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

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)475-477
Number of pages3
JournalJournal of Medicinal Chemistry
Volume25
Issue number4
StatePublished - 1982
Externally publishedYes

Fingerprint

Folic Acid Antagonists
Ornithine
Methotrexate
Lysine
Esters
Tetrahydrofolate Dehydrogenase
Acids
Condensation
ornithine-methotrexate

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Kempton, R. J., Black, A. M., Anstead, G. M., Ashok Kumar, A., Blankenship, D. T., & Freisheim, J. H. (1982). Lysine and ornithine analogues of methotrexate as inhibitors of dihydrofolate reductase. Journal of Medicinal Chemistry, 25(4), 475-477.

Lysine and ornithine analogues of methotrexate as inhibitors of dihydrofolate reductase. / Kempton, Robert J.; Black, Angelique M.; Anstead, Gregory M; Ashok Kumar, A.; Blankenship, Dale T.; Freisheim, James H.

In: Journal of Medicinal Chemistry, Vol. 25, No. 4, 1982, p. 475-477.

Research output: Contribution to journalArticle

Kempton, RJ, Black, AM, Anstead, GM, Ashok Kumar, A, Blankenship, DT & Freisheim, JH 1982, 'Lysine and ornithine analogues of methotrexate as inhibitors of dihydrofolate reductase', Journal of Medicinal Chemistry, vol. 25, no. 4, pp. 475-477.
Kempton RJ, Black AM, Anstead GM, Ashok Kumar A, Blankenship DT, Freisheim JH. Lysine and ornithine analogues of methotrexate as inhibitors of dihydrofolate reductase. Journal of Medicinal Chemistry. 1982;25(4):475-477.
Kempton, Robert J. ; Black, Angelique M. ; Anstead, Gregory M ; Ashok Kumar, A. ; Blankenship, Dale T. ; Freisheim, James H. / Lysine and ornithine analogues of methotrexate as inhibitors of dihydrofolate reductase. In: Journal of Medicinal Chemistry. 1982 ; Vol. 25, No. 4. pp. 475-477.
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