Acid labile prodrugs
OwnerEran Eilat, Rina Arad-Yellininventors
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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.
Claims12
A pharmaceutically acceptable prodrug that is a covalent conjugate of a pharmacologically active compound and at least one blocking group, wherein the covalent bond is reactively labile at a pH value between pH 4.0 and 7.0, having the general formula:
- ##STR11## wherein, RX-denotes a pharmacologically active agent;
- X is selected from the group consisting of O and NH;
- R.sub.1, R.sub.2 and R.sub.3 are independently selected from the group consisting of branched or straight chain alkyl groups comprising 1-18 carbon atoms, aryl groups;
- and
- R.sub.2 and R.sub.3 may be combined to form a cyclic structure;
- Z is selected from the group consisting of OH, NHY, and SH;
- and
- Y is selected from the group consisting of H, R.sub.4, or NH.sub.2, wherein R.sub.4 is selected from the group of lower alkyl and aryl groups.
A pharmaceutically acceptable prodrug that is a covalent conjugate of a pharmacologically active compound and at least one blocking group, wherein the covalent bond is reactively labile at a pH value between pH 4.0 and 7.0, having the general formula:
- ##STR12## wherein, RX-denotes a pharmacologically active agent;
- X is selected from the group consisting of O and NH;
- R.sub.1, R.sub.2 and R.sub.3 are independently selected from the group consisting of branched or straight chain alkyl groups comprising 1-18 carbon atoms, and aryl groups;
- and, R.sub.2 and R.sub.3 may be combined to form a cyclic structure;
- Z is selected from the group consisting of OH, NHY, and SH;
- and
- Y is selected from the group consisting of H, R.sub.4, or NH.sub.2, wherein R.sub.4 is selected from the group of lower alkyl and aryl groups.
A pharmaceutical composition of matter comprising a pharmaceutically acceptable prodrug which is a conjugate of a pharmacologically active compound and at least one blocking group, characterized by the presence of a covalent bond between the blocking group and the active compound that is cleaved at pH values between 4.0 and 7.0, having the general formula:
- ##STR15## wherein, RX-denotes a pharmacologically active agent;
- X is selected from the group consisting of O and NH;
- R.sub.1, R.sub.2 and R.sub.3 are independently selected from the group consisting of branched or straight chain alkyl groups comprising 1-18 carbon atoms, aryl groups;
- and,
- R.sub.2 and R.sub.3 may be combined to form a cyclic structure;
- Z is selected from the group consisting of OH, NHY, and SH;
- and
- Y is selected from the group consisting of H, R.sub.4, or NH.sub.2, wherein R.sub.4 is selected from the group of lower alkyl and aryl groups.
A pharmaceutical composition of matter comprising a pharmaceutically acceptable prodrug which is a conjugate of a pharmacologically active compound and at least one blocking group, characterized by the presence of a covalent bond between the blocking group and the active compound that is cleaved at pH values between 4.0 and 7.0, having the general formula:
- ##STR16## wherein, RX-denotes a pharmacologically active agent;
- X is selected from the group consisting of O and NH;
- R.sub.1, R.sub.2 and R.sub.3 are independently selected from the group consisting of branched or straight chain alkyl groups comprising 1-18 carbon atoms, aryl groups;
- and, R.sub.2 and R.sub.3 may be combined to form a cyclic structure;
- Z is selected from the group consisting of OH, NHY, and SH;
- and
- Y is selected from the group consisting of H, R.sub.4, or NH.sub.2, wherein R.sub.4 is selected from the group of lower alkyl and aryl groups.
A method for treating a condition or disease in a mammal related to elevated hydrogen ion concentration, which comprises administering to a mammal having such condition a pharmaceutically acceptable prodrug, said prodrug being a covalent conjugate of a pharmacologically active compound and a blocking group, wherein the covalent bond is reactively labile at a pH value between pH 4.0 and 7.0, having the general formula:
- ##STR19## wherein, RX-denotes a pharmacologically active agent;
- X is selected from the group consisting of O and NH;
- R.sub.1, R.sub.2 and R.sub.3 are independently selected from the group consisting of branched or straight chain alkyl groups comprising 1-18 carbon atoms, aryl groups;
- and,
- R.sub.2 and R.sub.3 may be combined to form a cyclic structure;
- Z is selected from the group consisting of OH, NHY, and SH;
- and
- Y is selected from the group consisting of H, R.sub.4, or NH.sub.2, wherein R.sub.4 is selected from the group of lower alkyl and aryl groups.
Dependencies are inferred from the claim text.