Cysteinyl leukotriene antagonists

A compound of formula (Ia), or the pharmaceutically acceptable salt thereof,

• wherein,
• R1, R2 and R3 are independently selected from the group consisting of hydrogen, halogen, —OH, —CN, —NO2, —NH2, —C1-10 alkyl, —C3-10 cycloalkyl, —O—C1-8 alkyl, —O—C1-8 alkyl (alkoxy), —O—C3-8 cycloalkyl (cycloalkoxy), —S—C1-8 alkyl (thioalkoxy), —C(O)—C1-8 alkyl, —COOH, —C(O)NH2, —C(O)NH—C1-8 alkyl, —C(O)N(C1-8 alkyl)2, —C(O)O—C1-8 alkyl, —C1-8 haloalkyl (haloalkoxy), —C3-8 alkenyl, —C3-8 alkynyl, —OC(O)—NH2, —OC(O)—NH(C1-8 alkyl), —OC(O)—N(C1-8 alkyl)2, —NH(C1-8 alkyl), —N(C1-8 alkyl)2, —NH—SO2—C1-8 alkyl, —N(C1-8 alkyl)-SO2—C1-8 alkyl, —NH—C(O)—(C1-8 alkyl), —N(C1-8 alkyl)-C(O)—(C1-8 alkyl), —NH—C(O)O—C1-8 alkyl, —N(C1-8 alkyl)-C(O)O—C1-8 alkyl, —NH—C(O)—NH2, —NH—C(O)—NH(C1-8 alkyl), —N(C1-8 alkyl)-C(O)—NH(C1-8 alkyl), —N(C1-8 alkyl)-C(O)—N(C1-8 alkyl)2, —NH—C(O)—NH—SO2—C1-8 alkyl, —N(C1-8 alkyl)-C(O)—NHSO2—C1-8 alkyl, —N(C1-8 alkyl)-C(O)—N(C1-8 alkyl)-SO2—C1-8 alkyl, —S—C1-8 alkyl, —S(O)—C1-8 alkyl, —SO2—C1-8 alkyl, —S-aryl, —S(O)-aryl, SO2-aryl, —SO2NH2, —SO2NH—(C1-8 alkyl), —SO2N(C1-8 alkyl)2;
• W represents a group selected from —CH═ or —N═;
• X represents a group selected from —CH═CH—, —S—, or —N═CH—;
• Y represents a group selected from —CH═CH— or —C≡C—;
• A is a group selected from hydrogen, —OH, —OR, —SR, —O(CH2)n aryl, —O(CH2)n heteroaryl, —OCOR, —OCO-aryl, —SCOR, —SCO-aryl, —NRR′, —NRCOR′, —NRCO-aryl, —NRCO-aryl-COOR, —NRCH2ArCOOR, —NHCH2(CR,R′)OH, —NHCOCH2 heteroaryl, —NHCOCH2(CR,R′)CH2COOR, —NHCOCH2(P)-aryl-COOR, —NHCOCH2NRR′, —NRSO2R′, —NRSO2-aryl, —NRCONRR′, —NRCONR′-aryl, —NRCOCH2-aryl-COOR′, —NRPO(OR′)(OH);
• with a proviso that when A is —OR or —SR, then is P is selected from —O—, —S— or —NR— and when A is —NR—, P is selected from —O—, —S—, —NR— or —CH2—;
• P is selected from the group consisting of —O—, —S—, —CH2— and —NR—;
• or P may form a —CH═CH— moiety with the adjacent carbon atom;
• Q is a group selected from hydrogen, —CH3, —CF3, OR, —COOR, —CONRR′, —CR═CR—COOR′;
• —OCH2 aryl-COOR, —CH2O-aryl-COOR, —CONHSO2R, —CONHSO2 aryl, OCH2CONRR′, —NHSO2R, —NHSO2 aryl, —NHSO2NHR, —SO2NHR, —SO2NH aryl, —NHCOR, —NHCO(CRR′)—COOR, —C(R,R′)—COOR, tetrazole, —C(R,R′)OH, —C(R,R′)CONRR′, —CH2NRR′ or —OCH2C(R,R′)OH;
• R and R′ are independently selected from the group consisting of hydrogen, —C1-6 alkyl, —C3-6 cycloalkyl, —C1-3 alkyl (cycloalkyl), —C3-6 alkenyl and —C3-6 alkynyl or, R and R′ along with the atom to which they are attached, together can form a substituted or unsubstituted 5 to 8 membered cyclic ring;
• ‘n’ is an integer selected from 1, 2 or 3;
• ‘m’ is an integer selected from 0 to 4, both inclusive;
• with the proviso that when P is —CH2—, then A is —NR—.

