Acid-cleavable compound

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

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530300, 530350, 540476, 540576, 549 9, 564123, C07H 1524, C07D40300, C07D33700, C07C23300

Patent

active

058745491

ABSTRACT:
A bicyclic, non-aromatic hydrocarbon compound, optionally having one or more N, O or S atoms in the bicyclic skeleton, and having as substituents an acid group and an amido group, which are vicinal and in a syn-position, wherein the amido group is not anilido and the acid group is carboxyl or carboxyl in a form metabolizable to a free carboxyl group, and wherein said bicyclic skeleton is optionally unsaturated, except in the bond between said groups, acid-cleavably links an amide-containing active agent to a targeting agent, which is linked by a linker arm to the bicyclic skeleton.

REFERENCES:
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patent: 5017693 (1991-05-01), Hylarides et al.
Jerry March, Advanced Organic Chemistry, Third Edition, John Wiley & Sons, 1985, New York, pp. 745-758.
I. Pastan and M.C. Willingham, "The Pathway of Endocytosis," in I. Pastan and M.C. Willingham (ed.), Endocytosis, Plenum Press, New York and London, 1985, pp. 1-44.
Biochemistry 1989; 18; pp. 2501-2509; "New Protein Cross-Linking Reagents that are Cleaved by Mild Acid"; Srinivasachar et al.
J. Org. Chem. Soc. 1988, 53, 4130-5139; "Prodrugs Based on Masked Lactones. Cyclization of .tau.-Hydroxy Amides"; Johnson et al.
J. Amer. Chem. Soc. 1988, 110, 6794-6796; "Fast Hydrolysis of an Aliphatic Amide at Neutral pH and Ambient Temperature. A Peptidase Model"; Menger et al.
Biochemistry 1985, 24, 1517-1524; New Heterobifunctional Protein Cross-Linking Reagent that forms an Acid-Labile Link; Blattler et al.
Cancer Research 49, 4373-4384; Aug. 15, 1989; "Acid pH in Tumors and its Potential for Therapeutic Exploitation"; Ian F. Tannock et al.

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