Lipophila derivatives of muramylpeptides having properties of activating macrophages and compositions containing them

The invention relates to muramyleptide derivatives resulting essentially from the conjugation or the coupling, as the case may require, through an arm, between a muramylpeptide and a group containing two atoms contiguous with one another to each of which is attached a lipophile chain comprising from 8 to 100 carbon atoms, preferably from 14 to 24 carbon atoms. The derivatives according to the invention are endowed with remarkable stimulating properties with respect to the activation of macrophages, of which they amplify the tumoricidal properties.

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Claims

2. The muramylpeptide of claim 1 wherein X is a levogyratory aminoacyl residue or is glycyl.

3. The muramylpeptide of claim 2 wherein X is L-alanyl, L-seryl, L-valyl, L-leucyl, L-isoleucyl, L-threonyl or glycyl.

5. The muramylpeptide of claim 1 wherein R.sub.2 is an alkoxy group.

7. The muramylpeptide of claim 6 wherein R.sub.2 is alkoxy of 1 to 10 carbon atoms and Y is --NH.sub.2.

8. The muramylpeptide of claim 7 wherein R.sub.2 is alkoxy of 4 carbon atoms.

9. The muramylpeptide of claim 8 wherein R.sub.2 is n-butoxy.

10. The muramylpeptide of claim 6 wherein R.sub.3 and R.sub.4 are palmitoyl groups.

12. The muramylpeptide of claim 10 which is 6-O-(beta,gamma-dipalmitoyl-L-glyceryl)-capryl-N-acetyl-muramyl-L-alanyl-D -glutamine-butyl ester.

14. The muramylpeptide of claim 13 wherein R.sub.3 and R.sub.4 are palmitoyl groups.

15. The muramylpeptide of claim 14 which is alpha(N-acetyl-muramyl-L-alanyl-D-isoglutamine), beta, gamma-dipalmitoyl-sn-glycerol.

16. The muramylpeptide of claim 14 which is alpha(N-acetyl-muramyl-D-alanyl-D-isoglutamine), beta, gamma-dipalmitoyl-sn-glycerol.

17. The muramylpeptide of claim 14 which is alpha(N-acetyl-muramyl-L-alanyl-D-isoglutaminyl-L-alanine), beta, gamma-dipalmitoyl-sn-glycerol.

18. The muramylpeptide of claim 14 which is alpha(N-acetyl-muramyl-D-alanyl-D-isoglutaminyl-L-alanine), beta, gamma-dipalmitoyl-sn-glycerol.

19. A pharmaceutical composition for stimulating the activity of macrophage which comprises a physiologically acceptable carrier and a macrophage stimulant effective amount of said muramylpeptide of claim 1.

20. A method for activating macrophages in a host which comprises the step of: administering to said host a macrophage activating amount said muramylpeptide of claim 1.

21. A method for stimulating anti-infectious activity of macrophages in a host which comprises administering to said host a macrophage stimulating amount of said muramylpeptide of claim 1.

Referenced Cited
U.S. Patent Documents
3931139 January 6, 1976 Wissmann et al.
4101536 July 18, 1978 Yamamura et al.
4310514 January 12, 1982 Durette
4315913 February 16, 1982 Durette
4369178 January 18, 1983 Yamamura et al.
4579840 April 1, 1986 Hahn
4628045 December 9, 1986 Hahn
4672106 June 9, 1987 Hamaoka et al.
4681856 July 21, 1987 Hamaoka et al.
4683292 July 28, 1987 Hahn
Foreign Patent Documents
0025495 March 1981 EPX
0056992 August 1982 EPX
0102319 October 1984 EPX
0135788 April 1985 EPX
Other references
  • Rose et al., Cancer Treatment Report, vol. 66 No. 1, pp. 135-146, 1982. Long et al., Cancer Treatment Reports, vol. 71, No. 6, pp. 593-598, 1987. Rubin et al., Cancer Treatment Reports, vol. 71, No. 5, pp. 489-492, 1987.
Patent History
Patent number: RE35706
Type: Grant
Filed: Oct 25, 1994
Date of Patent: Dec 30, 1997
Assignee: VACSYN Inc. (Tampa, FL)
Inventors: Nigel Phillips (Pointe Claire), Fran.cedilla.oise Audibert (Neuilly sur Seine), Jean-Marie Bernard (Fontenay le Fleury), Louis Chedid (Paris), Pierre Lefrancier (Gif S/Yvette), Michel Level (Paris), Monique Parant (Paris)
Primary Examiner: Avis M. Davenport
Law Firm: Larson & Taylor
Application Number: 8/329,142
Classifications
Current U.S. Class: 514/8; Peptides Containing Saccharide Radicals, E.g., Bleomycins, Etc. (530/322); Oxygen Double Bonded And Nitrogen Bonded Directly To The Same Carbon (536/53)
International Classification: A61K 3814; A61K 3816; C07K 900;