CPC C07D 513/22 (2013.01) [A61K 31/404 (2013.01); A61K 31/439 (2013.01); A61K 31/47 (2013.01); A61P 11/00 (2018.01); C07D 515/22 (2013.01)] | 41 Claims |
1. A method of treating cystic fibrosis comprising administering to a patient in need thereof 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.
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