US 2024/0182465 A1 · FUSED RING SUBSTITUTED SIX-MEMBERED HETEROCYCLIC COMPOUND, PREPARATION METHOD THEREFOR AND USE THEREOF

Abstract

A compound having HPK1 inhibitory activity as shown in formula (IA) or (IC), and a pharmaceutically acceptable salt, a stereoisomer, a solvate or a prodrug thereof, and a pharmaceutical composition containing the compound, and use of same in preparation of a drug for preventing and/or treating diseases or conditions associated with HPK1 activity.

A compound of formula (IA), or a pharmaceutically acceptable salt, a stereoisomer, a solvate or a prodrug thereof:

wherein
Y is CH or N;
R1 is H, C1-6 alkyl, —C1-4 alkyl-hydroxy, —C1-4 alkyl-cyano, —C1-4 alkyl-carboxy, —C1-4 alkyl-C1-6 alkyl, —C1-4 alkyl-C1-6 alkoxy, C3-20 cycloalkyl, 3- to 20-membered heterocyclyl, C6-14 aryl, 5- or 6-membered monocyclic heteroaryl, 8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-C3-20 cycloalkyl, —C1-4 alkyl-O—C3-20 cycloalkyl, —C1-4 alkyl-3- to 20-membered heterocyclyl, —C1-4 alkyl-O-3- to 20-membered heterocyclyl, —C1-4 alkyl-C6-14 aryl, —C1-4 alkyl-O—C1-4 aryl, —C1-4 alkyl-5- or 6-membered monocyclic heteroaryl, —C1-4 alkyl-O-5- or 6-membered monocyclic heteroaryl, —C1-4 alkyl-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-O-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-NRaRb, —C1-4 alkyl-NRd—C(═O)—Rc, —C1-4 alkyl-NRd—C(═O)—NRaRb, —C1-4 alkyl-NRd—S(═O)2—Rc, —C1-4 alkyl-NRd—S(═O)2—NRaRb, —C1-4 alkyl-C(═O)—NRaRb, —C1-4 alkyl-S(═O)2—Rc, —C1-4 alkyl-S(═O)2—NRaRb, —C(═O)—C1-4 alkyl, —C(═O)—C3-20 cycloalkyl, —C(═O)-3- to 20-membered heterocyclyl, —C(═O)—C6-14 aryl, —C(═O)-5- or 6-membered monocyclic heteroaryl, —C(═O)-8- to 10-membered bicyclic heteroaryl, —C(═O)—NRaRb, —S(═O)2—Rc, or —S(═O)2—NRaRb;
wherein the C1-6 alkyl and the C1-6 alkoxy are each independently optionally substituted with halogen, deuterium, cyano, or hydroxyl;
the C3-20 cycloalkyl, the 3- to 20-membered heterocyclyl, the C6-14 aryl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are each independently optionally substituted with 1, 2, 3, or 4 group(s) selected from group S1;
the 3- to 20-membered heterocyclyl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl each independently contains 1, 2, 3, or 4 heteroatom(s) independently selected from N, O, and S as ring atoms;
Z, L1 and R4 are selected from one of the following combinations:
(a) Z is N;
-L1-R4 is absent;
(b) Z is C;
L1 is a bond, —C1-4 alkyl-, —C3-6 monocyclic cycloalkyl-, —O—, —S—, —NH—, —C(═O)—, —S(═O)—, or —S(═O)2—;
R4 is selected from the group consisting of H, halogen, cyano, hydroxyl, carboxyl, nitro, C1-6 alkyl, C1-6 alkoxy, C3-20 cycloalkyl, 3- to 20-membered heterocyclyl, C1-4 aryl, 5- or 6-membered monocyclic heteroaryl, 8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-hydroxyl, —C1-4 alkyl-cyano, —C1-4 alkyl-carboxyl, —C1-4 alkyl-C1-6 alkyl, —C1-4 alkyl-C1-6 alkoxy, —C1-4 alkyl-C3-20 cycloalkyl, —C1-4 alkyl-O—C3-20 cycloalkyl, —C1-4 alkyl-3- to 20-membered heterocyclyl, —C1-4 alkyl-O-3- to 20-membered heterocyclyl, —C1-4 alkyl-C6-14 aryl, —C1-4 alkyl-O—C6-14 aryl, —C1-4 