2,4-substituted pyrrolidine derivatives-CCR-3 receptor antagonists

A compound represented by Formula (Ia):

• 19
• wherein:
• R1 is hydrogen, alkyl, acyl, heteroalkyl, —CONR3R4 (where R3 and R4 are independently hydrogen or alkyl), —COOR5 (where R5 is hydrogen, alkyl or heteroalkyl), or —SO2R6 where R6 is alkyl;
• alk1 is an alkylene chain of 1 to 6 carbon atoms;
• X is —NHCO— or —CONH—;
• Y is —O—(CH2)—, —O—(CH2)2—, —O—(CHCH3)—, —NRb—(CH2)—, —NRb—(CH2)2—, —NRb—(CHCH3)— [where Rb is hydrogen, alkyl, acyl, —CONR7R8 (where R7 and R8 are independently hydrogen or alkyl), —COOR9 (where R9 is hydrogen, alkyl or heteroalkyl), aryl, or aralkyl)], —S(O)n-(CH2)—, —S(O)n-(CH2)2—, or —S(O)n-(CHCH3)— where n is 0 to 2;
• Ar1 is a heteroaryl group or phenyl group wherein the heteroaryl or phenyl group is substituted, in addition to the Ar2 group, with a substituent selected from the group consisting of hydrogen, halo, alkyl, alkoxy, nitro, amido, aminosulfonyl and sulfonylamino;
• Ar2 is aryl;
• alk2 is an alkylene chain of 1 to 6 carbon atoms wherein one of the carbon atoms is optionally replaced by —CO—, —NRc— [where Rc is hydrogen, alkyl, acyl, —CONR10R11 (where R10 and R11 are independently hydrogen or alkyl), —COOR12 (where R12 is hydrogen, alkyl or heteroalkyl), aryl, or aralkyl)] or —S(O)nl- wherein nl is 0 to 2;
• Ar3 is cycloalkyl, aryl or heteroaryl;
• or
• a pharmaceutically acceptable salts thereof.

A compound represented by Formula (Ib):

• 20
• wherein:
• R1 is hydrogen, alkyl, acyl, heteroalkyl, —CONR3R4 (where R3 and R4 are independently hydrogen or alkyl), —COOR5 (where R5 is hydrogen, alkyl or heteroalkyl), or —SO2R6 where R6 is alkyl;
• alk1 is an alkylene chain of 1 to 6 carbon atoms;
• X is —NHCO— or —CONH—;
• Y is:
• (i) —(CH2)—, —(CH2)2—, —(CH2)3—, —(CHCH3)—, —(CHCH3)—(CH2)—, or —(CH2)—(CHCH3)—;
• or
• (iii) —(CH2)—O—, —(CH2)2—O—, —(CHCH3)—O—, —(CH2)—NRb—, —(CH2)2—NRb—, or —(CHCH3)—NRb— [where Rb is hydrogen, alkyl, acyl, —CONR7R8 (where R7 and R8 are independently hydrogen or alkyl), —COOR9 (where R9 is hydrogen, alkyl or heteroalkyl), aryl, or aralkyl)] when X is —CONH—;
• Ar1 is a heteroaryl group or phenyl group wherein the heteroaryl or phenyl group is substituted, in addition to the Ar2 group, with a substituent selected from the group consisting of hydrogen, halo, alkyl, alkoxy, nitro, amido, aminosulfonyl and sulfonylamino;
• Ar2 is aryl;
• alk2 is an alkylene chain of 1 to 6 carbon atoms wherein one of the carbon atoms is optionally replaced by —CO—, —NRc— [where Rc is hydrogen, alkyl, acyl, —CONR10R11 (where R10 and R11 are independently hydrogen or alkyl), —COOR12 (where R12 is hydrogen, alkyl or heteroalkyl), aryl, or aralkyl)] or —S(O)nl- wherein nl is 0 to 2;
• Ar3 is cycloalkyl, aryl or heteroaryl;
• or
• a pharmaceutically acceptable salts thereof.

An intermediate of the Formula (II):

• 21
• wherein:
• R11 is hydrogen or alkoxy;
• R12 is alkoxy;
• R13 is hydrogen or alkyl.