| 主权项 |
1. A compound of Formula (I): or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein: R1 is selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-14 membered heteroaryl)-C1-4 alkyl-, (4-10 membered heterocycloalkyl)-C1-4 alkyl-, CN, NO2, ORa, SRa, NHORa, C(O)Ra, C(O)NRaRa, C(O)ORa, OC(O)Ra, OC(O)NRaRa, NHRa, NRaRa, NRaC(O)Ra, NRaC(O)ORa, NRaC(O)NRaRa, C(═NRa)Ra, C(═NRa)NRaRa, NRaC(═NRa)NRaRa, NRaS(O)Ra, NRaS(O)2Ra, NRaS(O)2NRaRa, S(O)Ra, S(O)NRaRa, S(O)2Ra, and S(O)2NRaRa, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-14 membered heteroaryl)-C1.4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl- of R1 are each optionally substituted with 1, 2, 3, or 4 Rb substituents; each Rb substituent is independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, (4-10 membered heterocycloalkyl)-C1-4 alkyl-, CN, OH, NH2, NO2, NHORc, ORc, SRc, C(O)Rc, C(O)NRcRc, C(O)ORc, OC(O)Rc, OC(O)NRcRc, C(═NRc)NRcRc, NRcC(═NRc)NRcRc, NHRc, NRcRc, NRcC(O)Rc, NRcC(O)ORc, NRcC(O)NRcRc, NRcS(O)Rc, NRcS(O)2Rc, NRcS(O)2NRcRc, S(O)Rc, S(O)NRcRc, S(O)2Rc and S(O)2NRcRc; wherein the C1-4 alkyl, C1-4 haloalkyl, C1-4 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl- of Rb are each optionally substituted with 1-3 independently selected Rd substituents; or two adjacent Rb substituents on the C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl ring of R1, taken together with the atoms to which they are attached, form a fused phenyl ring, a fused 5- or 6-membered heterocycloalkyl ring, a fused 5- or 6-membered heteroaryl ring, or a fused C5-6 cycloalkyl ring, wherein the fused 5- or 6-membered heterocycloalkyl ring and fused 5- or 6-membered heteroaryl ring each have 1-4 heteroatoms as ring members selected from N, O and S and wherein the fused phenyl ring, fused 5- or 6-membered heterocycloalkyl ring, fused 5- or 6-membered heteroaryl ring, and fused C5-6 cycloalkyl are each optionally substituted with 1 or 2 independently selected Rr substituents; each Ra is independently selected from H, CN, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl- of Ra are each optionally substituted with 1, 2, 3, 4, or 5 Rd substituents; each Rd is independently selected from C1-4 alkyl, C1-4 haloalkyl, halo, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, CN, NH2, NHORe, ORe, SRe, C(O)Re, C(O)NReRe, C(O)ORe, OC(O)Re, OC(O)NReRe, NHRe, NReRe, NReC(O)Re, NReC(O)NReRe, NReC(O)ORe, C(═NRe)NReRe, NReC(═NRe)NReRe, S(O)Re, S(O)NReRe, S(O)2Re, NReS(O)2Re, NReS(O)2NReRe, and S(O)2NReRe, wherein the C1-4 alkyl, C3-10 cycloalkyl and 4-10 membered heterocycloalkyl of Rd are each further optionally substituted with 1-3 independently selected Rr substituents; each Rc is independently selected from H, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl- of Rc are each optionally substituted with 1, 2, 3, 4, or 5 Rf substituents independently selected from C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, (4-10 membered heterocycloalkyl)-C1-4alkyl-, halo, CN, NHORg, ORg, SRg, C(O)Rg, C(O)NRgRg, C(O)ORg, OC(O)Rg, OC(O)NRgRg, NHRg, NRgRg, NRgC(O)Rg, NRgC(O)NRgRg, NRgC(O)ORg, C(═NRg)NRgRg, NRgC(═NRg)NRgRg, S(O)Rg, S(O)NRgRg, S(O)2Rg, NRgS(O)2Rg, NRgS(O)2NRgRg, and S(O)2NRgRg; wherein the C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl- of Rf are each optionally substituted with 1, 2, 3, 4, or 5 Rn substituents independently selected from C1-4 alkyl, C1-4 haloalkyl, halo, CN, Ro, NHORo, ORo, SRo, C(O)Ro, C(O)NRoRo, C(O)ORo, OC(O)Ro, OC(O)NRoRo, NHRo, NRoRo, NRoC(O)Ro, NRoC(O)NRoRo, NRoC(O)ORo, C(═NRo)NRoRo, NRoC(═NRo)NRoRo, S(O)Ro, S(O)NRoRo, S(O)2Ro, NRoS(O)2Ro, NRoS(O)2NRoRo, and S(O)2NRoRo; each Rg is independently selected from H, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl- and (4-10 membered heterocycloalkyl)-C1-4 alkyl- of Rg are each optionally substituted with 1-3 independently selected Rp substituents; or any two Ra substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 Rh substituents independently selected from C1-6 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, 5-6 membered