发明名称 Cap/endo dual inhibitors and their use in the treatment, amelioration or prevention of a viral disease
摘要 The present invention relates to a compound having the general formula (V), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof,;;which are useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.
申请公布号 US2017000788(A1) 申请公布日期 2017.01.05
申请号 US201615169850 申请日期 2016.06.01
申请人 F. Hoffmann-La Roche AG ;Savira pharmaceuticals GmbH ;European Molecular Biology Laboratory 发明人 Schulz-Gasch Tanja;Weikert Robert;Neidhart Werner;Buschmann Helmut;Szolar Oliver;Wolkerstorfer Andrea;Handler Norbert;Roch Franz-Ferdinand;Cusack Stephen
分类号 A61K31/506;A61K31/4985 主分类号 A61K31/506
代理机构 代理人
主权项 1. A method of treating, ameliorating or preventing a viral disease, comprising: administering to a patient in need thereof an effective amount of a compound having the general formula (V), or a pharmaceutically acceptable salt, racemate, enantiomer, or diastereomer or mixture thereof: wherein: R51 is selected from —H, -(optionally substituted C1-6 alkyl) and —C(O)-(optionally substituted C1-6 alkyl); or R51 is selected from —C(O)—R, —C(O)—OR, —PO(ORA)(ORB) and —OC(O)OR, where R, RA and RB are independently selected from C1-6 alkyl, aryl, and heteroaryl, where the C1-6 alkyl, aryl, or heteroaryl can be optionally substituted with —OH or —O—C1-6 alkyl, R52 is selected from —H, -(optionally substituted C1-6 alkyl), —(CH2)q-(optionally substituted heterocyclyl), —(CH2)q-(optionally substituted carbocyclyl), —(CH2)p—OR55, and —(CH2)p—NR56R57; R53 is selected from —R54 and —X51R54; R54 is a bicyclic fused ring system comprising from 10 to 14 ring atoms and 1 to 4 nitrogen atoms as ring atoms, wherein the bicyclic fused ring system can optionally be substituted; R55 is selected from —H, —C1-6 alkyl, and —(CH2CH2O)rH; R56 is selected from —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 carbocyclyl), —C1-4 alkyl-(optionally substituted C3-7 carbocyclyl), -(optionally substituted heterocyclyl having 3 to 7 ring atoms), and —C1-4 alkyl-(optionally substituted heterocyclyl having 3 to 7 ring atoms); R57 is selected from —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 carbocyclyl), —C1-4 alkyl-(optionally substituted C3-7 carbocyclyl), -(optionally substituted heterocyclyl having 3 to 7 ring atoms), and —C1-4 alkyl-(optionally substituted heterocyclyl having 3 to 7 ring atoms); R58 is selected from —H and —C1-6 alkyl; X51 is -L1-(A-(L2)m)n—; X52 is selected from NR56, N(R56)C(O), C(O)NR56, O, C(O), C(O)O, OC(O); N(R56)SO2, SO2N(R56), S, SO, and SO2; L1 is selected from NR56, N(R56)C(O), C(O)NR56, O, C(O), C(O)O, OC(O); N(R56)SO2, SO2N(R56), N(R56)SO2N(R56), S, SO, SO2 and (optionally substituted heterocyclyl having 3 to 7 ring atoms)-NR56; L2 is selected from NR56, N(R56)C(O), C(O)NR56, O, C(O), C(O)O, OC(O); N(R56)SO2, SO2N(R56), N(R56)SO2N(R56), S, SO, SO2 and (optionally substituted heterocyclyl having 3 to 7 ring atoms)-NR56; A is selected from (CR*R**)t, optionally substituted C3-7 carbocyclyl, optionally substituted heterocyclyl having 3 to 7 ring atoms and combinations thereof; R* is independently for each occurrence selected from —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 carbocyclyl), —C1-4 alkyl-(optionally substituted C3-7 carbocyclyl), -(optionally substituted heterocyclyl having 3 to 7 ring atoms), and —C1-4 alkyl-(optionally substituted heterocyclyl having 3 to 7 ring atoms); R** is independently for each occurrence selected from —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 carbocyclyl), —C1-4 alkyl-(optionally substituted C3-7 carbocyclyl), -(optionally substituted heterocyclyl having 3 to 7 ring atoms), and —C1-4 alkyl-(optionally substituted heterocyclyl having 3 to 7 ring atoms); or R* and R** can optionally form an optionally substituted C3-7 carbocyclyl group or optionally substituted heterocyclyl group having 3 to 7 ring atoms; R*** is independently for each occurrence selected from —H, a —C1-6 alkyl group, and a —C1-6 alkyl group which is substituted by one or more halogen atoms; m is 0 or 1; n is 0 or 1; p is 1 to 4; q is 0 to 4; r is 1 to 3; s is 0 to 4; and t is 1 to 6; the alkyl group can be optionally substituted with one or more substituents which are independently selected from halogen, —CN, —NR56R57, —OH, and —O—C1-6 alkyl; the bicyclic fused ring system can be optionally substituted with one or more substituents which are independently selected from (═O), halogen, —CN, —CF3, —(CH2)s—X52—R58, —C1-6 alkyl, —C3-7 carbocyclyl, —C1-4 alkyl-C3-7 carbocyclyl, -(heterocyclyl having 3 to 7 ring atoms), and —C1-4 alkyl-(heterocyclyl having 3 to 7 ring atoms); and the hydrocarbon group, heterocyclyl group, and/or carbocyclyl group can be optionally substituted with one or more substituents which are independently selected from halogen, —CN, —CF3, —(CH2)s—X52—R58, —C1-6 alkyl, —C3-7 carbocyclyl, —C1-4 alkyl-C3-7 carbocyclyl, -(heterocyclyl having 3 to 7 ring atoms), and —C1-4 alkyl-(heterocyclyl having 3 to 7 ring atoms).
地址 Basel CH