A New Synthesis of p-Methylaminobenzoyl-L-glutamic Acid<sup>1</sup>

Fu, S.-C. J.; Reiner, M.Th.; Loo, Ti Li

doi:10.1021/jo01015a527

Cited by 20 publications

(18 citation statements)

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“…4-Amino-10-methylpteroylgutamyl-y-fluoroglutamate was prepared as described (15). N-Methyl-p-aminobenzoyl-y-DL-4-fluoroglutamate di-t-butyl ester [N-CH3pABA-FGlu(OBut)2] was synthesized from (Z)-N-CH3pABA (17) and FGlu(OBu')2 as described for similar glutamate derivatives (18). Cell Culture and Drug Interaction Studies.…”

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confidence: 99%

gamma-Fluoromethotrexate: synthesis and biological activity of a potent inhibitor of dihydrofolate reductase with greatly diminished ability to form poly-gamma-glutamates.

Galivan¹,

Inglese²,

McGuire³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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A methotrexate (MTX) analog containing fluorine at the rcarbon of the glutamate moiety, -fluoromethotrexate (FMTX), has been synthesized and evaluated for its biochemical and pharmacological properties. FMTX inhibition of dihydrofolate reductase from several sources is nearly equivalent to that shown by MTX. Most important, FMTX is an exceedingly poor substrate for folylpoly (-glutamate) Utilizing the H35 hepatoma cell culture system (3, 5, 6), we are attempting to definitively establish the role of glutamylation in the activity of MTX. The approach has been to employ a MTX derivative that is accumulated by cells and inhibits DHFR as effectively as does MTX but cannot be glutamylated. The derivative we have employed, t-fluoromethotrexate (FMTX), is an analog of MTX containing fluorine in place of hydrogen on the y carbon of glutamate (Fig. 1). Recent studies with partially purified folylpoly(-glutamate) synthetase (FPGS; EC 6.3.2.17) isolated from rat liver have shown that DL-threo-4-fluoroglutamate (threo-FGlu) acts as a chain-terminating inhibitor of the FPGS reaction (15). The data support the hypothesis that the incorporation of a molecule of FGlu into growing polyglutamate chains leads to a product, R-Glu-y-FGlu, that undergoes further glutamylation at a markedly reduced rate. These results suggest that the synthesis of reduced folates or antifolates (e.g., MTX) containing FGlu in place of glutamate would lead to molecules with greatly diminished ability to form poly(-glutamate) derivatives. The topic of this report is the influence of the fluorine substitution on the toxicity of MTX in cultured hepatic cells. In particular, short-term exposure to FMTX causes growth inhibition that is several orders of magnitude weaker than that obtained with MTX. To establish that limited glutamylation is a major reason for these results, it is necessary to demonstrate (i) that both agents exert similar inhibitory effects toward the target enzyme DHFR, (ii) that FMTX and MTX are accumulated to a similar extent in H35 cells, and (iii) that FMTX is poorly glutamylated by H35 cells. These observations are evaluated with Abbreviations: MTX, methotrexate; FMTX, y-fluoromethotrexate; FGlu, DL-4-fluoroglutamate; DHFR, dihydrofolate reductase; FPGS, folylpoly(y-glutamate) synthetase. 2598The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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confidence: 99%

gamma-Fluoromethotrexate: synthesis and biological activity of a potent inhibitor of dihydrofolate reductase with greatly diminished ability to form poly-gamma-glutamates.

Galivan¹,

Inglese²,

McGuire³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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“…The following spectral properties were observed: IR (KBr) ν: 3100 (Ar-H), 1638 (HC=N), 1305 (SO 2 ), 1142 (SO 2 ), 770 (Ar-H). 1 Proper Schiff base (3, 1 mmol) was added with shaking to a cold freshly prepared solution of diazomethane (3 mmol) in dioxane/water (4.5 ml) [5]. A cork stopper was then placed in the flask and the reaction mixture was allowed to stand at room temperature for 5-10 days.…”

Section: -Methylsulfonyl-n-benzylidenaniline (3a)mentioning

confidence: 99%

“…The inhibition of cyclooxygenase (COX) was considered to be responsible for both the therapeutic and side effect of NSAIDs. In 1990 the existence of a second COX enzyme, named COX-2 was described [1,2]. COX-2 was postulated to be the isoform involved in inflammatory process [1].…”

