Acid labile prodrugs

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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Details

514451, 549417, 549418, 549419, A61K 3135, C07D31500

Patent

active

060309970

ABSTRACT:
The invention relates to a pharmaceutically acceptable prodrug which is a covalent conjugate of a pharmacologically active compound and a blocking group, characterized by the presence of a covalent bond which is cleaved at pH values below 7.0. The prodrug may be used in a technique for treating a condition or disease in a mammal related to elevated hydrogen ion concentrations, whereby on administering it to a mammal having such a condition or disease, the pharmacologically active compound is activated selectively within tissues having such elevated hydrogen ion concentrations.

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Sieber, P., et al.: 77. Selektive acidolytische Spaltung von Aralkyloxycarbonyl-Aminoschutzgruppen, in Helv. Chim. Acta. 51 614-622, 1968.
Nyilas, A., et al.: Arenesulfonylethoxycarbonyl-A Set of Amino Protecting Groups for DNA and RNA Synthesis, in Nucleosides Nucleotides, 7 787-793, 1988.
Koole, L.H., et al.: Synthesis of Phosphate Methylated DNA Fragments Using 9-Fluorenylmethoxycarbonyl as Transient Base Protecting Group, in J. Org. Chem. 54 1657-1664, 1989.
Wood C.A., et al.: The Influence of Tobramycin Dosage Regimins on Nephrotoxicity, Ototoxicit,y and Antibacterial Efficacy in a Rat Model of Subcutaneous Abscess, in The Journal of Infectious Disease, 158:1 13-22, 1988.
Lavie, E., et al.: Monoclonal Antibody L6-daunomycin Conjugates Constructed to Release Free Drug at Lower pH of Tumor Tissue, Cancer Immunol Immunother. 33 223-230, 1991.

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