| CPC C07D 239/34 (2013.01) [A61P 35/00 (2018.01); C07D 403/06 (2013.01); C07K 14/001 (2013.01)] | 23 Claims |
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1. A compound of Formula (I):
 or a pharmaceutically acceptable salt thereof, wherein:
X is N;
Y is N;
Z is CR5;
or Y and Z taken together form an optionally substituted five- to six-membered heteroaryl, or an optionally substituted five- to six-membered heterocyclyl;
R1 is H, —O-(optionally substituted C3-C8 cycloalkyl), —O-(optionally substituted C1-C6 alkyl), —O-(optionally substituted C6-C10 aryl), —O-(optionally substituted five- to six-membered heteroaryl), —O-(optionally substituted five- to six-membered heterocyclyl), or optionally substituted C3-C8 cycloalkyl;
or R1 together with the carbon atoms to which it is shown attached and X form an optionally substituted five- to six-membered heterocyclyl;
R3 is optionally substituted C3-C8 cycloalkyl, optionally substituted C3-C8 cycloalkenyl, optionally substituted C6-C10 aryl, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkenyl, —NR2, —N(R)(optionally substituted C3-C8 cycloalkyl), —S-(optionally substituted C1-C6 alkyl), —O-(optionally substituted C1-C6 alkyl), —O-(optionally substituted C3-C8 cycloalkyl), optionally substituted four- to six-membered heterocyclyl or heterocyclenyl, optionally substituted five- to six-membered heteroaryl, or —O-(optionally substituted C3-C8 cycloalkyl);
or R3 taken together with the carbon atom to which it is shown attached and Y form an optionally substituted five- to six-membered heterocyclyl or heterocyclenyl;
R5 is H, C1-C6 alkyl, —NR2, or —N(R)—C(═O)—(C1-C6 alkyl);
each R independently is H, or optionally substituted C1-C6 alkyl;
W is W1, W2, W3, W4, or W5;
W1 is:
 wherein:
the bonds represented by
 indicate that can exist as either a (Z)- or (E)-geometric isomer wherein
 indicates the point of attachment;
R6 is H;
R7 is H, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, or optionally substituted five- to six-membered heterocyclyl;
R7a is H or deuterium;
R8 is H;
R9 is H; and
R10 is optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, or optionally substituted five- to six-membered heterocyclyl;
or R6 together with the nitrogen atom to which it is shown attached and R7 and R7a together with the carbon atom to which they are shown attached form an azetidinyl ring;
or R6 together with the nitrogen atom to which it is shown attached and R7, R7a, and R8 together with the carbon atoms to which they are shown attached form an azetidinyl or pyrrolodinyl ring;
or R6 together with the nitrogen atom to which it is shown attached and R7, R7a, R8, and R9 together with the carbon atoms to which they are shown attached form a dihydropyrrolyl ring;
or R8, R9, and R10 together with the carbon atoms to which they are shown attached form a 1,1-dioxido-2H-thietyl ring;
W2 is:
 wherein:
the bonds represented by
indicate that can exist as either a (Z)- or (E)-geometric isomer, wherein
 indicates the point of attachment;
R11 is H;
R12 is H or optionally substituted C1-C6 alkyl;
R12a is H; and
R13 and R14 are each H;
or R11 together with the nitrogen atom to which it is shown attached and R12, R12a, and R13 together with the carbon atoms to which they are shown attached form an optionally substituted azetidinyl ring;
W3 is:
 wherein:
 indicates the point of attachment;
R15 is H;
R16 is H or optionally substituted C1-C6 alkyl, or optionally substituted C3-C8 cycloalkyl;
W4 is:
 wherein:
 indicates the point of attachment;
R17 is H;
R18 is H or optionally substituted C1-C6 alkyl; and
each Ra independently is optionally substituted C1-C6 alkyl; and
W5 is:
 wherein:
the bond represented by
indicates that can exist as either a (Z)- or (E)-geometric isomer, and wherein
 indicates the point of attachment;
m is 1, 2, or 3; and
R19 is selected from the group consisting of C1-C6 alkyl and —O—(C1-C6 alkyl).
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