Hydroxyindole carboxylic acid based inhibitors for oncogenic src homology-2 domain containing protein tyrosine phosphatase-2 (shp2)
AssigneeIndiana University Research and Technology Corporation
InventorsZhong-Yin Zhang, Li-Fan Zeng
Life of this patent
Estimating the term…
Abstract
Inhibitors of protein tyrosine phosphatases are disclosed. The inhibitors include hydroxyindole carboxylic acids having a linker and an amine scaffold that are potent inhibitors of Src homology 2-domain containing protein tyrosine phosphatase-2.
Claims20
A hydroxyindole carboxylic;
- acid for inhibiting a protein tyrosine phosphatase, the hydroxyindole carboxylic acid comprising formula (I):
- wherein L1 is selected from the group consisting of a single bond, —(C1-6 alkyl)-, —(C2-6 alkenyl)-, —(C0-6 alkyl)-(C3-6 cycloalkyl)-(C0-6 alkyl)-, o-phenyl, m-phenyl, p-phenyl, a 3-7 member single aromatic or aliphatic ring, an unsubstituted or substituted fused 5-12 member aromatic or aliphatic ring system, wherein the substitution is selected from the group consisting of nitrogen, oxygen and sulfur;
- L2 is selected from the group consisting of a bond,
- wherein n is 0-3;
- and
- R1=NRaRb, wherein Ra or Rb can each independently be selected from the group consisting of hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl;
- unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted fused 5-12 member aromatic or aliphatic ring system, wherein the substitution on the fused 5-12 member aromatic or aliphatic ring system is selected from the group consisting of nitrogen, oxygen and sulfur.
A hydroxyindole carboxylic acid for inhibiting a protein tyrosine phosphatase, the hydroxyindole carboxylic acid comprising formula (II):
- wherein L1 is selected from the group consisting of a single bond, —(C1-6 alkyl)-, —(C2-6 alkenyl)-, —(C0-6 alkyl)-(C3-6 cycloalkyl)-(C0-6 alkyl)-, o-phenyl, m-phenyl, p-phenyl, a 3-7 member single aromatic or aliphatic ring, an unsubstituted or substituted fused 5-12 member aromatic or aliphatic ring system, wherein the substitution is selected from the group consisting of nitrogen, oxygen and sulfur;
- R1=NRaRb, wherein Ra or Rb can each independently be selected from the group consisting of hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl;
- unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted fused 5-12 member aromatic or aliphatic ring system, wherein the substitution on the fused 5-12 member aromatic or aliphatic ring system is selected from the group consisting of nitrogen, oxygen and sulfur.
A hydroxyindole carboxylic acid for inhibiting a protein tyrosine phosphatase, the hydroxyindole carboxylic acid comprising formula (III):
- wherein L1 is selected from the group consisting of a single bond, —(C1-6 alkyl)-, —(C2-6 alkenyl)-, —(C0-6 alkyl)-(C3-6 cycloalkyl)-(C0-6 alkyl)-, o-phenyl, m-phenyl, p-phenyl, a 3-7 member single aromatic or aliphatic ring, an unsubstituted or substituted fused 5-12 member aromatic or aliphatic ring system, wherein the substitution is selected from the group consisting of nitrogen, oxygen and sulfur;
- n is 0-3;
- and
- R1=NRaRb, wherein Ra or Rb can each independently be selected from the group consisting of hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted used 5-12 member aromatic or aliphatic ring system, wherein the substitution on the fused 5-12 member aromatic or aliphatic ring system is selected from the group consisting of nitrogen, oxygen and sulfur.
A hydroxyindole carboxylic acid for inhibiting a protein tyrosine phosphatase, the hydroxyindole carboxylic acid comprising formula (IV):
- wherein R1=NRaRb, wherein Ra or Rb can each independently be selected from the group consisting of hydrogen, unsubstituted or substituted all unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted fused 5-12 member aromatic or aliphatic ring system, wherein the substitution on the fused 5-12 member aromatic or aliphatic ring system is selected from the group consisting of nitrogen, oxygen and sulfur.
A hydroxyindole carboxylic acid for inhibiting a protein tyrosine phosphatase, the hydroxyindole carboxylic acid comprising formula (V):
- wherein R1=NRaRb, wherein Ra or Rb can each independently be selected from the group consisting of hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted fused 5-12 member aromatic or aliphatic ring system, wherein the substitution on the fused 5-12 member aromatic or aliphatic ring system is selected from the group consisting of nitrogen, oxygen and sulfur.
A hydroxyindole carboxylic acid for inhibiting a protein tyrosine phosphatase, the hydroxyindole carboxylic acid comprising formula (VI):
Dependencies are inferred from the claim text.