Protein secretion inhibitors

A compound, or pharmaceutically acceptable salt thereof, having a structure of formula (II):

• wherein
• R1 is H, C1-3alkyl, or SO2C1-6alkyl;
• Het is oxazole, imidazole, pyrazole, isoxazole, morpholine, tetrahydroquinoline, oxazolidinone, piperidinone, dihydrooxazole, pyrazine, pyrimidine, imidazo[1,2-a]pyridine, 5,6,7,8-tetrahydroimidazo[1,5-a]pyridine, pyridine-2(1H)-one, 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole, or quinoline, or
• when at least one of n and m is 1 or 2, Het can be pyridine, and when n is 1 or 2, Het can be diazinyl;
• n is 0, 1, or 2;
• each RE, when present, is independently halo, C1-6alkyl, C0-6alkylene-C(O)N(RN)2, C0-6alkylene-N(RN)C(O)RN, C0-6alkylene-CN, C0-6alkylene-ORN, C0-6alkylene-N(RN)2, C1-6haloalkyl, C1-6haloalkoxy, C1-6hydroxyalkyl, C0-6alkylene-CO2RN, or C0-6alkylene-[C(O)]0-1-3-6 membered aromatic or non-aromatic ring having 0-2 ring heteroatoms independently selected from N, O and S;
• wherein when RE comprises a 3-6 membered ring, it is optionally substituted with 1-2 groups independently selected from halo, C1-6alkyl, CN, C1-6haloalkyl, CO2RN, C(O)RN, CON(RN)2, N(RN)CORN, and ORN;
• m is 0, 1, or 2;
• each Rx, when present, is independently halo or C1-6alkyl;
• o is 0 or 1;
• Rz, when present, is CN, halo, C(O)N(RN)2, C1-6alkyl, C1-6alkoxy, C1-6hydroxyalkyl, or C1-6haloalkyl;
• and
• each RN is independently H, C1-6alkyl, C1-6hydroxyalkyl, or C1-6haloalkyl.

A compound, or pharmaceutically acceptable salt thereof, having a structure of formula (III):

• wherein
• R1 is H, C1-3alkyl, or SO2C1-6alkyl;
• RA is H, C1-6alkyl, ORN, N(RN)2, OC1-6alkylene-N(RN)2, or OC1-6alkylene-ORN;
• n is 0, 1, or 2;
• ring A is phenyl or a 6-membered heteroaryl having 1 or 2 nitrogen ring atoms;
• each RB, when present, is independently C1-6alkyl, C1-6alkoxy, C1-6haloalkoxy, C1-3alkylene-C1-3alkoxy, C1-6 haloalkyl, C1-6hydroxyalkyl, halo, C0-3alkylene-CO2RN, C0-3alkylene-C(O)N(RN)2, C0-3alkylene-N(RN)2, OC1-3alkylene-N(RN)2, NO2, C0-3alkylene-N(RN)C(O)RN, C0-3alkylene-N(RN)C(O)ORN, OC1-3alkylene-N(RN)C(O)RN, C0-3alkylene-N(RN)C(O)N(RN)2, C0-3alkylene-N(RN)SO2RN, C0-3alkylene-OC(O)N(RN)2, C0-3alkylene-Het, C0-3alkylene-OHet, C0-3alkylene-NHCO2Het, C0-3alkylene-OC(O)Het, C0-3alkylene-N(RN)Het or C0-3alkylene-N(RN)C(O)Het;
• Het is an aromatic or non-aromatic 4-7 membered ring having 0-3 ring heteroatoms selected from N, O, and S;
• Het is optionally substituted with 1 substituent selected from C1-6alkyl, ORN, halo, oxo, C(O)RN, C(O)N(RN)2, SORN, SO2N(RN)2, and SO2RN;
• R3 is C1-6alkylene-X, C2-6alkenylene-X, C0-2alkylene-C3-6carbocycle-C0-2alkylene-X, or Ar, and the alkylene is optionally substituted with ORN;
• X is H, OC1-3alkyl, C≡CRN;
• CN, CO2RN;
• CON(RN)2, or Ar,
• Ar is a 3-10 membered aromatic or non-aromatic monocyclic or polycyclic ring having 0-4 ring heteroatoms selected from N, O, and S, with the proviso that when Ar is a 6-membered aromatic ring, it has 0 or 2-4 ring heteroatoms,
• Ar is optionally substituted with C1-3alkyl, C0-2alkylene-CN, CON(RN)2, tetrazole, oxazole, or 1-2 halo;
• o is 0 or 1;
• Rz, when present, is CN, halo, C(O)N(RN)2, C1-6alkyl, C1-6alkoxy, C1-6hydroxyalkyl, or C1-6haloalkyl;
• and
• each RN is independently H, C1-6alkyl, C1-6hydroxyalkyl, or C1-6haloalkyl.

A compound, or pharmaceutically acceptable salt thereof, having a structure of formula (IV):

• R1 is H, C1-3alkyl, or SO2C1-6alkyl;
• Het is 3-10 membered aromatic or non-aromatic heterocycle having 1-4 ring heteroatoms selected from N, O, and S;
• n is 0, 1, or 2;
• and
• each RE, when present, is independently halo, C1-6alkyl, phenyl, C(O)N(RN)2, CN, C0-6alkylene-ORN, C0-6alkylene-N(RN)2, C1-6haloalkyl, C1-6haloalkoxy, C3-6cycloalkyl, or CO2RN;
• wherein when RE is phenyl, it is optionally substituted with 1-2 groups independently selected from halo, C1-6alkyl, CN, C1-6haloalkyl, C1-6haloalkoxy, CO2RN, CON(RN)2, N(RN)CORN, and ORN;
• R3 is C1-6alkylene-X, C2-6alkenylene-X, Ar, or C0-2alkylene-C3-6carbocycle-C0-2alkylene-X;
• X is H, OC1-3alkyl, C≡CRN;
• CN, CO2RN;
• CON(RN)2, or Ar,
• Ar is a 3-10 membered aromatic or non-aromatic ring having 0-4 ring heteroatoms selected from N, O, and S, with the proviso that when Ar is a 6-membered aromatic ring, it has 0 or 2-4 ring heteroatoms;
• Ar is optionally substituted with C1-3alkyl, C0-2alklene-CN, CON(RN)2, tetrazole, oxazole, or 1-2 halo;
• o is 0 or 1;
• Rz, when present, is CN, halo, C(O)N(RN)2, C1-6alkyl, C1-6alkoxy, C1-6hydroxyalkyl, or C1-6haloalkyl;
• and
• each RN is independently H, C1-6alkyl, C1-6hydroxyalkyl, or C1-6haloalkyl.