uPAR-uPA interaction inhibitors and methods for treating cancer
View Patent ↗The invention described herein pertains to compounds, compositions and formulations comprising the compounds, and methods for use of the compounds, compositions and/or formulations in the treatment of diseases responsive to the inhibition of uPAR-uPA interactions, such as cancer.
1. A method for imaging or diagnosing a population of pathogenic cells, the method comprising contacting the population with one or more compositions comprising a therapeutically effective amount of one or more compounds of the formula
or a pharmaceutically acceptable salt thereof, wherein
X is NH 2 , alkylamino, dialkylamino, or an optionally substituted nitrogen-containing heterocycle attached at nitrogen;
Y is optionally substituted aryl or optionally substituted heteroaryl; and
R A represents two substituents, each independently selected from the group consisting of hydrogen, halo, hydroxy, amino, thio, carboxylate, sulfinyl, sulfonyl, phosphinyl, phosphonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl, each of which is optionally substituted; or R A is a fused aryl or heteroaryl, each of which is optionally substituted, and measuring a signal from the population.
2. The method of claim 1 , wherein the signal is a fluorescence signal.
3. The method of claim 1 , wherein the measuring step includes determining the red shift of the fluorescent signal.
4. A pharmaceutical composition comprising a therapeutically effective amount of one or more compounds of the formula
or a pharmaceutically acceptable salt thereof, wherein R A is an optionally substituted fused aryl, X is an optionally substituted nitrogen-containing heterocycle attached at nitrogen and Y is an optionally substituted aryl, such that the compound is of the formula
or a pharmaceutically acceptable salt thereof, wherein
X 1 represents five substituents, each independently selected from the group consisting of hydrogen, halo, hydroxy, amino, thio, carboxylate, sulfinyl, sulfonyl, phosphinyl, phosphonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, each of which is optionally substituted;
Y 1 represents five substituents, each independently selected from the group consisting of hydrogen, halo, hydroxy, amino, thio, carboxylate, sulfinyl, sulfonyl, phosphinyl, phosphonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, each of which is optionally substituted; and
R A1 represents four substituents, each independently selected from the group consisting of hydrogen, halo, hydroxy, amino, thio, carboxylate, sulfinyl, sulfonyl, phosphinyl, phosphonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, each of which is optionally substituted.
5. The pharmaceutical composition of claim 4 , wherein, in the one or more compounds, or a pharmaceutically acceptable salt thereof, each X 1 is selected from hydrogen and alkyl; and each Y 1 is selected from hydrogen and carboxylate.
6. The pharmaceutical composition of claim 4 , wherein Y 1 in the one or more compounds, or a pharmaceutically acceptable salt thereof, is a single carboxylate.
7. A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula
or a pharmaceutically acceptable salt thereof.
8. The pharmaceutical composition of claim 4 , wherein the compound is a compound of the formula
or a pharmaceutically acceptable salt thereof.
9. The pharmaceutical composition of claim 4 , wherein the compound is a compound of the formula
or a pharmaceutically acceptable salt thereof.
10. The pharmaceutical composition of claim 4 , wherein the compound is a compound of the formula
or a pharmaceutically acceptable salt thereof.