Therapeutic agents

A compound of the Formula I:

• wherein:
• —L— represents a double bond and r and s each represent 1 or —L— represents a triple bond and r and s each represent 0;
• G is selected from O, S and NR5;
• Y is selected from N and CR6;
• Q1 is selected from aryl and heteroaryl, and wherein Q1 is optionally substituted by one or more substituents, which may be the same or different, selected from halogeno, trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, amino, carboxy, carbamoyl, (1-6C)alkyl, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy, (2-6C)alkenyloxy, (2-6C)alkynyloxy, (1-6C)alkylthio, (1-6C)alkylsulfsulfinyl, (1-6C)alkylsulfsulfonyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, (1-6C)alkoxycarbonyl, N-(1-6C)alkylcarbamoyl, N, N-di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, (2-6C)alkanoyloxy, (2-6C)alkanoylamino, N-(1-6C)alkyl-(2-6C)alkanoylamino, (3-6C)alkenoylamino, N-(1-6C)alkyl-(3-6C)alkenoylamino, (3-6C)alkynoylamino, N-(1-6C)alkyl-(3-6C)alkyoylamino, N-(1-6C)alkylsulfsulfamoyl, N, N-di-[(1-6C)alkyl]sulfsulfamoyl, (1-6C)alkanesulfsulfonylamino, N-(1-6C)alkyl-(1-6C)alkanesulfsulfonylamino, from a group of the formula:
• —X1—R7
• wherein X1 is a direct bond or is selected from O and N(R8), wherein R8 is hydrogen or (1-6C)alkyl, and R7 is halogeno-(1-6C)alkyl, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, cyano-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl or di-[(1-6C)alkyl]amino-(1-6C)alkyl, and from a group of the formula:
• —X2—Q2
• wherein X2 is a direct bond or is selected from O, S, SO, SO2, N(R), CO, CH(OR9), CON(R9), N(R9)CO, N(R9)CON(R9), SO2N(R9), N(R9)SO2, C(R9)2O, C(R9)2S and N(R)C(R9)2, wherein R9 is hydrogen or (1-6C)alkyl, and Q2 is aryl, aryl-(1-6C)alkyl, heteroaryl, heteroaryl-(1-6C)alkyl, heterocyclyl or heterocyclyl-(1-6C)alkyl which optionally bears 1, 2 or 3 substituents, which may be the same or different, selected from trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, amino, carboxy, carbamoyl, (1-6C)alkyl, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy, (2-6C)alkenyloxy, (2-6C)alkynyloxy, (1-6C)alkylthio, (1-6C)alkylsulfinyl, (1-6C)alkylsulfonyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, (1-6C)alkoxycarbonyl, N-(1-6C)alkylcarbamoyl, N, N-di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, (2-6C)alkanoyloxy, (2-6C)alkanoylamino, N-(1-6C)alkyl-(2-6C)alkanoylamino, N-(1-6C)alkylsulfamoyl, N, N-di-[(1-6C)alkyl]sulfamoyl, (1-6C)alkanesulfonylamino and N-(1-6C)alkyl-(1-6C)alkanesulfonylamino, or from a group of the formula:
• —X3—R10
• wherein X3 is a direct bond or is selected from O and N(R11), wherein R11 is hydrogen or (1-6C)alkyl, and R10 is halogeno-(1-6C)alkyl, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, cyano-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl or di-[(1-6C)alkyl]amino-(1-6C)alkyl, and any heterocyclyl group within Q2 optionally bears 1 or 2 oxo or thioxo substituents;
• R is selected from hydrogen, amino, hydroxy, halogeno, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, carboxy, (1-6C)alkoxycarbonyl and N-(heterocyclyl(3-8C)cycloalkyl)carbamoyl;
• R1 is selected from hydrogen, halogeno, trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, amino, mercapto, carbamoyl, (1-6C)alkyl, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy, (2-6C)alkenyloxy, (2-6C)alkynyloxy, (1-6C)alkylthio, (1-6C)alkylsulfinyl, (1-6C)alkylsulfonyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, (1-6C)alkoxycarbonyl, N-(1-6C)alkylcarbamoyl, N, N-di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, (2-6C)alkanoyloxy, (2-6C)alkanoylamino, N-(1-6C)alkyl-(2-6C)alkaoylamino, (3-6C)alkenoylamino, N-(1-6C)alkyl-(3-6C)alkenoylamino, (3-6C)alkynoylamino, N-(1-6C)alkyl-(3-6C)alkynoylamino, N-(1-6C)alkylsulfamoyl, N, N-di-[(1-6C)alkyl]sulfamoyl, (1-6C)alkanesulfonylamino and N-(1-6C)alkyl-(1-6C)alkanesulfonylamino;
