Depsipeptides containing N-substituted glycine residue

Details Depsipeptides containing N-substituted glycine residue Depsipeptides containing N-substituted glycine residue

1998-12-21

1999-12-14

Tsang, Cecilia J.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

530323, 530330, A61K 3800

Patent

active

060018151

ABSTRACT:
A depsipeptide containing N-substituted glycine residue having the formula (1) or (2): ##STR1## (wherein R.sub.1 is a straight or branched alkyl group of 5-20 carbon atoms or a straight or branched alkoxymethyl group of 5-15 carbon atoms; R.sub.2 is a group of the formula --A--B--W--(D).sub.m --(E).sub.n, --A--B--W--(D).sub.m --(E).sub.n --F or --A--B--W--(D).sub.m --(E).sub.n --F--Z; R.sub.3 is a hydroxyl group, a lower alkoxy group, a benzyloxy group, or a group of the formula --Z, --Z--G or --Z--G--J; A, B, D, E, F, G and J independently are an N-substituted glycine residue or a residue of an amino acid selected from the group consisting of alanine, valine, leucine, serine, etc.; W and Z independently are a residue of an amino acid selected from the group consisting of an aspartic acid, a glutamic acid, etc.; at least one of A, B, D, E, F, G and J is an N-substituted glycine residue) or a pharmacologically acceptable salt thereof.
The above depsipeptides have a promoting activity on the production of apolipoprotein E, and are useful as a therapeutic agent for neurologic damages, especially dementia, and hyperlipemia.

REFERENCES:
patent: 5801143 (1998-09-01), Hiramoto et al.
Michael J. Ignatius, et al., "Expression of Apolipoprotein E During Nerve Degeneration and Regeneration", Proc. Natl. Acad. Sci. USA, vol. 83, Feb. 1986, pp. 1125-1129.
Nobuhiro Yamada, et al., "Increased Clearance of Plasma Cholesterol after Injection of Apolipoprotein E into Watanabe Heritable Hyperlipidemic Rabbits", Proc. Natl. Acad. Sci. USA, vol. 86, Jan. 1989, pp. 665-669.
Hitoshi Shimano, et al., "Plasma Lipoprotein Metabolism in Transgenic Mice Overexpressing Apolipoprotein E", Journal of Clinical Investigation, vol. 90, Nov. 1992, pp. 2084-2091.

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