Isoxazole analogs as mediators of transcriptional induction of E-cadherin

摘要

In one aspect, the invention relates to N-((arylamino)alkyl)-5-arylisoxazole-3-carboxamide analogs, derivatives thereof, and related compounds, which are useful as mediators of transcriptional induction of E-cadherin; synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders associated with E-cadherin activity using the compounds and compositions. 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.

主权项

1. A compound having a structure represented by a formula: wherein m is an integer selected from 3 and 4; wherein n is an integer selected from 0 and 1; wherein Q is selected from NR5, O, and S;
wherein R5, when present, is selected from hydrogen and C1-C4 alkyl; wherein each of R1 and R2 is independently selected from hydrogen and C1-C4 alkyl; wherein R3 is selected from hydrogen and (CHR6)pAr2;
wherein p, when present, is an integer selected from 0 and 1;wherein R6, when present, is selected from hydrogen and C1-C4 alkyl; wherein Ar2, when present, is selected from aryl and heteroaryl, and Ar2 is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —OH, —CN, —N3, —NH2, —C(O)(C1-C4 alkyl), C1-C4 alkyl, C1-C4 alkoxy, C1-C4 monohaloalkyl, C1-C4 polyhaloalkyl, C1-C4 alkylamino, and C1-C4 dialkylamino; wherein R4 is selected from CH2Ar3 and Ar4;
wherein Ar3, when present, is selected from aryl and heteroaryl, and Ar3 is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —OH, —CN, —N3, —NH2, —C(O)(C1-C4 alkyl), C1-C4 alkyl, C1-C4 alkoxy, C1-C4 monohaloalkyl, C1-C4 polyhaloalkyl, C1-C4 alkylamino, and C1-C4 dialkylamino, provided that when R2 is hydrogen then Ar3, when present, cannot be a structure selected from: wherein Ar4, when present, is selected from aryl and heteroaryl, and Ar4 is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —OH, —CN, —N3, —NH2, —C(O)(C1-C4 alkyl), C1-C4 alkyl, C1-C4 alkoxy, C1-C4 monohaloalkyl, C1-C4 polyhaloalkyl, C1-C4 alkylamino, and C1-C4 dialkylamino, provided that when R2 is hydrogen then Ar4, when present, cannot be a structure selected from:and
wherein Ar1, when present, is selected from aryl and heteroaryl, and wherein Ar1, when present, is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —OH, —CN, —N3, —NH2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 monohaloalkyl, C1-C4 polyhaloalkyl, C1-C4 alkylamino, and C1-C4 dialkylamino, or a pharmaceutically acceptable salt thereof.