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confidence: 99%

“…In 1990 the existence of a second COX enzyme, named COX-2 was described [1,2]. COX-2 was postulated to be the isoform involved in inflammatory process [1]. 1,2-Diaryl heterocycles such as rofecoxib and celecoxib are selective COX-2 inhibitors with superior gastrointestinal safety profile.…”

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confidence: 99%

“…However, the cycloaddition was not observed and unchanged starting material was isolated. Finally, cycloaddtion could be achieved with diazomethane in dioxane/water [5] and 1-(4-methylsulfonylphenyl)-5-aryl-4,5-dihydro-1H- [1,2,3] triazole 4 was obtained in moderate yield ( Table 2).…”

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confidence: 99%

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Syntheses of 1-(4-methylsulfonylphenyl)-5-aryl-1,2,3-triazoles and -(4-aminosulfonylphenyl)-5-aryl-1,2,3-triazoles

Daha

Matloubi

Tabatabi

et al. 2005

Journal of Heterocyclic Chemistry

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Condensation of 4-methylsulfonylaniline with aryl aldehyde in ethanol-tetrahydrofuran afforded the imino compound 3. 1,3-Cycloaddtion of diazomethane with compound 3 followed by oxidazation of the triazoline 4 with potassium permanganate gave 1-(4-methylsulfonylphenyl)-5-aryl-1,2,3-triazoles 5. Similarly, condensation of 4-(N,N-dibenzylaminosulfonyl)aniline with aryl aldehyde followed by l,3-cycloaddition of diazomethane with the imino compound 11 and the subsequent oxidation of triazoline 12 with potassium permanganate yielded the triazole 13. Debenzylation of compound 13 with sulfuric acid gave the desired compound 1-(4-aminosulfonylphenyl)-5-aryl-1,2,3-triazoles 14.

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New polymer materials based on silicone‐acrylic copolymer to improve fastness properties of reactive dyes on cotton fabrics

Xie

Hou

Zhang

2006

J of Applied Polymer Sci

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New polymer materials, based on siliconeacrylic copolymer containing cationic groups, were synthesized through radical mechanism and ring-opening polymerization of cyclosiloxane. The polymers of polyacrylate/ polysiloxane improved the fastness properties of reactive dyes on cotton. In comparison with those of polyacrylatecontaining cationic groups, the wash fastness and wet rubbing fastness of the dyed cotton fabric treated with the new polymer materials were better. The handle of the fabric with aftertreatment was also good.

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A New Synthesis of p-Methylaminobenzoyl-L-glutamic Acid¹

Cited by 20 publications

References 0 publications

gamma-Fluoromethotrexate: synthesis and biological activity of a potent inhibitor of dihydrofolate reductase with greatly diminished ability to form poly-gamma-glutamates.

gamma-Fluoromethotrexate: synthesis and biological activity of a potent inhibitor of dihydrofolate reductase with greatly diminished ability to form poly-gamma-glutamates.

Syntheses of 1-(4-methylsulfonylphenyl)-5-aryl-1,2,3-triazoles and -(4-aminosulfonylphenyl)-5-aryl-1,2,3-triazoles

New polymer materials based on silicone‐acrylic copolymer to improve fastness properties of reactive dyes on cotton fabrics

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A New Synthesis of p-Methylaminobenzoyl-L-glutamic Acid1

Cited by 20 publications

References 0 publications

gamma-Fluoromethotrexate: synthesis and biological activity of a potent inhibitor of dihydrofolate reductase with greatly diminished ability to form poly-gamma-glutamates.

gamma-Fluoromethotrexate: synthesis and biological activity of a potent inhibitor of dihydrofolate reductase with greatly diminished ability to form poly-gamma-glutamates.

Syntheses of 1-(4-methylsulfonylphenyl)-5-aryl-1,2,3-triazoles and -(4-aminosulfonylphenyl)-5-aryl-1,2,3-triazoles

New polymer materials based on silicone‐acrylic copolymer to improve fastness properties of reactive dyes on cotton fabrics

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A New Synthesis of p-Methylaminobenzoyl-L-glutamic Acid¹