• R2 is selected from hydrogen, halogeno, amino, hydroxy, halogeno, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylthio, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, aryl(1-6C)alkylamino, arylamino, heterocyclyl and (2-6C)alkanoylamino;
• R3 is selected from hydrogen, (1-6C)alkyl, hydroxy(1-6C)alkyl, carboxy, (1-6C)alkoxycarbonyl, carbamoyl, N-(1-6C)alkylcarbamoyl, N, N-di-[(1-6C)alkyl]carbamoyl and N-(heterocyclyl(3-8C)cycloalkyl)carbamoyl;
• R5 is, independently, as defined for R4 and R6, provided that R5 is not halogeno;
• R4 and R6 which may be the same or different, are selected from hydrogen, halogeno, trifluoromethyl, trifluoromethoxy, cyano, isocyano, nitro, hydroxy, mercapto, amino, formyl, carboxy, carbamoyl, sulfamoyl, (1-6C)alkyl, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy, (2-6C)alkenyloxy, (2-6C)alkynyloxy, (1-6C)alkylthio, (1-6C)alkylsulfinyl, (1-6C)alkylsulfonyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, (1-6C)alkoxycarbonyl, N-(1-6C)alkylcarbamoyl, N, N-di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, (2-6C)alkanoyloxy, (2-6C)alkanoylamino, N-(1-6C)alkyl-(2-6C)alkanoylamino, (3-6C)alkenoylamino, N-(1-6C)alkyl-(3-6C)alkenoylamino, (3-6C)alkynoylamino, N-(1-6C)alkyl-(3-6C)alkynoylamino, N-(1-6C)alkylsulfamoyl, N, N-di-[(1-6C)alkyl]sulfamoyl, (1-6C)alkanesulfonylamino and N-(1-6C)alkyl-(1-6C)alkanesulfonylamino, or from a group of the formula:
• Q4—X5—
• wherein X5 is a direct bond or is selected from O, S, SO, SO2, N(R12), CO, CH(OR12);
• CON(R2), N(R12)CO, SO2N(R12), N(R12)SO2, OC(R2)2, SC(R2)2 and N(R2)C(R12)2, wherein R12 is hydrogen or (1-6C)alkyl, and Q4 is aryl, aryl-(1-6C)alkyl, (3-7C)cycloalkyl, (3-7C)cycloalkyl-(1-6C)alkyl, (3-7C)cycloalkenyl, (3-7C)cycloalkenyl-(1-6C)alkyl, heteroaryl, heteroaryl-(1-6C)alkyl, heterocyclyl or heterocyclyl-(1-6C)alkyl,
• and wherein adjacent carbon atoms in any (2-6C)alkylene chain within an R4, R5 or R6 substituent are optionally separated by the insertion into the chain of a group selected from O, S, SO, SO2, N(R13), CO, CH(OR13), CON(R13), N(R13)CO, SO2N(R13), N(R13)SO2, CH═CH and C≡C wherein R13 is hydrogen or (1-6C)alkyl,
• and wherein any CH2═CH— or HC≡C— group within an R4, R5 or R6 substituent optionally bears at the terminal CH2═or HC≡ position a substituent selected from halogeno, carboxy, carbamoyl, (1-6C)alkoxycarbonyl, N-(1-6C)alkylcarbamoyl, N, N-di-[(1-6C)alkyl]carbamoyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl and di-[(1-6C)alkyl]amino-(1-6C)alkyl or from a group of the formula:
• Q5—X6—
• wherein X6 is a direct bond or is selected from CO and N(R14)CO, wherein R14 is hydrogen or (1-6C)alkyl, and Q5 is aryl, aryl-(1-6C)alkyl, heteroaryl, heteroaryl-(1-6C)alkyl, heterocyclyl or heterocyclyl-(1-6C)alkyl,
• and wherein any CH2 or CH3 group within a R4, R5 or R6 substituent optionally bears on each said CH2 or CH3 group one or more halogeno or (1-6C)alkyl substituents or a substituent selected from hydroxy, cyano, amino, carboxy, carbamoyl, (1-6C)alkoxy, (1-6C)alkylthio, (1-6C)alkylsulfinyl, (1-6C)alkylsulfonyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino,
