Pyrrole antifungal agents

A pharmaceutical composition comprising (i) a first antifungal agent which is a pyrrole derivative of formula (I) or a pharmaceutically acceptable salt thereof, (ii) a second antifungal agent, and (iii) a pharmaceutically acceptable carrier or diluent:

• wherein:
• R1 represents hydrogen, unsubstituted or substituted C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —COR′ or —SO2(C1-C4 alkyl), or a group -A2, -L2-A2, -L3-A2, -A2-L3-A3 or -A4;
• A1 represents a C3-C6 cycloalkyl or an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• A2 and A3 are the same or different and represent C3-C6 cycloalkyl or an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• A4 is an unsubstituted or substituted 5- to 12-membered heterocyclyl group wherein 1 or 2 ring carbon atoms are replaced with a group selected from >C(═O), >S(═O)2, >C(═NOR7), >C═CH2 or >C(—OCH2CH2O—), where R7 is hydrogen or a C1-C4 alkyl group;
• L1 represents a bond, a C1-C6 alkylene group in which none, one, two or three —CH2— groups are independently replaced by —O—, —S— or —NR′—, or a 5- to 12-membered heterocyclyl group;
• L2 represents —NR′—, —O—, —CO—, —OCO—, —OCONR′R″—, —CONR′R″— or —SO2—;
• L3 represents a bond or a C1-C4 alkylene group in which none, one or two —CH2— groups are independently replaced by —O—, —S— or —NR′—;
• n is 1 or 2;
• R6 represents hydrogen or C1-C4 alkyl;
• R5 represents an unsubstituted or substituted group selected from C6-C10 aryl, a 5- to 12-membered heterocyclyl group, C1-C8 alkyl and C3-C6 cycloalkyl, halogen or a group of formula —B1-B2 or —B3;
• B1 represents an unsubstituted or substituted C6-C10 aryl group;
• B2 represents an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• B3 is an unsubstituted or substituted 5- to 12-membered heterocyclyl group where 1 or 2 ring carbon atoms are replaced with a group selected from >C(═O), >S(═O)2, >C(═NOR11), >C═CH2 or >C(—OCH2CH2O—), where R11 is hydrogen or a C1-C4 alkyl group;
• R2 and R3 independently represent C6-C10 aryl, a 5- to 12-membered heterocyclyl group, C3-C6 cycloalkyl, hydrogen, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C6 cycloalkyl, —OR′, —SR′, —SOR′, —SO2R′, —SO2NR′R″, —SO3H, —NR′R″, —NR′COR′, —CO2R′, —CONR′R″, —COR′, —OCOR′, —CF3, —NSO2R′ or —OCONR′R″, or a group (C1-4) alkyl-A5, wherein none, one or two —CH2— groups are independently replaced by —O—, —S— or —NR'- and wherein AS represents C6-10 aryl or a 5- to 12-membered heterocyclyl group;
• or R2 and R3 together with the ring atoms to which they are bonded form a 5- to 7-membered, saturated or partially saturated ring containing a nitrogen atom from the adjacent pyrrole ring, and optionally one or two further heteroatoms selected from N, O and S, with the proviso that R2 and R3 do not form, together with the pyrrole ring to which they are bonded, tetrahydroindolizine ring;
• R4 represents hydrogen, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —OR′, —CONR′R″, —COR′, —CN, —NO2, —NR′R″, CF3, —Y—Z, C6-C10 aryl, or 5- to 12-membered heterocyclyl group, or a group of formula -Alk6-L5-A12, where Alk6 is a C1-C4 alkylene group, L5 is a group of formula —O—C(═O)—, —C(═O)— or —NR13—C(═O)— and R13 is hydrogen or C1-C4 alkyl, and A12 is an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• Y represents C1-C8 alkylene, C2-C8 alkenylene or C2-C8 alkynylene;
