| 主权项 |
1. A compound of Formula IA:or a single enantiomer, a racemic mixture, a diastereomer, a mixture of diastereomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt or solvate thereof;
A1, A2, and E are each independently (a) a bond; or (b) C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, C2-20 cycloalkylene, C6-20 arylene, heteroarylene; or heterocyclylene; L1 and L2 are each independently (a) a bond; (b) C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, C3-7 cycloalkylene, C6-14 arylene, heteroarylene, or heterocyclylene; or (c) —C(O)—, —C(O)O—, —C(O)NR1a—, —C(═NR1a)NR1c, —O—, —OC(O)O—, —OC(O)NR1a—, —OC(═NR1a)NR1c—, —OP(O)(OR1a)—, —OP(O)(OR1a)O—, —NR1a—, —NR1aC(O)NR1c—, —NR1aC(═NR1b)NR1c—, —NR1aS(O)NR1c—, —NR1aS(O)2NR1c—, —S—, —S(O)—, —S(O)2—, —S(O)NR1a—, or —S(O)2NR1a—; wherein at least one of L1 and L2 is heteroarylene or heterocyclylene, which is substituted with —C1-6 alkylene-OP(O)(ORP1)2 (in one embodiment, —CH2—OP(O)(ORP1)2) or —C1-6 alkylene-O-linked amino acid or a derivative thereof (in one embodiment, —CH2—OC(O)C(Raa)2NR1bR1c); Z1 and Z2 are each independently a bond, —O—, —S—, —S(O)—, —S(O2)—, or —N(RN)—; R1 and R2 are each independently (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; (c) —C(O)R1a,—C(O)CH(N(R1c)C(O)OR1b)R1a, —C(O)OR1a, —C(O)NR1bR1c, —C(NR1a)NR1bR1c, —P(O)(OR1a)R1d, —CH2P(O)(OR1a)R1d, —S(O)R1a, —S(O)2R1a, —S(O)NR1bR1c, or —S(O)2NR1bR1c; (d) —C1-6 alkylene-OP(O)(ORP1)2, in one embodiment, —CH2—OP(O)(ORP1)2; or (e) —C1-6 alkylene-O-linked amino acid or a derivative thereof, in one embodiment, —CH2—OC(O)C(Raa)2NR1bR1c;
each R3 and R4 is independently (a) cyano, halo, or nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (c) —C(O)R1a, —C(O)OR1a, —C(O)NR1bR1c, —C(NR1a)NR1bR1c, —OR1a, —OC(O)R1a, —OC(O)OR1a, —OC(O)NR1bR1c, —OC(═NR1a)NR1bR1c, —OS(O)R1a, —OS(O)2R1a, —OS(O)NR1bR1c, —OS(O)2NR1bR1c, —NR1bR1c, —NR1aC(O)R1d, —NR1aC(O)OR1d, —NR1aC(O)NR1bR1c, —NR1aC(═NR1d)NR1bR1c, —NR1aS(O)R1d, —NR1aS(O)2R1d, —NR1aS(O)NR1bR1c, —NR1aS(O)2NR1bR1c, —P(O)(OR1a)R1d, —CH2P(O)(OR1a)R1d, —SR1a, —S(O)R1a, —S(O)2R1a, —S(O)NR1bR1c, or —S(O)2NR1bR1c; or two R3 or two R4 that are attached to the same ring are linked together to form a bond, —O—, —NRN—, —S—, C1-6 alkylene, C1-6 heteroalkylene, C2-6 alkenylene, or C2-6 heteroalkenylene; each RN is independently (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; (c) —C(O)OR1a, —C(O)NR1bR1c, —C(NR1a)NR1bR1c, —OR1a, —OC(O)R1a, —OC(O)OR1a, —OC(O)NR1bR1c, —OC(═NR1a)NR1bR1c, —OS(O)R1a, —OS(O)2R1a, —OS(O)NR1bR1c, —OS(O)2NR1bR1c, —NR1bR1c, —NR1aC(O)R1d, —NR1aC(O)OR1d, —NR1aC(O)NR1bR1c, —NR1aC(═NR1d)NR1bR1c, —NR1aS(O)R1d, —NR1aS(O)2R1d, —NR1aS(O)NR1bR1c, —NR1aS(O)2NR1bR1c, —P(O)(OR1a)R1d, —CH2P(O)(OR1a)R1d, —S(O)R1a, —S(O)2R1a, —S(O)NR1bR1c, or —S(O)2NR1bR1c; (d) —C1-6 alkylene-OP(O)(ORP1)2, in one embodiment, —CH2—OP(O)(ORP1)2; or (e) —C1-6 alkylene-O-linked amino acid or a derivative thereof, in one embodiment, —CH2—OC(O)C(Raa)2NR1bR1c; each RP1 is independently (a) hydrogen; (b) a