Antibacterial and antifungal nucleosides

Details Antibacterial and antifungal nucleosides Antibacterial and antifungal nucleosides

1996-11-12

1998-07-21

Kight, John

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 2855, 530350, 514 19, 514 49, 514 50, C07H 19067

Patent

active

057836892

ABSTRACT:
5'-O-Acyl-5-fluorouridines and 5'-O-acyl-5-sluorocytidines are prepared by the direct acylation of the 5'-hydroxyl group with amino acids under Mitsunobu conditions and the amino acyl derivatives are coupled with other amino acids or peptides to provide antibacterial and antifungal derivatives of the nucleosides. For example, 5-fluorouridine is acylated at the 5'-hydroxyl group with an amino protected L-valine and the acylation product is deprotected to provide 5'-O-(L-valinyl)-5-fluorouridine having activity against Gram-positive bacteria including resistant staphylococcus. Preferred peptide derivatives comprise the tripeptides of ornithine and lysine wherein the terminal amino group is substituted by both hydroxy and acetyl. The latter peptides inhibit the growth of C. albicans.

REFERENCES:
patent: 3575959 (1971-04-01), Shen et al.
patent: 4340728 (1982-07-01), Endo et al.
patent: 4851519 (1989-07-01), Lambert et al.
patent: 4886785 (1989-12-01), Lambert et al.
patent: 4892939 (1990-01-01), Sakai et al.
patent: 5010060 (1991-04-01), Lambert et al
Yamazaki et al., "Difference Between Cancer Cells and the Corresponding Normal Tissue in View of Stereoselective Hydrolysis of Synthetic Esters," Biochem. Biophys. Acta, 1243(3), 300-308 (Apr. 13, 1995).
Mori et al., "Novel Derivatives of 5-Fluorouridine and 5-Fluorouracil Having Potent Antitumor and Lowe Immunosuppressive Activities," Japanese J. Pharmacology, 58(3), 269-282 (Mar. 1992).
Ghosh et al., "Design, Synthesis, and Biological Evaluation of Isocyanurate-Based Antifungal and Macrolide Antibiotic Conjungates: Iron Transport-Mediated Drug Delivery," Bioorg. Med. Chem., 3(11), 1519-1525 (1995); Chem. Abstr., 124(3), p. 522, Abstr. No. 25440k (Jan. 15, 1996); only Abstract supplied.
Hu and Miller, J. Org.Chem. 1994, 59, 4858-4861.
M. Ghosh and M. J.Miller, Bioorganic & Medicinal Chemistry, vol. 3, No. 11, pp. 1519-1525, 1995.
Dissertation by Julia A. McKee with Title (partial) "Iron Transport Mediated Drug Delivery", etc. pp. 128-163 and 240-253, presented Aug. '91 and deposited in Univ. of ND Library ca. 1992 (Notre Dame= ND).

Affiliated with

Also associated with

Rating

Antibacterial and antifungal nucleosides does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Antibacterial and antifungal nucleosides, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Antibacterial and antifungal nucleosides will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1647970