• Z represents halogen, C3-C6 cycloalkyl, —OR′, —SR′, —SOR′, —SO2R′, —SO2NR′R″, —SO3H, —NR′R″, —NR′COR′, —NO2, —CO2R′, —CONR′R″, —COR′, —OCOR′, —CN, —CF3, —NSO2R′, —OCONR′R″ or —CR′═NOR″;
• and
• R′ and R″ independently represent hydrogen, C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl;
• wherein an alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclyl group or moiety can be substituted or unsubstituted;
• and wherein:
• a substituted alkyl, alkenyl or alkynyl group or moiety is a said alkyl, alkenyl or alkynyl group or moiety which is substituted with up to three substituents selected from halogen, hydroxy, amino, (C1-C4 alkyl)amino, di(C1-C4 alkyl)amino, C1-C4 alkoxy, —S(C1-C4 alkyl), —CO2H, —CO2(C1-C4 alkyl), phenyl, 5- or 6-membered heterocyclyl, CONRb′Rb″ and NRb′CO(C1-C4 alkyl) where Rb′ and Rb″ are the same or different and represent hydrogen or unsubstituted C1-C4 alkyl, wherein the substitutents on a substituted alkyl, alkenyl or alkynyl group or moiety are themselves unsubstituted or, the case of C1-C4 alkoxy substituents, may be further substituted with unsubstituted methoxy or ethoxy;
• a substituted cycloalkyl group is a said cycloalkyl group which is substituted with up to three substituents selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Z and —Y—Z;
• a substituted aryl or heterocyclyl group or moiety is a said aryl or heterocyclyl group or moiety which is substituted with up to three substituents selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Z and —Y—Z.

A kit comprising, in admixture or in separate containers, a first antifungal agent which is a pyrrole derivative of formula (I) or a pharmaceutically acceptable salt thereof and a second antifungal agent:

• wherein:
• R1 represents hydrogen, unsubstituted or substituted C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —COR′ or —SO2(C1-C4 alkyl), or a group -A2, -L2-A2, -L3-A2, -A2-L3-A3 or -A4;
• A1 represents a C3-C6 cycloalkyl or an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• A2 and A3 are the same or different and represent C3-C6 cycloalkyl or an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• A4 is an unsubstituted or substituted 5- to 12-membered heterocyclyl group wherein 1 or 2 ring carbon atoms are replaced with a group selected from >C(═O), >S(═O)2, >C(═NOR7), >C═CH2 or >C(—OCH2CH2O—), where R7 is hydrogen or a C1-C4 alkyl group;
• L1 represents a bond, a C1-C6 alkylene group in which none, one, two or three —CH2— groups are independently replaced by —O—, —S— or —NR′—, or a 5- to 12-membered heterocyclyl group;
• L2 represents —NR′—, —O—, —CO—, —OCO—, —OCONR′R″—, —CONR′R″— or —SO2—;
• L3 represents a bond or a C1-C4 alkylene group in which none, one or two —CH2— groups are independently replaced by —O—, —S— or —NR′—;
• n is 1 or 2;
• R6 represents hydrogen or C1-C4 alkyl;
• R5 represents an unsubstituted or substituted group selected from C6-C10 aryl, a 5- to 12-membered heterocyclyl group, C1-C8 alkyl and C3-C6 cycloalkyl, halogen or a group of formula —B1-B2 or —B3;
• B1 represents an unsubstituted or substituted C6-C10 aryl group;
• B2 represents an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• B3 is an unsubstituted or substituted 5- to 12-membered heterocyclyl group where 1 or 2 ring carbon atoms are replaced with a group selected from >C(═O), >S(═O)2, >C(═NOR11), >C═CH2 or >C(—OCH2CH2O—), where R11 is hydrogen or a C1-C4 alkyl group;
