Claims
- 1. A substituted glutarimide compound of formula I
- 2. An enantiomer, or a salt thereof with a physiologically compatible acid, of a compound according to claim 1.
- 3. A mixture of enantiomers, or salts thereof with a physiologically compatible acid, of at least a compound according to claim 1.
- 4. A racemate, or a salt thereof with a physiologically compatible acid, of a compound according to claim 1.
- 5. A diastereomer, or mixture of diastereomers thereof, or a salt thereof with a physiologically compatible acid, of a compound according to claim 1.
- 6. A compound according to claim 1, selected from the group consisting of:
2-[(3S)-(2,6-dioxopiperidin-3-ylamino)methyl] bezoic acid, 2-[(3R)-(2,6-dioxopiperidin-3-ylamino)methyl] benzoic acid, 2-[(3S)-(2,6-dioxopiperidin-3-ylamino)methyl]-N,N-diethylbenzamide, (3S)-[2-morpholine-4-carbonyl)benzylamino] piperidine-2,6-dione, {2-[(3S)-(2,6-dioxopiperidin-3-ylamino)methyl] benzoylamino} methyl acetate, 2-[(3S)-(2,6-dioxopiperidin-3-ylamino)methyl] benzamide, 2-[(3S)-(2,6-dioxopiperidin-3-ylamino)methyl]-N-ethyl benzamide, (3S)-[2-pyrrolidine-1-carbonyl)benzylamino] piperidine-2,6-dione, 2-[(3S)-(2,6-dioxopiperidin-3-ylamino)methyl] benzoic acid hydrazide, 2-[(3S)-(2,6-dioxopiperidin-3-ylamino)methyl]-N-phenyl benzamide, 2-[(3R)-(2,6-dioxopiperidin-3-ylamino)methyl] -N-phenyl benzamide, 2-[(3R)-(2,6-dioxopiperidin-3-ylamino)methyl] -N,N-diethyl benzamide, 2-[(3R)-(2,6-dioxopiperidin-3-ylamino)methyl] benzamide, 2-[(3S)-(2,6-dioxopiperidin-3-ylamino)methyl] methyl benzoate, 2-[(3S)-(2,6-dioxopiperidin-3-ylamino)methyl] benzyl benzoate, 2-(2,6-dioxopiperidin-3-yl methyl sulfanyl) methyl benzoate, N-{2-[2,6-dioxopiperidin-3-ylamino)methyl] phenyl} acetamide, N-{2-[2,6-dioxopiperidin-3-ylamino)methyl] phenyl} formamide, 3-(2,6-dioxopiperidin-3-yl methyl sulfanyl)-6-nitro methylbenzoate, and 2-amino-5-(2,6-dioxopiperidin-3-yl methyl sulfanyl) methyl benzoate.
- 7. A pharmaceutical composition comprising as an active agent at least one compound according to claim 1, and a pharmaceutically acceptable excipient.
- 8. A method for modulating immune action in a mammal in need thereof, comprising administering to the mammal an effective immunomodulatory amount of a compound of claim 1.
- 9. A method according to claim 8, wherein the mammal is a human.
- 10. A method for the treatment of angiopathies, or hematological or oncological diseases, comprising administering to a patient in need thereof an effective amount of a compound according to claim 1.
- 11. A method for the production of a substituted glutarimide compound according to claim 1, the method comprising
cyclizing a glutaric acid derivative of formula II, 14wherein X, R1 and R2 are as defined in formula I; and A is OH, and B is NH2 or NHOH; or A is NH2 or NHOH, and B is OH, in the presence of an activating reagent.
- 12. A method according to claim 11, wherein the activating agent is carbonyl diimidazole.
- 13. A method according to claim 11, wherein X is CH2—NH, and wherein cyclization is performed with the —NH group of X protected by a protective group, which protective group is removed after cyclization.
- 14. A method according to claim 13, wherein the protective group is a benzyloxycarbonyl group.
- 15. A method for the production of a substituted glutarimide compound according to claim 1, the method comprising
heating a glutaric acid derivative of formula II, 15wherein X, R1 and R2 are as defined in formula I, and A and B are both OH, in acetic anhydride to obtain an anhydride by cyclization, and heating the anhydride with a nitrogen source to obtain a compound of formula I.
- 16. A method according to claim 15, wherein the nitrogen source is urea.
- 17. A method for producing a substituted glutarimide of formula I according to claim 1, the method comprising oxidizing a lactam of formula
- 18. A method according to claim 17, wherein the lactam is oxidized with at least one oxidizer selected from the group consistin of m-chloroperbenzoic acid, ruthenium(IV) oxide and sodium periodate.
- 19. A method for producing a substituted glutarimide of formula I according to claim 1 wherein X stands for a CH2—NH group, the method comprising
alkylating an α-aminoglutarimide compound of formula IV, 17with a compound of formula V, 18in which R1 and R2 are as defined for formula I, and Y is selected from the group consisting of chlorine, bromine, iodine, and a toluene-4-sulfonate group.
- 20. A method for producing a substituted glutarimide of formula I according to claim 1 wherein X stands for a CH2—NH group, the method comprising
reacting by reductive amination a compound of formula VI with a compound of formula IV, 19in which R1 and R2 are as defined for formula I, to obtain the substituted glutarimide.
- 21. A method according to claim 20, wherein the compound of formula VI and the compound of formula IV are reduced by a member selected from the group consisting of sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride, a borane-pyridine complex, and a catalytically excited hydrogen.
- 22. A method for producing a substituted glutarimide of formula I according to claim 1 wherein X is a CH2—NH group, the method comprising:
alkylating a compound of formula VII, 20in which R1 and R2 are as defined for formula I, with an α-bromoglutarimide of formula VIII 21
- 23. A method for producing a substituted glutarimide of formula I according to claim 1 wherein X is an S—CH2 group, the method comprising
adding in a solvent a mercaptan of formula X 22in which R1 and R2 are as defined for formula I, to a 3-methylene glutarimide of formula IX, 23
- 24. A method according to claim 23, wherein the solvent is acetonitrile or toluene.
- 25. A method according to claim 24 wherein the solvent further comprises a tertiary amine.
- 26. A method according to claim 25, wherein the tertiary amine is triethylamine or diisopropyl ethylamine.
- 27. A method according to claim 24, wherein the mercaptan is added to the 3-methylene glutarimide at a temperature between about 80° C. and about 110° C.
- 28. A method for producing a substituted glutarimide of formula I according to claim 1 wherein R2 is an amino group, the method comprising reducing a compound of formula I wherein R2═NO2 by catalytically excited hydrogen in an acid-containing organic solvent.
- 29. A method according to claim 28, wherein the organic solvent is ethyl acetate.
- 30. A method according to claim 28, wherein the reduction is performed using a palladium catalyst or with a metal in an acid solution.
- 31. A method according to claim 30, wherein the metal is tin or iron.
Priority Claims (1)
Number |
Date |
Country |
Kind |
100 02 509.9 |
Jan 2000 |
DE |
|
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation-in-part of international patent application no. PCT/EP01/00155, filed Jan. 9, 2001, designating the United States of America, the entire disclosure of which is incorporated herein by reference. Priority is claimed based on Federal Republic of Germany patent application no. 100 02 509.9, filed Jan. 21, 2000.
Divisions (1)
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Number |
Date |
Country |
Parent |
10198073 |
Jul 2002 |
US |
Child |
10653188 |
Sep 2003 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
PCT/EP01/00155 |
Jan 2001 |
US |
Child |
10198073 |
Jul 2002 |
US |