MrgprX2 antagonists for the treatment of inflammatory disorders

A method for treating an inflammatory disorder that activates MrgprX2, the method comprising administering to a subject in need thereof a composition comprising:

• a therapeutically effective amount of an MrgprX2 antagonist comprising a compound having the following Formula I:
• wherein:
• A1 is:
• RA is selected from H, C1-3 alkyl, halogen, and CN;
• W is -(L1)p-A2;
• L1 is O or CH2;
• p is 1;
• R3 is H;
• m is 1;
• q is 1;
• k is 1;
• R1 is:
• C1-6 alkyl optionally substituted with 1, 2 or 3 independently selected R50 groups;
• C3-6 cycloalkyl optionally substituted with 1, 2 or 3 independently selected R50 groups;
• or
• a 3-10 membered heterocycloalkyl having 1-3 ring heteroatoms independently selected from N, O and S, which is optionally substituted with 1, 2 or 3 independently selected R51 groups;
• each R50 is independently selected from hydroxy;
• —NR20R21;
• C1-3 haloalkyl;
• halogen;
• CN;
• C3-6 cycloalkyl which is optionally substituted with 1-3 R25 groups;
• C1-3 alkoxy;
• and C1-3 hydroxyalkyl;
• each R20 and R21 is independently selected from H, C1-6 alkyl and —SO2NR30R31;
• each R25 is hydroxy;
• each R51 is independently selected from C1-6 alkyl;
• —SO2NR30R31;
• —C(═O)—O—R32;
• halogen;
• hydroxy;
• cyano;
• C1-3 hydroxyalkyl;
• —C(═O)—NR33R34;
• —C(═O)—R35;
• CN;
• —SO2R22;
• C1-3 haloalkyl;
• NR33R34;
• and C1-3 alkoxy;
• each R22 is independently C1-6 alkyl;
• each R30 and R31 is independently selected from H and C1-6 alkyl;
• each R32 is independently selected from H and C1-6 alkyl;
• each R33 and R34 is independently selected from H and C1-6 alkyl;
• each R35 is independently C1-6 alkyl;
• R2 is H, C1-6 alkyl or C3-6 cycloalkyl;
• A2 is phenyl or pyridyl, which are optionally substituted with one R60 group or two R60 groups;
• and
• each R60 is independently selected from halogen, CN, hydroxy, C1-3 alkoxy, C1-3 haloalkoxy, C1-3 haloalkyl, —C(═O)—O—R35 and C1-3 alkyl, which are optionally substituted with 1-3 substituents independently selected from hydroxy, CN and C1-3 alkoxy;
• or a stereoisomer, solvate, tautomer, or pharmaceutically acceptable salt thereof;
• and
• a pharmaceutically acceptable excipient.