Claims for Patent: 11,066,417

Summary for Patent: 11,066,417

Title:	Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulators
Abstract:	Compounds of Formula (I): pharmaceutically acceptable salts thereof, deuterated derivatives of any of the foregoing, and metabolites of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed.
Inventor(s):	Jeremy J. Clemens, Alexander Russell Abela, Corey Don Anderson, Brett B. Busch, Weichao George Chen, Thomas Cleveland, Timothy Richard Coon, Bryan Frieman, Senait G. Ghirmai, Peter Grootenhuis, Anton V. Gulevich, Sara Sabina Hadida Ruah, Clara Kuang-Ju Hsia, Ping Kang, Haripada Khatuya, Jason McCartney, Mark Thomas Miller, Prasuna Paraselli, Fabrice Pierre, Sara E. Swift, Andreas Termin, Johnny Uy, Carl V. Vogel, Jinglan Zhou
Assignee:	Vertex Pharmaceuticals Inc
Application Number:	US16/276,350
Patent Claims:	1. A compound of Formula (I): a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: Ring A is a phenyl, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring B is a pyridinyl ring; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; X is O, NH, or an N(C1-C4 alkyl); each R1 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; m is 0, 1, 2, 3, or 4; each R2 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; n is 0, 1, or 2; each R3 is methyl; each R4 is independently chosen from halogens, an oxo group, a hydroxyl group, a cyano group, and —(Y)k—R7 groups, or optionally two R4, together with the atom(s) they are attached to, form a 5-6 membered cycloalkyl or heterocyclyl ring that is optionally and independently substituted with one or more groups chosen from halogens, C1-C2 alkyl groups, haloalkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; wherein: k is 0, 1, 2, 3, 4, 5, or 6; each Y is independently chosen from C(R5)(R6) groups, —O—, and —NRa— groups, wherein a heteroatom in —(Y)k—R7 is not bonded to another heteroatom in —(Y)k—R7, wherein: each R5 and R6 is independently chosen from hydrogen, halogens, a hydroxyl group, C1-C4 alkyl groups, and C3-5 cycloalkyl groups, or R5 and R6 on the same carbon together form a C3-5 cycloalkyl group or oxo; each of R5 and R6 is optionally independently substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, halogens, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Ra is independently chosen from hydrogen and C1-C2 alkyl groups; and R7 is chosen from hydrogen, halogens, a cyano group, and C3-C10 cycloalkyl groups optionally substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, and halogens; q is 1, 2, 3 or 4; and Z is a divalent linker of formula (L)r, wherein: r is 1, 2, 3, 4, 5, or 6; each L is independently chosen from C(R8)(R9) groups, —O—, and —NRb— groups, wherein a heteroatom in Z is not bonded to another heteroatom in Z, wherein: each R8 and R9 is independently chosen from hydrogen, halogens, C1-C2 haloalkyl groups, C1-C2 alkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Rb is independently chosen from hydrogen and C1-C2 alkyl groups. 2. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein the compound of Formula (I) is a compound of Formula (II-A) or (II-B): a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: the carbon denoted by * has S-stereochemistry or R-stereochemistry; Ring A is a phenyl, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring B is a pyridinyl ring; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; each R1 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; m is 0, 1, 2, 3, or 4; each R2 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; n is 0, 1, or 2; each R3 is methyl; each R4 is independently chosen from halogens, a hydroxyl group, an oxo group, a cyano group, and —(Y)k—R7 groups, or optionally two R4, together with the atom(s) they are attached to, form a 5-6 membered cycloalkyl or heterocyclyl ring that is optionally and independently substituted with one or more groups chosen from halogens, C1-C2 alkyl groups, haloalkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups, wherein: k is 0, 1, 2, 3, 4, 5, or 6; each Y is independently chosen from C(R5)(R6) groups, —O—, and —NRa— groups, wherein a heteroatom in —(Y)k—R7 is not bonded to another heteroatom in —(Y)k—R7, wherein: each R5 and R6 is independently chosen from hydrogen, halogens, a hydroxyl group, C1-C4 alkyl groups, and C3-5 cycloalkyl groups, or R5 and R6 on the same carbon together form a C3-5 cycloalkyl group or oxo; each of R5 and R6 is optionally independently substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, halogens, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Ra is independently chosen from hydrogen and C1-C2 alkyl groups; and R7 is chosen from hydrogen, halogens, a cyano group, and C3-C10 cycloalkyl groups optionally substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, and halogens; q is 1, 2, 3, or 4; Z is a divalent linker of formula (L)r, wherein: r is 1,2, 3, 4, 5, or 6; each L is independently chosen from C(R8)(R9) groups, —O—, and —NRb— groups, wherein a heteroatom in Z is not bonded to another heteroatom in Z, wherein: each R8 and R9 is independently chosen from hydrogen, halogens, C1-C2 alkyl groups, C1-C2 haloalkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Rb is independently chosen from hydrogen and C1-C2 alkyl groups. 3. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein the compound of Formula (I) is a compound of Formula (III-A) or (III-B): a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: the carbon denoted by * has S-stereochemistry or R-stereochemistry; Ring A is a phenyl, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; each R1 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; m is 0, 1, 2, 3, or 4; each R2 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; n is 0, 1, or 2; each R3 is methyl; each R4 is independently chosen from halogens, an oxo group, a hydroxyl group, a cyano group, and —(Y)k—R7 groups or optionally two R4, together with the atom(s) they are attached to, form a 5-6 membered cycloalkyl or heterocyclyl ring that is optionally and independently substituted with one or more groups chosen from halogens, C1-C2 alkyl groups, haloalkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups, wherein: k is 0, 1, 2, 3, 4, 5, or 6; each Y is independently chosen from C(R5)(R6) groups, —O—, and —NRa— groups, wherein a heteroatom in —(Y)k—R7 is not bonded to another heteroatom in —(Y)k—R7, wherein: each R5 and R6 is independently chosen from hydrogen, halogens, a hydroxyl group, C1-C4 alkyl groups, and C3-5 cycloalkyl groups, or R5 and R6 on the same carbon together form a C3-5 cycloalkyl group or oxo; each of R5 and R6 is optionally independently substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, halogens, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Ra is independently chosen from hydrogen and C1-C2 alkyl groups; and R7 is chosen from hydrogen, halogens, a cyano group, and C3-C10 cycloalkyl groups optionally substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, and halogens; q is 1 or 2; Z is a divalent linker of formula (L) r, wherein: r is 3, 4, or 5; each L is independently chosen from C(R8)(R9) groups, —O—, and —NRb— groups, wherein a heteroatom in Z is not bonded to another heteroatom in Z, wherein: each R8 and R9 is independently chosen from hydrogen, halogens, C1-C2 alkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Rb is independently chosen from hydrogen and C1-C2 alkyl groups. 4. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein the compound of Formula (I) is a compound of Formula (IV-A): a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: the carbon denoted by * has S-stereochemistry or R-stereochemistry; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; each R1 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; m is 0, 1, 2, 3, or 4; each R2 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; n is 0, 1, or 2; each R3 is methyl; each R4 is independently chosen from halogens, an oxo group, a hydroxyl group, a cyano group, and —(Y)k—R7 groups, or optionally two R4, together with the atom(s) they are attached to, form a 5-6 membered cycloalkyl or heterocyclyl ring that is optionally and independently substituted with one or more groups chosen from halogens, C1-C2 alkyl groups, haloalkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups, wherein: k is 0, 1, 2, 3, 4, 5, or 6; each Y is independently chosen from C(R5)(R6) groups, —O—, and —NRa— groups, wherein a heteroatom in —(Y)k—R7 is not bonded to another heteroatom in —(Y)k—R7, wherein: each R5 and R6 is independently chosen from hydrogen, halogens, a hydroxyl group, C1-C4 alkyl groups, and C3-5 cycloalkyl groups, or R5 and R6 on the same carbon together form a C3-5 cycloalkyl group or oxo; each of R5 and R6 is optionally independently substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, halogens, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Ra is independently chosen from hydrogen and C1-C2 alkyl groups; and R7 is chosen from hydrogen, halogens, a cyano group, and C3-C10 cycloalkyl groups optionally substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, and halogens; q is 1 or 2; Z is a divalent linker of formula (L) r, wherein: r is 3, 4, or 5; each L is independently chosen from C(R8)(R9) groups, —O—, and —NRb— groups, wherein a heteroatom in Z is not bonded to another heteroatom in Z, wherein: each R8 and R9 is independently chosen from hydrogen, halogens, C1-C2 alkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Rb is independently chosen from hydrogen and C1-C2 alkyl groups. 5. