C5aR1 ANTAGONISTS PYRIDAZINONE AND THEIR USES

Claims

This specification provides compounds that modulate (e.g., antagonize) the complement component 5a receptor 1 (C5aR1), a G protein-coupled receptor for C5a that is associated with autoimmune, inflammatory, and neurodegenerative disorders. Pharmaceutical compositions and kits comprising these compounds are also provided, as well as methods for treating C5aR1-related diseases and disorders in a subject by administering the compounds and / or compositions described herein.

1. A compound having formula (1), or a pharmaceutically acceptable salt thereof, wherein: R1 is an optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, or optionally substituted heterocyclyl; R2 is an optionally substituted carbocyclyl or an optionally substituted heterocyclyl; R3 is hydrogen, halogen, optionally substituted alkyl, or optionally substituted aryl; R4 is hydrogen, optionally substituted heteroaryl, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, -ORA, N(RA)2, -C(=O)N(RA)2, -C(=NR A)NR A OR A, or -NR AC(=O)RA; and Y is -C(R5)2- or a bond; each R5 is independently hydrogen, halogen, or optionally substituted alkyl;and each RA is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroaliphatic, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, or a protecting group when attached to an oxygen atom, or two instances of RA together with the atoms to which they are attached form a substituted or unsubstituted heteroaryl or a substituted or unsubstituted heterocyclyl.

55. A pharmaceutical composition comprising a compound of any of claims 1-54, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.