| 主权项 |
1. A compound having the structure:or a pharmaceutically acceptable salt thereof,wherein:
X is O, S or CH2; B is a natural or non-natural purine or pyrimidine base, or B is selected from one of the following groups: Y is N or —C(R19)—; Z is N or CH; R1 is H, R2 is H or:or R1 and R2 join to form a group having the formula: R3 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C7 cycloalkyl; R4, R5, R7 and R8 are each independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, halo, —OR20, —SR20 or —N(R20)2; R6, R9 and R10 are each independently selected from H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, 5- or 6-membered monocyclic heteroaryl, 9- or 10-membered bicyclic heteroaryl, 4 to 7-membered heterocycloalkyl, halo, —OR20, —SR20, —S(O)2R20; —S(O)2N(R20)2, —NHC(O)OR20, —NHC(O)N(R20)2, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 haloalkyl), —CN, —NO2, —N(R20)2, —NH(C1-C6 alkylene)-(5- or 6-membered monocyclic heteroaryl), —NH(C1-C6 alkylene)-(9- or 10-membered bicyclic heteroaryl), —C(O)R20, —C(O)OR20, —C(O)N(R20)2 and —NHC(O)R20, wherein said C2-C6 alkenyl group and said C2-C6 alkynyl group can be optionally substituted a halo group; each occurrence of R12 is independently selected from H, —(C1-C6 alkylene)-T-R21, —(C1-C6 alkylene)m-(C6-C10 aryl), —(C1-C6 alkylene)m-(4 to 7-membered heterocycloalkyl), —(C1-C6 alkylene)m-(4 to 7-membered heterocycloalkenyl), —CH(C6-C10 aryl)-C(O)OR20 and:wherein said C6-C10 aryl moiety of said —(C1-C6 alkylene)m-(C6-C10 aryl) group, said 4 to 7-membered heterocycloalkyl moiety of said —(C1-C6 alkylene)m-(4 to 7-membered heterocycloalkyl) group and said 4 to 7-membered heterocycloalkenyl moiety of said —(C1-C6 alkylene)m-(4 to 7-membered heterocycloalkenyl) group can be optionally substituted with up to three groups, each independently selected from C1-C6 alkyl, halo, —OR20, C1-C6 haloalkyl, —N(R20)2, —C(O)OR20, —C(O)N(R20)2 and —NHC(O)R20;
R13 is H, —(C1-C6 alkylene)-T-R21 or —(C1-C6 alkylene)m-(C6-C10 aryl), or R12 and R13 can join to form a C2-C4 alkylene group between the oxygen atoms that R12 and R13 are attached to, wherein said C2-C4 alkylene group is substituted with at least one C6-C10 aryl group, wherein said C6-C10 aryl moiety of said —(C1-C6 alkylene)m-(C6-C10 aryl) group can be optionally substituted with up to three groups, each independently selected from group can be optionally substituted with up to three groups, each independently selected from C1-C6 alkyl, halo, —OR20, C1-C6 haloalkyl, —N(R20)2, —C(O)OR20, —C(O)N(R20)2 and —NHC(O)R20; R14 is H, C6-C10 aryl, 5- or 6-membered monocyclic heteroaryl or 9- or 10-membered bicyclic heteroaryl, wherein said C6-C10 aryl group, said 5- or 6-membered monocyclic heteroaryl group and said 9- or 10-membered bicyclic heteroaryl group can be optionally substituted with R22; R15 is H, C1-C6 alkyl, C3-C7 cycloalkyl, phenyl or benzyl, wherein said C1-C6 alkyl can be optionally substituted with a group selected from halo, —OR20, —SR20, guanidino, —N(R20)2, —C(O)OR20, —C(O)N(R20)2, —NHC(O)R20, 5- or 6-membered monocyclic heteroaryl and 9- or 10-membered bicyclic heteroaryl, and wherein said phenyl group and said benzyl group can be optionally substituted with up to 2 groups, each independently selected