Compounds as modulators of PGD2 receptors and / or CRTH2 and their use in treating asthma and allergic inflammation

摘要

Compound having the formula II: or a salt or solCompuesto having the formula II: or a pharmaceutically acceptable salt or solvate thereof, in pharmaceutically acceptable dude thereof, the Queb is a ring fused 5-membered conqueB is a ring fused 5-membered ring containing 0, 1, 2 or 3 heteroatoms selected from N, having 0, 1, 2 or 3 heteroatoms selected from N, O and S; optionally, B is substituted with Haloge O yS; optionally, B is substituted by halogen, (C1-C3), (C1-C3), cicloalqno, (C1-C3), (C1-C3) alkyl, (C3-C5) cycloalkyl, (C3-C5 ), Uilo aminoalkyl (C3-C5) cycloalkyl, (C3-C5), alkylamino (C1-C3), hydroxyl, oxo, -OR ', -CONR'R ", -N (R") C (O (C1- C3), hydroxyl, oxo, -OR ', -CONR'R ", -N (R") C (O) R', -CO2R ', -CN, aryl or heteroaryl; X is a inthe) R', - CO2R ', -CN, aryl or heteroaryl; X is a divalent linkage selected from -O-, -S (O) k-, -CRaRb-ce divalent selected from -O-, -S (O) k-, -CRaRb-, -C (O) -, - and NR 8 -C (NR9) -; Y is a divalen bond, -C (O) -, -NR8- and -C (NR9) -; Y is a divalent linkage selected -SO2NH-, -SO2NMe-, -C (O) NH-, -SO2NH- -nte selected, -SO2NMe-, -C (O) NH-, -NH-, -NHCO2- and -NHC (O) -NMe; Z is -CO2R12, -C (O) NR12H-, -NHCO2- and -NHC (O) -NMe; Z is -CO2R12, -C (O) NR12R13 or heteroaryl; L is a divalent linking seleccR13 or heteroaryl; L is a divalent linkage selected from methylene, ethylene, chloromethylene, hidroxionado methylene, ethylene, chloromethylene, hydroxymethylene and methylmethylene; R2 is a ring bencimetileno and methylmethylene; R2 is a benzene ring which is unsubstituted or substituted with hay which is unsubstituted or substituted with halogen, -OR 'or -R', wherein R 'is alkyl (C1-C8alógeno, -OR' or - R ', wherein R' is (C1-C8) -alkyl or (C1-C8); R5 and R6 are independent) -alkyl or (C1-C8); R5 and R6 are independently hydrogen, halogen, (C1-C8) fluoromente hydrogen, halogen, (C1-C8) fluoroalkyl (C1-C4) heteroalkyl, (C2-C8), aryl, hetealquilo (C1-C4) heteroalkyl, (C2-C8), aryl, heteroaryl, aryl (C1-C4) alkyl, -NR'R ", -OR ', -NO2, roarilo, aryl (C1-C4) alkyl, -NR'R", -OR' , -NO2, -CN, -C (O) R ', -CO2R', -C (O) NR'R ", (C1-C4) - CN, -C (O) R ', -CO2R' , -C (O) NR'R ", (C1-C4) -C (O) NR'R", -S (O) mR ', -S (O) k NR'R ", -OC (O) OR ', -OC (OC (O) NR'R ", -S (O) mR', -S (O) k NR'R", -OC (O) OR ', -OC (O) R', - OC (O) NR'R ", N (R '') C (O) NR'R", -N (R ") C (O) R ', -) R', -OC (O) NR ' R ", N (R '') C (O) NR'R", -N (R ") C (O) R ', -N (R") S (O) kR' or -N (R " ) C (O) OR '; R8, R10 and R11 are InN (R ") S (O) kR 'or -N (R") C (O) OR'; R8, R10 and R11 are independently hydrogen, (C1-C8) fluordependientemente hydrogen, (C1-C8) fluoroalkyl (C1-C4) heteroalkyl, (C2-C8), aryl, hetoalquilo (C1-C4) heteroalkyl, (C2-C8), aryl, heteroaryl, aryl (C1-C4), -C (O) R ', -CO2R', -Ceroarilo, aryl (C1-C4), -C (O) R ', -CO2R' , -C (O) NR'R ", -S (O) mR 'or -S (O) k NR'R"; R9 is hydrogen, (O) NR'R ", -S (O) mR' or - S (O) k NR'R "; R9 is hydrogen, (C1-C6) heteroalkyl, (C2-C6), arilalquilalquilo (C1-C6) heteroalkyl, (C2-C6), aryl- (C1-C4), -OR 'or -NR'R "; R12 and R13 are independieno (C1-C4), -OR' or -NR'R"; R12 and R13 are independently hydrogen, (C1-C6) heteroalkyl temente hydrogen, (C1 C6) heteroalkyl, (C2-C6), aryl, aryl (C1-C4) or heteroaryl; (C2-C6), aryl, aryl (C1-C4) or heteroaryl; each R14 is independently halogen, alkyl (each R14 is independently halogen, (C1-C8) fluoroalkyl (C1-C4) alkyl, (C2-C5), C1-C8) fluoroalkyl (C1-C4) alkyl, (C2 -C 5), -OR ', -NR'R ", -NO2, -CN, -C (O) R' or aryl; Ra and Rb so-oR ', NR'R", -NO 2, -CN, -C (O) R 'or aryl; Ra and Rb are independently hydrogen, (C1-C6) independently hn hydrogen, (C1-C6) heteroalkyl, (C2-C6), aryl- (C1-C4), -OR 'or-eteroalquilo (C2-C6) , aryl (C1-C4), -OR 'or -NR'R "; each R', R" and R '' 'is independently hiNR'R "; each R', R" and R '' 'is independently hydrogen , (C1-C6) alkyl, (C3C8) cidrógeno, (C1-C6) alkyl, (C3C8) cycloalkyl (C3C8), aryl or aryl (C1-C4); ecloalquenilo (C3C8), aryl or aryl (C1-C4); the subscript k is 0, 1 or 2; the subscript m is 0, 1, l subscript k is 0, 1 or 2; the subscript m is 0, 1, 2 or 3; and the subscript n is 0, 1, 2, 3 or 4. 2 or 3; and the subscript n is 0, 1, 2, 3 or 4.