alkyl-5- or 6-membered monocyclic heteroaryl, —C1-4 alkyl-O-5- or 6-membered monocyclic heteroaryl, —C1-4 alkyl-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-O-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-NRaRc, —C1-4 alkyl-C(═O)—NRaRb, —C1-4 alkyl-NRd—C(═O)—Rc, —C1-4 alkyl-NRd—C(═O)—NRaRb, —C1-4 alkyl-S(═O)2—Rc, —C1-4 alkyl-NRd—S(═O)2—Rc, —C1-4 alkyl-S(═O)2—NRaRb, —C1-4 alkyl-NRd—S(═O)2—NRaRb, —C(═O)—C1-6 alkyl, —C(═O)—C3-20 cycloalkyl, —C(═O)-3- to 20-membered heterocyclyl, —C(═O)—C6-14 aryl, —C(═O)-5- or 6-membered monocyclic heteroaryl, —C(═O)-8- to 10-membered bicyclic heteroaryl, —C(═O)—NRaRb, —NRd—C(═O)—Rc, —NRd—C(═O)—NRaRb, —S(═O)2—Rc, —NRd—S(═O)2—Rc, —S(═O)2—NRaRb, —NRd—S(═O)2—NRaRb, —NRaRb, —ORc;
the C1-6 alkyl and the C1-6 alkoxy are each independently optionally substituted with halogen, deuterium, cyano, or hydroxy;
the C3-20 cycloalkyl, the 3- to 20-membered heterocyclyl, the C6-14 aryl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are each independently optionally substituted with 1, 2, 3, or 4 group(s) selected from group S1;
the 3- to 20-membered heterocyclyl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl each independently contains 1, 2, 3, or 4 heteroatom(s) independently selected from N, O, and S as ring atoms;
is phenyl or 5- or 6-membered monocyclic heteroaryl;
the 5- or 6-membered monocyclic heteroaryl contains 1, 2, or 3 heteroatom(s) independently selected from N, O, and S as ring atoms;
the phenyl or the 5- or 6-membered monocyclic heteroaryl are each independently optionally substituted with m1 R2 group(s);
m1 is 1, 2, 3, or 4;
the R2 is
wherein
R2a is H, deuterium, C1-6 alkyl, phenyl, or deuterated C1-6 alkyl, and R2b is H, deuterium, C1-6 alkyl, or deuterated C1-6 alkyl;
or R2a and R2b together with the carbon atom to which the R2a and R2b are attached form a C3-6 monocyclic cycloalkyl group;
and the bond between R2a and the carbon atom is a single bond;
R2c is H, deuterium, C1-6 alkyl, deuterated C1-6 alkyl, —C1-4 alkyl-C3-6 monocyclic cycloalkyl, or C3-6 monocyclic cycloalkyl;
R2d is H, deuterium, C1-6 alkyl, deuterated C1-6 alkyl, C3-20 cycloalkyl, or 3- to 20-membered heterocyclyl;
or
when R2a and R2d together with the nitrogen atom to which the R2a and R2d are attached form a 3- to 20-membered heterocyclyl group, a 5- or 6-membered monocyclic heteroaryl group, or an 8- to 10-membered bicyclic heteroaryl group, R2c is H, deuterium, C1-6 alkyl, or deuterated C1-6 alkyl;
R2b is H, deuterium, C1-6 alkyl, or deuterated C1-6 alkyl, and the bond between R2a and the carbon atom is a single bond;
or R2b is absent, and the bond between R2a and the carbon atom is a double bond;
the 3- to 20-membered heterocyclyl, the 5- or 6-membered monocyclic heteroaryl, or the 8- to 10-membered bicyclic heteroaryl each independently contains one nitrogen atom and optionally 1 or 2 heteroatom(s) independently selected from N, O, and S as ring atoms;
and the 3- to 20-membered heterocyclyl, the 5- or 6-membered monocyclic heteroaryl and the 8- to 10-membered bicyclic heteroaryl are each independently optionally substituted with 1, 2, 3, or 4 group(s) selected from group S1;