• R2 and R3 independently represent C6-C10 aryl, a 5- to 12-membered heterocyclyl group, C3-C6 cycloalkyl, hydrogen, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C6 cycloalkyl, —OR′, —SR′, —SOR′, —SO2R′, —SO2NR′R″, —SO3H, —NR′R″, —NR′COR′, —CO2R′, —CONR′R″, —COR′, —OCOR′, —CF3, —NSO2R′ or —OCONR′R″, or a group (C1-4) alkyl-A5, wherein none, one or two —CH2— groups are independently replaced by —O—, —S— or —NR′— and wherein A5 represents C6-10 aryl or a 5- to 12-membered heterocyclyl group;
• or R2 and R3 together with the ring atoms to which they are bonded form a 5- to 7-membered, saturated or partially saturated ring containing a nitrogen atom from the adjacent pyrrole ring, and optionally one or two further heteroatoms selected from N, O and S, with the proviso that R2 and R3 do not form, together with the pyrrole ring to which they are bonded, a tetrahydroindolizine ring;
• R4 represents hydrogen, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —OR′, —CONR′R″, —COR′, —CN, —NO2, —NR′R″, CF3, —Y—Z, C6-C10 aryl, or 5- to 12-membered heterocyclyl group, or a group of formula -Alk6-L5-A12, where Alk6 is a C1-C4 alkylene group, L5 is a group of formula —O—C(═O)—, —C(═O)— or —NR13—C(═O)— and R13 is hydrogen or C1-C4 alkyl, and A12 is an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• Y represents C1-C8 alkylene, C2-C8 alkenylene or C2-C8 alkynylene;
• Z represents halogen, C3-C6 cycloalkyl, —OR′, —SR′, —SOR′, —SO2R′, —SO2NR′R″, —SO3H, —NR′R″, —NR′COR′, —NO2, —CO2R′, —CONR′R″, —COR′, —OCOR′, —CN, —CF3, —NSO2R′, —OCONR′R″ or —CR′═NOR″;
• and
• R′ and R″ independently represent hydrogen, C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl;
• wherein an alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclyl group or moiety can be substituted or unsubstituted;
• and wherein:
• a substituted alkyl, alkenyl or alkynyl group or moiety is a said alkyl, alkenyl or alkynyl group or moiety which is substituted with up to three substituents selected from halogen, hydroxy, amino, (C1-C4 alkyl)amino, di(C1-C4 alkyl)amino, C1-C4 alkoxy, —S(C1-C4 alkyl), —CO2H, —CO2(C1-C4 alkyl), phenyl, 5- or 6-membered heterocyclyl, CONRb′Rb″ and NRb′CO(C1-C4 alkyl) where Rb′ and Rb″ are the same or different and represent hydrogen or unsubstituted C1-C4 alkyl, wherein the substitutents on a substituted alkyl, alkenyl or alkynyl group or moiety are themselves unsubstituted or, the case of C1-C4 alkoxy substituents, may be further substituted with unsubstituted methoxy or ethoxy;
• a substituted cycloalkyl group is a said cycloalkyl group which is substituted with up to three substituents selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Z and —Y—Z;
• a substituted aryl or heterocyclyl group or moiety is a said aryl or heterocyclyl group or moiety which is substituted with up to three substituents selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Z and —Y—Z.

A compound which is a pyrrole derivative of formula (I) or a pharmaceutically or agriculturally acceptable salt thereof:

• wherein R1 represents hydrogen, unsubstituted or substituted C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —COR′ or —SO2(C1-C4 alkyl), or a group -A2, -L2-A2, -L3-A2, -A2-L3-A3 or -A4;
