Pyrazole compounds as CRTH2 antagonists

Abstract

The present invention relates to pyrazole compound of formula (la) or (lb), wherein R a and Rb are independently selected hydrogen, hydroxy, halogen, C1-C6-alkyl, C1-C6 haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy and C3-C8-cycloalkyl, or Ra and R b together with the carbon atom they are bound to form may form a carbonyl group, or Ra and Rb together with the carbon atom they are bound to form a 3- to 8-membered ring, wherein said ring may contain 1 or 2 heteroatoms selected from O, N and S as ring member and wherein the ring members of said ring may optionally be independently substituted by hydroxy, halogen, C1-C6-alkyl, C1-C6 haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy and C3-C8-cycloalkyl; R c and Rd are independently selected hydrogen, hydroxy, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy and C3-C8-cycloalkyl, or Ra and Rb together with the carbon atom they are bound to form may form a carbonyl group, or Ra and Rb together with the carbon atom they are bound to form a 3- to 8-membered ring, wherein said ring may contain 1 or 2 heteroatoms selected from O, N and S as ring member and wherein the ring members of said ring may optionally be independently substituted by hydroxy, halogen, C1-C6-alkyl, C1-C6- haloalkyl, C1 -C6-alkoxy, C1-C6-haloalkoxy and C3-C8-cycloalkyl; Y 1 , Y2 , Y3 , Y4 and Y5 are independently selected from N and CRy , wherein each Ry is independently selected from H, hydroxy, halogen, cyano, nitro, SF5, C(O)NRfR g , C1-C6-alkyl, hydroxy-C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkyl, C3- C8-cycloalkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-alkoxy-C1-C6-alkoxy, C1-C6-haloalkoxy, C3-C8-cycloalkoxy, C1-C6-alkylamino, di-C1-C6-alkylamino, C1-C6-alkylsulfonyl, phenyl, phenoxy, 5- or 6-membered heterocyclyl and 5- or 6-membered heterocyclyloxy, wherein Rf and Rg are independently from each other selected from H, C1-C6-alkyl, C1-C6-haloalkyl, C3-C8-cycloalkyl, C3-C8-cycloalkenyl and 5- or 6- membered heterocyclyl or Rf and Rg together with the nitrogen atom to which they are bound form a cyclic amine, which may comprise a further heteroatom selected from O, N and S as a ring member; Z is selected from O, S and NRz , wherein Rz is H, C1-C6-alkyl or benzyl; R 1 and R2 are independently from each other selected from H, halogen, C1-C6-alkyl, C2- C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy, C1-C6-alkylthio, -NRfR g , C3-C8-cycloalkyl, C3-C8-cycloalkyl-C1-C6-alkyl, C3-C8-cycloalkyl-C2-C6-alkenyl, C3-C8-cycloalkenyl, C3-C8-cycloalkenyl-C1-C6-alkyl, C3-C8-cycloalkenylC2-C6-alkenyl, phenyl, phenyl-C1-C6-alkyl, phenyl-C2-C6-alkenyl, naphthyl, naphthyl-C1-C6-alkyl, naphthyl-C2-C6-alkenyl, heterocyclyl, heterocyclyl-C1-C6-alkyl, and heterocyclylC2-C6-alkenyl, n is an integer selected from 0, 1, 2 or 3; and R 3 if present are selected independently from each other from halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy and C3-C8-cycloalkyl. To their use as medicament, to pharmaceutical formulation containing said compound and to pharmaceutical formulation said compound in combination with one or more active substances.