. Pharm. Med. Chem.

213

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A series of 7‐amino‐ and 7‐oxo‐5‐aryl‐6‐cyanopyrido[2, 3‐d]pyrimidines, 4 and 11, respectively, and pyrimido [5′, 4′:5, 6]pyrido[2, 3‐d]pyrimidine derivatives 6 and 7 was synthesized and investigated as antiviral agents. Different synthetic strategies for the preparation of the target compounds were explored. A synthetic procedure for 4 and 11 starting with 6‐amino‐1, 2, 3, 4‐tetrahydro‐2, 4‐dioxopyrimidine, proper aldehyde, and malononitrile or ethyl cyanoacetate, respectively, in a one‐pot reaction proved to be the method of choice for preparation of compounds of such type. Construction of another pyrimidine ring on the pyridine nucleus of compound 4 was achieved either by reaction with phenyl iso(thio)cyanate or with formic acid to yield 6 and 7, respectively. The structure of the prepared compounds was confirmed through elemental analysis and spectral investigation. Most of the newly synthesized compounds were subjected to antiviral activity testing against herpes simplex virus (HSV) where some of them show good activities.

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The chemistry of methotrexate and its analogues

Cited by 55 publications

References 112 publications

One-pot, three-component, catalyst-free synthesis of novel derivatives of pyrido-[2,3-d]pyrimidines under ultrasonic irradiations

One-pot, three-component, catalyst-free synthesis of novel derivatives of pyrido-[2,3-d]pyrimidines under ultrasonic irradiations

Lipophilic methotrexate conjugates with glucose‐lipoamino acid moieties: Synthesis and in vitro antitumor activity

Pyrido [2, 3-d]pyrimidines and Pyrimido[5′, 4′:5, 6]pyrido[2, 3-d]pyrimidines as New Antiviral Agents: Synthesis and Biological Activity

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