| 主权项 |
1. A compound of the Formula:or a pharmaceutically acceptable salt thereof, wherein
U1 and U2 are both N and U3 is C—Re; or U3 is N, one of U1 and U2 is N, and the other is C—Rd; or U3 is C—Re, one of U1 and U2 is N, and the other is C—Rd; V1 is O, S, NRV, CO, CH2, or CF2; RV is H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, or aryl; Rd is H, halo, CN, alkyl, cycloalkyl, alkoxy, haloalkyl, alkenyl, haloalkenyl or halocycloalkyl; Re is H or NH2; or, Rd and Re, together with the ring atom to which each is attached, form a 5- or 6-membered ring containing one, two or three heteroatoms, independently selected from N, S and O, wherein the 5- or 6-membered ring so formed is independently substituted by Rh; Rh is H, C1-4 alkyl, or halo; Rg is H, F, —P(O)(R3A)(R3B), —S(O)N(R3C)(R3D), —S(O)2R3E, —C(O)N(R3F)(R3G), —OC(O)N(R3F)(R3G), —NR3HC(O)OR3I, a 5- or 6-membered heterocyclic ring comprising 1, 2, 3 or 4 N atoms; each R3A, R3B, R3C, R3D, R3E, R3F, R3G, R3H, and R3I is, independently, selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, and heteroalkyl, or R3A and R3B, or R3C and R3D, or R3F and R3G, together with the atom to which each is attached, form an optionally substituted 5- or 6-membered heterocyclic ring; Rg2 is H, F, W1, —P(O)(R3A)(R3B), —S(O)N(R3C)(R3D), —S(O)2R3E, —C(O)N(R3F)(R3G), —OC(O)N(R3F)(R3G), —NR3HC(O)OR3I, C1-6 alkoxy, C1-4 alkyl, or, Rg2 and Rg together with the atom to which each is attached form an optionally substituted 5- to 7-membered heterocyclic ring comprising 1-3 heteroatoms independently selected from P, N, O and S; Rg1 is H, F, —OR2, —P(O)(R3A)(R3B), —S(O)N(R3C)(R3D), —S(O)2R3E, —C(O)N(R3F)(R3G), —OC(O)N(R3F)(R3G), —NR3HC(O)OR3I, or an optionally substituted 5- or 6-membered heterocyclic ring; Ring A is: Rb2 is H, F, or an optionally substituted 5- or 6-membered heterocyclic ring containing 1, 2 or 3 N or O atoms; Rb4 is H, F, W1, C1-6 alkoxy, C3-6 alkenyloxy, C3-6 cycloalkoxy, —OC(O)N(R5A)(R5B), —NR5CC(O)OR5D, or an optionally substituted 5- or 6-membered heterocyclic ring comprising 1, 2 or 3 N or O atoms; each R5A, R5B, R5C, and R5D is independently selected from H, alkyl, alkenyl, alkynyl, and heteroalkyl, or R5A and R5B, together with the atom to which each is attached, form an optionally substituted 5- or 6-membered heterocyclic ring; Ra1 is H, halo, W1, —CN, —NO2, —R1, —OR2, —O—NR1R2, —NR1R2, —NR1—NR1R2, —NR1—OR2, —C(O)YR2, —OC(O)YR2, —NR1C(O)YR2, —SC(O)YR2, —NR1C(═S)YR2, —OC(═S)YR2, —C(═S)YR2, —YC(═NR1)YR2, —YC(═N—OR1)YR2, —YC(═N—NR1R2)YR2, —YP(═O)(YR1)(YR2), —S(O)rR2, —SO2NR1R2, —NR1SO2NR1R2, or X1 and X2 are each independently CH or N; or Ra1 and Rb4, together with the atom to which each is attached, form an optionally substituted 5- or 6-membered heterocyclic ring comprising 1, 2 or 3 heteroatoms independently selected from N and O; Ra2 is H, halo, C1-6 alkyl, C2-6 alkenyl, C3-6 cycloalkyl, C1-6 alkoxy, C2-6 alkenyloxy, C3-6 cycloalkyloxy or 4- to 7-membered heterocyclyl, wherein the alkyl, alkenyl, cycloalkyl, alkoxy, C2-6 alkenyloxy, cycloalkyloxy and heterocyclyl are optionally substituted with one or more halo, amino, C1-6 alkylamino, or di-C1-6 alkylamino groups; Y is independently a bond, —O—, —S— or —NR1—; R1 and R2 are independently H or R15; R4 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic and heteroaryl; W1 is —NR7C(O)C(R11)═CR9R10, —C(O)C(R11)═CR9R10, —CH2P(O)C(R11)═CR9R10, —OP(O)C(R8)=CR9R10, —NR7S(O)2C(R9)(R10)(RX), —NR7S(O)2C(R11)═CR9R10, —NR7C(O)C≡C—R14, —NR7C(O)C(R9)(R10)(RX), RX is halo; R7 is H, alkyl or heteroalkyl, wherein the alkyl and heteroalkyl groups are independently optionally substituted with an amino, alkylamino or dialkylamino group; R8 is C1-6 alkyl; R9 and R10 are independently H, halo, —C(O)R16, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclyl or heteroaryl, wherein R9 and R10, if not H, are optionally substituted with one or more halo, amino, alkylamino, dialkylamino, alkoxy, cycloalkyl, heterocyclyl or heteroaryl groups, wherein said group, if not halo, is optionally substituted with one or more halo, C1-4 alkyl, alkoxyl, halo(C1-4)alkyl or C3-7 cycloalkyl groups; R11 is H, halo, —C(O)—OR12, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic, or