or
when R2c and R2d together with the nitrogen atom to which the R2c and R2d are attached form a 3- to 20-membered heterocyclyl group, a 5- or 6-membered monocyclic heteroaryl group, or an 8- to 10-membered bicyclic heteroaryl group, R2a is H, deuterium, C1-6 alkyl, or deuterated C1-6 alkyl, R2b is H, deuterium, C1-6 alkyl, or deuterated C1-6 alkyl, and the bond between R2a and the carbon atom is a single bond;
the 3- to 20-membered heterocyclyl, the 5- or 6-membered monocyclic heteroaryl, or the 8- to 10-membered bicyclic heteroaryl each independently contains one nitrogen atom and optionally 1 or 2 heteroatom(s) independently selected from N, O, and S as ring atoms;
and the 3- to 20-membered heterocyclyl, the 5- or 6-membered monocyclic heteroaryl and the 8- to 10-membered bicyclic heteroaryl are each independently optionally substituted with 1, 2, 3, or 4 group(s) selected from group S1;
or
the R2 is
is 3- to 20-membered heterocyclyl, 5- or 6-membered monocyclic heteroaryl, or 8- to 10-membered bicyclic heteroaryl containing one nitrogen atom and attached to other moieties of a molecule through the nitrogen atom;
further optionally contains 1 or 2 heteroatom(s) independently selected from N, O, and S as ring atoms;
the 3- to 20-membered heterocyclyl, the 5- or 6-membered monocyclic heteroaryl and the 8- to 10-membered bicyclic heteroaryl are each independently optionally substituted with 1, 2, 3, or 4 group(s) selected from group S1;
is phenyl or 5- or 6-membered monocyclic heteroaryl;
the 5- or 6-membered monocyclic heteroaryl contains 1, 2, or 3 heteroatom(s) independently selected from N, O, and S as ring atoms;
the phenyl and the 5- or 6-membered monocyclic heteroaryl are each independently optionally substituted with m2 R3 group(s);
m2 is 1, 2, 3, or 4;
each R3 is independently selected from the group consisting of H, oxo (═O), halogen, cyano, hydroxyl, carboxyl, nitro, C1-6 alkyl, C1-6 alkoxy, C3-20 cycloalkyl, 3- to 20-membered heterocyclyl, C6-14 aryl, 5- or 6-membered monocyclic heteroaryl, 8- to 10-membered bicyclic heteroaryl, —O—C3-20 cycloalkyl, —O-3- to 20-membered heterocyclyl, —O—C6-14 aryl, —O-5- or 6-membered monocyclic heteroaryl, —O-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-hydroxyl, —C1-4 alkyl-cyano, —C1-4 alkyl-C1-6 alkyl, —C1-4 alkyl-C1-6 alkoxy, —C1-4 alkyl-C3-20 cycloalkyl, —C1-4 alkyl-O—C3-20 cycloalkyl, —C1-4 alkyl-3- to 20-membered heterocyclyl, —C1-4 alkyl-O-3- to 20-membered heterocyclyl, —C1-4 alkyl-C6-14 aryl, —C1-4 alkyl-O—C6-14 aryl, —C1-4 alkyl-5- or 6-membered monocyclic heteroaryl, —C1-4 alkyl-O-5- or 6-membered monocyclic heteroaryl, —C1-4 alkyl-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-O-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-NRaRb, —C1-4 alkyl-C(═O)—NRaRb, —C1-4 alkyl-NRd—C(═O)—Rc, —C1-4 alkyl-NRd—C(═O)—NRaRb, —C1-4 alkyl-S(═O)2—Rc, —C1-4 alkyl-NRd—S(═O)2—Rc, —C1-4 alkyl-S(═O)2—NRaRb, —C1-4 alkyl-NRd—S(═O)2—NRaRb, —C1-4 alkyl-carboxy, —C(═O)—C1-6 alkyl, —C(═O)O—C1-6 alkyl, —C(═O)—C1-4 alkyl-hydroxy, —C(═O)—C1-4 