Compounds

Abstract

The present invention relates to a compound of formula (Ia), 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, optionally substituted heteroaryl and alkyl; R8 is selected from H, alkyl, haloalkyl and halo; R9 is H, C1-C3-alkyl, or halo; R10 and R11, together with the nitrogen to which they are attached, form an azepanyl group, wherein (a) said azepanyl group is substituted by one or more substituents, or (b) one or two carbons in said azepanyl group are replaced by a group selected from O, NH, S and CO, and said azepanyl group is optionally further substituted; or R10 and R11, together with the nitrogen to which they are attached, form an azetidinyl, pyrrolidinyl or piperidinyl group wherein (a) said azetidinyl, pyrrolidinyl or piperidinyl group is substituted by one or more substituents, or (b) one or two carbons in said azetidinyl, pyrrolidinyl or piperidinyl group are replaced by a group selected from NH, S and CO; 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; 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, or said bicyclic group is optionally fused to a 5 or 6-membered aryl or heteroaryl group; R13 and R14 are each independently H or alkyl. Further aspects of the invention relate to such compounds for use in the field of immune-oncology and related applications.

Description

[0001] The present invention relates to compounds capable of modulating ERAP1. The compounds have potential therapeutic applications in the treatment of a variety of disorders including proliferative, viral, immune and inflammatory disorders. Background technique [0002] ERAP1 (endoplasmic reticulum aminopeptidase 1; also known as APPILS or ARTS1) is an aminopeptidase that is important in the production of partial antigens and neoantigens as part of the antigen presentation pathway 1 . The antigen presentation pathway begins with the breakdown of proteins into peptides by the proteasome. These peptides are transported to the endoplasmic reticulum, where a fraction of the peptides are processed by ERAP1 and bound to major histocompatibility complex class I (MHC class I) 1 . Antigens bound to MHC class I are then transported to the cell surface and presented to CD8 + T cells, and are recognized as self or non-self material. Neoantigens are antigens that are specific to ca...

AI Technical Summary

Problems solved by technology

Thus, modulators of ERAP1 activity, whether used alone or in combination with current cancer immunotherapeutics, including checkpoint inhibitors, could be useful in cancer therapy because modulators of ERAP1 activity alter the expression of ERAP1 presented on the surface of cancer cells. Antigens and neoantigens, and make these antigens and neoantigens more visible to the immune system, causing the tumor to attack and destroy

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