Cyclic amine derivatives-CCR-3 receptor antagonists

A compound selected from compounds of Formula (I):

• 47
• wherein:
• T and U are both nitrogen;
• or
• one of T and U is —N—and the other is carbon;
• or
• one of T and U is —(N+R10)—X and the other is carbon where R10 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, amidoalkyl, sulfonylaminoalkyl, or aralkyl and X is a pharmaceutically acceptable counterion provided that n is 1;
• R1 and R2 are, independently of each other, hydrogen or alkyl;
• n is an integer from 0 to 2, provided that when n is 0, either T or U is carbon;
• m is an integer from 0 to 3;
• Ar and Ar1 are, independently of each other, aryl or heteroaryl;
• F is alkylene, alkenylene or a bond, provided that when T and U are nitrogen and F is alkylene, then R4 is not aryl.
• Each R is independently hydrogen or alkyl, or R together with either R3 or R4 and the atoms to which they are attached form a carbocycle or a heterocycle;
• R3 and R4 are, independently of each other, selected from:
• (i) hydrogen, alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heteroalkyl, cyano or -(alkylene)-C(O)-Z where Z is alkyl, haloalkyl, alkoxy, haloalkyloxy, hydroxy, amino, mono- or disubstituted amino, aryl, aralkyl, aryloxy, aralkyloxy, heteroaryl, heteroaryloxy or heteroaralkyloxy, provided that when T and U are both nitrogen or one of T and U is —N—and the other is carbon, then both R3 and R4 are not hydrogen;
• or
• (ii) R3 and R4 together with the carbon atom to which they are attached form a carbocycle or a heterocycle;
• E is —C(O)N(R5)—, —SO2N(R5)—, —N(R6)C(O)N(R5)—, —N(R6)SO2N(R5)—, —N(R6)C(S)N(R5)—, —N(R6)C(O)—, —N(R6)C(O)O—, —OC(O)N(R6)—or —N(R6)SO2—wherein:
• R5 is:
• (i) hydrogen, alkyl, acyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, heteroaryl, heteroaralkyl, heterocyclylalkyl, heteroalkyl, or -(alkylene)-C(O)-Z where Z is alkyl, haloalkyl, alkoxy, haloalkyloxy, hydroxy, amino, mono- or disubstituted amino, aryl, aralkyl, aryloxy, aralkyloxy, heteroaryl, heteroaryloxy or heteroaralkyloxy;
• or
• (ii) R5 together with either R3 or R4 and the atoms to which they are attached forms a heterocycloamino group;
• and
• R6 is hydrogen, alkyl, acyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, heteroaryl, heteroaralkyl, heterocyclylalkyl, heteroalkyl, or -(alkylene)-C(O)-Z where Z is alkyl, haloalkyl, alkoxy, haloalkyloxy, hydroxy, amino, mono- or disubstituted amino, aryl, aralkyl, aryloxy, aralkyloxy, heteroaryl, heteroaryloxy or heteroaralkyloxy,
• provided that when T is nitrogen and E is —C(O)N(R5)—, —SO2N(R5)—, —N(R6)C(O)N(R5)—, —N(R6)SO2N(R5)—or —N(R6)C(S)N(R5)—, then m>0;
• Q is —R7—W—R8—wherein:
• R7 is an alkylene chain of between 1-6 carbon atoms inclusive;
• R8 is a bond or an alkylene chain of between 1-4 carbon atoms inclusive;
• W is a bond or a group selected from —C(O)—, —NR9—, —O—, —S(O)0.2—, —C(O)N(R9)—, —N(R9)C(O)—, —N(R9)SO2—, —SO2N(R9)—, —N(R9)C(O)N(R9)—, —N(R9)SO2N(R9)—or —N(R9)C(S)N(R9)—wherein:
• R9 is hydrogen, alkyl, acyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, heteroaryl, heteroaralkyl, heterocycloalkyl, heteroalkyl, or -(alkylene)-C(O)-Z where Z is alkyl, haloalkyl, alkoxy, haloalkyloxy, hydroxy, amino, mono- or disubstituted amino, aryl, aralkyl, aryloxy, aralkyloxy, heteroaryl, heteroaryloxy or heteroaralkyloxy, provided that when T is nitrogen and U is carbon then W is not —C(O)N(R9)—, and prodrugs, individual isomers, mixtures of isomers and pharmaceutically acceptable salts thereof.