Heterocyclic thioesters

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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548533, A61K 3140, C07D20706

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active

057863784

ABSTRACT:
This invention relates to neurotrophic low molecular weight, small molecule heterocyclic thioesters and ketones having an affinity for FKBP-type immunophilins, and their use as inhibitors of the enzyme activity associated with immunophilin proteins, particularly peptidyl-prolyl isomerase, or rotamase, enzyme activity.

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Gold, Bruce G. et al., "Multiple signals underlie the axotomy-induced up-regulation of c-JUN in adult sensory neurons," Neuroscience Letters, 176 (1994) 123-127.
Gold, Bruce G. et al., "Immunosuppressant FK506 Increases the Rate of Axonal Regeneration in Rat Sciatic Nerve," The Journal of Neuroscience, Nov. 1995, 15(11), 7509-7516.
Gold, Bruce G. et al., "The Immunosuppressant FK506 Increases functional recovery and nerve regeneration following peripheral nerve injury," Restorative Neurology and Neuroscience, 6 (1994) 284-296.
Hauske, James R. et al., "Design and Synthesis of Novel FKBP Inhibitors," J. Med. Chem., 1992, 35, pp. 4284-4296.
Holt, Dennis A. et al. "Structure-Activity Studies of Synthetic FKBP Ligands as Peptidyl-Prolyl Isomerase Inhibitors," Bioorganic & Medicinal Chemistry Letters, 1994, vol. 4, No. 2, pp. 315-320.
Snyder, Solomon H. and Sabatini David M., "Immunophilins and the Nervous System," Nature Medicine, 1995, vol. 1, No. 1, pp. 32-37.

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