A compound of formula (Ib), or the pharmaceutically acceptable salt thereof,

• wherein,
• R1, R2 and R3 are independently selected from the group consisting of hydrogen, halogen, —OH, —CN, —NO2, —NH2, —C1-10-alkyl, —C3-10 cycloalkyl, —O—C1-8 alkyl (alkoxy), —O—C3-8 cycloalkyl (cycloalkoxy), —S—C1-8 alkyl (thioalkoxy), —C(O)—C1-8 alkyl, —COOH, —C(O)NH2, —C(O)NH—C1-8 alkyl, —C(O)N(C1-8 alkyl)2, —C(O)O—C1-8 alkyl, —C1-8 haloalkyl (haloalkoxy), —C3-8 alkenyl, —C3-8 alkynyl, —OC(O)—NH2, —OC(O)—NH(C1-8 alkyl), —OC(O)—N(C1-8 alkyl)2, —NH(C1-8 alkyl), —N(C1-8 alkyl)2, —NH—SO2—C1-8 alkyl, —N(C1-8 alkyl)-SO2—C1-8 alkyl, —NH—C(O)—(C1-8 alkyl), —N(C1-8 alkyl)-C(O)—(C1-8 alkyl), —NH—C(O)O—C1-8 alkyl, —N(C1-8 alkyl)-C(O)O—C1-8 alkyl, —NH—C(O)—NH2, —NH—C(O)—NH(C1-8 alkyl), —N(C1-8 alkyl)-C(O)—NH(C1-8 alkyl), —N(C1-8 alkyl)-C(O)—N(C1-8 alkyl)2, —NH—C(O)—NH—SO2—C1-8 alkyl, —N(C1-8 alkyl)-C(O)—NHSO2—C1-8 alkyl, —N(C1-8 alkyl)-C(O)—N(C1-8 alkyl)-SO2—C1-8 alkyl, —S—C1-8 alkyl, —S(O)—C1-8 alkyl, —SO2—C1-8 alkyl, —S-aryl, —S(O)-aryl, SO2-aryl, —SO2NH2, —SO2NH—(C1-8 alkyl), —SO2N(C1-8 alkyl)2;
• W represents a group selected from —CH═ or —N═;
• X represents a group selected from —CH═CH—, —S—, or —N═CH—;
• Y represents a group selected from —CH═CH— or —C≡C—;
• A and B are independently selected from —OR′, —SR, —NRR′ or —NRCOR′;
• or, A and B together can form a substituted or unsubstituted 5 to 8 membered cyclic ring containing at least two heteroatoms selected from oxygen and sulfur;
• or, A and B together represent group consisting of C═O, C═S, C═N(OR) or C═NNRR′;
• P is selected from the group consisting of —O—, —S—, —CH2— and —NR—;
• or P may form a —CH═CH— moiety with the adjacent carbon atom;
• Q is a group selected from hydrogen, —CH3, —CF3, OR, —COOR, —CONRR′, —CR═CR—COOR′;
• —OCH2 aryl-COOR, —CH2O-aryl-COOR, —CONHSO2R, —CONHSO2 aryl, —OCH2CONRR′, —NHSO2R, —NHSO2 aryl, —NHSO2NHR, —SO2NHR, —SO2NH aryl, —NHCOR, —NHCO(CRR′)—COOR, —C(R,R′)—COOR, tetrazole, —C(R,R′)OH, —C(R,R′)CONRR′, —CH2NRR′ or —OCH2C(R,R′)OH;
• R and R′ are independently selected from the group consisting of hydrogen, —C1-6 alkyl, —C1-6 cycloalkyl, —C1-3 alkyl (cycloalkyl), —C3-6 alkenyl and —C3-6 alkynyl or, R and R′ along with the atom to which they are attached, together can form a substituted or unsubstituted 5 to 8 membered cyclic ring;
• ‘n’ is an integer selected from 1, 2 or 3;
• ‘m’ is an integer selected from 0 to 4, both inclusive;
• with the proviso that when P is —CH2—, then A and B both represent groups connected to carbon through heteroatom.

