| abstract |
The present invention relates to a specific cyclic amine derivative of the formula 1, a CCR-3 receptor antagonist, a pharmaceutical composition comprising the same, a method of using the compound, and a method of preparing the compound:n n n n n n n n n n In this formula,n n n T and U are both nitrogen, or one of T and U is nitrogen and the other is carbon;n n n R 1 and R 2 are each independently hydrogen or alkyl;n n n n is an integer of 0 to 2, provided that when n is 0, one of T and U is carbon;n n n m is an integer from 0 to 3;n n n Ar and Ar 1 are each independently aryl or heteroaryl;n n n F is alkylene, alkenylene or a bond, with the proviso that T and U are nitrogen and F is alkylene renil when R 4 is not an aryl;n n n R is each independently hydrogen or alkyl, or R forms a carbocycle or heterocycle with one of R < 3 > and R < 4 >n n n R 3 and R 4 are each independently (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-substituted or disubstituted amino, aryl, aralkyl, aryloxy, aralkyl Heteroaryl, heteroaryloxy or heteroaralkyloxy, provided that both R 3 and R 4 are not hydrogen, or (ii) R 3 and R 4 together with the carbon atoms to which they are attached form a Form a carbocycle or heterocycle;n n n E is -C (O) N (R 5 ) -, -SO 2 N (R 5) -, -N (R 6) C (O) N (R 5) -, -N (R 6) SO 2 N (R 5) -, -N ( R 6) C (S) N (R 5) -, -N (R 6) C (O) -, -N (R 6) C (O) O-, -OC (O) N (R 6 ) - or -N (R 6 ) SO 2 -n n n R 5 is selected from the group consisting of hydrogen, alkyl, acyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, heteroaryl, heteroaralkyl, heterocyclylalkyl, heteroalkyl or - (O) -Z wherein Z is selected from the group consisting of alkyl, haloalkyl, alkoxy, haloalkyloxy, hydroxy, amino, mono-or disubstituted amino, aryl, aralkyl, aryloxy, aralkyloxy, heteroaryl, heteroaryloxy Or (ii) R 5 is taken together with one of R 3 and R 4 and the carbon atoms to which they are attached to form a heterocycloamino group;n n n R 6 is (i) hydrogen, alkyl, acyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkyl, alkenyl, heteroaryl, heteroaralkyl, heterocyclylalkyl, heteroalkyl, or - (alkylene ) -C (O) -Z wherein Z is selected from the group consisting of alkyl, haloalkyl, alkoxy, haloalkyloxy, hydroxy, amino, monosubstituted or disubstituted amino, aryl, aralkyl, aryloxy, aralkyloxy, heteroaryl, Heteroaryloxy, or heteroaralkyloxy);n n n However, T is nitrogen and E is -C (O) N (R 5 ) -, -SO 2 N (R 5) -, -N (R 6) C (O) N (R 5) -, -N ( R 6 ) SO 2 N (R 5 ) - or -N (R 6 ) C (S) N (R 5 ) -, m is greater than 0;n n n Q is -R 7 -WR 8 -;n n n R 7 is an alkylene chain having 1 to 6 carbon atoms;n n n R 8 is an alkylene chain or a bond having 0 to 4 carbon atoms;n n n W is a bond or -C (O) -, -NR 9 -, -O-, -S (O) 0-2 -, C (O) N (R 9) -, -N (R 9) C (O ) -, -N (R 9) SO 2 -, -SO 2 N (R 9) -, -N (R 9) C (O) N (R 9) -, -N (R 9) SO 2 N ( R 9) - and -N (R 9) C (S ) N (R 9) - a group selected from and;n n n R 9 is hydrogen, alkyl, acyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, heteroaryl, heteroaralkyl, heterocycloalkyl, heteroalkyl or - (alkylene) -C O) -Z wherein Z is selected from the group consisting of alkyl, haloalkyl, alkoxy, haloalkyloxy, hydroxy, amino, mono-or disubstituted amino, aryl, aralkyl, aryloxy, aralkyloxy, heteroaryl, heteroaryloxy or Heteroarylalkyloxy);n n n Provided that when T is nitrogen and U is carbon, then W is not -C (O) N (R 9 ) -. |