from C1-C6 alkyl, halo and —OR20; R16 is H, C1-C6 alkyl, C3-C7 cycloalkyl, phenyl or benzyl, wherein said C1-C6 alkyl can be optionally substituted with a group selected from halo, —OR20, —SR20, guanidino, —N(R20)2, —C(O)OR20, —C(O)N(R20)2, —NHC(O)R20, 5- or 6-membered monocyclic heteroaryl and 9- or 10-membered bicyclic heteroaryl, and wherein said phenyl group and said benzyl group can be optionally substituted with up to 2 groups, each independently selected from C1-C6 alkyl, halo and —OR20; R17 is H, C1-C20 alkyl, C2-C20 alkenyl, —(C1-C3 alkylene)m-C3-C7 cycloalkyl, —(C1-C3 alkylene)m-C6-C10 aryl or adamantyl, wherein said C1-C20 alkyl group, said C2-C20 alkenyl group, said C6-C10 aryl group and said adamantyl group can be optionally substituted with up to three groups, each independently selected from halo, —OR20, —C(O)OR20, CN, NO2, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C3-C7 cycloalkyl, C6-C10 aryl, 5- or 6-membered monocyclic heteroaryl, 9- or 10-membered bicyclic heteroaryl, —N(R20)2, —C(O)N(R20)2—SR20, —S(O)R20, —S(O)2R20, —S(O)2N(R20)2, —NHC(O)R20, —NHC(O)OR20 and —NHC(O)N(R20)2 and; R18 is H, C1-C6 alkyl, C3-C7 cycloalkyl, —(C1-C3 alkylene)m-C6-C10 aryl, —(C1-C3 alkylene)-C(O)OR20, -5- or 6-membered monocyclic heteroaryl, 9- or 10-membered bicyclic heteroaryl, 4 to 7-membered heterocycloalkyl or:wherein said C6-C10 aryl group, said 5- or 6-membered monocyclic heteroaryl group and said 9- or 10-membered bicyclic heteroaryl group can be optionally substituted with up to five groups, each independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo, —OR20, —SR20, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 haloalkyl), —CN, —NO2, —N(R20)2, —C(O)OR20, —C(O)N(R20)2 and —NHC(O)R20;
R19 is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, halo, —OR20, —SR20, N(R20)2, C3-C7 cycloalkyl, C6-C10 aryl, 5- or 6-membered monocyclic heteroaryl or 9- or 10-membered bicyclic heteroaryl; each occurrence of R20 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, —(C1-C3 alkylene)m-(C3-C7 cycloalkyl), —(C1-C3 alkylene)m-(C6-C10 aryl), —(C1-C3 alkylene)m-(4 to 7-membered heterocycloalkyl), —(C1-C3 alkylene)m-(5- or 6-membered monocyclic heteroaryl) or —(C1-C3 alkylene)m-(9- or 10-membered bicyclic heteroaryl), wherein said C3-C7 cycloalkyl group, said C6-C10 aryl group, said 4 to 7-membered heterocycloalkyl group, said -(5- or 6-membered monocyclic heteroaryl group or said 9- or 10-membered bicyclic heteroaryl group can be optionally substituted with R26; each occurrence of R21 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C3-C7 cycloalkenyl, 5- or 6-membered monocyclic heteroaryl, 9- or 10-membered bicyclic heteroaryl, —OR20, —O—(C1-C6 haloalkyl) or —N(R20)2, wherein said C2-C6 alkenyl group, said C2-C6 alkynyl group, said C3-C7 cycloalkyl group, said C3-C7 cycloalkenyl group, said C6-C10 aryl group, said 5- or 6-membered monocyclic heteroaryl group and said 9- or 10-membered bicyclic heteroaryl group can be optionally substituted with up to five groups, each independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo, —OR20, —SR20, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 haloalkyl), —CN, —NO2, —N(R20)2, —C(O)R20, —C(O)OR20, —C(O)N(R20)2 and —NHC(O)R20; R22 represents from