• A2 and A3 are the same or different and represent C3-C6 cycloalkyl or an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• A4 is an unsubstituted or substituted 5- to 12-membered heterocyclyl group wherein 1 or 2 ring carbon atoms are replaced with a group selected from >C(═O), >S(═O)2, >C(═NOR7), >C═CH2 or >C(OCH2CH2O), where R7 is hydrogen or a C1-C4 alkyl group;
• L1 represents a bond, a C1-C6 alkylene group in which none, one, two or three —CH2— groups are independently replaced by —O—, —S— or —NR′—, or a 5- to 12-membered heterocyclyl group;
• L2 represents —NR′—, —O—, —CO—, —OCO—, —OCONR′R″—, —CONR′R″— or —SO2—;
• L3 represents a bond or a C1-C4 alkylene group in which none, one or two —CH2— groups are independently replaced by —O—, —S— or —NR′—;
• n is 1 or 2;
• R5 represents an unsubstituted or substituted group selected from C6-C10 aryl, a 5- to 12-membered heterocyclyl group, C1-C8 alkyl and C3-C6 cycloalkyl, halogen or a group of formula B1 B2 or —B3;
• B1 represents an unsubstituted or substituted C6-C10 aryl group;
• B2 represents an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• B3 is an unsubstituted or substituted 5- to 12-membered heterocyclyl group where 1 or 2 ring carbon atoms are replaced with a group selected from >C(═O), >S(═O)2, >C(═NOR11), >C═CH2 or >C(OCH2CH2O), where R11 is hydrogen or a C1-C4 alkyl group;
• R3 represents C6-C10 aryl, a 5- to 12-membered heterocyclyl group, C3-C6 cycloalkyl, hydrogen, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C6 cycloalkyl, —OR′, —SR′, —SOR′, —SO2R′, —SO2NR′R″, —SO3H, —NR′R″, —NR′COR′, —CO2R′, —CONR′R″, —COR′, —OCOR′, —CF3, —NSO2R′ or —OCONR′R″, or a group (C1-4) alkyl-A5, wherein none, one or two —CH2— groups are independently replaced by —O—, —S— or —NR′— and wherein AS represents C6-10 aryl or a 5- to 12-membered heterocyclyl group;
• A1 is a C3-C6 cycloalkyl or an unsubstituted or substituted C6-C10 aryl, 5- or 6-membered heterocyclyl or 8- to 10-membered bicyclic heterocyclyl group;
• R6 represents hydrogen;
• R2 represents C6-C10 aryl, a 5- to 12-membered heterocyclyl group other than benzothiophene, unsubstituted C3-C6 cycloalkyl, hydrogen, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C6 cycloalkyl, —OR′, —SR′, —SOR′, —SO2R′, —SO2NR′R″, —SO3H, —NR′R″, —NR′COR′, —CO2R′, —CONR′R″, —COR′, —OCOR′, —CF3, —NSO2R′ or —OCONR′R″, or a group (C1-4) alkyl-A5, wherein none, one or two —CH2— groups are independently replaced by —O—, —S— or —NR′— and wherein A5 represents C6-10 aryl or a 5- to 12-membered heterocyclyl group;
• or R2 together with R3 and the ring atoms to which they are bonded form a 5- to 7-membered, saturated or partially saturated ring containing a nitrogen atom from the adjacent pyrrole ring, and optionally one or two further heteroatoms selected from N, O and S, with the proviso that R2 and R3 do not form, together with the pyrrole ring to which they are bonded, a tetrahydroindolizine ring;
• wherein when R2 represents aryl or heterocyclyl it is unsubstituted or substituted with one or more unsubstituted substituents selected from halogen, —NRa′Ra″, —CO2Ra′, —CONRa′Ra″, —OCONRa″Ra″, —OCORa′, —COCF3 and hydroxyl, or C1-C6 alkyl or C1-C4 alkoxy which are unsubstituted or substituted with a hydroxyl or unsubstituted C1-C4 alkoxy group;
• wherein Ra′ and Ra″ are independently selected from hydrogen, unsubstituted C1-C4 alkyl and C1-C4 alkyl substituted with a hydroxyl or unsubstituted C1-C4 alkoxy group