• (1-6C)alkoxycarbonyl, N-(1-6C)alkylcarbamoyl, N, N-di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, (2-6C)alkanoyloxy, (2-6C)alkanoylamino, N-(1-6C)alkyl-(2-6C)alkanoylamino, N-(1-6C)alkylsulfamoyl, N, N-di-[(1-6C)alkyl]sulfamoyl, (1-6C)alkanesulfonylamino and N-(1-6C)alkyl-(1-6C)alkanesulfonylamino, or from a group of the formula:
• —X7—Q6
• wherein X7 is a direct bond or is selected from O, S, SO, SO2, N(R5), CO, CH(OR15), CON(R15), N(R15)CO, SO2N(R15), N(R15)SO2, C(R15)2O, C(R15)2S and N(R15)C(R15)2, wherein R15 is hydrogen or (1-6C)alkyl, and Q6 is aryl, aryl-(1-6C)alkyl, (3-7C)cycloalkyl, (3-7C)cycloalkyl-(1-6C)alkyl, (3-7C)cycloalkenyl, (3-7C)cycloalkenyl-(1-6C)alkyl, heteroaryl, heteroaryl-(1-6C)alkyl, heterocyclyl or heterocyclyl-(1-6C)alkyl,
• and wherein any aryl, heteroaryl, heterocyclyl, cycloalkyl or cycloalkenyl group within a substituent on R4, R5 or R6 optionally bears 1 or more substituents, which may be the same or different, selected from halogeno, trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, amino, carboxy, carbamoyl, (1-6C)alkyl, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy, (2-6C)alkenyloxy, (2-6C)alkynyloxy, (1-6C)alkylthio, (1-6C)alkylsulfinyl, (1-6C)alkylsulfonyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, (1-6C)alkoxycarbonyl, N-(1-6C)alkylcarbamoyl, N, N-di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, (2-6C)alkanoyloxy, (2-6C)alkanoylamino, N-(1-6C)alkyl-(2-6C)alkanoylamino, N-(1-6C)alkylsulfamoyl, N, N-di-[(1-6C)alkyl]sulfamoyl, (1-6C)alkanesulfonylamino, N-(1-6C)alkyl-(1-6C)alkanesulfonylamino, from a group of the formula:
• —X8—R16
• wherein X8 is a direct bond or is selected from O and N(R17), wherein R17 is hydrogen or (1-6C)alkyl, and R16 is halogeno-(1-6C)alkyl, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, cyano-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(1-6C)alkyl, (2-6C)alkanoylamino-(1-6C)alkyl or (1-6C)alkoxycarbonylamino-(1-6C)alkyl, and from a group of the formula:
• —X9—Q7
• wherein X9 is a direct bond or is selected from O, S, SO, SO2, N(R18), CO, CH(OR18), CON(R18), N(R18)CO, SO2N(R18), N(R18)SO2, C(R18)2O, C(R18)2S and N(R18)C(R18)2, wherein R18 is hydrogen or (1-6C)alkyl, and Q7 is aryl, aryl-(1-6C)alkyl, (3-7C)cycloalkyl, (3-7C)cycloalkyl-(1-6C)alkyl, (3-7C)cycloalkenyl, (3-7C)cycloalkenyl-(1-6C)alkyl, heteroaryl, heteroaryl-(1-6C)alkyl, heterocyclyl or heterocyclyl-(1-6C)alkyl which optionally bears 1 or 2 substituents, which may be the same or different, selected from halogeno, trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, amino, carboxy, carbamoyl, (1-6C)alkyl, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy, (2-6C)alkenyloxy, (2-6C)alkynyloxy, (1-6C)alkylthio, (1-6C)alkylsulfinyl, (1-6C)alkylsulfonyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, (1-6C)alkoxycarbonyl, N-(1-6C)alkylcarbamoyl, N, N-di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, (2-6C)alkanoyloxy, (2-6C)alkanoylamino, N-(1-6C)alkyl-(2-6C)alkanoylamino, N-(1-6C)alkylsulfamoyl, N, N-di-[(1-6C)alkyl]sulfamoyl, (1-6C)alkanesulfonylamino and N-(1-6C)alkyl-(1-6C)alkanesulfonylamino,
• or when G is NR5, R4 and R5 together with the atoms to which they are attached form a fused 5- or 6-membered heteroaryl or heterocyclyl ring, and wherein said fused 5- or 6-membered ring optionally bears one or more substituents as defined for R4,
• and any fused 5- or 6-membered heterocyclyl ring so formed optionally bears 1 or 2 oxo or thioxo substituents,
• and wherein any heterocyclyl group within any R4, R5 or R6 substituent optionally bears 1 or 2 oxo or thioxo substituents;
• or a pharmaceutically-acceptable salt thereof.