| abstract |
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, C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, cyclopropyl, halo, —S(O) n R 6 , —SO 2 NR 7 R 8 , —NR 7 R 8 , —NR 7 C(O)R 6 , —CO 2 R 7 , —C(O)NR 7 R 8 , —C(O)R 7 6 , —NO 2 , —CN or a group —OR 9 ; wherein each R 6 is independently C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, cycloalkyl, aryl, or heteroaryl; R 7 , R 8 are independently C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, cycloalkyl, cycloalkyl-(C 1 -C 6 alkyl)-, aryl, heteroaryl or hydrogen; R 9 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, cycloalkyl, cylcoalkyl-(C 1 -C 6 alkyl)-, or a group —SO 2 R 6 ; A is —CHR 10 —, —C(O)—, —S(O) n —, —O—, or —NR 10 — wherein n is an integer from 0-2 and R 10 is hydrogen C 1 -C 3 alkyl, or C 1 -C 6 -fluoroalkyl group; B is a direct bond, or a divalent radical selected from —CH 2 —, —CH 2 CH 2 —, —CHR 11 —, —CR 11 R 12 —, —CH 2 CHR 11 —, CH 2 CR 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 C 1 -C 3 alkyl, cyclopropyl, C 1 -C 6 -fluoroalkyl; R 12 is methyl or fluoromethyl; p is independently 1 or 2; and Z is —O—, —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)NHSO 2 R 6 or SO 2 NHC(═O)R 6 ; and Y is aryl, heteroaryl, aryl-fused-heterocycloalkyl, heteroaryl-fused-cycloalkyl, heteroaryl-fused-heterocycloalkyl or aryl-fused-cycloalkyl group. |