heteroaryl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, halo, CN, ORi, SRi, NHORi, C(O)Ri, C(O)NRiRi, C(O)ORi, OC(O)Ri, OC(O)NRiRi, NHRi, NRiRi, NRiC(O)Ri, NRiC(O)NRiRi, NRiC(O)ORi, C(═NRi)NRiRi, NRiC(═NRi)NRiRi, S(O)Ri, S(O)NRiRi, S(O)2Ri, NRiS(O)2Ri, NRiS(O)2NRiRi, and S(O)2NRiRi, wherein the C1-6 alkyl, C3-10 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, and 5-6 membered heteroaryl of Rh are each further optionally substituted by 1, 2, or 3 substituents independently selected from C3-6 cycloalkyl, C6-10 aryl, 5- or 6-membered heteroaryl, C2-4 alkenyl, C2-4 alkynyl, halo, C1-4 alkyl, C1-4 haloalkyl, CN, NHORk, ORk, SRk, C(O)Rk, C(O)NRkRk, C(O)ORk, OC(O)Rk, OC(O)NRkRk, NHRk, NRkRk, NRkC(O)Rk, NRkC(O)NRkRk, NRkC(O)ORk, C(═NRk)NRkRk, NRkC(═NRk)NRkRk, S(O)Rk, S(O)NRkRk, S(O)2Rk, NRkS(O)2Rk, NRkS(O)2NRkRk, and S(O)2NRkRk; or two Rh groups attached to the same carbon atom of the 4- to 10-membered heterocycloalkyl taken together with the carbon atom to which they attach form a C3-6 cycloalkyl or 4- to 6-membered heterocycloalkyl having 1-2 heteroatoms as ring members selected from O, N or S; or any two Rc substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected Rh substituents; or any two Re substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected Rh substituents; or any two Rg substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected Rh substituents; or any two Ri substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected Rh substituents; or any two Rk substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected Rh substituents; or any two Ro substituents together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 independently selected Rh substituents; and each Re, Ri, Rk, Ro or Rp is independently selected from H, C1-4 alkyl, C3-6 cycloalkyl, C6-10 aryl, 5- or 6-membered heteroaryl, C1-4 haloalkyl, C2-4 alkenyl, and C2-4 alkynyl, wherein the C1-4 alkyl, C3-6 cycloalkyl, C6-10 aryl, 5- or 6-membered heteroaryl, C2-4 alkenyl, and C2-4 alkynyl of Re, Ri, Rk, Ro or Rp are each optionally substituted with 1, 2 or 3 W substituents; each Rr is independently selected from OH, CN, amino, halo, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C3-6 cycloalkyl, NHR9, NR9R9, and C1-4 haloalkoxy, wherein the C1-4 alkyl of Rr is optionally substituted with OH, CN, NH2, C1-4 alkoxy, C340 cycloalkyl, and 4-10 membered heterocycloalkyl, wherein each R9 is independently H or C1-6 alkyl; R2 is H, OH, ORa, NHRa or NRaRa; R3 is H, halo or CN; each R4 is independently selected from H, halo, CN, OH, NH2, NHCH3, N(CH3)2, C1-4 alkyl, C1-4 alkoxy, C1-2 haloalkyl, C1-2 haloalkoxy, ethenyl, C2-4 alkynyl and cyclopropyl, wherein the C1-4 alkyl and C1-4 alkoxy are each optionally substituted with CN or CH3O—; each R5 is independently selected from H, halo, CN, OH, NH2, NHCH3, N(CH3)2, C1-4 alkyl, C1-4 alkoxy, C1-2 haloalkyl, C1-2 haloalkoxy, ethenyl, C2-4 alkynyl, C3-6 cycloalkyl, C6-10 aryl, and 5- or 6-membered heteroaryl, wherein the C1-4 alkyl and C1-4 alkoxy are each optionally substituted with CN or CH3O—; each R6 is independently selected from H, halo, CN, OH, NH2, NHCH3, N(CH3)2, C1-4 alkyl, C1-4 alkoxy, C1-2 haloalkyl, C1-2 haloalkoxy, ethenyl, C2-4 alkynyl, C3-6 cycloalkyl, C6-10 aryl, and 5- or 6-membered heteroaryl, wherein the C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, C6-10 aryl, and 5- or 6-membered heteroaryl are each optionally substituted with OH, CN or CH3O—; or any two R6 substituents attached to the same carbon atom, taken together with the carbon atom to which they are attached, form C3-10 cycloalkyl or a 4-, 5-, or 6-membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-, 5-, or 6-membered heterocycloalkyl are each optionally substituted with 1-3 independently selected Rp substituents; R8 is H, C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-4 alkyl-, wherein the C1-4 alkyl, C3-6 cycloalkyl and C3-6 cycloalkyl-C1-4 alkyl are each optionally substituted with OH, CN or CH3O—; X is N or CR7, wherein R7 is H, halo, NH2, C1-4 alkoxy, C1-4 alkyl-NH— or (C1-4 alkyl)2N—; the subscript m is an integer of 1 or 2; the subscript n is an integer of 1, 2 or 3; and the subscript p is an integer of 1, 2 or 3. |
