US 2024/0299554 A1 · PRODRUGS WITH 1-(DISULFANYL)ALKYLOXY-CARBONYL UNITS

Abstract

The invention is in the field of medical sciences. It provides new pharmaceutical methods and preparations. The invention relates to methods for improving the pharmacokinetic, physicochemical or pharmaceutical properties of drugs by converting the drug into a promoiety-containing 1-substituted disulfanylalkyl carbonate, thiocarbamate or carbamate prodrug. In particular, the invention relates to methods for improving the solubility, permeability, stability and/or oral bioavailability of a drug by converting the drug into a promoiety-containing 1-(disulfanylalkyl) carbonate, thiocarbonate or carbamate prodrug. The invention also provides new compositions comprising a drug covalently attached to a promoiety-containing 1-(disulfanylalkyl) carbonate, thiocarbonate or carbamate. More in particular, the invention relates to a method for increasing the oral bioavailability of a drug by covalently attaching a promoiety-containing 1-disulfanylalkyloxycarbonyl unit to a hydroxyl or amine containing drug in which the promoiety contains a 1-O—, 1-S—, 6-O— or 6-S-linked monosaccharide.

Claims16

Dependent claims

A compound according to Formula I or a pharmaceutically acceptable salt thereof:

wherein each solid line represents a covalent bond, wherein H is hydrogen, O is oxygen, C is carbon, S is sulfur, and C═O is a carbonyl group;
wherein R1 is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, and t-butyl, preferably R1 is hydrogen or methyl;
wherein G is an organic structure and [C] represents a carbon atom of G, preferably wherein G[C] is selected from a covalently bound group of saturated and unsaturated, cyclic and noncyclic, aromatic and non-aromatic organic structures containing C and H atoms and optionally containing one or more N, O, F, Cl, Br, I, B, P, and S atoms with the provision that the disulfide is always covalently attached to a primary, secondary or tertiary carbon atom C in G, and preferably with a further provision that this particular carbon atom C does not contain an OH, SH or NH group, a double bonded oxygen or a double bonded sulfur;
wherein DM is a drug moiety and [Z] represents a part of DM and is selected from the group consisting of O, S, and N.

1 more element

A reagent compound according to Formula VIII:

wherein R28 is methyl or 4-tolyl;
wherein R1 is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, and t-butyl, preferably R1 is hydrogen or methyl;
and
wherein R29 is pentafluorophenyl or 4-nitrophenyl.

1 more element

Dependencies are inferred from the claim text.

Prodrugs with 1-(disulfanyl)alkyloxy-carbonyl units

Life of this patent

Prodrugs with 1-(disulfanyl)alkyloxy-carbonyl units

Life of this patent

Abstract

Claims16