Modulators of alpha-1 antitrypsin

A compound of formula (I):

• a tautomer, a pharmaceutically acceptable salt, or a deuterated derivative thereof;
• wherein:
• (i) R0 is
• (a) a C1-C8 linear, branched, or cyclic alkyl group, wherein the alkyl group is optionally substituted with 1-4 RA;
• or
• (b) a 5- to 14-membered aromatic ring optionally substituted with 1-4 RA;
• wherein each RA is independently a halogen, cyano, hydroxy, thiol, sulfonic acid, sulfonamide, sulfinamide, amino, amide, carboxylic acid, 5- to 10-membered aromatic ring, or a C1-C6 linear, branched, or cyclic group,
• wherein the amide nitrogen atom in the amide of RA is optionally substituted with a heterocyclyl group that is optionally further substituted with oxo,
• wherein each C1-C6 linear, branched, or cyclic group is, independently, an alkyl, alkoxy, thioalkyl, alkylsulfoxide, alkylsulfonyl, alkylsulfonamide, alkylsulfinamide, aminoalkyl, or alkylamide,
• wherein each 5- to 10-membered aromatic ring or C1-C6 linear, branched, or cyclic group, independently, is optionally substituted with 1-4 substituents, wherein each substituent, independently, is a halogen, a C1-C6 linear, branched, or cyclic group, or a methoxy, or
• wherein an RA group is optionally linked to an RB group or to an R2 group;
• (ii) R1 is
• (a) a hydrogen,
• (b) a C1-C8 linear, branched, or cyclic alkyl group, wherein the alkyl group is optionally substituted with 1-4 substituents, wherein each substituent, independently, is a
• halogen,
• cyano,
• cyanoalkyl,
• hydroxy,
• alkylsulfonyl, or
• C1-C6 linear, branched, or cyclic group, wherein the C1-C6 linear, branched, or cyclic group is an alkyl or alkoxy group, and wherein the C1-C6 linear, branched, or cyclic group is optionally substituted with 1-4 substituents, wherein each substituent, independently, is a
• halogen,
• hydroxy, or
• C1-C6 linear, branched, or cyclic alkoxy group,
• (c) a C1-C8 linear, branched, or cyclic alkoxy or cyclic thioalkyl group optionally substituted with 1-4 substituents, wherein each substituent independently is a
• halogen,
• cyano,
• cyanoalkyl;
• sulfone,
• sulfonamide,
• hydroxy, or
• a C1-C6 linear, branched, or cyclic alkyl group optionally substituted with 1-4 halogens or alkoxy groups;
• (d) a C1-C6 linear, branched, or cyclic alkylsulfonyl group optionally substituted with C1-C6 linear or branched alkyl groups;
• (e) an aminosulfonyl group, optionally substituted with 1 or 2 substituents, wherein each substituent independently is a
• C1-C6 linear, branched, or cyclic alkyl group;
• (f) a C1-C6 linear, branched, or cyclic alkylsulfonyl amino group;
• (g) a phosphine oxide group, optionally substituted with 1 or 2 substituents, wherein each substituent, independently, is a
• C1-C6 linear, branched, or cyclic alkyl group;
• (h) a C1-C6 linear, branched, or cyclic trialkylsilyl group;
• or
• (i) a C1-C6 alkylamide;
• (iii) R2 is
• (iv) each of X1 and X2, independently, is a hydrogen, halogen, cyano, hydroxy, C1-C6 linear, branched, or cyclic group, wherein each C1-C6 linear, branched, or cyclic group, independently, is an alkyl, alkoxy, thioalkyl, or aminoalkyl group, and wherein each C1-C6 linear, branched, or cyclic group is optionally substituted by 1-4 independently chosen halogens;
• (v) each of W1 and W2 independently is a C or N;
• (vi) each
• is a single or double bond, provided that no more than one
• is a double bond;
• (vii) each R3 independently, is a hydrogen, halogen, cyano, C1-C6 linear, branched, or cyclic alkyl group, or C1-C6 linear, branched, or cyclic alkoxy group, wherein the C1-C6 linear, branched, or cyclic alkyl group and the C1-C6 linear, branched, or cyclic alkoxy group is optionally substituted with 1-4 substituents, wherein each substituent, independently, is a halogen, hydroxy or carboxylic acid;
• (viii) n is 0, 1, 2, or 3;
• and
• (ix) two of Z1, Z2, and Z3 are nitrogen, and the third is carbon or nitrogen, wherein the valences of carbon or nitrogen are completed with hydrogen, halogen, C1-C6 linear, branched, or cyclic alkyl groups, or C1-C6 linear, branched, or cyclic alkoxy groups, wherein the C1-C6 linear, branched, or cyclic alkyl groups and the C1-C6 linear, branched, or cyclic alkoxy groups are optionally substituted with 1-4 substituents, wherein each substituent, independently, is halogen, hydroxy, or carboxylic acid.