alkyl-C1-6 alkoxy, —C(═O)—C1-4 alkyl-O—C3-20 cycloalkyl, —C(═O)—C3-20 cycloalkyl, —C(═O)O—C3-20 cycloalkyl, —C(═O)—C1-4 alkyl-C3-20 cycloalkyl, —C(═O)-3- to 20-membered heterocyclyl, —C(═O)—C1-4 alkyl-3- to 20-membered heterocyclyl, —C(═O)—C6-14 aryl, —C(═O)-5- or 6-membered monocyclic heteroaryl, —C(═O)-8- to 10-membered bicyclic heteroaryl, —C(═O)—NRaRb, —NRd—C(═O)—Rc, —NRd—C(═O)—NRaRb, —S(═O)2—Rc, —NRd—S(═O)2—Rc, —S(═O)2—NRaRb, —NRd—S(═O)2—NRaRb, —NRaRb, —ORc, —C1-4 alkyl-P(═O)(C1-6 alkyl)2, —P(═O)(C1-6 alkyl)2;
wherein the C1-6 alkyl and the C1-6 alkoxy are each independently optionally substituted with 1, 2, 3, or 4 group(s) selected from halogen, deuterium, cyano, 5- to 6-membered heterocyclyl, and hydroxyl;
the C3-20 cycloalkyl, the 3- to 20-membered heterocyclyl, the C6-14 aryl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are each independently optionally substituted with 1, 2, 3, or 4 group(s) selected from group S2;
the 3- to 20-membered heterocyclyl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl each independently contains 1, 2, 3, or 4 heteroatom(s) independently selected from N, O, and S as ring atoms;
or
is C5-7 monocyclic cycloalkyl or 5-, 6- or 7-membered monocyclic heterocyclyl;
the 5-, 6- or 7-membered heterocyclyl each independently contains 1, 2, or 3 heteroatom(s) independently selected from N, O, and S as ring atoms;
the C5-7 monocyclic cycloalkyl and the 5-, 6- or 7-membered monocyclic heterocyclyl are each independently optionally substituted with m2 R3 group(s);
m2 is 1, 2, 3, or 4;
each R3 is independently selected from the group consisting of H, oxo (═O), halogen, cyano, hydroxyl, carboxyl, nitro, C1-6 alkyl, C1-6 alkoxy, C3-20 cycloalkyl, 3- to 20-membered heterocyclyl, C6-14 aryl, 5- or 6-membered monocyclic heteroaryl, 8- to 10-membered bicyclic heteroaryl, —O—C3-20 cycloalkyl, —O-3- to 20-membered heterocyclyl, —O—C1-14 aryl, —O-5- or 6-membered monocyclic heteroaryl, —O-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-hydroxyl, —C1-4 alkyl-cyano, —C1-4 alkyl-C1-6 alkyl, —C1-4 alkyl-C1-6 alkoxy, —C1-4 alkyl-C3-20 cycloalkyl, —C1-4 alkyl-O—C3-20 cycloalkyl, —C1-4 alkyl-3- to 20-membered heterocyclyl, —C1-4 alkyl-O-3- to 20-membered heterocyclyl, —C1-4 alkyl-C6-14 aryl, —C1-4 alkyl-O—C6-14 aryl, —C1-4 alkyl-5- or 6-membered monocyclic heteroaryl, —C1-4 alkyl-O-5- or 6-membered monocyclic heteroaryl, —C1-4 alkyl-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-O-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-NRaRb, —C1-4 alkyl-C(═O)—NRaRb, —C1-4 alkyl-NRd—C(═O)—Rc, —C1-4 alkyl-NRd—C(═O)—NRaRb, —C1-4 alkyl-S(═O)2—Rc, —C1-4 alkyl-NRd—S(═O)2—Rc, —C1-4 alkyl-S(═O)2—NRaRb, —C1-4 alkyl-NRd—S(═O)2—NRaRb, —C1-4 alkyl-carboxy, —C(═O)—C1-6 alkyl, —C(═O)O—C1-6 alkyl, —C(═O)—C1-4 alkyl-hydroxy, —C(═O)—C1-4 alkyl-C1-6 alkoxy, —C(═O)—C1-4 alkyl-O—C3-20 cycloalkyl, —C(═O)—C3-20 cycloalkyl, —C(═O)O—C3-20 cycloalkyl, —C(═O)—C1-4 alkyl-C3-20 cycloalkyl, —C(═O)-3- to 20-membered heterocyclyl, —C(═O)—C1-4 alkyl-3- to 20-membered heterocyclyl, —C(═O)—C6-14 aryl, —C(═O)-5- or 6-membered monocyclic heteroaryl, —C(═O)-8- to 10-membered bicyclic heteroaryl, —C(═O)—NRaRb, —NRd—C(═O)—Rc, —NRd—C(═O)—NRaRb, —S(═O)2—Rc, —NRd—S(═O)2—Rc, —S(═O)2—NRaRb, —NRd—S(═O)2—NRaRb, —NRaRb, —ORc, —C1-4 alkyl-P(═O)(C1-6 alkyl)2, —P(═O)(C1-6 alkyl)2, ═CR3aR3b;