one to five substituent groups, each independently selected from C1-C6 alkyl, halo, —OR20, —SR20, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 haloalkyl), —CN, —NO2, —N(R20)2, —C(O)OR20, —C(O)N(R20)2 and —NHC(O)R20, or any two R22 groups on adjacent ring carbon atoms can combine to form —O—R23—O—; R23 is ˜[C(R24)2]n—; each occurrence of R24 is independently H or C1-C6 alkyl; each occurrence of R25 is independently selected from H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, —(C1-C3 alkylene)m-(C6-C10 aryl), —(C1-C6 alkylene)-C(O)—(C1-C6 alkyl), —(C1-C6 alkylene)-C(O)O(C1-C6 alkyl), 4 to 7-membered heterocycloalkyl, 5- or 6-membered monocyclic heteroaryl and 9- or 10-membered bicyclic heteroaryl, wherein said C1-C6 alkyl group, said C2-C6 alkenyl group, said C2-C6 alkynyl group, said C3-C7 cycloalkyl group, said C6-C10 aryl group, said 4 to 7-membered heterocycloalkyl group, said -(5- or 6-membered monocyclic heteroaryl group or said 9- or 10-membered bicyclic heteroaryl group can be optionally substituted with R26; or two R25 groups, together with the common nitrogen atom to which they are attached, join to form a 4- to 7-membered heterocycloalkyl group; R26 represents from one to five substituent groups, each independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo, —OR27, —SR27, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, —O(C1-C6 haloalkyl), —CN, —NO2, —N(R27)2, —C(O)OR27, —C(O)N(R27)2 and —NHC(O)R27; each occurrence of R27 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, —(C1-C3 alkylene)m-(C3-C7 cycloalkyl), —(C1-C3 alkylene)m-(C6-C1° aryl), —(C1-C3 alkylene)m-(4 to 7-membered heterocycloalkyl), —(C1-C3 alkylene)m-(5- or 6-membered monocyclic heteroaryl) or —(C1-C3 alkylene)m-(9- or 10-membered bicyclic heteroaryl); R28 is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C3-C7 cycloalkenyl, 5- or 6-membered monocyclic heteroaryl, 9- or 10-membered bicyclic heteroaryl, —OR20, —O—(C1-C6 haloalkyl) or —N(R20)2, wherein said C2-C6 alkenyl group, said C2-C6 alkynyl group, said C3-C7 cycloalkyl group, said C3-C7 cycloalkenyl group, said C6-C10 aryl group, said 5- or 6-membered monocyclic heteroaryl group and said 9- or 10-membered bicyclic heteroaryl group can be optionally substituted with up to five groups, each independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo, —OR20, —SR20, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 haloalkyl), —CN, —NO2, —N(R20)2, —C(O)R20, —C(O)OR20, —C(O)N(R20)2 and —NHC(O)R20; each occurrence of R29 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, —(C1-C3 alkylene)m-(C3-C7 cycloalkyl), —(C1-C3 alkylene)m-(C6-C10 aryl), —(C1-C3 alkylene)m-(4 to 7-membered heterocycloalkyl), —(C1-C3 alkylene)m-(5- or 6-membered monocyclic heteroaryl) or —(C1-C3 alkylene)m-(9- or 10-membered bicyclic heteroaryl), wherein said C3-C7 cycloalkyl group, said C6-C10 aryl group, said 4 to 7-membered heterocycloalkyl group, said -(5- or 6-membered monocyclic heteroaryl group or said 9- or 10-membered bicyclic heteroaryl group can be optionally substituted with R26; each occurrence of T is independently —S—, —O—, —SC(O)—, —SC(S)—, —OC(O)— and —OC(S)—; each occurrence of m is independently 0 or 1; and each occurrence of n is independently 1 or 2. |