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein the compound of Formula (I) is a compound of Formula (IV-B): a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: the carbon denoted by * has S-stereochemistry or R-stereochemistry; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; each R1 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; m is 0, 1, 2, 3, or 4; each R2 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; n is 0, 1, or 2; each R3 is methyl; each R4 is independently chosen from halogens, an oxo group, a hydroxyl group, a cyano group, and —(Y)k—R7 groups, or optionally two R4, together with the atom(s) they are attached to, form a 5-6 membered cycloalkyl or heterocyclyl ring that is optionally and independently substituted with one or more groups chosen from halogens, C1-C2 alkyl groups, haloalkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups, wherein: k is 0, 1, 2, 3, 4, 5, or 6; each Y is independently chosen from C(R5)(R6) groups, —O—, and —NRa— groups, wherein a heteroatom in —(Y)k—R7 is not bonded to another heteroatom in —(Y)k—R7, wherein: each R5 and R6 is independently chosen from hydrogen, halogens, a hydroxyl group, C1-C4 alkyl groups, and C3-5 cycloalkyl groups, or R5 and R6 on the same carbon together form a C3-5 cycloalkyl group or oxo; each of R5 and R6 is optionally independently substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, halogens, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Ra is independently chosen from hydrogen and C1-C2 alkyl groups; and R7 is chosen from hydrogen, halogens, a cyano group, and C3-C10 cycloalkyl groups optionally substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, and halogens; q is 1 or 2; r is 3 or 4; each R8 and R9 is independently chosen from hydrogen, halogens, C1-C2 alkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Rb is independently chosen from hydrogen and C1-C2 alkyl groups. 6. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein the compound of Formula (I) is a compound of Formula (IV-C): a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: the carbon denoted by * has S-stereochemistry or R-stereochemistry; each R1 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; m is 0, 1, 2, 3, or 4; each R2 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; n is 0, 1, or 2; each R3 is methyl; each R4 is independently chosen from halogens, an oxo group, a hydroxyl group, a cyano group, and —(Y)k—R7 groups, or optionally two R4, together with the atom(s) they are attached to, form a 5-6 membered cycloalkyl or heterocyclyl ring that is optionally and independently substituted with one or more groups chosen from halogens, C1-C2 alkyl groups, haloalkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups, wherein: k is 0, 1, 2, 3, 4, 5, or 6; each Y is independently chosen from C(R5)(R6) groups, —O—, and —NRa— groups, wherein a heteroatom in —(Y)k—R7 is not bonded to another heteroatom in —(Y)k—R7, wherein: each R5 and R6 is independently chosen from hydrogen, halogens, a hydroxyl group, C1-C4 alkyl groups, and C3-5 cycloalkyl groups, or R5 and R6 on the same carbon together form a C3-5 cycloalkyl group or oxo; each of R5 and R6 is optionally independently substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, halogens, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Ra is independently chosen from hydrogen and C1-C2 alkyl groups; and R7 is chosen from hydrogen, halogens, a cyano group, and C3-C10 cycloalkyl groups optionally substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, and halogens; q is 1 or 2; r is 3 or 4; each R8 and R9 is independently chosen from hydrogen, halogens, C1-C2 alkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Rb is independently chosen from hydrogen and C1-C2 alkyl groups. 7. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein the compound of Formula (I) is a compound of Formula (V-A): a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: the carbon denoted by * has S-stereochemistry or R-stereochemistry; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; each R1 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; m is 0, 1, 2, 3, or 4; each R2 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; n is 0, 1, or 2; each R3 is methyl; each R4 is independently chosen from halogens, an oxo group, a hydroxyl group, a cyano group, and —(Y)k—R7 groups, or optionally two R4, together with the atom(s) they are attached to, form a 5-6 membered cycloalkyl or heterocyclyl ring that is optionally and independently substituted with one or more groups chosen from halogens, C1-C2 alkyl groups, haloalkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups, wherein: k is 0, 1, 2, 3, 4, 5, or 6; each Y is independently chosen from C(R5)(R6) groups, —O—, and —NRa— groups, wherein a heteroatom in —(Y)k—R7 is not bonded to another heteroatom in —(Y)k—R7, wherein: each R5 and R6 is independently chosen from hydrogen, halogens, a hydroxyl group, C1-C4 alkyl groups, and C3-5 cycloalkyl groups, or R5 and R6 on the same carbon together form a C3-5 cycloalkyl group or oxo; each of R5 and R6 is optionally independently substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, halogens, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Ra is independently chosen from hydrogen and C1-C2 alkyl groups; and R7 is chosen from hydrogen, halogens, a cyano group, and C3-C10 cycloalkyl groups optionally substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, and halogens; q is 1 or 2; Z is a divalent linker of formula (L)r, wherein: r is 3, 4, or 5; each L is independently chosen from C(R8)(R9) groups, —O—, and —NRb— groups, wherein a heteroatom in Z is not bonded to another heteroatom in Z, wherein: each R8 and R9 is independently chosen from hydrogen, halogens, C1-C2 alkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Rb is independently chosen from hydrogen and C1-C2 alkyl groups. 8. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein the compound of Formula (I) is a compound of Formula (V-B): a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: the carbon denoted by * has S-stereochemistry or R-stereochemistry; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; each R1 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; m is 0, 1, 2, 3, or 4; each R2 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; n is 0, 1, or 2; each R3 is methyl; each R4 is independently chosen from halogens, an oxo group, a hydroxyl group, a cyano group, and —(Y)k—R7 groups, or optionally two R4, together with the atom(s) they are attached to, form a 5-6 membered cycloalkyl or heterocyclyl ring that is optionally and independently substituted with one or more groups chosen from halogens, C1-C2 alkyl groups, haloalkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups, wherein: k is 0, 1, 2, 3, 4, 5, or 6; each Y is independently chosen from C(R5)(R6) groups, —O—, and —NRa— groups, wherein a heteroatom in —(Y)k—R7 is not bonded to another heteroatom in —(Y)k—R7, wherein: each R5 and R6 is independently chosen from hydrogen, halogens, a hydroxyl group, C1-C4 alkyl groups, and C3-5 cycloalkyl groups, or R5 and R6 on the same carbon together form a C3-5 cycloalkyl group or oxo; each of R5 and R6 is optionally independently substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, halogens, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Ra is independently chosen from hydrogen and C1-C2 alkyl groups; and R7 is chosen from hydrogen, halogens, a cyano group, and C3-C10 cycloalkyl groups optionally substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, and halogens; q is 1 or 2; r is 3, 4, or 5; and each R8 and R9 is independently chosen from hydrogen, halogens, C1-C2 alkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups. 9. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein the compound of Formula (I) is a compound of Formula (VI-A) or (VI-B): a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: the carbon denoted by * has S-stereochemistry or R-stereochemistry; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; each R1 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; m is 0, 1, 2, 3, or 4; each R2 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; n is 0, 1, or 2; each R3 is methyl; each R4 is independently chosen from halogens, an oxo group, a hydroxyl group, a cyano group, and —(Y)k—R7 groups, or optionally two R4, together with the atom(s) they are attached to, form a 5-6 membered cycloalkyl or heterocyclyl ring that is optionally and independently substituted with one or more groups chosen from halogens, C1-C2 alkyl groups, haloalkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups, wherein: k is 0, 1, 2, 3, 4, 5, or 6; each Y is independently chosen from C(R5)(R6) groups, —O—, and —NRa— groups, wherein a heteroatom in —(Y)k—R7 is not bonded to another heteroatom in —(Y)k—R7, wherein: each R5 and R6 is independently chosen from hydrogen, halogens, a hydroxyl group, C1-C4 alkyl groups, and C3-5 cycloalkyl groups, or R5 and R6 on the same carbon together form a C3-5 cycloalkyl group or oxo; each of R5 and R6 is optionally independently substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, halogens, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Ra is independently chosen from hydrogen and C1-C2 alkyl groups; and R7 is chosen from hydrogen, halogens, a cyano group, and C3-C10 cycloalkyl groups optionally substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, and halogens; q is 1 or 2; Z is a divalent linker of formula (L) r, wherein: r is 3, 4, or 5; each L is independently chosen from C(R8)(R9) groups, —O—, and —NRb— groups, wherein a heteroatom in Z is not bonded to another heteroatom in Z, wherein: each R8 and R9 is independently chosen from hydrogen, halogens, C1-C2 alkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Rb is independently chosen from hydrogen and C1-C2 alkyl groups. 10. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein the compound of Formula (I) is a compound of Formula (VI-C) or (VI-D): a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: the carbon denoted by * has S-stereochemistry or R-stereochemistry; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; each R1 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; m is 0, 1, 2, 3, or 4; each R2 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; n is 0, 1, or 2; each R3 is methyl; each R4 is independently chosen from halogens, an oxo group, a hydroxyl group, a cyano group, and —(Y)k—R7 groups, or optionally two R4, together with the atom(s) they are attached to, form a 5-6 membered cycloalkyl or heterocyclyl ring that is optionally and independently substituted with one or more groups chosen from halogens, C1-C2 alkyl groups, haloalkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups, wherein: k is 0, 1, 2, 3, 4, 5, or 6; each Y is independently chosen from C(R5)(R6) groups, —O—, and —NRa— groups, wherein a heteroatom in —(Y)k—R7 is not bonded to another heteroatom in —(Y)k—R7, wherein: each R5 and R6 is independently chosen from hydrogen, halogens, a hydroxyl group, C1-C4 alkyl groups, and C3-5 cycloalkyl groups, or R5 and R6 on the same carbon together form a C3-5 cycloalkyl group or oxo; each of R5 and R6 is optionally independently substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, halogens, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Ra is independently chosen from hydrogen and C1-C2 alkyl groups; and R7 is chosen from hydrogen, halogens, a cyano group, and C3-C10 cycloalkyl groups optionally substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, and halogens; q is 1 or 2; r is 3 or 4; and each R8 and R9 is independently chosen from hydrogen, halogens, C1-C2 alkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups. 11. A compound selected from: a deuterated derivative thereof, or a pharmaceutically acceptable salt of any of the compounds, or a pharmaceutically acceptable salt of any deuterated derivatives of those compounds. 12. A pharmaceutical composition comprising a compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, and optionally one or more of: (a) Compound II: a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing; (b) Compound III or Compound III-d: a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing; and (c) a pharmaceutically acceptable carrier. 13. A method of preparing a compound of Formula (I): a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, comprising coupling the NH group of Ring C and the Qb group of Ring B of a compound of Formula (Y-I): a salt thereof, or a deuterated derivative of any of the foregoing, wherein: Qb is a halogen; Ring A is a phenyl, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring B is a pyridinyl ring; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; X is O, NH, or an N(C1-C4 alkyl); each R1 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; m is 0, 1, 2, 3, or 4; each R2 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; n is 0, 1, or 2; each R3 is methyl; each R4 is independently chosen from halogens, an oxo group, a hydroxyl group, a cyano group, and —(Y)k—R7 groups, or optionally two R4, together with the atom(s) they are attached to, form a 5-6 membered cycloalkyl or heterocyclyl ring that is optionally and independently substituted with one or more groups chosen from halogens, C1-C2 alkyl groups, haloalkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; wherein: k is 0, 1, 2, 3, 4, 5, or 6; each Y is independently chosen from C(R5)(R6) groups, —O—, and —NRa— groups, wherein a heteroatom in —(Y)k—R7 is not bonded to another heteroatom in —(Y)k—R7, wherein: each R5 and R6 is independently chosen from hydrogen, halogens, a hydroxyl group, C1-C4 alkyl groups, and C3-5 cycloalkyl groups, or R5 and R6 on the same carbon together form a C3-5 cycloalkyl group or oxo; each of R5 and R6 is optionally independently substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, halogens, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Ra is independently chosen from hydrogen and C1-C2 alkyl groups; and R7 is chosen from hydrogen, halogens, a cyano group, and C3-C10 cycloalkyl groups optionally substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, and halogens; q is 1, 2, 3 or 4; and Z is a divalent linker of formula (L)r, wherein: r is 1, 2, 3, 4, 5, or 6; each L is independently chosen from C(R8)(R9) groups, —O—, and —NRb— groups, wherein a heteroatom in Z is not bonded to another heteroatom in Z, wherein: each R8 and R9 is independently chosen from hydrogen, halogens, C1-C2 haloalkyl groups, C1-C2 alkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Rb is independently chosen from hydrogen and C1-C2 alkyl groups; to form a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing. 14. A method of preparing a compound of Formula (I) a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein Ring D is comprising reacting a compound of Formula (X), a salt thereof, or a deuterated derivative of any of the foregoing, with a compound of Formula (Z-1), a salt thereof, or a deuterated derivative of any of the foregoing: wherein: Qa is a halogen; Ring A is a