wherein two hydrogen atoms attached to a same carbon atom can be substituted with two R3 groups such that the two R3 groups together with the carbon atom to which the two R3 groups are attached form a C3-6 monocyclic cycloalkyl group or a 3- to 6-membered monocyclic heterocyclyl group;
or two hydrogen atoms attached to different carbon atoms are substituted with two R3 groups, and the two R3 groups join to form —CH2—, —CH2CH2—, or —CH2CH2CH2—;
wherein the C1-6 alkyl and the C1-6 alkoxy are each independently optionally substituted with 1, 2, 3, or 4 group(s) selected from halogen, deuterium, cyano, 5- to 6-membered heterocyclyl, and hydroxyl;
the C3-20 cycloalkyl, the 3- to 20-membered heterocyclyl, the C6-14 aryl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are each independently optionally substituted with 1, 2, 3, or 4 group(s) selected from group S2;
the 3- to 20-membered heterocyclyl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl each independently contains 1, 2, 3, or 4 heteroatom(s) independently selected from N, O, and S as ring atoms;
wherein R3a and R3b are each independently hydrogen, halogen, cyano, C1-6 alkyl, halogenated C1-6 alkyl, C6-14 aryl, or 5- or 6-membered monocyclic heteroaryl;
the C6-14 aryl or the 5- or 6-membered monocyclic heteroaryl is optionally substituted with 1, 2, or 3 group(s) selected from halogen, cyano, C1-4 alkyl, C1-4 alkoxy, halogenated C1-4 alkyl, halogenated C1-4 alkoxy;
or R3a and R3b together with the carbon atom to which the R3 and R3b are attached form a C3-6 monocyclic cycloalkyl group or a 3- to 6-membered monocyclic heterocyclyl group;
the C3-6 monocyclic cycloalkyl or the 3- to 6-membered monocyclic heterocyclyl is optionally substituted with 1, 2, or 3 group(s) selected from halogen, cyano, C1-4 alkyl, C1-4 alkoxy, halogenated C1-4 alkyl, halogenated C1-4 alkoxy, C6-14 aryl, 5- or 6-membered monocyclic heteroaryl;
among the above groups, each group from group S1 is independently selected from the group consisting of oxo (═O), halogen, cyano, hydroxyl, carboxyl, nitro, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-20 cycloalkyl, 3- to 20-membered heterocyclyl, C6-14 aryl, 5- or 6-membered monocyclic heteroaryl, 8- to 10-membered bicyclic heteroaryl, —O—C3-20 cycloalkyl, —O-3- to 20-membered heterocyclyl, —O—C6-14 aryl, —O-5- or 6-membered monocyclic heteroaryl, —O-8- to 10-membered bicyclic heteroaryl, —C≡C—C3-20 cycloalkyl, —C≡C-3- to 20-membered heterocyclyl, —C≡C—C6-14 aryl, —C≡C-5- or 6-membered monocyclic heteroaryl, —C≡C-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-hydroxy, —C1-4 alkyl-cyano, —C1-4 alkyl-C1-6 alkyl, —C1-4 alkyl-C1-6 alkoxy, —C1-4 alkyl-C3-20 cycloalkyl, —C1-4 alkyl-O—C3-20 cycloalkyl, —C1-4 alkyl-3- to 20-membered heterocyclyl, —C1-4 alkyl-O-3- to 20-membered heterocyclyl, —C1-4 alkyl-C6-14 aryl, —C1-4 alkyl-O—C6-14 