Bifunctional antifungal agents and methods of treating fungal infection
AssigneesYale University, Merck Sharp & Dohme Corp.
InventorsDAVID A. SPIEGEL, EGOR CHIRKIN, TERRY ROEMER, PHILIPPE NANTERMET
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Abstract
The present invention is directed to bifunctional compounds which are useful in the treatment of fungal infections. The present compounds contains at least one fungal binding moiety (FBM) which is linked to at least one antibody binding moiety (ABM or ABT group) through a linker group, which optionally comprises a connector group. Compounds according to the present invention are useful in the treatment of fungal infections as described herein.
Claims44
A compound according to the chemical structure:
- Wherein each R1 is independently H, C1-C3 alkyl or a group;
- Each R2 is H, a group or a group, with the proviso that at
- least one R2 group is a group;
- Each n′ is independently 1-6;
- Each R3 is independently H, Cl or a group;
- Where RN is H or a C1-C3 alkyl group optionally substituted with one or two hydroxyl groups;
- Each R5 is independently H, CO2RE, SO3H, L-PG or L-ABT;
- RE is H, a C1-C6 alkyl group or a L-ABT group;
- PG is a protecting group;
- Each R4 is independently H, Cl, a L-ABT group or a
- group with the proviso that at least one R4 is a L-ABT group or a group;
- Where RN and n′ are the same as above;
- and
- R1 is H, PG or a L-ABT group;
- Where L is a linker group optionally containing at least one connector group CT;
- and
- ABT is an antibody binding moiety comprising a hapten which is capable of binding to an antibody present in a patient prior to the administration of the compound to the patient, or a pharmaceutically acceptable salt, stereoisomer, enantiomer, solvate or polymorph thereof.
A compound according to the chemical structure:
- Where each R1 and RN is independently H or a C1-C3 alkyl group which is optionally substituted with one or two hydroxyl groups;
- R5 is independently H, SO3H, L-PG or L-ABT;
- L is a linker group containing at least one connector CT group;
- PG is a protecting group;
- ABT is an antibody binding moiety comprising a hapten which is capable of binding to an antibody present in a patient;
- Each n′ is independently 1-6;
- and
- Each R1 is a L-Pg group or a L-ABT group, preferably according to the chemical structure:
- where each n is independently 1-45;
- n″ is 1-10;
- PG is a protecting group and
- ABT is an antibody binding group;
- or
- a pharmaceutically acceptable salt, stereoisomer (a diastereomer or enantiomer), solvate or polymorph thereof.
A compound according to the chemical structure:
- or
- A pharmaceutically acceptable salt, stereoisomer, solvate or polymorph thereof.
A compound according to FIG. 5, scheme 4 hereof, or a pharmaceutically acceptable salt, stereoisomer, solvate or polymorph thereof.
Dependencies are inferred from the claim text.