Lysine and Ornithine Analogues of Methotrexate as Inhibitors of Dihydrofolate Reductase

Robert J. Kempton; Angelique M. Black; Gregory M. Anstead; A. Ashok Kumar; Dale T. Blankenship; James H. Freisheim

doi:10.1021/jm00346a026

Lysine and Ornithine Analogues of Methotrexate as Inhibitors of Dihydrofolate Reductase

Robert J. Kempton, Angelique M. Black, Gregory M. Anstead, A. Ashok Kumar, Dale T. Blankenship, James H. Freisheim

Producción científica: Comment/debate › revisión exhaustiva

29 Citas (Scopus)

Resumen

The ornithine (6a) and lysine (6b) analogues of methotrexate (1) have been synthesized via condensation of 4-amino-4-deoxy-N¹⁰-methylpteroic acid (2) with N^δ-carbobenzoxy-l-ornithine tert-butyl ester (3a) and N^ϵ-carbobenzoxy-l-lysine tert-butyl ester (3b), respectively. Removal of the protecting groups gave 6a and 6b. Compounds 6a and 6b and their precursor Cbz acids (5a and 5b) show significant inhibition of dihydrofolate reductase.

Idioma original	English (US)
Páginas (desde-hasta)	475-477
Número de páginas	3
Publicación	Journal of Medicinal Chemistry
Volumen	25
N.º	4
DOI	https://doi.org/10.1021/jm00346a026
Estado	Published - 1982
Publicado de forma externa	Sí

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Molecular Medicine

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@article{3330467a758247138ac7555d07e5a4e7,

title = "Lysine and Ornithine Analogues of Methotrexate as Inhibitors of Dihydrofolate Reductase",

abstract = "The ornithine (6a) and lysine (6b) analogues of methotrexate (1) have been synthesized via condensation of 4-amino-4-deoxy-N10-methylpteroic acid (2) with Nδ-carbobenzoxy-l-ornithine tert-butyl ester (3a) and Nϵ-carbobenzoxy-l-lysine tert-butyl ester (3b), respectively. Removal of the protecting groups gave 6a and 6b. Compounds 6a and 6b and their precursor Cbz acids (5a and 5b) show significant inhibition of dihydrofolate reductase.",

author = "Kempton, {Robert J.} and Black, {Angelique M.} and Anstead, {Gregory M.} and Kumar, {A. Ashok} and Blankenship, {Dale T.} and Freisheim, {James H.}",

year = "1982",

doi = "10.1021/jm00346a026",

language = "English (US)",

volume = "25",

pages = "475--477",

journal = "Journal of Medicinal Chemistry",

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T1 - Lysine and Ornithine Analogues of Methotrexate as Inhibitors of Dihydrofolate Reductase

AU - Kempton, Robert J.

AU - Black, Angelique M.

AU - Anstead, Gregory M.

AU - Kumar, A. Ashok

AU - Blankenship, Dale T.

AU - Freisheim, James H.

PY - 1982

Y1 - 1982

N2 - The ornithine (6a) and lysine (6b) analogues of methotrexate (1) have been synthesized via condensation of 4-amino-4-deoxy-N10-methylpteroic acid (2) with Nδ-carbobenzoxy-l-ornithine tert-butyl ester (3a) and Nϵ-carbobenzoxy-l-lysine tert-butyl ester (3b), respectively. Removal of the protecting groups gave 6a and 6b. Compounds 6a and 6b and their precursor Cbz acids (5a and 5b) show significant inhibition of dihydrofolate reductase.

AB - The ornithine (6a) and lysine (6b) analogues of methotrexate (1) have been synthesized via condensation of 4-amino-4-deoxy-N10-methylpteroic acid (2) with Nδ-carbobenzoxy-l-ornithine tert-butyl ester (3a) and Nϵ-carbobenzoxy-l-lysine tert-butyl ester (3b), respectively. Removal of the protecting groups gave 6a and 6b. Compounds 6a and 6b and their precursor Cbz acids (5a and 5b) show significant inhibition of dihydrofolate reductase.

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DO - 10.1021/jm00346a026

M3 - Comment/debate

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JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 4

ER -

Lysine and Ornithine Analogues of Methotrexate as Inhibitors of Dihydrofolate Reductase

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