Small molecule modulators of pantothenate kinases
AssigneeSt. Jude Children's Research Hospital
InventorsLalit Kumar Sharma, Richard E. Lee, Charles O. Rock, Suzanne Jackowski, Mi Kyung Yun, Chitra Subramanian, Jiuyu Liu
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Abstract
The present disclosure relates to chemical compounds that modulate pantothenate kinase (PanK) activity for the treatment of metabolic disorders (such as diabetes mellitus type II), neurologic disorders (such as pantothenate kinase-associated neurodegeneration), pharmaceutical compositions containing such compounds, and their use in treatment. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
Claims9
A method of increasing pantothenate kinase activity in a subject, comprising providing to the subject an effective amount of a compound having a structure represented by a formula:
- or a pharmaceutically acceptable salt thereof,
- wherein A is CH2;
- Q1 is CH, and wherein R2 is selected from —SCH3, C1-C8 acyclic alkyl, C2-C8 acyclic alkenyl, C1-C8 monohaloalkyl, C1-C8 polyhaloalkyl, C1-C8 alkoxyhaloalkyl, cyclopropyl, cyclobutyl, and oxetane, wherein the cyclopropyl, cyclobutyl, and oxetene are optionally substituted with 1, 2, or 3 groups independently selected from —OH, C1-C4 alkyl, and C1-C4 alkoxy;
- or
- Q1 is N, and R2 is selected from halogen, —SCH3, C1-C8 acyclic alkyl, C2-C8 acyclic alkenyl, C1-C8 monohaloalkyl, C1-C8 polyhaloalkyl, C1-C8 alkoxyhaloalkyl, cyclopropyl, cyclobutyl, and oxetane, wherein the cyclopropyl, cyclobutyl, and oxetene are optionally substituted with 1, 2, or 3 groups independently selected from —OH, C1-C4 alkyl, and C1-C4 alkoxy;
- Q2 is a structure selected from:
- each of R3a and R3b is independently selected from hydrogen, halogen, —OH, C1-C4 alkoxy, and C1-C4 alkyl;
- and
- R4 is halogen or —CN.
Dependencies are inferred from the claim text.