| 主权项 |
1. A compound of Formula I: or a pharmaceutically acceptable salt, a prodrug, solvate, a tautomer, an isomer or a deuterated analog thereof, wherein: (i) Y2 is N and Y3 is C; or (ii) Y2 is C and Y3 is N; Y1 is CH or N; L is a bond optionally substituted C1-6alkylene, optionally substituted deuterated C1-6alkylene, —C(R6R7)—, —C(O)NR9—, —CH2N(R9)—, —SO2N(R9)—, —N(R9)C(O)N(R9)—, —N(R9)SO2—, —N(R9)CH2—, —OC1-4alkylene-, —C1-4alkylene-O—, —NR9C(O)—, —N(R9)SO2—, —C(O)—, —S(O)—, —SO2—, —O—, —S—, —P(O)(Ra)—, optionally substituted C2-6alkenylene, optionally substituted —CH═C(Rb)— or optionally substituted —Si(Rc)(Rc)—; or R6 and R7 taken together with the carbon atom to which they attach form an optionally substituted 3- to 6-membered ring having from 0-2 heteroatoms selected from O, N or S or an oxo; Ra is optionally substituted C1-6alkyl, optionally substituted aryl or optionally substituted heteroaryl; Rb is H or C1-6alkyl; or Rb and R1 taken together with the carbon atom to which they attach form an optionally substituted 3- to 6-membered carbocyclic ring or an optionally substituted 4- to 8-membered heterocyclic ring having from 1-2 heteroatoms as ring members selected from O, N or S, wherein the nitrogen or sulfur ring atoms can be optionally oxidized; each Rc is independently C1-6alkyl or C1-6alkoxy; R9 is H, C1-4alkyl or C1-4haloalkyl; R1, R2, R4, R6 and R7 are each independently H, D, optionally substituted C1-6alkyl, optionally substituted C1-6 alkenyl, optionally substituted C1-6 alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted cycloalkylalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted —Si(Rc)(Rc) or R13 selected from halogen, —CN, —OH, —NH2, —NO2, —C(O)OH, —C(S)OH, —C(O)NH2, —C(S)NH2, —S(O)2NH2, —NHC(O)NH2, —NHC(S)NH2, —NHS(O)2NH2, —C(NH)NH2, —CH═C(Rg)(Rg), —ORg, —SRg, —OC(O)Rg, —OC(S)Rg, —P(═O)HRg, —P(═O)RgRg, —PH(═O)ORg, —P(═O)(ORg)2, —OP(═O)(ORg)2, —C(O)H, —O(CO)ORg, —C(O)Rg, —C(S)Rg, —C(O)ORg, —C(S)ORg, —S(O)Rg, —S(O)2Rg, —C(O)NHRg, —C(S)NHRg, —C(O)NRgRg, —C(S)NRgRg, —S(O)2NHRg, —S(O)2NRgRg, —C(NH)NHRg, —C(NH)NRgRg, —NHC(O)Rg, —NHC(S)Rg, —NRgC(O)Rg, —NRgC(S)Rg, —NHS(O)2Rg, —NRgS(O)2Rg, —NHC(O)NHRg, —NHC(S)NHRg, —NRgC(O)NH2, —NRgC(S)NH2, —NRgC(O)NHRg, —NRgC(S)NHRg, —NHC(O)NRgRg, —NHC(S)NRgRg, —NRgC(O)NRgRg, —NRgC(S)NRgRg, —NHS(O)2NHRg, —NRgS(O)2NH2, —NRgS(O)2NHRg, —NHS(O)2NRgRg, —NRgS(O)2NRgRg, —NHRg or —NRgRg, wherein each Rg is independently H, optionally substituted C1-6alkyl, optionally substituted C1-6 alkenyl, optionally substituted C1-6 alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted cycloalkylalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl or optionally substituted heterocycloalkylalkyl; or two Rg groups when attached to the same carbon or nitrogen atom are taken together to form a 3- to 6-membered carbocyclic ring or 3- to 8-membered heterocyclic ring having from 1-2 heteroatoms as ring members selected from O, N or S, wherein the nitrogen or sulfur ring atoms are optionally oxidized; wherein the aliphatic or aromatic portion of Rg is optionally substituted with from 1-3 Rh substituents independently selected from