Indolizine Derivatives as Ligands of the Crth2 Receptor

A pharmaceutical composition comprising a compound of formula (I) or a salt, N-oxide, hydrate or solvate thereof:

• wherein
• R1, R2. R3 and R4 each independently are hydrogen, C1-C6alkyl, fully or partially fluorinated C1-C6alkyl, halo, —S(O)nR10, —SO2N(R10)2, —N(R10)2, —C(O)N(R10)2, —NR10C(O)R9, —CO2R10, —C(O)R9, —NO2, —CN or —OR11;
• wherein each R9 is independently C1-C6alkyl, aryl, or heteroaryl;
• R10 is independently hydrogen, C1-C6alkyl, aryl, or heteroaryl;
• R11 is hydrogen, C1-C6alkyl, fully or partially fluorinated C1-C6alkyl or a group —SO2R10;
• n is 0, 1 or 2;
• R5 is C1-C6alkyl, fully or partially fluorinated C1-C6 alkyl, C1-C6alkenyl, C1-C6alkynyl, optionally substituted aryl, or optionally substituted heteroaryl;
• R6 is hydrogen, C1-C6alkyl or fully or partially fluorinated C1-C6alkyl;
• R7 and R8 are independently hydrogen or C1-C6alkyl, or R7 and R8 together with the atom to which they are attached form a cycloalkyl group;
• and
• X is —CHR6—, —S(O)n, —NR6SO2— or —SO2NR6— wherein n is 0, 1 or 2;
• and a pharmaceutically acceptable carrier.

A method of treatment of asthma, chronic obstructive pulmonary disease, rhinitis, allergic airway syndrome, or allergic rhinobronchitis, comprising administering to a patient suffering such disease an effective amount of a compound of formula (1) or a salt, N-oxide, hydrate or solvate thereof:

• wherein
• R1, R2. R3 and R4 each independently are hydrogen, C1-C6alkyl, fully or partially fluorinated C1-C6alkyl, halo, —S(O)nR10, —SO2N(R10)2, —N(R10)2, —C(O)N(R10)2, —NR10C(O)R9, —CO2R10, —C(O)R9, —NO2, —CN or —OR11;
• wherein each R9 is independently C1-C6alkyl, aryl, or heteroaryl;
• R10 is independently hydrogen, C1-C6alkyl, aryl, or heteroaryl;
• R11 is hydrogen, C1-C6alkyl, fully or partially fluorinated C1-C6alkyl or a group —SO2R10;
• n is 0, 1 or 2;
• R5 is C1-C6alkyl, fully or partially fluorinated C1-C6alkyl, C1-C6alkenyl, C1-C6alkynyl, optionally substituted aryl, or optionally substituted heteroaryl;
• R6 is hydrogen, C1-C6alkyl or fully or partially fluorinated C1-C6alkyl;
• R7 and R8 are independently hydrogen or C1-C6alkyl, or R7 and R8 together with the atom to which they are attached form a cycloalkyl group;
• and
• X is —CHR6—, —S(O)n—, —NR6SO2— or —SO2NR6— wherein n is 0, 1 or 2.