heteroaryl, wherein R11, if not H, is optionally substituted with one or more halo, amino, alkoxyl, cycloalkyl, heterocyclic or heteroaryl groups, wherein said group, if not halo, is optionally substituted with one or more halo or alkyl, alkoxyl, cycloalkyl or heterocyclyl groups, wherein the alkyl, alkoxyl, cycloalkyl and heterocyclyl group is optionally substituted with one or more alkyl, halo or hydroxyl substituents; or R9 and R11, taken together with the atom to which each is attached, form a cycloalkenyl or heterocyclic ring; R12 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic, or heteroaryl; R13 is H or C1-4 alkyl; R14 is RT or RW; R15 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, 4- to 7-membered heterocyclyl, or heteroaryl, wherein each R15 is optionally substituted with one or more halo, cycloalkyl, heterocyclic or heteroaryl groups, wherein said cycloalkyl, heterocyclic or heteroaryl groups(s) are independently optionally substituted with one or more halo, alkyl, haloalkyl, hydroxyalkyl, amino, dialkylamino or cycloalkyl groups; R16 is OH, —O-alkyl, cycloalkyl, heterocyclyl, —NH2, —NH-alkyl, or —N-dialkyl wherein the alkyl, cycloalkyl or heterocyclyl moiety is optionally substituted with halo, amino, alkylamino, dialkylamino, alkyl or hydroxyl; RT is H or —CH3; RW is halo; substituted methyl; or an optionally substituted group selected from (C2-6)alkyl, (C1-6)heteroalkyl, heterocyclyl, aryl and heteroaryl; wherein the substituents on the optionally substituted (C2-6)alkyl, (C1-6)heteroalkyl, heterocyclyl, aryl and heteroaryl groups are selected from halo, haloalkyl, alkoxy, heterocyclyl, substituted heterocyclyl, amino, alkylamino, and dialkylamino, and in the case of an optionally substituted heterocyclyl, the optional substituents may further be selected from hydroxyl, alkyl, haloalkyl, hyroxyalkyl, alkoxyalkyl, amino, alkylamino and dialkylamino; wherein (a) the compound is not one of the following two compounds: (b) at least one of Ra1, Rg2, and Rb4 is W1; (c) the compound comprises at least one —P(O)(R3A)(R3B); and (d) the compound further has one or more of the following features: Rd is halo(C3-5)cycloalkyl; Ra2 is halo; substituted alkyl, substituted alkoxy, or optionally substituted cycloalkyl, wherein substituents on the alkyl, alkoxy or cycloalkyl groups are selected from halo, amino and dialkylamino groups; Ra1 is an optionally substituted 4-membered heterocycle; Ra1 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl or heteroalkyl, and is substituted with one or more groups selected from halo, OH, heterocyclyl, substituted heterocyclyl, heteroaryl, and substituted heteroaryl; Ra1 is heterocyclyl or heterocyclyl-O—, wherein Ra1 is substituted with one or more groups selected from —OH, halo, 4-membered heterocyclyl, substituted 4-membered heterocyclyl and R18, wherein R18 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl or heteroalkyl, and R18 is optionally substituted; Ra1 and Rb4, together with the atom to which each is attached, form an optionally substituted 5-membered heterocyclic ring; Ra2 is an optionally substituted 4- to 7-membered membered heterocycle; Rb4 is —NR7C(O)C(R11)═CR9R10 or —NR7C(O)C C≡C—RW; Rg1 is —OR2; R9or R10 is cycloalkyl, —CO2H, —CO2-alkyl, —C(O)-heterocyclyl, —C(O)NH2, —C(O)NH-alkyl or —C(O)N-dialkyl wherein an alkyl, cycloalkyl or heterocyclyl substituent or portion of a substituent is optionally substituted with amino, alkylamino, dialkylamino, alkyl or hydroxyl; one or more of R9, R10 and R11 is halo, haloalkyl, alkyl, alkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl or arylalkyl wherein alkyl, heterocylic, heteroaryl or aryl substituent, or an alkyl, heterocylic, heteroaryl or aryl portion of a substituent, is optionally substituted with one or more groups selected from halo, haloalkyl, hydroxyl, hydroxyalkyl, amino, alkylamino, dialkylamino, alkyl, alkenyl, SO2alkyl, oxo, heterocyclyl and heterocycle substituted with one or more alkyl, amino alkylamino, dialkylamino, hydroxyl, hydroxyalkyl, SO2alkyl substituents; and, R9 and R11, taken together with the atom to which each is attached, form a cycloalkenyl or heterocyclic ring. |
