Recent　studies　revealed　that　MALT1　is　a　promising　therapeutic　target　for　the　treatment　of　ABC-DLBCL.　Among　several　reported　MALT1　inhibitors,　MI-2　as　an　irreversible　inhibitor　represents　a　new　class　of　ABC-DLBCL　therapeutics.　Due　to　its　inherent　potential　cross-reactivity,　further　structure-activity　relationship　(SAR)　study　is　imperative.　In　this　work,　five　focused　compound　libraries　based　on　the　chemical　structure　of　MI-2　are　designed　and　synthesized.　The　systematic　SARs　revealed　that　the　side　chain　of　2-methoxyethoxy　has　little　impact　on　the　activity　and　can　be　replaced　by　other　functionalized　groups,　providing　new　MI-2　analogues　with　retained　or　enhanced　potency.　Compounds　81-83　with　terminal　hydroxyl　group　as　side　chain　displayed　enhanced　activities　against　MALT1.　Replacement　of　triazole　core　with　pyrazole　is　also　tolerant,　while　structural　modifications　on　other　sites　are　detrimental.　These　findings　will　facilitate　further　development　of　small-molecule　MALT1　inhibitors.　(C)　2018　Elsevier　Ltd.　All　rights　reserved.