monovalent cation, in one embodiment, Na+ or K+, in another embodiment, Li+, Rb+, or Cs+; or (c) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or two RP1 together are a divalent cation, in one embodiment, Mg2+ or Ca2+; each R1a, R1b, R1c, and R1d is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or R1a and R1c together with the C and N atoms to which they are attached form heterocyclyl; or R1b and R1c together with the N atom to which they are attached form heterocyclyl; each Raa independently is a side chain of a naturally occurring or non-naturally occurring amino acid; in one embodiment, each Raa independently is hydrogen, C1-6 alkyl, heteroalkyl, C6-14 aryl-C16 alkyl and heteroaryl-C16 alkyl; each m and n is independently an integer of 1, 2, 3, or 4; and each s and t is independently an integer of 0, 1, 2, 3, 4, 5, 6, or 7; with the proviso that the compound is neither wherein each alkyl, alkylene, heteroalkylene, alkenyl, alkenylene, heteroalkenylene, alkynyl, alkynylene, cycloalkyl, cycloalkylene, aryl, arylene, aralkyl, heteroaryl, heteroarylene, heterocyclyl, and heterocyclylene is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, where each Q is independently selected from (a) oxo, cyano, halo, or nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; or (c) —C(O)Ra, —C(O)ORa, —C(O)NRbRc, —C(NRa)NRbRc, —ORa, —OC(O)Ra, —OC(O)ORa, —OC(O)NRbRc, —OC(═NRa)NRbRc, —OP(O)(ORe)2, —OS(O)Ra, —OS(O)2Ra, —OS(O)NRbRc, —OS(O)2NRbRc, —NRbRc, —NRaC(O)Rd, —NRaC(O)ORd, —NRaC(O)NRbRc, —NRaC(═NRd)NRbRc, —NRaS(O)Rd, —NRaS(O)2Rd, —NRaS(O)NRbRc, —NRaS(O)2NRbRc, —P(O)(ORa)Rd, —CH2P(O)(ORa)Rd, —CH2OP(O)(ORe)2, —CH2OC(O)C(Ra)2NRbRc, —SRa, —S(O)Ra, —S(O)2Ra, —S(O)NRbRc, or —S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rd is independently (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; or (iii) Rb and Rc together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; and each Re is independently (i) hydrogen; (ii) a monovalent cation (e.g., Na+ or K+); (iii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; or (iv) two Re together are a divalent cation (e.g., Mg2+ or Ca2+); wherein each Qa is independently selected from (a) oxo, cyano, halo, or nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (c) —C(O)Rf, —C(O)ORf, —C(O)NRgRh, —C(NRf)NRgRh, —ORf, —OC(O)Rf, —OC(O)ORf, —OC(O)NRgRh, —OC(═NRf)NRgRh, —OP(O)(ORn)2, —OS(O)Rf, —OS(O)2Rf, —OS(O)NRgRh, —OS(O)2NRgRh, —RgRh, —NRfC(O)Rk, —NRfC(O)ORk, —NRfC(O)NRgRh, —NRfC(═NRk)NRgRh, —NRfS(O)Rk, —NRfS(O)2Rk, —NRfS(O)NRgRh, —NRfS(O)2NRgRh, —P(O)(ORf)Rk, —CH2P(O)(ORf)Rk, —SRf, —S(O)Rf, —S(O)2Rf, —S(O)NRgRh, or —S(O)2NRgRh; wherein each Rf, Rg, Rh, and Rk is independently (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) Rg and Rh together with the N atom to which they are attached form heterocyclyl; and each Rn is independently (i) hydrogen; (ii) a monovalent cation (e.g., Na+ or K+); (iii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iv) two Rn together are a divalent cation (e.g., Mg2+ or Ca2+). |