phenyl, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring B is a pyridinyl ring; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; X is O, NH, or an N(C1-C4 alkyl); each R1 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; m is 0, 1, 2, 3, or 4; each R2 is independently chosen from C1-C2 alkyl groups, C1-C2 alkoxyl groups, C1-C2 haloalkyl groups, C1-C2 haloalkoxyl groups, halogens, a cyano group, and a hydroxyl group; n is 0, 1, or 2; each R3 is methyl; each R4 is independently chosen from halogens, an oxo group, a hydroxyl group, a cyano group, and —(Y)k—R7 groups, or optionally two R4, together with the atom(s) they are attached to, form a 5-6 membered cycloalkyl or heterocyclyl ring that is optionally and independently substituted with one or more groups chosen from halogens, C1-C2 alkyl groups, haloalkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; wherein: k is 0, 1, 2, 3, 4, 5, or 6; each Y is independently chosen from C(R5)(R6) groups, —O—, and —NRa— groups, wherein a heteroatom in —(Y)k—R7 is not bonded to another heteroatom in —(Y)k—R7, wherein: each R5 and R6 is independently chosen from hydrogen, halogens, a hydroxyl group, C1-C4 alkyl groups, and C3-5 cycloalkyl groups, or R5 and R6 on the same carbon together form a C3-5 cycloalkyl group or oxo; each of R5 and R6 is optionally independently substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, halogens, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Ra is independently chosen from hydrogen and C1-C2 alkyl groups; and R7 is chosen from hydrogen, halogens, a cyano group, and C3-C10 cycloalkyl groups optionally substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, and halogens; q is 1, 2, 3 or 4; and Z is a divalent linker of formula (L)r, wherein: r is 1, 2, 3, 4, 5, or 6; each L is independently chosen from C(R8)(R9) groups, —O—, and —NRb— groups, wherein a heteroatom in Z is not bonded to another heteroatom in Z, wherein: each R8 and R9 is independently chosen from hydrogen, halogens, C1-C2 haloalkyl groups, C1-C2 alkyl groups, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Rb is independently chosen from hydrogen and C1-C2 alkyl groups. 15. The compound of claim 1, wherein the compound is in the form of a pharmaceutically acceptable salt. 16. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein Ring A is a phenyl ring, a pyridyl ring, or a pyrazolyl ring, wherein Ring A is optionally substituted with (R1)m. 17. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein each R1 is independently chosen from deuterium, C1-C2 alkyl groups, and a hydroxyl group, and m is 0 or 1. 18. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein n is 0. 19. The compound of claim 1 or claim 5, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein Ring D is a 5-membered heteroaryl ring substituted with (R4)q. 20. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein Ring D is a phenyl ring, pyridinyl ring, pyrazolyl ring, imidazolidinone ring, a pyrrolidinone ring, or a pyridinone ring, wherein Ring D is substituted with (R4)q. 21. The compound of claim 1 or claim 5, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein Ring D is a pyrazolyl ring, or a pyridinone ring, wherein Ring D is substituted with (R4)q. 22. The compound of claim 3, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein Ring D is a pyrazolyl ring, wherein Ring D is substituted with (R4)q. 23. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein Ring D is wherein indicates the point of attachment of Ring D to Ring B. 24. The compound of claim 1 or claim 5, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein Ring D is wherein indicates the point of attachment of Ring D to Ring B. 25. The compound of claim 24, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein each R4 is independently chosen from an oxo group or —(Y)k—R7 groups, wherein: k is 0, 1, 2, 3, 4, 5, or 6; each Y is independently chosen from C(R5)(R6) groups, —O—, and —NRa— groups, wherein a heteroatom in —(Y)k—R7 is not bonded to another heteroatom in —(Y)k—R7, and wherein: each R5 and R6 is independently chosen from hydrogen, deuterium, halogens, a hydroxyl group, C1-C4 alkyl groups, and C3-5 cycloalkyl groups, or R5 and R6 on the same carbon together form a C3-5 cycloalkyl group; each of R5 and R6 is optionally independently substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, halogens, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Ra is independently chosen from hydrogen and C1-C2 alkyl groups; and R7 is chosen from hydrogen, halogens, a cyano group, and C3-C10 cycloalkyl groups optionally substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, and halogens. 