Aminoquinoline Derivatives and Uses Thereof

A method of treating inflammation or inflammation associated disease or disorder in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of Formula (I)-Formula(X) and any pharmaceutically acceptable salt, hydrate, solvate, ester, stereoisomer mixture, or enantiomer thereof, where

• wherein:
• X, Y, and Z are independently CR18, N, O, or S;
• one of Z1 and Z2 is N and the other is CR14;
• R10-R18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• and
• L is a linker
• wherein:
• X and Y are independently CR18, N, O, or S;
• one of Z1 and Z2 is N and the other is CR14;
• R11-R18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• ----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted;
• and
• L is a linker;
• wherein:
• A and B are independently CR18 or N;
• one of Z1 and Z2 is N and the other is CR14;
• R10-R18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• and
• L is a linker;
• wherein:
• X and Z are independently CR18, N, O, or S;
• one of Z1 and Z2 is N and the other is CR14;
• R11-R18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• ----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted;
• and
• L is a linker;
• wherein:
• X, Y, and Z are independently CR18, N, O, or S;
• one of Z1 and Z2 is N and the other is CR14;
• R10-R18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• and
• ----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted;
• wherein:
• X, Y, and Z are independently CR18, N, O, or S;
• R10, R11, R18 and R21-R28 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• ----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted;
• and
• L is a linker;
• wherein:
• X, Y, and Z are independently CR18, N, O, or S;
• one of Z1 and Z2 is N and the other is CR14;
• R10-R22 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted.
• wherein:
• X, Y, and Z are independently CR18, N, O, or S;
• one of Z1 and Z2 is N and the other is CR14;
• R10-R21 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• wherein:
• X, Y, and Z are independently CR18, N, O, or S;
• one of Z1 and Z2 is N and the other is CR14;
• R10-R22 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• wherein:
• R is hydrogen, CH3, Cl, CF3 or CN;
• R1 is cyclic or acyclic amine;
• and
• L is an optionally substituted C2-C30 alkyl, optionally substituted aromatic ring, optionally substituted heteroaryl ring, saturated cyclic ring;
• amino acid, or peptide.

A method for inducing differentiation of a stem cell into a dopaminergic neuron, the method comprising contacting said cell with a compound selected from the group consisting of Formula (I)-Formula(X) in an amount sufficient to cause differentiation of said stem cell, where

• wherein:
• X, Y, and Z are independently CR18, N, O, or S;
• one of Z1 and Z2 is N and the other is CR14;
• R10-R18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• and
• L is a linker
• wherein:
• X and Y are independently CR18, N, O, or S;
• one of Z1 and Z2 is N and the other is CR14;
• R11-R18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• ----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted;
• and
• L is a linker;
• wherein:
• A and B are independently CR18 or N;
• one of Z1 and Z2 is N and the other is CR14;
• R10-R18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• and
• L is a linker;
• wherein:
• X and Z are independently CR18, N, O, or S;
• one of Z1 and Z2 is N and the other is CR14;
• R11-R18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• ----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted;
• and
• L is a linker;
• wherein:
• X, Y, and Z are independently CR18, N, O, or S;
• one of Z1 and Z2 is N and the other is CR14;
• R10-R18 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• and
• ----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted;
• wherein:
• X, Y, and Z are independently CR18, N, O, or S;
• R10, R11, R18 and R21-R28 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• ----- forms a cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted;
• and
• L is a linker;
• wherein:
• X, Y, and Z are independently CR18, N, O, or S;
• one of Z1 and Z2 is N and the other is CR14;
• R10-R22 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted.
• wherein:
• X, Y, and Z are independently CR18, N, O, or S;
• one of Z1 and Z2 is N and the other is CR14;
• R10-R21 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• wherein:
• X, Y, and Z are independently CR18, N, O, or S;
• one of Z1 and Z2 is N and the other is CR14;
• R10-R22 are independently H, linear or branched alkyl, linear or branched alkenyl, linear or branched alkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halogen, trifluoromethyl, alkoxy, nitro, cyano, carbonyl, hydroxyl, phenoxy, amino, alkylamino, thiol, or alkylthio, each of which can be optionally substituted;
• wherein:
• R is hydrogen, CH3, Cl, CF3 or CN;
• R1 is cyclic or acyclic amine;
• and
• L is an optionally substituted C2-C30 alkyl, optionally substituted aromatic ring, optionally substituted heteroaryl ring, saturated cyclic ring;
• amino acid, or peptide.