Erap1 modulating compounds

A method of treating or preventing a disorder selected from the group consisting of a proliferative disorder, an immune disorder, a viral disorder, and an inflammatory disorder in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of formula (Id), or a pharmaceutically acceptable salt or hydrate thereof,

• wherein:
• the group X—Y is —NHSO2— or —SO2NH—;
• R1 is H or alkyl;
• R2 is selected from COOH and a tetrazolyl group;
• R3 is selected from H, Cl and alkyl;
• R4 is selected from H, Cl and F;
• R5 is selected from H, alkyl, alkenyl, alkynyl, haloalkyl, SO2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy;
• R6 is H;
• R7 is CN, SO2-alkyl, SO2NR13R14 or a heteroaryl group, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH;
• R8 is selected from H, alkyl, haloalkyl and halo;
• R9 is H, C1-C3-alkyl or halo;
• R10 is H or alkyl;
• R11 is alkyl optionally substituted by one or more substituents selected from NH2, OH, and NHCO2R12, wherein R12 is alkyl;
• or
• R10 and R11, together with the nitrogen to which they are attached, form a 4, 5, 6 or 7-membered monocyclic heterocycloalkyl group, wherein one or two carbons in the monocyclic heterocycloalkyl group are optionally replaced by a group selected from O, NH, S and CO, and said monocyclic heterocycloalkyl group is optionally substituted by one or more groups selected from alkyl, CN, cycloalkyl, OH, alkoxy, halo, haloalkyl and heteroaryl, wherein said heteroaryl group is in turn optionally further substituted with one or more groups selected from halo and alkyl;
• or
• R10 and R11, together with the nitrogen to which they are attached, form an 8, 9 or 10-membered bicyclic heterocycloalkyl group, wherein one or two carbons in the bicyclic heterocycloalkyl ring are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic heterocycloalkyl group is optionally substituted by one or more groups selected from alkyl, CN, cycloalkyl, OH, alkoxy, halo, haloalkyl and heteroaryl;
• or
• R10 and R11, together with the nitrogen to which they are attached, form a 6 to 12-membered bicyclic group containing a spirocyclic carbon atom, wherein one or two carbons in the bicyclic group are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic group is optionally substituted by one or more groups selected from alkyl, CN, cycloalkyl, OH, alkoxy, halo, haloalkyl and heteroaryl, or said bicyclic group is optionally fused to a 5 or 6-membered aryl or heteroaryl group;
• and
• R13 and R14 are each independently H or alkyl.

An in vitro or in vivo method for producing an antigen-presenting cell which presents a neo-antigen, said method comprising inducing with a compound of formula (Id):

• or a pharmaceutically acceptable salt or hydrate thereof a neo-antigen in said antigen-presenting cell, wherein:
• the group X—Y is —NHSO2— or —SO2NH—;
• R1 is H or alkyl;
• R2 is selected from COOH and a tetrazolyl group;
• R3 is selected from H, Cl and alkyl;
• R4 is selected from H, Cl and F;
• R5 is selected from H, alkyl, alkenyl, alkynyl, haloalkyl, SO2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy;
• R6 is H;
• R7 is CN, SO2-alkyl, SO2NR13R14 or a heteroaryl group, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH;
• R8 is selected from H, alkyl, haloalkyl and halo;
• R9 is H, C1-C3-alkyl or halo;
• R10 is H or alkyl;
• R11 is alkyl optionally substituted by one or more substituents selected from NH2, OH, and NHCO2R12, wherein R12 is alkyl;
• or
• R10 and R11, together with the nitrogen to which they are attached, form a 4, 5, 6 or 7-membered monocyclic heterocycloalkyl group, wherein one or two carbons in the monocyclic heterocycloalkyl group are optionally replaced by a group selected from O, NH, S and CO, and said monocyclic heterocycloalkyl group is optionally substituted by one or more groups selected from alkyl, CN, cycloalkyl, OH, alkoxy, halo, haloalkyl and heteroaryl, wherein said heteroaryl group is in turn optionally further substituted with one or more groups selected from halo and alkyl;
• or
• R10 and R11, together with the nitrogen to which they are attached, form an 8, 9 or 10-membered bicyclic heterocycloalkyl group, wherein one or two carbons in the bicyclic heterocycloalkyl ring are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic heterocycloalkyl group is optionally substituted by one or more groups selected from alkyl, CN, cycloalkyl, OH, alkoxy, halo, haloalkyl and heteroaryl;
• or
• R10 and R11, together with the nitrogen to which they are attached, form a 6 to 12-membered bicyclic group containing a spirocyclic carbon atom, wherein one or two carbons in the bicyclic group are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic group is optionally substituted by one or more groups selected from alkyl, CN, cycloalkyl, OH, alkoxy, halo, haloalkyl and heteroaryl, or said bicyclic group is optionally fused to a 5 or 6-membered aryl or heteroaryl group;
• and
• R13 and R14 are each independently H or alkyl.

A method of treating or preventing a disorder selected from the group consisting of a proliferative disorder, an immune disorder, a viral disorder, and an inflammatory disorder in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof,

• wherein:
• the group X—Y is —NHSO2— or —SO2NH—;
• R1 is H or alkyl;
• R2 is selected from COOH and a tetrazolyl group;
• R3 is selected from H, Cl and alkyl;
• R4 is selected from H, Cl and F;
• R5 is selected from H, alkyl, alkynyl, alkenyl, haloalkyl, SO2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy;
• R6 is H;
• R7 is selected from H, CN, haloalkyl, Cl, F, SO2-alkyl, SO2NR13R14, heteroaryl and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH;
• R8 is selected from H, alkyl, haloalkyl and halo;
• R9 is H, C1-C3-alkyl or halo;
• R10 is H or alkyl;
• R11 is alkyl optionally substituted by one or more substituents selected from NH2, OH, and NHCO2R12, wherein R12 is alkyl;
• or
• R10 and R11, together with the nitrogen to which they are attached, form a 4, 5, 6 or 7-membered monocyclic heterocycloalkyl group, wherein one or two carbons in the monocyclic heterocycloalkyl group are optionally replaced by a group selected from O, NH, S and CO, and said monocyclic heterocycloalkyl group is optionally substituted by one or more groups selected from alkyl, CN, cycloalkyl, OH, alkoxy, halo, haloalkyl and heteroaryl, wherein said heteroaryl group is in turn optionally further substituted with one or more groups selected from halo and alkyl;
• or
• R10 and R11, together with the nitrogen to which they are attached, form an 8, 9 or 10-membered bicyclic heterocycloalkyl group, wherein one or two carbons in the bicyclic heterocycloalkyl ring are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic heterocycloalkyl group is optionally substituted by one or more groups selected from alkyl, CN, cycloalkyl, OH, alkoxy, halo, haloalkyl and heteroaryl;
• or
• R10 and R11, together with the nitrogen to which they are attached, form a 6 to 12-membered bicyclic group containing a spirocyclic carbon atom, wherein one or two carbons in the bicyclic group are optionally replaced by a group selected from O, NH, S and CO, and said bicyclic group is optionally substituted by one or more groups selected from alkyl, CN, cycloalkyl, OH, alkoxy, halo, haloalkyl and heteroaryl, or said bicyclic group is optionally fused to a 5 or 6-membered aryl or heteroaryl group;
• and
• R13 and R14 are each independently H or alkyl.