• R4 represents hydrogen, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —OR′, —CONR′R″, —CN, —NO2, —NR′R″, CF3, —Y—Z, C6-C10 aryl, or 5- to 12-membered heterocyclyl group, or a group of formula -Alk6-L5-A12, where Alk6 is a C1-C4 alkylene group, L5 is a group of formula —O—C(═O)—, —C(═O)— or —NR13—C(═O)— and R13 is hydrogen or C1-C4 alkyl, and A12 is an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• Y represents C1-C8 alkylene, C2-C8 alkenylene or C2-C8 alkynylene;
• Z represents halogen, C3-C6 cycloalkyl, —OR′, —SR′, —SOR′, —SO2R′, —SO2NR′R″, —SO3H, —NR′R″, —NR′COR′, —NO2, —CO2R′, —CONR′R″, —COR′, —OCOR′, —CN, —CF3, —NSO2R′, —OCONR′R″ or —CR′═NOR″;
• and
• R′ and R″ independently represent hydrogen, C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl;
• wherein an alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclyl group or moiety can be substituted or unsubstituted;
• and wherein:
• a substituted alkyl, alkenyl or alkynyl group or moiety is a said alkyl, alkenyl or alkynyl group or moiety which is substituted with up to three substituents selected from halogen, hydroxy, amino, (C1-C4 alkyl)amino, di(C1-C4 alkyl)amino, C1-C4 alkoxy, —S(C1-C4 alkyl), —CO2H, —CO2(C1-C4 alkyl), phenyl, 5- or 6-membered heterocyclyl, CONRb′Rb″ and NRb′CO(C1-C4 alkyl) where Rb′ and Rb″ are the same or different and represent hydrogen or unsubstituted C1-C4 alkyl, wherein the substitutents on a substituted alkyl, alkenyl or alkynyl group or moiety are themselves unsubstituted or, the case of C1-C4 alkoxy substituents, may be further substituted with unsubstituted methoxy or ethoxy;
• a substituted cycloalkyl group is a said cycloalkyl group which is substituted with up to three substituents selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Z and —Y—Z;
• a substituted aryl or heterocyclyl group or moiety on A1 to A5, A12, R3, the ring formed by R2 and R3, R4, R5, L1, or B1 to B3, is a said aryl or heterocyclyl group or moiety which is substituted with up to three substituents selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Z and —Y—Z.

A compound which is a pyrrole derivative of formula (IB) or a pharmaceutically or agriculturally acceptable salt thereof:

• wherein:
• R1 represents hydrogen, unsubstituted or substituted C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —COR′ or —SO2(C1-C4 alkyl), or a group -A2, -L2-A2, -L3-A2, -A2-L3-A3 or -A4;
• A1 represents a C3-C6 cycloalkyl or an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• A2 and A3 are the same or different and represent C3-C6 cycloalkyl or an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• A4 is an unsubstituted or substituted 5- to 12-membered heterocyclyl group wherein 1 or 2 ring carbon atoms are replaced with a group selected from >C(═O), >S(═O)2, >C(═NOR7), >C═CH2 or >C(—OCH2CH2O—), where R7 is hydrogen or a C1-C4 alkyl group;
• L1 represents a bond, a C1-C6 alkylene group in which none, one, two or three —CH2— groups are independently replaced by —O—, —S— or —NR′—, or a 5- to 12-membered heterocyclyl group;
• L2 represents —NR′—, —O—, —CO—, —OCO—, —OCONR′R″—, —CONR′R″— or —SO2—;
• L3 represents a bond or a C1-C4 alkylene group in which none, one or two —CH2— groups are independently replaced by —O—, —S— or —NR′—;
• n is 1 or 2;
• R6 represents hydrogen or C1-C4 alkyl;
• R5 represents an unsubstituted or substituted group selected from C6-C10 aryl, a 5- to 12-membered heterocyclyl group, C1-C8 alkyl and C3-C6 cycloalkyl, halogen or a group of formula —B1-B2 or —B3;
