Substituted quinolines as antitumor agents

A compound of Formula (Ia),

• or a pharmaceutically acceptable salt thereof;
• wherein:
• n is 0 or 1;
• Y is selected from —NH—, —O—, —S—, or —NR7— where R7 is alkyl of 1-6 carbon atoms;
• R5 is cyano, fluoro, chloro or bromo;
• R6 is a group —R8—X—R9 where
• R8 is a divalent cycloalkyl of 3 to 7 carbon atoms, which may be optionally further substituted with one or more alkyl of 1 to 6 carbon atom groups;
• or is a divalent pyridinyl, pyimidinyl, or phenyl ring;
• wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally further substituted with one or more groups selected from halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, and benzoylamino;
• where X is selected from —NH—, —O—, —S—, CH2 or —NR7′— where R7′ is alkyl of 1-6 carbon atoms, and
• R9 is a group (CH2)mR10 where m is 0 or an integer of from 1-3 and R10 is an optionally substituted aryl or optionally substituted cycloalkyl ring of up to 10 carbon atoms, or R10 is a optionally substituted heterocyclic ring or an N-oxide of any nitrogen containing ring;
• R1, R2, R4 are independently selected from hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C1-3alkyl, —NR11R12— (wherein R11 and R12, which may be the same or different each represents hydrogen, or C1-3alkyl), or a group R13—X1—(CH2)x wherein x is 0 or an integer of from 1 to 3, X1 represents a direct bond, —O—, —CH2—, —OC(O)—, —C(O)—, —S—, —SO—, —SO2—, —NR14C(O)—, —NR14C(O)O—, —C(O)NR15—, —C(O)ONR15—, —SO2NR16—, —NR17SO2— —NR18— or —NR18NR18— (wherein R14, R15, R16, R17 and R18 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl)), and R13 is hydrogen, optionally substituted hydrocarbyl, or optionally substituted heterocyclyl;
• and
• R3 is a group of formula R13a—(CH2)y—X1—(CH2)x where R13 a is as defined for R13 above, and X1 and x are as defined above, y is 0 or an integer between 1 and 5, wherein (CH2)y is optionally interposed by an X1 group;
• provided that R13a is selected from phenyl or optionally substituted heterocyclyl and the optional substituents for phenyl and aromatic heterocyclyl rings are selected from:
• C2-5alkenyl, C2-5alkynyl, C1-5alkanoyl, C1-5alkoxycarbonyl, C1-3alkanoylC1-3alkyl, C1-3alkoxyC1-3alkyl, C1-5alkylthio, C1-5alkylsulphanyl, C1-5alkylsulphonyl, N,N-di-C1-5alkylamino, cyanoC1-5alkyl and the optional substituents for non-aromatic heterocyclyl rings further include hydroxyC1-5alkoxy, amino, aminoC1-5alkyl, N—C1-5alkylamino, carboxy, cyano, —CONRzzRzz′— and —NRzz″CORzz′″ (wherein Rzz, Rzz′, Rzz″ and Rzz′″ each independently represent hydrogen, C1-5alkyl or C1-3alkoxyC1-3alkyl).