The United States of America, as Represented by the Secretary, Department of Health and Human Services

Genbin Shi

Xinhua Ji

Gary X Shaw

The disclosure provides linked purine pterin compounds of Formula I that are novel inhibitors of HPPK, a kinase responsible for an essential step in the biosynthesis of folic acid. (Formula I) The variables, e.g., A1-A3, R1-R4, B1-B2, and L1 are defined in the disclosure. These linked purine pterin inhibitors bind to HPPK with high affinity and specificity. Pharmaceutical compositions containing the HPPK inhibitors and methods of treating a bacterial infection in a patient with one or more of the HPPK inhibitors of the disclosure are also provided. 

HPPK inhibitors useful as antibacterial agents

The disclosure provides linked purine pterin compounds and analogs thereof that are novel HPPK inhibitors. The HPPK inhibitors described herein are compounds and the pharmaceutically acceptable salts thereof of general Formula I  The variables, e.g. Ato A, Rto R, L, L, B, and Bare described herein. Compounds and salts of Formula I bind to HPPK with high affinity and specificity. Pharmaceutical compositions containing an HPPK inhibitor of Formula I and methods of treating a bacterial infection in a patient by providing one or more HPPK inhibitors of Formula I to the patient are also provided. Processes and intermediates useful for preparing compounds of Formula I are also provided. Methods of using the disclosed compounds to guide the development of additional novel anti-bacterial agents are also provided.

Linked purine pterin HPPK inhibitors useful as antibacterial agents

The disclosure provides linked purine pterin compounds and analogs thereof that are novel HPPK inhibitors. The HPPK inhibitors described herein are compounds and the pharmaceutically acceptable salts thereof of general Formula I The variables, e.g. Ato A, Rto R, L, L, B, and Bare described herein. Compounds and salts of Formula I bind to HPPK with high affinity and specificity. Pharmaceutical compositions containing an HPPK inhibitor of Formula I and methods of treating a bacterial infection in a patient by providing one or more HPPK inhibitors of Formula I to the patient are also provided. Processes and intermediates useful for preparing compounds of Formula I are also provided. Methods of using the disclosed compounds to guide the development of additional novel anti-bacterial agents are also provided.

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Frederick, MD, United States of America

Genbin Shi