Chemical conjugates of evans blue derivatives and their use as radiotherapy and imaging agents
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsXiaoyuan Chen, Orit Jacobson Weiss
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Abstract
The present invention is directed to a compound of Formula I or Formula III or a pharmaceutically acceptable ester, amide, solvate, or salt thereof, or a salt of such an ester or amide or a solvate of such an ester amide or salt: wherein the definitions R1-R13 and L1-L4 are provided in the disclosure, and wherein R14 is a peptide. The compounds of Formula I may be covalently bonded to a peptide via a linker to provide a compound of Formula III and thereby extend the half-life of the therapeutic compound. The invention is also directed to pharmaceutical compositions of the disclosed compounds, as well as their use in the diagnosis or treatment of diseases.
Claims46
A compound of Formula I or a pharmaceutically acceptable ester, amide, solvate, or salt thereof, or a salt of such an ester or amide or a solvate of such an ester amide or salt,
- wherein:
- R1, R2, R3, R4, R5, R6, R7, R5, R9, R10, and R11 are chosen independently from hydrogen, halogen, hydroxyl, cyano, C1-C6alkoxy, C1-C6haloalkyl, and C1-C6haloalkoxy;
- R12 is hydrogen, C1-C6alkyl, or C1-C6haloalkyl;
- L1 is (CH2)m— wherein m is an integer from 0 to 12, wherein each CH2 can be individually replaced with —O—, —NH(CO)—, or —(CO)—NH—, providing no two adjacent CH2 groups are replaced;
- L2 is —(CH2)m— wherein n is an integer from 0 to 12, wherein each CH2 can be individually replaced with —O—, —NH(CO)—, or —(CO)—NH—, providing no two adjacent CH2 groups are replaced;
- L3 is —(CH2)p— wherein p is an integer from 0 to 12, wherein each CH2 can be individually replaced with —O—, —NH(CO)—, or —(CO)—NH—, providing no two adjacent CH2 groups are replaced;
- and
- R13 is a chelating group.
A compound of Formula III or a pharmaceutically acceptable ester, amide, solvate, or salt thereof, or a salt of such an ester or amide or a solvate of such an ester amide or salt,
- wherein:
- R1, R2, R3, R4, R5, R6, R7, R5, R9, R10, and R11 are chosen independently from hydrogen, halogen, hydroxyl, cyano, C1-C6alkoxy, C1-C6haloalkyl, and C1-C6haloalkoxy;
- R12 is hydrogen, C1-C6alkyl, or C1-C6haloalkyl;
- R14 is a peptide;
- L1 is —(CH2)m— wherein m is an integer from 0 to 12, wherein each CH2 can be individually replaced with —O—, —NH(CO)—, or —(CO)—NH—, providing no two adjacent CH2 groups are replaced;
- L2 is —(CH2)n— wherein n is an integer from 0 to 12, wherein each CH2 can be individually replaced with —O—, —NH(CO)—, or —(CO)—NH—, providing no two adjacent CH2 groups are replaced;
- L3 is —(CH2)p— wherein p is an integer from 0 to 12, wherein each CH2 can be individually replaced with —O—, —NH(CO)—, or —(CO)—NH—, providing no two adjacent CH2 groups are replaced;
- and
- L4 is —(CH2)q— wherein q is an integer from 0 to 12, wherein each CH2 can be individually replaced with —O—, —NH(CO)—, or —(CO)—NH—, providing no two adjacent CH2 groups are replaced;
- and
- R13 is a chelating group.
Dependencies are inferred from the claim text.