Deuterated rapamycin compounds, method and uses thereof

Details Deuterated rapamycin compounds, method and uses thereof Deuterated rapamycin compounds, method and uses thereof

2005-09-06

2005-09-06

Kifle, Bruck (Department: 1624)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

Reexamination Certificate

active

06939878

ABSTRACT:
The synthesis of deuterated analogues of rapamycin is disclosed together with a method for use for inducing immunosupression and in the treatment of transplantation rejection, graft vs host disease, autoimmune diseases, diseases of inflammation leukemia/lymphoma, solid tumors, fungal infections, hyperproliferative vascular disorders. Also described is a method for the synthesis of water soluble deuteratred rapamycin compounds and their use as described above.

REFERENCES:
Connelly, P.R., et al. (1993). Probing hydration contributions to the thermodynamics of ligand binding by proteins. Enthalpy and heat capacity changes of tacrolimus and rapamycin binding to FK506 binding protein in D2O and H2O. Biochemistry, 32(21):5583-5590.
Curran, D.P., et al. (1992). Intramolecular Hydrogen Transfer Reactions of o- (Bromophenyl)dialkylsilyl Ehters. Preparation of Rapamycin-d.sub.1. Tetrahedron Letters 33(17):2295-2298.
Park, S.T., et al. (1992). PPIase catalysis by human FK506-binding protein proceeds through a conformational twist mechansim. J Biol Chem. 267(5):3316-3324.
Sticker, D., Senior Technical Information Specialist of Chemical Abstract Service, C.A.S., Commerical Database Search of Deuterated Rapamycin, search conducted Mar. 9, 2000.
Dennis P. Curran, et al.,Intramolecular Hydrogen Transfer Reactions of o-(Bromophenyl)dialkylsilyl Ethers. Preparation of Rapamycin-d.,Tetrahedron Letters, vol. 33, No. 17, 1992, pp. 2295-2298.
Don Sticker, Senior Technical Information Specialist of Chemical Abstract Service, C.A.S., Commerical Database Search of Deuterated Rapamycin, search conducted Mar. 9, 2000.
Park et al.,Jr. Bio Chem.,vol. 267, No. 5 (15) pp 3316-3324, 1992.
Connelly et al,Biochemistry, vol. 32, pp 5583-5590 (1993).

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