aryl, —C1-4 alkyl-5- or 6-membered monocyclic heteroaryl, —C1-4 alkyl-O-5- or 6-membered monocyclic heteroaryl, —C1-4 alkyl-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-O-8- to 10-membered bicyclic heteroaryl, —S(═O)2—C1-6 alkyl, —S(═O)2—C3-20 cycloalkyl, —S(═O)2-3- to 20-membered heterocyclyl, —S(═O)2-5- or 6-membered monocyclic heteroaryl, —S(═O)2-8- to 10-membered bicyclic heteroaryl, —C(═O)O—C1-6 alkyl, —C(═O)O—C3-20 cycloalkyl, —C(═O)O-3- to 20-membered heterocyclyl, —C(═O)O-5- or 6-membered monocyclic heteroaryl, —C(═O)O-8- to 10-membered bicyclic heteroaryl, —C(═O)—C1-4 alkyl, —C(═O)—C3-20 cycloalkyl, —C(═O)—C6-14 aryl, —NRa1Rb1, —C(═O)—NRa1Rb1, —ORc1, —C1-4 alkyl-S(═O)2—C1-6 alkyl, —C1-4 alkyl-S(═O)2—C3-20 cycloalkyl, —C1-4 alkyl-S(═O)2-3- to 20-membered heterocyclyl, —C1-4 alkyl-C(═O)O—C1-4 alkyl, —C1-4 alkyl-C(═O)O—C3-20 cycloalkyl, —C1-4 alkyl-C(═O)—C1-6 alkyl, —C1-4 alkyl-C(═O)—C3-20 cycloalkyl, —C1-4 alkyl-C(═O)—C6-14 aryl, —C(═O)-5- or 6-membered monocyclic heteroaryl, —C(═O)-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-NRa1Rb1, —C1-4 alkyl-C(═O)—NRa1Rb1, —C≡C—C(═O)—NRa1Rb1, —C≡C—C1-4 alkyl-C(═O)—NRa1Rb1, —C1-4 alkyl-ORc1, —C1-4 alkyl-P(═O)—(C1-6 alkyl)2, —P(═O)—(C1-6 alkyl)2, —C1-4 alkyl-NRd1—C(═O)—Rc1, —C1-4 alkyl-NRd1—C(═O)—NRa1Rb1, —C1-4 alkyl-NRd1—S(═O)2—Rc1, —C1-4 alkyl-S(═O)2—NRa1Rb1, —C1-4 alkyl-NRd1—S(═O)2—NRa1Rb1—NRd1—C(═O)—Rc1, —NRd1—C(═O)—NRa1Rb1, —NRd1—S(═O)2—Rc1, —S(═O)2—NRa1Rb1, —NRdl-S(═O)2—NRa1Rb1, wherein the C1-6 alkyl, the C1-6 alkoxy, the C2-6 alkenyl, and the C2-6 alkynyl are each independently optionally substituted with 1, 2, or 3 group(s) selected from halogen, deuterium, cyano, or hydroxyl;
the C3-20 cycloalkyl, the 3- to 20-membered heterocyclyl, the C6-14 aryl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are each independently optionally substituted with 1, 2, 3, or 4 group(s) selected from group S3;
the 3- to 20-membered heterocyclyl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl each independently contains 1, 2, 3, or 4 heteroatom(s) independently selected from N, O, and S as ring atoms;
among the above groups, each group from group S2 is independently selected from the group consisting of oxo (═O), halogen, cyano, hydroxyl, carboxyl, nitro, C1-6 alkyl, C2-6 alkynyl, C1-6 alkoxy, C3-20 cycloalkyl, 3- to 20-membered heterocyclyl, C6-14 aryl, 5- or 6-membered monocyclic heteroaryl, 8- to 10-membered bicyclic heteroaryl, —O-3- to 20-membered heterocyclyl, —O-5- or 6-membered monocyclic heteroaryl, —O-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-hydroxyl, —C1-4 alkyl-cyano, —C1-4 alkyl-C1-6 alkyl, —C1-4 alkyl-C1-6 alkoxy, —C1-4 alkyl-C3-20 cycloalkyl, —C1-4 alkyl-O—C3-20 cycloalkyl, —C1-4 alkyl-3- to 20-membered heterocyclyl, —C1-4 alkyl-O-3- to 20-membered heterocyclyl, —C1-4 alkyl-5- or 6-membered monocyclic heteroaryl, —C1-4 alkyl-O-5- or 6-membered monocyclic heteroaryl, —C1-4 alkyl-8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-O-8- to 10-membered bicyclic heteroaryl, —S(═O)2—C1-6 alkyl, —S(═O)2—C3-20 cycloalkyl, —S(═O)2-3- to 20-membered heterocyclyl, —S(═O)2-5- or 