Quinolines and their therapeutic use

摘要

Compounds of formula [1] are CRTH2 antagonists, useful in the treatment of conditions having an inflammatory component; in which: R<1>, R<2>, R<3>, R<4> and R<5> are independently hydrogen, C1-C6alkyl, C1- C6fluoroalkyl, cyclopropyl, halo, -S(O)nR<6>, -SO2NR<7>R<8>, -NR<7>R<8>, -NR<7>C(O)R<6>, -CO2R<7>, -C(O)NR<7>R<8>, -C(O)R<6>, -NO2, -CN or a group -OR<9>; wherein each R<6> is independently C1-C6alkyl, C1-C6fluoroalkyl, cycloalkyl, aryl, or heteroaryl; R<7>, R<8> are independently C1-C6alkyl, C1-C6fluoroalkyl, cycloalkyl, cycloalkyl-(C1-C6alkyl)-, aryl, heteroaryl or hydrogen; R<9> is hydrogen, C1-C6alkyl, C1-C6fluoroalkyl, cycloalkyl, cylcoalkyl-(C1-C6alkyl)-, or a group -SO2R<6>; A is -CHR<10>-, -C(O)-, -S(O)n-, -0-, or -NR<10>- wherein n is an integer from 0-2 and R<10> is hydrogen, C1-C3alkyl, or C1-C6fluoroalkyl group; B is a direct bond, or a divalent radical selected from -CH2-, -CH2CH2-, -CHR<11>-, -CR<11>R<12>-, -CH2CHR<11>-, -CH2CR<11>R<12>-, -CHR<11>CHR<12>-, and divalent radicals of formula -(CR<11>R<12>)P-Z- wherein Z is attached to the ring carrying R<1>, R<2> and R<3>; wherein R<11> is C1-C3alkyl, cyclopropyl, C1-C6fluoroalkyl; R<12> is methyl or fluoromethyl; p is independently 1 or 2; and Z is -0-, -NH-, or -S(O)n-, wherein n is an integer from 0-2; X is a carboxylic acid, tetrazole, 3-hydroxyisoxazole, hydroxamic acid, phosphinate, phosphonate, phosphonamide, or sulfonic acid group, or a group of formula C(=O)NHSO2R<6>or SO2NHC(=O)R<6>; and Y is aryl, heteroaryl, aryl-fused- heterocycloalkyl, heteroaryl-fused-cycloalkyl, heteroaryl-fused-heterocycloalkyl or aryl-fused-cycloalkyl group.