| 主权项 |
1. A compound of Formula I:or a pharmaceutically acceptable salt thereof, wherein:
each of R1 and R2 is independently C1-6 alkyl that is optionally substituted with one or more substituents each independently selected from the group consisting of OH, halogen, C1-4 alkoxy, C1-4 haloalkoxy, and C3-7 cycloalkyl, wherein the C3-7 cycloalkyl is optionally substituted with one or more substituents each independently selected from the group consisting of OH, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy; or R1 and R2, together with the N atom to which they are attached, form 4- to 14-membered heterocycloalkyl that is optionally substituted with R8 and optionally substituted with one or more independently selected R9 or R30; each of R3 and R4 is independently H, halogen, OH, C1-6 alkyl, or C3-7 cycloalkyl, wherein the C1-6 alkyl of R3 and R4 is optionally substituted with one or more substituents each independently selected from the group consisting of OH, halogen, C1-4 alkoxy, C1-4 haloalkoxy, and C3-6 cycloalkyl, and wherein the C3-7 cycloalkyl of R3 and R4 is optionally substituted with one or more substituents each independently selected from the group consisting of OH, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy; or R3 and R4, together with the C atom to which they are attached, form a C3-7 cycloalkyl that is optionally substituted with one or more substituents each independently selected from the group consisting of OH, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy; each of R5 and R6 is independently H, C1-6 alkyl, or C3-7 cycloalkyl, wherein the C1-6 alkyl of R5 and R6 is optionally substituted with one or more substituents each independently selected from the group consisting of OH, halogen, C1-4 alkoxy, C1-4 haloalkoxy, and C3-6 cycloalkyl, and wherein the C3-7 cycloalkyl of R5 and R6 is optionally substituted with one or more substituents each independently selected from the group consisting of OH, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy; or R5 and R6, together with the C atom to which they are attached, form C3-7 cycloalkyl that is optionally substituted with one or more substituents each independently selected from the group consisting of OH, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy; R7 is H, C1-6 alkyl, C3-7 cycloalkyl, or R10, wherein the C1-6 alkyl of R7 is optionally substituted with one or more substituents each independently selected from the group consisting of OH, halogen, C1-4 alkoxy, C1-4 haloalkoxy, and C3-6 cycloalkyl, and wherein the C3-7 cycloalkyl of R7 is optionally substituted with one or more substituents each independently selected from the group consisting of OH, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy; or R7 and R6, together with the intervening moiety of “C(R5)—O” to which they are attached, form 4- to 7-membered heterocycloalkyl or 5- to 10-membered heteroaryl that is optionally substituted with one or more substituents each independently selected from the group consisting of OH, oxo, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy, and wherein each of the ring-forming atoms of the 4- to 7-membered heterocycloalkyl is independently C, N, O, S, or P and wherein each of the ring-forming atoms of the 5- to 10-membered heteroaryl is C, N, O, or S; or R7 and R3, together with the intervening moiety of “C(R4)—C(R5R6)—O” to which they are attached, form 5- to 7-membered heterocycloalkyl or 5- to 10-membered heteroaryl that is optionally substituted with one or more substituents each independently selected from the group consisting of OH, oxo, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy, and wherein each of the ring-forming atoms of the 5- to 7-membered heterocycloalkyl is independently C, N, O, S, or P, and wherein each of the ring-forming atoms of the 5- to 10-membered heteroaryl is C, N, O, or S; R8 is -L1-R11, -L2-R12, -L3-R13, -L4-R14, —C(R15)(Cy1)(Cy2), —C(R15)(Cy1)[—NR23—S(═O)2-Cy2], or -L5-N(-L6-Cy3)(-L7-Cy4); each R9 is independently OH, oxo, halogen, optionally substituted C1-4 alkyl, optionally substituted C1-4 alkoxy, or optionally substituted C3-6 cycloalkyl; R10 is —P(═O)(OR81)(OR82) or —S(═O)2OR90; each of L1, L2, L3, and L4 is independently absent, —(CR21R22)m—, —NR23—, —O—, —C(═O)—, —S(═O)2—, —S(═O)2—(CR21R22)n—, —C(═O)—(CR21R22)n—, —S(═O)2—NR23—, —C(═O)—NR23—, —(CR21R22)f1—NR23—(CR21R22)f2—, —(CR21R22)f1—O—(CR21R22)f2—, —C(═O)—NR23—(CR21R22)p—, or —S(═O)2— NR23—(CR21R22)p—; L5 is absent or —(CR21R22)—; L6 is absent or —(CR21R22)—; L7 is absent, —(CR21R22)—, or —S(═O)2—; R11 is 5- to 10-membered heteroaryl optionally substituted with one or more independently selected R31; R12 is 4- to 14-membered heterocycloalkyl optionally substituted with one or more independently selected R32; R13 is C6-10 aryl optionally substituted with one or more independently selected R33; R14 is C3-14 cycloalkyl optionally substituted with one or more independently selected R34; R15 is H, OH, halogen, C1-4 alkoxy, C1-4 alkyl, or cyclopropyl; each of R21 and R22 is independently H, OH, halogen, C1-3 alkyl, or cyclopropyl, wherein the C1-3 alkyl is optionally substituted