• B1 represents an unsubstituted or substituted C6-C10 aryl group;
• B2 represents an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• B3 is an unsubstituted or substituted 5- to 12-membered heterocyclyl group where 1 or 2 ring carbon atoms are replaced with a group selected from >C(═O), >S(═O)2, >C(═NOR11), >C═CH2 or >C(—OCH2CH2O—), where R11 is hydrogen or a C1-C4 alkyl group;
• R2 is a group of formula -Alk1-X—Ra′, wherein Alk1 is an unsubstituted or substituted C1-C6 alkylene group, X is a group —O—, —S—, NRa″—, —CO2—, —CONRa″—, —OCO—, —OCONRa″— or —SO2—, and Ra′ and Ra″ are independently selected from hydrogen and unsubstituted or substituted C1-C4 alkyl;
• R3 represents C6-C10 aryl, a 5- to 12-membered heterocyclyl group, C3-C6 cycloalkyl, hydrogen, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C6 cycloalkyl, —OR′, —SR′, —SOR′, —SOX, —SO2NR′R″, —SO3H, —NR′R″, —NR′COR′, —CO2R′, —CONR′R″, —COR′, —OCOR′, —CF3, —NSO2R′ or —OCONR′R″, or a group (C1-4) alkyl-A5, wherein none, one or two —CH2— groups are independently replaced by —O—, —S— or —NR′— and wherein AS represents C6-10 aryl or a 5- to 12-membered heterocyclyl group;
• R4 represents hydrogen, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, —OR′, —CONR′R″, —COR′, —CN, —NO2, —NR′R″, CF3, —Y—Z, C6-C10 aryl, or 5- to 12-membered heterocyclyl group, or a group of formula -Alk6-L5-A12, where Alk6 is a C1-C4 alkylene group, L5 is a group of formula —O—C(═O)—, —C(═O)— or —NR13—C(═O)— and R13 is hydrogen or C1-C4 alkyl, and A12 is an unsubstituted or substituted C6-C10 aryl or 5- to 12-membered heterocyclyl group;
• Y represents C1-C8 alkylene, C2-C8 alkenylene or C2-C8 alkynylene;
• Z represents halogen, C3-C6 cycloalkyl, —OR′, —SR′, —SOR′, —SO2R′, —SO2NR′R″, —SO3H, —NR′R″, —NR′COR′, —NO2, —CO2R′, —CONR′R″, —COR′, —OCOR′, —CN, —CF3, —NSO2R′, —OCONR′R″ or —CR′═NOR″;
• and
• R′ and R″ independently represent hydrogen, C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl;
• wherein an alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclyl group or moiety can be substituted or unsubstituted;
• and wherein:
• a substituted alkyl, alkenyl or alkynyl group or moiety is a said alkyl, alkenyl or alkynyl group or moiety which is substituted with up to three substituents selected from halogen, hydroxy, amino, (C1-C4 alkyl)amino, di(C1-C4 alkyl)amino, C1-C4 alkoxy, —S(C1-C4 alkyl), —CO2H, —CO2(C1-C4 alkyl), phenyl, 5- or 6-membered heterocyclyl, CONRb′Rb″ and NRb′CO(C1-C4 alkyl) where Rb′ and Rb″ are the same or different and represent hydrogen or unsubstituted C1-C4 alkyl, wherein the substitutents on a substituted alkyl, alkenyl or alkynyl group or moiety are themselves unsubstituted or, the case of C1-C4 alkoxy substituents, may be further substituted with unsubstituted methoxy or ethoxy;
• a substituted cycloalkyl group is a said cycloalkyl group which is substituted with up to three substituents selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Z and —Y—Z;
• a substituted aryl or heterocyclyl group or moiety is a said aryl or heterocyclyl group or moiety which is substituted with up to three substituents selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Z and —Y—Z;
• wherein the compound is not 3-[2-(4-fluoro-phenylaminooxalyl)-pyrrol-1-yl]-propionic acid or 3-{2-[2-(3,4-Dimethoxy-phenyl)-ethylaminooxalyl]-pyrrol-1-yl}-propionic acid.