26. The compound of claim 24, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein each R4 is independently chosen from an oxo group or —O—(Y)k—R7 groups, wherein: k is 0, 1, 2, 3, 4, or 5; each Y is independently chosen from C(R5)(R6) groups, —O—, and —NRa— groups, wherein a heteroatom in —(Y)k—R7 is not bonded to another heteroatom in —(Y)k—R7, and wherein: each R5 and R6 is independently chosen from hydrogen, deuterium, halogens, a hydroxyl group, C1-C4 alkyl groups, and C3-5 cycloalkyl groups, or R5 and R6 on the same carbon together form a C3-5 cycloalkyl group or oxo; each of R5 and R6 is optionally independently substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, halogens, a hydroxyl group, C1-C2 alkoxyl groups, and C1-C2 haloalkoxyl groups; and each Ra is independently chosen from hydrogen and C1-C2 alkyl groups; and R7 is chosen from hydrogen, halogens, a cyano group, and C3-C10 cycloalkyl groups optionally substituted with one or more groups chosen from C1-C2 alkyl groups, C1-C2 haloalkyl groups, and halogens. 27. The compound of claim 24, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein each R4 is independently chosen from wherein indicates the point of attachment of R4 to Ring D. 28. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein k is 3, 4, 5, or 6. 29. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein q is 1. 30. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein Z is a divalent linker of formula (L)r, wherein: r is 3, 4, or 5; each L is independently chosen from C(R8)(R9) groups, —O—, and —NRb— groups, wherein a heteroatom in Z is not bonded to another heteroatom in Z, and wherein: each R8 and R9 is independently chosen from hydrogen and deuterium; and each Rb is independently chosen from hydrogen and C1-C2 alkyl groups. 31. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein Z is a divalent linker of formula (L)r, wherein: r is 3, 4, or 5; each L is independently chosen from C(R8)(R9) groups and —NRb— groups, wherein a heteroatom in Z is not bonded to another heteroatom in Z, and: each R8 and R9 is independently chosen from hydrogen and deuterium; and each Rb is independently chosen from hydrogen and methyl. 32. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein Z is a divalent linker of formula (L)r, wherein: r is 3, 4, or 5; each L is independently chosen from C(R8)(R9) groups and —NRb— groups, wherein a heteroatom in Z is not bonded to another heteroatom in Z, and wherein: each R8 and R9 is independently chosen from hydrogen and deuterium; and each Rb is hydrogen. 33. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein Z is a divalent linker of formula (L)r, wherein: r is 3, 4, or 5; each L is independently chosen from C(R8)(R9) groups, —O—, and —NRb— groups, wherein a heteroatom in Z is not bonded to another heteroatom in Z, wherein: each R8 and R9 is hydrogen; and each Rb is independently chosen from hydrogen and C1-C2 alkyl groups. 34. The compound of claim 1, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein each R3 is independently CD3. 35. The compound of claim 5, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: r is 3 or 4; each R8 and R9 is independently chosen from hydrogen and deuterium; and each Rb is independently chosen from hydrogen and C1-C2 alkyl groups. 36. The compound of claim 5, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: r is 3 or 4; each R8 and R9 is independently chosen from hydrogen and deuterium; and each Rb is hydrogen. 37. The compound of claim 6, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: r is 3 or 4; and each R8 and R9 is independently chosen from hydrogen and deuterium. 38. The compound of claim 6, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: r is 3 or 4; and each R8 and R9 is hydrogen. 39. The compound of claim 6, a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing, wherein: r is 3 or 4; and each R8 and R9 is hydrogen. 40. A compound of the formula: a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing. 41. A compound of the formula: or a pharmaceutically acceptable salt thereof. 42. The compound of claim 41, wherein the compound is in the form of a pharmaceutically acceptable salt. 43. The compound of claim 42, wherein the pharmaceutically acceptable salt is a calcium salt. 44. The compound of claim 42, wherein the pharmaceutically acceptable salt is a sodium salt. 45. The compound of claim 42, wherein the pharmaceutically acceptable salt is a potassium salt. 46. A pharmaceutical composition comprising the compound, salt, or deuterated derivative of any one of claims 40 to 45, and optionally one or more of: (a) Compound II: a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing; (b) Compound III or Compound III-d: a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing; and (c) a pharmaceutically acceptable carrier. 47. A pharmaceutical composition comprising the pharmaceutically acceptable salt of any one of claims 42 to 45, and optionally one or more of: (a) Compound II: a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing; (b) Compound III or Compound III-d: a pharmaceutically acceptable salt thereof, or a deuterated derivative of any of the foregoing; and (c) a pharmaceutically acceptable carrier.