Substituted 2, 4-diamino-quinoline derivatives for use in the treatment of proliferative diseases

A compound having a structure represented by formula (I):

• wherein
• L1 is a single bond, or substituted or unsubstituted alkylene, substituted or unsubstituted alkenylene, or substituted or unsubstituted alkynylene;
• L2 is a single bond or carbonyl;
• R1 is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
• R2 is hydroxyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted alkoxycarbonylamino, substituted or unsubstituted aryloxycarbonylamino, substituted or unsubstituted heteroaryloxycarbonylamino, substituted or unsubstituted alkylaminocarbonylamino, substituted or unsubstituted arylaminocarbonylamino, substituted or unsubstituted heteroarylaminocarbonylamino, or NR5R6 wherein each R5 and R6 is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heterocycloalkyl;
• Q1, Q2, Q3 and Q4 are each independently H, hydroxyl, halo, amino, nitro, thiol, carboxyl, cyano, azido, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted sulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted dialkylamino, substituted or unsubstituted arylamino, substituted or unsubstituted heteroarylamino, substituted or unsubstituted acyl, substituted or unsubstituted acylamino, substituted or unsubstituted aminocarbonyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted aryloxycarbonyl, substituted or unsubstituted heteroaryloxycarbonyl, substituted sulfo, substituted sulfonyl, substituted sulfinyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted sulfonylamino, substituted or unsubstituted aminocarbonylamino, substituted or unsubstituted aminocarbonyloxy, substituted or unsubstituted alkoxycarbonylamino, substituted or unsubstituted aryloxycarbonylamino, or substituted or unsubstituted heteroaryloxycarbonylamino;
• R3a is halo, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted aryloxycarbonyl, substituted or unsubstituted heteroaryloxycarbonyl, or substituted or unsubstituted aminocarbonyl;
• each R3b is independently H, hydroxyl, halo, azido, amino, nitro, thiol, cyano, carboxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, or substituted or unsubstituted heterocycloalkyl;
• R3c is H;
• W is optionally present and if present is H, hydroxyl, halo, azido, amino, nitro, thiol, cyano, carboxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted sulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted dialkylamino, substituted or unsubstituted arylamino, substituted or unsubstituted heteroarylamino, substituted or unsubstituted acyl, substituted or unsubstituted acylamino, substituted or unsubstituted aminocarbonyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted aryloxycarbonyl, substituted or unsubstituted heteroaryloxycarbonyl, substituted sulfo, substituted sulfonyl, substituted sulfinyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted sulfonylamino, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted aminocarbonylamino, substituted or unsubstituted aminocarbonyloxy, substituted or unsubstituted alkoxycarbonylamino, substituted or unsubstituted aryloxycarbonylamino, or substituted or unsubstituted heteroaryloxycarbonylamino;
• m is 0, 1, 2, 3, or 4;
• if m is 0, then d is independently 0, 1 or 2;
• if m is 1, then d is independently 0, 1, 2 or 3;
• if m is 2, then d is independently 0, 1, 2, 3 or 4;
• if m is 3, then d is independently 0, 1, 2, 3, 4 or 5 or if m is 4 then d is independently 0, 1, 2, 3, 4, 5 or 6;
• or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, or an isotopic variant, tautomer, or stereoisomer thereof.

A compound selected from the group consisting of:

• (2S) 2-(4-chlorobenzylamino)-4-[2-(hydroxymethyl)pyrrolidin-1-yl]quinoline,
• (2S) 2-(4-chlorobenzylamino)-4-[2-(methoxymethyl)pyrrolidin-1-yl]quinoline,
• (2R)-2-(4-chlorobenzylamino)-4-[2-(hydroxymethyl)-pyrrolidin-1-yl]-quinoline,
• 2-(4-chlorobenzylamino)-4-(4-hydroxypiperidin-1-yl)quinoline,
• 2-(4-chlorobenzylamino)-4-[4-(iso-propoxy)-piperidin-1-yl]-quinoline,
• 2-(4-chlorobenzylamino)-4-(4-phenoxypiperidin-1-yl)-quinoline,
• 2-(4-chlorobenzylamino)-4-[4-(m-tolyloxy)piperidin-1-yl]quinoline,
• 2-(4-chlorobenzylamino)-4-[4-(pyridin-4-yloxy)piperidin-1-yl]quinoline,
• 2-(4-chlorobenzylamino)-4-[4-(pyrazin-2-yloxy)piperidin-1-yl]quinoline,
• (3R) 2-(4-chlorobenzylamino)-4-(3-hydroxypyrrolidin-1-yl)quinoline,
• (3R) 2-(4-chlorobenzylamino)-4-[3-(phenoxy)pyrrolidin-1-yl]quinoline,
• (3R) 2-(4-chlorobenzylamino)-4-[3-(pyridin-2-yloxy)pyrrolidin-1-yl]quinoline,
• (3S) 2-(4-chlorobenzylamino)-4-(3-hydroxypyrrolidin-1-yl)-quinoline,
• (3S) 2-(4-chlorobenzylamino)-4-[3-(pyridin-2-yloxy)pyrrolidin-1-yl]quinoline.
• or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, or an isotopic variant, tautomer, or stereoisomer thereof.