halogen, —CN, —OH, —NH2, —NO2, —CH═C(Ri)(Ri), —C(O)OH, —C(S)OH, —C(O)NH2, —C(S)NH2, —S(O)2NH2, —NHC(O)NH2, —NHC(S)NH2, —NHS(O)2NH2, —C(NH)NH2, —OR′, —SR′, —OC(O)R′, —OC(S)R′, —P(═O)HRi, —P(═O)RiRi, —PH(═O)ORi, —P(═O)(ORi)2, —OP(═O)(ORi)2, —C(O)H, —O(CO)ORi, —C(O)Ri, —C(S)Ri, —C(O)ORi, —C(S)ORi, —S(O)Ri, —S(O)2Ri, —C(O)NHRi, —C(S)NHRi, —C(O)NRiRi, —C(S)NRiRi, —S(O)2NHRi, —S(O)2NRiRi, —C(NH)NHRi, —C(NH)NRiRi, —NHC(O)Ri, —NHC(S)Ri, —NRiC(O)Ri, —NRiC(S)Ri, —NHS(O)2Ri, —NRiS(O)2Ri, —NHC(O)NHRi, —NHC(S)NHRi, —NRiC(O)NH2, —NRiC(S)NH2, —NRiC(O)NHRi, —NRiC(S)NHRi, —NHC(O)NRiRi, —NHC(S)NRiRi, —NRiC(O)NRiRi, —NRiC(S)NRiRi, —NHS(O)2NHRi, —NRiS(O)2NH2, —NRiS(O)2NHRi, —NHS(O)2NRiRi, —NRiS(O)2NRiRi, Ri, —NHRi or —NRiRi, wherein each Ri is independently C1-6alkyl, aryl, aryl-C1-2alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, heteroaryl, heteroaryl-C1-4alkyl, heterocycloalkyl or heterocycloalkyl-C1-4alkyl, wherein each Ri is further optionally substituted with from 1-3 Rp groups independently selected from halogen, CN, —OH, —NH2, —N(Rq)(Rq), —NO2, —C(O)OH, —C(O)NH2, —S(O)2NH2, —NHC(O)NH2, —C(NH)NH2, —P(═O)HRq, —P(═O)RqRq, —PH(═O)ORq, —P(═O)(ORq)2, —OP(═O)(ORq)2, —OC(O)Rq, —OC(S)Rq, —C(O)Rq, —C(S)Rq, —C(O)ORq, —S(O)2Rq, —C(O)NHRq, C1-6alkyl, C1-6alkoxy, halogen, C1-6haloalkyl or C1-6haloalkoxy, wherein Rq is C1-6alkyl; R3 is H, halogen, —CN, optionally substituted C1-6alkyl, optionally substituted deuterated C1-6alkyl, optionally substituted aryl, optionally substituted aryl-C1-4alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-C1-4alkyl, optionally substituted C3-8 cycloalkyl, optionally substituted C3-8 cycloalkenyl, optionally substituted C3-8 cycloalkyl-C1-4alkyl, optionally substituted C2-6 alkynyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkyl-C1-4alkyl or Rj selected from halogen, —CN, —OH, —NH2, —NO2, —C(O)OH, —C(S)OH, —C(O)NH2, —C(S)NH2, —S(O)2NH2, —NHC(O)NH2, —NHC(S)NH2, —NHS(O)2NH2, —C(NH)NH2, —CH═C(Rk)(Rk), —ORk, —SRk, —OC(O)Rk, —OC(S)Rk, —P(═O)HRk, —P(═O)RkRk, —PH(═O)ORk, —P(═O)(ORk)2, —OP(═O)(ORk)2, —C(O)H, —O(CO)ORk, —C(O)Rk, —C(S)R″, —C(O)ORk, —C(S)ORk, —S(O)Rk, —S(O)2Rk, —C(O)NHRk, —C(S)NHRk, —C(O)NRkRk, —C(S)NRkRk, —S(O)2NHRk, —S(O)2NRkRk, —C(NH)NHRk, —C(NH)NRkRk, —NHC(O)Rk, —NHC(S)Rk, —NRkC(O)Rk, —NRkC(S)Rk, —NHS(O)2Rk, —NRkS(O)2Rk, —NHC(O)NHRk, —NHC(S)NHRk, —NRkC(O)NH2, —NRkC(S)NH2, —NRkC(O)NHRk, —NRkC(S)NHRk, —NHC(O)NRkRk, —NHC(S)NRkRk, —NRkC(O)NRkRk, —NRkC(S)NRkRk, —NHS(O)2NHRk, —NRkS(O)2NH2, —NRkS(O)2NHRk, —NHS(O)2NRkRk, —NRkS(O)2NRkRk, —NHRk or —NRkRk; or two Rk groups when attached to the same carbon or nitrogen atom are taken together to form a 3- to 6-membered carbocyclic ring or 3- to 8-membered heterocyclic ring having from 1-2 heteroatoms as ring members selected from O, N or S, wherein the nitrogen or sulfur ring atoms are optionally oxidized; wherein each Rk is independently H, C1-6alkyl or aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl or cycloalkylalkyl, wherein Rk is optionally substituted with from 1-3 Rh; R5 is an optionally substituted 5- or 6-membered heteroaryl having from 1 to 4 heteroatoms as ring members selected from O, N or S; or an optionally substituted heterocycloalkyl; and is a single bond or a double bond to maintain ring A being aromatic, with the proviso that the compound is other than 3,5-dimethyl-4-(1H-pyrrolo[2,3-b]pyridin-5-yl)isoxazole; or R3 and -L-R1 are not simultaneously hydrogen. |
