Dpp1 inhibitors with polycyclic linkers and uses thereof

A compound of formula (I)

• or a pharmaceutically acceptable salt or deuterated form thereof,
• wherein:
• R0 is
• 5-12 membered monocyclic heterocyclyl containing 1-3 heteroatoms selected from N, S, or O, wherein the monocyclic heterocycle is optionally substituted with 1-3 R8, or
• 5-12-membered polycyclic heterocyclyl containing 1-3 heteroatoms selected from N, S, or O, wherein the polycyclic heterocycle is optionally substituted with 1-3 R8,
• each R8 is independently selected from H, halogen, oxo, cyano, hydroxyl, NH2, NH(C1-6alkyl), N(C1-6alkyl)2, COOH, C1-6 alkyl, C1-6 alkyl-OH, —CONH2, —S(═O)NH2, —S(O)2NH2, C1-6alkoxy, halogenated C1-6alkoxy, C1-6 alkylene-carbocyclyl, or C1-6 alkylene-heteroaryl;
• L is polycyclic cycloalkylene, polycyclic arylene, or polycyclic heteroarylene, wherein a first atom of a first ring of the polycyclic arylene or heteroarylene is connected to
• and a second atom of a second ring of the polycyclic arylene or heteroarylene is connected to R1;
• wherein L is independently substituted by 0-4 R10;
• each R10 is independently ═O, halogen, C1-6alkyl, C1-6alkoxy, S—C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, cyano, hydroxy, NH2, —NH—C1-6 alkyl, N(C1-6alkyl)2, COOH, COC1-6 alkyl, COOC1-6alkyl, CON1-6alkyl, CON(C1-6alkyl)2, NHCOC1-6alkyl, or heterocycle;
• wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, and heterocycle are independently optionally substituted with 1-3 substituents selected from halogen, cyano, hydroxyl, NH2 and COOH;
• R1 is
• 5-12 membered carbocyclyl optionally substituted with 1-3 Rg,
• 6-18 membered aryl optionally substituted with 1-3 Rg,
• 5-12 membered monocyclic heterocyclyl containing 1-3 heteroatoms selected from N, S or O, wherein the monocyclic heterocyclyl is optionally substituted with 1-3 Rg,
• 5-12 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, Sor O, wherein the monocyclic heteroaryl is optionally substituted with 1-3 Rg,
• 7-14 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, wherein the bicyclic heteroaryl is optionally substituted with 1-4 Rg, or
• 7-20 membered tricyclic heteroaryl containing 1-3 heteroatoms selected from N, S or O, wherein the tricyclic heteroaryl is optionally substituted with 1-5 Rg,
• each Rg is independently selected from hydrogen, SF5, ═O, halogen, cyano, hydroxyl, nitro, NH2, —COOH, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyloxy, C2-6alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyl, C2-6 alkenyl, C2-5 alkynyl, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —COC1-6alkyl, —COOC1-6 alkyl, —CONH2, —CONHC1-6 alkyl, —CONHC3-6 cycloalkyl, —CON(C1-6 alkyl)2, —NHCOC1-6alkyl, —NHCOC3-5cycloalkyl, —P(O)(C1-6 alkyl), —S(O)C1-6alkyl, —S(O)2C1-6 alkyl, —S(O)2C3-6cycloalkyl, —SO2-3-7 membered heterocyclyl, —S(O)NH2, —S(O)NHC1-6 alkyl, —S(O)N(C1-6 alkyl)2, —S(O)2N—H2, —OSO2—C1-6alkyl, C1-6alkylene-O—C1-6alkyl, C3-8-cycloalkenyloxy, aryl, heteroaryl, 3-7-membered heterocycle containing 1-3 heteroatoms selected from N, S and O, and the Rg is optionally further substituted with 1-3 groups selected from C1-6 alkyl, C1-6 haloalkyl, C1-6-alkylene-OH, —CONH2, NH2, C1-6 alkoxy, hydroxyl, —COOH, halogen, or a 5-7-membered heterocycle containing 1-3 heteroatoms selected from N, S or O, wherein the 5-7-membered heterocycle is optionally substituted with 1-2 groups selected from ═O, halogen, cyano, C1-6 alkyl, and C1-6 haloalkyl.