Hydroxylamine-based bcr-abl1 inhibitors for treatment of cancer
AssigneeUniversity of Georgia Research Foundation, Inc.
InventorsDavid CRICH, Jarvis Dawson HILL
Life of this patent
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Abstract
In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, the disclosure, in one aspect, relates to scaffold molecules that inhibit breakpoint cluster region, chromosome 22 (BCR) and Abelson proto-oncogene 1, chromosome 9 (ABL1) in a subject, methods of making same, pharmaceutical compositions comprising same, and methods of treating cancers involving aberrant BCR and ABL1 activity. In another aspect, the compounds described herein can evade P-gp-mediated efflux in a subject, which makes the compounds effective in treating a Philadelphia chromosome positive (Ph+) leukemia.
Claims43
A compound having structure I or the pharmaceutically acceptable salt thereof
- wherein
- R1 is hydrogen, a substituted or unsubstituted linear or branched alkyl group, a substituted or unsubstituted cycloalkyl group or heterocycloalkyl group, or a substituted or unsubstituted aryl group;
- n is an integer from 1 to 5, where each R2 is independently hydrogen, a substituted or unsubstituted linear or branched alkyl group, a substituted or unsubstituted cycloalkyl group or heterocycloalkyl group, a substituted or unsubstituted aryl group, a halide, or an alkoxy group;
- m is an integer from 1 to 3, where each R3 is independently hydrogen, a substituted or unsubstituted linear or branched alkyl group, a substituted or unsubstituted cycloalkyl group or heterocycloalkyl group, a substituted or unsubstituted aryl group, a halide, or an alkoxy group;
- o is an integer from 1 to 10;
- p is 1 or 2;
- V is N or CH;
- W is N or CH;
- X is O or NR4, wherein R4 is hydrogen, a substituted or unsubstituted linear or branched alkyl group, a substituted or unsubstituted cycloalkyl group or heterocycloalkyl group, or a substituted or unsubstituted aryl group;
- Y is O, NR5, or CR6aR6b, wherein R5 is hydrogen, deuterium, a substituted or unsubstituted linear or branched alkyl group, a substituted or unsubstituted cycloalkyl group or heterocycloalkyl group, or a substituted or unsubstituted aryl group, and
- R6a and R6b are independently hydrogen, deuterium, a substituted or unsubstituted linear or branched alkyl group, a substituted or unsubstituted cycloalkyl group or heterocycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted amino group;
- R7a, R7b, R7c, R7d, R7e, R7f, R7g, and R7h are independently hydrogen, deuterium, or a substituted or unsubstituted alkyl group;
- R3 is cyano;
- and
- each Z is independently hydrogen or deuterium.
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Dependencies are inferred from the claim text.