6-membered monocyclic heteroaryl, —S(═O)2-8- to 10-membered bicyclic heteroaryl, —C(═O)O—C1-4 alkyl, —C(═O)O—C3-20 cycloalkyl, —C(═O)O-3- to 20-membered heterocyclyl, —C(═O)O-5- or 6-membered monocyclic heteroaryl, —C(═O)O-8- to 10-membered bicyclic heteroaryl, —NRa1Rb1, —C(═O)—NRa1Rb1, —ORc1, —C1-4 alkyl-C(═O)O—C1-6 alkyl, —C1-4 alkyl-C(═O)O—C3-20 cycloalkyl, —C1-4 alkyl-NRa1Rb1, —C1-4 alkyl-C(═O)—NRa1Rb1, —C≡C—C(═O)—NRa1Rb1, —C≡C—C1-4 alkyl-C(═O)—NRa1Rb1, —C1-4 alkyl-ORc1, —C1-4 alkyl-P(═O)—(C1-4 alkyl)2, —P(═O)—(C1-6 alkyl)2, —C1-4 alkyl-NRd1—C(═O)—Rc1, —C1-4 alkyl-NRd1—C(═O)—NRa1Rb1, —C1-4 alkyl-NRd1—S(═O)2—Rc1, —C1-4 alkyl-S(═O)2—NRa1Rb1, —C1-4 alkyl-NRd1—S(═O)2—NRa1Rb1, —NRd1—C(═O)—Rc1, —NRd1—C(═O)—NRa1Rb1, —NRd1—S(═O)2—Rc1, —S(═O)2—NRa1Rb1, —NRd1—S(═O)2—NRa1Rb1, wherein the C1-6 alkyl, the C1-4 alkoxy, and the C2-6 alkynyl are each independently optionally substituted with 1, 2, or 3 group(s) selected from halogen, deuterium, cyano, or hydroxyl;
the C3-20 cycloalkyl, the 3- to 20-membered heterocyclyl, the C1-4 aryl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are each independently optionally substituted with 1, 2, 3, or 4 group(s) selected from group S3;
the 3- to 20-membered heterocyclyl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl each independently contains 1, 2, 3, or 4 heteroatom(s) independently selected from N, O, and S as ring atoms;
among the above groups, each Ra, Rb, Ra1, and Rb1 is independently H, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, —C1-4 alkyl-hydroxy, —C1-4 alkyl-cyano, —C1-4 alkyl-halogenated C1-6 alkyl, —C1-4 alkyl-deuterated C1-6 alkyl, —C1-4 alkyl-C1-6 alkoxy, —C1-4 alkyl-halogenated C1-6 alkoxy, —C1-4 alkyl-deuterated C1-6 alkoxy, C3-6 monocyclic cycloalkyl, —C1-4 alkyl-C3-6 monocyclic cycloalkyl, —C1-4 alkyl-O—C3-6 monocyclic cycloalkyl, 3- to 6-membered monocyclic heterocyclyl, —C1-4 alkyl-3- to 6-membered monocyclic heterocyclyl, —C1-4 alkyl-O-3- to 6-membered monocyclic heterocyclyl, phenyl, —C1-4 alkyl-phenyl, 5- or 6-membered monocyclic heteroaryl, —C1-4 alkyl-5- or 6-membered monocyclic heteroaryl, 8- to 10-membered bicyclic heteroaryl, —C1-4 alkyl-8- to 10-membered bicyclic heteroaryl, —S(═O)2—C1-6 alkyl, —S(═O)2—C3-6 monocyclic cycloalkyl, —S(═O)2-3- to 6-membered monocyclic heterocyclyl, —C(═O)—C1-6 alkyl, —C(═O)—C3-6 monocyclic cycloalkyl, —C(═O)-3- to 6-membered monocyclic heterocyclyl;
wherein the C3-6 monocyclic cycloalkyl, the 3- to 6-membered monocyclic heterocyclyl, the phenyl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are optionally substituted with 1 or 2 group(s) selected from the group consisting of halogen, hydroxyl, carboxyl, nitro, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, deuterated C1-6 alkoxy, —NH2, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —C1-4 alkyl-P(═O)—(C1-6 alkyl)2, —P(═O)—(C1-6 alkyl)2;
or
each Ra and Rb together with the nitrogen atom to which the Ra and Rb are attached form a 3- to 20-membered heterocyclyl group, each Ra1 and Rb1 together with the nitrogen atom to which the Ra1 and Rb1 are attached form a 3- to 20-membered heterocyclyl group;
