Immunostimulating swainsonine analogs
AssigneeToronto Research Chemicals, Inc.
InventorDavid Dime
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Abstract
Immunostimulting swainsonine derivatives and methods for their synthesis are provided.
Claims7
A swainsonine compound for use as an inhibitor of Golgi alpha-manosidase II and an immunostimulator having the formula illustrated below, ##STR1## or a salt of said compound, where R is selected from the group consisting of C.dbd.O(CH.sub.2).sub.2 CH.sub.3, Si(CH.sub.3).sub.3, C.dbd.OC.sub.6 H.sub.5, C.dbd.O(CH.sub.2).sub.6 CH.sub.3, C.dbd.O(CH.sub.2).sub.2 COOH, Si(C.sub.6 H.sub.5).sub.2 C(CH.sub.3)3, Si(CH.sub.3).sub.2 C(CH.sub.3)3, C.dbd.O(CH.sub.2).sub.16 CH.sub.3, C.dbd.O(CH.sub.2).sub.14 CH.sub.3, C.dbd.O(CH.sub.2).sub.12 CH.sub.3, C.dbd.OC.sub.6 H.sub.5, 2-furoyl, m-toluoyl, p-toluoyl, p-nitrobenzoyl, p-bromobenzoyl, benzyl, allyl, 4-methoxytrityl, triphenylmethyl, butyl, pentyl, hexyl, heptyl, octyl, dodecyl, hexadecyl, octadecyl, acetyl, propionyl, pivaloyl, phenoxypropionyl, imadazolyl, imadazoylthiocarbonyl, 2,3,4,6-tetra-O-acetyl-.beta.-D-glucopyranosyl, .beta.-D-glucopyranosyl, 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl, alpha-D-mannopyranosyl, 2,3,4,6-tetra-O-acetyl-.beta.-D-mannopyranosyl, .beta.-D-mannopyranosyl, 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-.beta.-D-glucopyranosyl, 2-acetamido-2-deoxy-.beta.-D-glucopyranosyl, 2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl, alpha-L-fucopyranosyl, 2,3,4,6-tetra-O-acetyl-.beta.-D-galactopyranosyl, .beta.-D-glactopyranosyl, 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-.beta.-D- galactopyranosyl, 2-acetamido-2-deoxy-.beta.-D-galactopyranosyl, 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-alpha-D-galactopyranosyl, 2-acetamido-2deoxy-alpha-D-galactopyranosyl, N-acetylneuraminyl, lactosaminyl, and .beta.-D-glucuronyl.
A compound comprising a swainsonine analog for use as an inhibitor of Golgi alpha-mannosidase II and an immunostimulator selected from the group consisting of:
- 1S-8a.beta.-2.alpha.-trimethylsilyloxyoctahydroindolizine-1.alpha.,8.beta.- diol,
- 1S-8a.beta.-2.alpha.-succinyloxyoctahydroindolizine-1.alpha.,8.beta.-diol,
- 1S-8a.beta.-2.alpha.-benzoyloxyoctahydroindolizine-1.alpha.,8.beta.-diol,
- 1S-8a.beta.-2.alpha.-p-toluoyloxyoctahydroindolizine-1.alpha.,8.beta.-diol,
- 1S-8a.beta.-2.alpha.-p-nitrobenzoyloxyoctahydroindolizine-1.alpha.,8.beta.- diol,
- 1S-8a.beta.-2.alpha.-octanoyloxyoctahydroindolizine-1.alpha.,8.beta.-diol,
- 1S-8a.beta.-2.alpha.-butanoyloxyoctahydroindolizine-1.alpha.,8.beta.-diol, (1S,2R,8R,8aR)-1,2,8-trihydroxy-1,2,3,5,8,8a-hexahydro-5-oxoindolizine, (1S,2R,8R,8aR)-1,2,8-triacetoxy-1,2,3,5,8,8a-hexahydro-5-oxoindolizine, 7-ethoxy-(1S,2R,8R,8aR)-1,2,8-trihydroxy-octahydro-5-oxoindolizine, 7-ethoxy-(1S,2R,8R,8aR)-1,2,8-trihydroxyoctahydroindolizine, 1S-7.beta.-bromo-1.alpha.,2.alpha.,6.alpha.,8.beta.-tetraacetoxy-8a.beta.- octahydro-5-oxoindolizine, 1S-6.beta.-bromo-1.alpha.,2.alpha.,7.alpha.,8.beta.-tetraacetoxy-8a.beta.- octahydro-5-oxoindolizine,
- 1S-7.beta.-bromo-1.alpha.,2.alpha.,6.alpha.,8.beta.-tetrahydroxy-8a.beta.-o ctahydroindolizine,
- 1S-1.alpha.,2.alpha.,6.alpha.,8.beta.-tetraacetoxy-8a.beta.-octahydro-5-oxo indolizine,
- 1S-1.alpha.,2.alpha.,6.alpha.,8.beta.-tetrahydroxy-8a.beta.-octahydroindoli zine,
- 1S-1.alpha.,2.alpha.,7.alpha.,8.beta.-tetraacetoxy-8a.beta.-octahydro-5-oxo indolizine,
- 1S-6.alpha.,7.beta.-dibromo-1.alpha.,2.alpha.,8.beta.-triacetoxy-8a.beta.-o ctahydro-5-oxoindolizine,
- 1S-6.alpha.,7.beta.-dibromo-1.alpha.,2.alpha.,8.beta.-trihydroxy-8a.beta.-o ctahydroindolizine,
- 1S-6.beta.,7.beta.-dihydroxy-1.alpha.,2.alpha.,8.beta.-triacetoxy-8a.beta.- octahydro-5-oxoindolizine,
- 1S-1.alpha.,2.alpha.,6.beta.,7.beta.,8.beta.-pentaacetoxy-8a.beta.-octahydr o-5-oxoindolizine,
- 1S-1.alpha.,2.alpha.,6.beta.,7.beta.,8.beta.-pentahydroxy-8a.beta.-octahydr oindolizine,
- 1S-1.alpha.,2.alpha.,8.beta.-trihydroxy-8a.beta.-octahydro-5-oxoindolizine,
- 1S-5-ethoxy-1.alpha.,2.alpha.,8.beta.-trihydroxy-8a.beta.-octahydroindolizi ne,
- 1S-8a.beta.-octahydroindolizine-1.alpha.,8.beta.-diol-2.alpha.-(2-acetamido -2-deoxy-.beta.-D-glucopyranoside),
- 1S-8a.beta.-octahydroindolizine-1.alpha.,8.beta.-diol-2.alpha.-(2-acetamido -2-deoxy-3,4,6-tri-O-acetyl-.beta.-D-glucopyranoside).
Dependencies are inferred from the claim text.