A compound which is a pyrrole derivative of formula (IA) or a pharmaceutically acceptable salt thereof:

• wherein:
• A1 represents phenyl, naphthyl, pyridyl, piperidinyl, benzofuranyl, isoquinolinyl or quinolinyl, each of which may be unsubstituted or substituted with one or more substituents selected from unsubstituted C1-C4 alkyl, C1-C4 alkyl substituted with an unsubstituted C1-C4 alkoxy group, unsubstituted C1-C4 alkoxy, —CO2H and halogen, or from a group of formula —(C1-C2 alkyl)-O—(C1-C4 alkyl)-NR′R″ where R′ and R″ are the same or different and represent hydrogen or C1-C4 alkyl, or R′ and R″, together with the nitrogen atom to which they are bonded, form a piperazinyl or morpholinyl group which is unsubstituted or substituted with 1 or 2 C1-C4 alkyl groups;
• n represents one or two;
• L1 represents a bond, a saturated 5- to 7-membered heterocyclyl group containing one or two nitrogen atoms, or an unsubstituted C1-C6 alkylene group wherein none, one or two —CH2— groups are independently replaced with —O— or —NR′—, wherein R′ is hydrogen, unsubstituted C1-C4 alkyl or C1-C4 alkyl substituted with an unsubstituted C1-C4 alkoxy group, and wherein the heterocyclyl group is unsubstituted or substituted with an unsubstituted group selected from C1-C4 alkyl, C1-C4 alkoxy, hydroxy and halogen;
• when L1 is a bond, R1 represents hydrogen, -A2, —SO2-A2, A2-L3-A3 or A4;
• and when L1 is other than a bond, R1 represents hydrogen or an unsubstituted group selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and —SO2(C1-C4 alkyl), or a group -A2, —SO2-A2, -L3-A2 or -A2-L3-A3;
• A2 and A3 independently represent phenyl or a 5- or 6-membered heterocyclyl group,
• wherein A2 and A3 are unsubstituted or substituted with one, two or three substituents selected from the unsubstituted substituents halogen, —COCF3,
• —OCONR′R″ and —NR′R″, and from C1-C4 alkyl and C1-C4 alkoxy groups which are unsubstituted or substituted with —OH, —OMe, —OEt or —O(C1-C4 alkyl)-O(C1-C2 alkyl), wherein R′ and R″ are independently selected from hydrogen, unsubstituted C1-C4 alkyl and C1-C4 alkyl substituted with a hydroxyl or unsubstituted C1-C4 alkoxy group;
• L3 represents a bond or unsubstituted methylene or ethylene;
• A4 represents unsubstituted dioxothiomorpholinyl, methoxyiminopiperidinyl, methoxyiminopyrrolidinyl, methylenepiperidinyl, dioxoazaspirodecyl or oxadihydropyrazolyl;
• R5 represents unsubstituted or substituted phenyl, unsubstituted C3-C6 cycloalkyl, unsubstituted or substituted pyridinyl or piperidinyl, or unsubstituted thiophenyl, furanyl or tetrahydropyranyl, the substituents being selected from halogen, unsubstituted C1-C4 alkyl, unsubstituted C1-C4 alkoxy or R5 is a C1-C8 alkyl group substituted with a C1-C4 alkoxy group;
• and
• either (i) R2 represents unsubstituted phenyl, hydrogen, halogen, unsubstituted C1-C4 alkoxy, unsubstituted C2-C4 alkenyl, unsubstituted C1-C4 alkyl, or C1-C4 alkyl or C2-C4 alkenyl substituted with —OMe, —OEt, —OPr, —OBu, —OCH2CH2OMe, —SMe, hydroxy, di(C1-C4 alkyl)amino, —COO(C1-C4 alkyl), —CONR′R″ or —NR′CO(C1-C4 alkyl) where R′ and R″ are the same or different and represent hydrogen or unsubstituted C1-C4 alkyl;
• or R2 represents a group (C1-C4) alkyl-A5, wherein none or one —CH2— groups are independently replaced by —O— and wherein A5 represents phenyl, pyridinyl or oxazolyl, each of which is unsubstituted or substituted with one or two substituents selected from halogen, C1-C4 alkyl and C1-C4 alkoxy;
• and R3 represents hydrogen, halogen, unsubstituted phenyl, unsubstituted C1-C4 alkoxy, unsubstituted C1-C4 alkyl, or C1-C4 alkyl substituted with —OMe or —OEt;
• or (ii) R2 and R3 together with the ring atoms to which they are bonded form a substituted or unsubstituted saturated or partially saturated 5- or 6-membered ring containing a nitrogen atom from the adjacent pyrrole ring and none or one further heteroatom selected from N and O, with the proviso that R2 and R3 do not form, together with the pyrrole ring to which they are bound, a tetrahydroindolizine ring, the substituents being selected from unsubstituted C1-C4 alkyl and unsubstituted C1-C4 alkoxy groups.