wherein the 3- to 20-membered heterocyclyl is each independently optionally substituted with 1 or 2 group(s) selected from the group consisting of halogen, hydroxyl, carboxyl, nitro, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, deuterated C1-6 alkoxy, —NH2, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —C1-4 alkyl-P(═O)—(C1-6 alkyl)2, —P(═O)—(C1-6 alkyl)2;
among the above groups, each Rd and Rd1 are independently H, C1-6 alkyl, or deuterated C1-6 alkyl;
among the above groups, each Rc and Rc1 are independently H, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, deuterated C1-6 alkoxy, —C1-4 alkyl-halogenated C1-6 alkyl, —C1-4 alkyl-deuterated C1-6 alkyl, —C1-4 alkyl-C1-6 alkoxy, —C1-4 alkyl-halogenated C1-6 alkoxy, —C1-4 alkyl-deuterated C1-6 alkoxy, C3-6 monocyclic cycloalkyl, —C1-4 alkyl-C3-6 monocyclic cycloalkyl, —C1-4 alkyl-O—C3-6 monocyclic cycloalkyl, 3- to 6-membered monocyclic heterocyclyl, —C1-4 alkyl-3- to 6-membered monocyclic heterocyclyl, —C1-4 alkyl-O-3- to 6-membered monocyclic heterocyclyl, phenyl, —C1-4 alkyl-phenyl, 5- or 6-membered monocyclic heteroaryl, —C1-4 alkyl-5- or 6-membered monocyclic heteroaryl, 8- to 10-membered bicyclic heteroaryl, or —C1-4 alkyl-8- to 10-membered bicyclic heteroaryl;
the C3-6 monocyclic cycloalkyl, the 3- to 6-membered monocyclic heterocyclyl, the phenyl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are optionally substituted with 1 or 2 group(s) selected from the group consisting of halogen, hydroxyl, carboxyl, nitro, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, deuterated C1-6 alkoxy, —NH2, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —C1-4 alkyl-P(═O)—(C1-6 alkyl)2, —P(═O)—(C1-6 alkyl)2;
among the above groups, each group from group S3 is independently selected from the group consisting of oxo (C═O), cyano, halogen, hydroxy, carboxy, nitro, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, deuterated C1-6 alkoxy, —NH2, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —C1-4 alkyl-P(═O)—(C1-6 alkyl)2, —P(═O)—(C1-6 alkyl)2, 3- to 6-membered monocyclic heterocyclyl;
among the above groups, the —C1-4 alkyl- or the —C3-6 monocyclic cycloalkyl- is unsubstituted;
or
hydrogen atoms of the —C1-4 alkyl- are each independently substituted with a group selected from halogen, cyano, hydroxy, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl, —CH2-hydroxy, —CH2-cyano, and phenyl, or two hydrogen atoms attached to a same carbon atom of the C1-4 alkyl are simultaneously substituted with —(CH2)j— to form a cycloalkyl group, wherein j is 2, 3, 4, 5, or 6;
hydrogen atoms of the —C3-6 monocyclic cycloalkyl- are each independently substituted with a group selected from halogen, cyano, hydroxy, C1-6 alkyl, halogenated C1-6 alkyl, deuterated C1-6 alkyl.

80 more elements

Fused ring substituted six-membered heterocyclic compound, preparation method therefor and use thereof

Life of this patent

Fused ring substituted six-membered heterocyclic compound, preparation method therefor and use thereof

Life of this patent

Abstract

Claims26