with one or more substituents each independently selected from the group consisting of OH, halogen, C1-3 alkoxy, C1-3 haloalkoxy, and cyclopropyl; R23 is H, C1-4 alkyl, or cyclopropyl; each of R30, R31, R32, R33, and R34 is independently selected from the group consisting of halogen, —N(Ra)(Rb), —N(Rc)(C(═O)Rd), —N(Rc)(S(═O)2Rd), —C(═O)—N(Ra)(Rb), —C(═O)—Rd, —C(═O)—ORd, —OC(═O)—Rd, —N(Rc)(S(═O)2Rd), —S(═O)2—N(Ra)(Rb), —SRd, —S(═O)2Rd, —ORd, —OR35, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, (C3-10 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, (C3-10 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl- is optionally substituted with one or more independently selected R36; and wherein each of the C1-6 alkyl, C3-10 cycloalkyl, 4- to 10-membered heterocycloalkyl, (C3-10 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl- is further optionally substituted one or more oxo; each R35 is independently selected from the group consisting of H, C1-6 alkyl, C3-10 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, (C3-10 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the C1-6 alkyl, C3-10 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, (C3-10 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl- is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —CN, —C(═O)C1-4 alkyl, —C(═O)OH, —C(═O)O—C1-4 alkyl, —C(═O)NHC1-4 alkyl, —C(═O)N(C1-4 alkyl)2, oxo, —OH, —OC(═O)—C1-4 alkyl, —OC(═O)O—C1-4 alkyl, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, —NHC(═O)C1-4 alkyl, —NHC(═O)OC1-4 alkyl, —NHC(═O)NHC1-4 alkyl, and C1-4 alkoxy; each R36 is independently selected from the group consisting of halogen, —OH, —NO2, —CN, —SF5, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, —N(Ra)(Rb), —N(Rc)(C(═O)Rd), —C(═O)—N(Ra)(Rb), —C(═O)—Rd, —C(═O)—ORd, —OC(═O)—Rd, —N(Rc)(S(═O)2Rd), —S(═O)2—N(Ra)(Rb), —SRd, —S(═O)2Rd, and —ORd, wherein each of the C1-6 alkyl, C3-7 cycloalkyl, and heterocycloalkyl is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, —CN, —OH, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C3-6 cycloalkyl, —N(Ra)(Rb), —N(Rc)(C(═O)Rd), —C(═O)—ORd, —C(═O)H, —C(═O)Rd, —C(═O)N(Ra)(Rb), —N(Rc)(S(═O)2Rd), —S(═O)2—N(Ra)(Rb), —SRd, —S(═O)2Rd, and —ORd; each of R81, R82, and R90 is independently selected from the group consisting of H, C1-6 alkyl, C3-7 cycloalkyl, and (C3-7 cycloalkyl)-C1-4 alkyl-, wherein each of the C1-6 alkyl, C3-7 cycloalkyl, and (C3-7 cycloalkyl)-C1-4 alkyl- is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, —CN, —OH, oxo, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C3-6 cycloalkyl; or OR81 and OR82, together with the P(═O) to which they are attached, form 4- to 10-membered heterocycloalkyl that is further optionally substituted with one or more substituents each independently selected from the group consisting of halogen, —CN, —OH, oxo, —NH2, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, and C3-6 cycloalkyl; each of Cy1, Cy2, Cy3, and Cy4 is independently selected from the group consisting of R11, R12, R13, and R14; each Ra is independently H, C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, or (C3-7 cycloalkyl)-C1-4 alkyl-; each Rb is independently H or selected from the group consisting of C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, a 4- to 10-membered heterocycloalkyl, C610 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with one or more substituents each independently selected from the group consisting of —OH, —CN, C1-4 alkyl, C3-7 cycloalkyl, C1-4 hydroxylalkyl, —S—C1-4 alkyl, —C(═O)H, —C(═O)—C1-4 alkyl, —C(═O)—O—C1-4 alkyl, —C(═O)—NH2, —C(═O)—N(C1-4 alkyl)2, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy; or Ra and Rb, together with the N atom to which they are attached, form a 4- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl, each optionally substituted with one or more substituents each independently selected from the group consisting of halogen, —OH, oxo, —C(═O)H, —C(═O)OH, —C(═O)—C1-4 alkyl, —C(═O)—NH2, —C(═O)—N(C1-4 alkyl)2, —CN, C1-4 alkyl, C3-6 cycloalkyl, (C3-6 cycloalkyl)-C1-2 alkyl-, C1-4 alkoxy, C1-4 hydroxylalkyl, C1-4 haloalkyl, and C1-4 haloalkoxy; each Rc is independently selected from the group consisting of H, C1-4 alkyl, C3-7 cycloalkyl, and (C3-7 cycloalkyl)-C1-4 alkyl-; each Rd is independently selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, a 4- to 14-membered heterocycloalkyl, C6-10 aryl, a 5- to 10-membered heteroaryl, (C3-7 cycloalkyl)-C1-4 alkyl-, (4- to 10-membered heterocycloalkyl)-C1-4 alkyl-, (C6-10 aryl)-C1-4 alkyl-, and (5- to 10-membered heteroaryl)-C1-4 alkyl-, wherein each of the selections from the group is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, —CF3, —CN, —OH, oxo, —S—C1-4 alkyl, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy; each of f1 and f2 is independently 0, 1, or 2, provided that the sum of f1 and f2 is 1, 2, or 3; m is 1, 2, or 3; n is 1, 2, or 3; p is 1, or 2; and r is 0 or 1, provided that when r is 1 and each of R3, R4, R5 and R6 is H, then the moiety of “—N(R1)(R2)” is other than optionally substituted 4-oxo-3H-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-7-yl. |