A compound of formula (Ic), or the pharmaceutically acceptable salt thereof,

• wherein,
• R1 and R2 are independently selected from the group consisting of hydrogen, halogen, 20-OH, —CN, —NO2, —NH2, —C1-10-alkyl, —C3-10 cycloalkyl, —O—C1-8 alkyl (alkoxy), —O—C3-8 cycloalkyl (cycloalkoxy), —S—C1-8 alkyl (thioalkoxy), —C(O)—C1-8 alkyl, —COOH, —C(O)NH2, C(O)NH—C1-8 alkyl, —C(O)N(C1-8 alkyl)2, —C(O)O—C1-8 alkyl, —C1-8 haloalkyl (haloalkoxy), —C2-8 alkenyl, —C2-8 alkynyl, —OC(O)—NH2, —OC(O)—NH(C1-8 alkyl), —OC(O)—N(C1-8 alkyl)2, —NH2, —NH(C1-8 alkyl), —N(C1-8 alkyl)2, —NH—SO2—C1-8 alkyl, —N(C1-8 alkyl)-SO2—C1-8 alkyl, —NH—C(O)—(C1-8 alkyl), —N(C1-8 alkyl)-C(O)—(C1-8 alkyl), —NH—C(O)O—C1-8 alkyl, —N(C1-8 alkyl)-C(O)O—C1-8 alkyl, —NH—C(O)—NH2, —NH—C(O)—NH(C1-8 alkyl), —N(C1-8 alkyl)-C(O)—NH(C1-8 alkyl), —N(C1-8 alkyl)-C(O)—N(C1-8 alkyl)2, —NH—C(O)—NH—SO2—C1-8 alkyl, —N(C1-8 alkyl)-C(O)—NHSO2—C1-8 alkyl, —N(C1-8 alkyl)-C(O)—N(C1-8 alkyl)-SO2—C1-8 alkyl, —S—C1-8 alkyl, —S(O)—C1-8 alkyl, —SO2—C1-8 alkyl, —S-aryl, —S(O)-aryl, SO2-aryl, —SO2NH2, —SO2NH—(C1-8 alkyl), —SO2N(C1-8 alkyl)2;
• W represents a group selected from —CH═ or —N═;
• X represents a group selected from —CH═CH—, —S—, or —N═CH—;
• Y represents a group selected from —CH═CH— or —C≡C—;
• A and B are independently selected from hydrogen, —OR′, —SR, —NRR′ and —NRCOR;
• with a proviso that when B is hydrogen, P is selected from —O—, —S— or —NR—;
• or, A and B together can form a substituted or unsubstituted 5 to 8 membered cyclic ring containing at least two heteroatoms selected from oxygen and sulfur;
• or, A and B together represent group consisting of C═O, C═S, C═N(OR) or C═NNRR′;
• P is selected from the group consisting of —O—, —S—, —CH2— and —NR—;
• or P may form a —CH═CH— moiety with the adjacent carbon atom;
• with a proviso that when B is hydrogen then P is selected from the group consisting of —O—, —S— and —NR—.
• Q is a group selected from hydrogen, —CH3, —CF3, OR, —COOR, —CONRR′, —CR═CR—COOR′;
• —OCH2 aryl-COOR, —CH2O-aryl-COOR, —CONHSO2R, —CONHSO2 aryl, —OCH2CONRR′, —NHSO2R, —NHSO2 aryl, —NHSO2NHR, —SO2NHR, —SO2NH aryl, —NHCOR, —NHCO(CRR′)—COOR, —C(R,R′)—COOR, tetrazole, —C(R,R′)OH, —C(R,R′)CONRR′, —CH2NRR′ or —OCH2C(R,R′)OH;
• R and R′ are independently selected from the group consisting of hydrogen, —C1-6 alkyl, —C3-6 cycloalkyl, —C1-3 alkyl (cycloalkyl), —C3-6 alkenyl and —C3-6 alkynyl or, R and R′ along with the atom to which they are attached, together can form a substituted or unsubstituted 5 to 8 membered cyclic ring;
• ‘n’ is an integer selected from 1, 2 or 3;
• ‘m’ is an integer selected from 0 to 4, both inclusive.