发明名称 2'-DISUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
摘要 2′-disubstituted substituted nucleoside derivatives of formula (I) and pharmaceutically acceptable salts thereof are disclosed: (1), wherein A is N3 or NH2 and X, Y, R1, R2, R3, R4, R5 and R18 are as defined herein. Compositions comprising at least one 2′-disubstituted nucleoside derivative, and methods of using the 2′-disubstituted nucleoside derivatives for treating or preventing HCV infection in a patient are disclosed.;
申请公布号 US2016045526(A1) 申请公布日期 2016.02.18
申请号 US201314436687 申请日期 2013.10.11
申请人 Merck Sharp & Dohme Corp. 发明人 Girijavallabhan Vinay;Bogen Stephane;Pan Weidong;Dang Qun;Davies Ian
分类号 A61K31/706;A61K31/7056;A61K45/06;C07H7/06 主分类号 A61K31/706
代理机构 代理人
主权项 1. A compound having the formula (I):or a pharmaceutically acceptable salt thereof,wherein: A is —NH2 or —N3; X is O, N, S or CH2; Y is N or —C(R6)—; R1 is H, R2 is H, —C(O)—(C1-C6 alkyl) oror 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 and R5 are each independently selected from H, —OR12, —NHC(O)OR12, —NHC(O)N(R12)2, —N(R12)2 and —NHC(O)R12; R6 is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, halo, —OR12, —SR12, —N(R12)2, C3-C7 cycloalkyl, C6-C10 aryl, 5- or 6-membered monocyclic heteroaryl or 9- or 10-membered bicyclic heteroaryl; R7 is H, C6-C10 aryl, 5- or 6-membered monocyclic heteroaryl, 9- or 10-membered bicyclic heteroaryl, or —(C1-C3 alkylene)-C(O)O—(C1-C6 alkyl), 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 R13, R8 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, —OR12, —SR12, guanidino, —N(R12)2, —C(O)OR12, —C(O)N(R12)2, —NHC(O)R12, 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 —OR12; R9 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, —OR12, —SR12, guanidino, —N(R12)2, —C(O)OR12, —C(O)N(R12)2, —NHC(O)R12, 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 —OR12; R10 is H, C1-C20 alkyl, C2-C20 alkenyl, —(C1-C3 alkylene)m-(C3-C7 cycloalkyl), —(C1-C3 alkylene)m-(C6-C10 aryl) or —(C1-C3 alkylene)m-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, —OR12, —C(O)OR12, 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(R12)2, —C(O)N(R12)2—SR12, —S(O)R12, —S(O)2R12, —S(O)2N(R12)2, —NHC(O)R12, —NHC(O)OR12 and —NHC(O)N(R12)2; R11 is H, C1-C20 alkyl, C2-C20 alkenyl, —(C1-C3 alkylene)m-(C3-C7 cycloalkyl), C3-C7 cycloalkyl, —(C1-C3 alkylene)m-C6-C10 aryl or —(C1-C3 alkylene)m-adamantyl, 5- or 6-membered monocyclic heteroaryl, 9- or 10-membered bicyclic heteroaryl, wherein said C1-C20 alkyl group, said C2-C20 alkenyl group, said C6-C10 aryl group, said adamantyl 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, C3-C7 cycloalkyl, C6-C10 aryl, 5- or 6-membered monocyclic heteroaryl, 9- or 10-membered bicyclic heteroaryl, halo, —OR12, —SR12, —S(O)R12, —S(O)2R12, —S(O)2N(R12)2, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 haloalkyl), —CN, —NO2, —N(R12)2, —C(O)OR12, —C(O)N(R12)2 and —NHC(O)R12, —NHC(O)OR12 and —NHC(O)N(R12)2; each occurrence of R12 is independently H, C1-C10 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 R16; R13 represents from one to five substituent groups, each independently selected from C1-C6 alkyl, halo, —OR12, —SR12, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 haloalkyl), —CN, —NO2, —N(R12)2, —C(O)OR12, —C(O)N(R12)2 and —NHC(O)R12, or any two R13 groups on adjacent ring carbon atoms can combine to form —O—R14—O—; R14 is —[C(R15)2]n—; each occurrence of R15 is independently H or C1-C6 alkyl; R16 represents from one to five substituent groups, each independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo, —OR17, —SR17, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 haloalkyl), —CN, —NO2, —N(R17)2, —C(O)OR17, —C(O)N(R17)2 and —NHC(O)R17; each occurrence of R17 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); R18 is H, C1-C6 alkyl, —O(C1-C6 alkyl), C1-C6 alkynyl, C1-C6 alkenyl, or CN; and each occurrence of m is independently 0 or 1, and each occurrence of n is independently 1, 2, or 3.
地址 Rahway NJ US