Azole nucleosides and use as inhibitors of rna and DNA varial polymerases

Abstract

Azole nucleosides represented by the formulae (I) and (II); wherein A = C or N B = C or N X = H; C1-C6 alkyl, cycloalkyl, alkenyl, cycloalkenyl, alky nyl, aryl, heterocyclo, halogen such as F, C1, Br and I; OH, NH2, NH-(C1-C6 alkyl, cycloalkyl, aryl, or heterocyclo); Z = H; C1-C6 alkyl, cycloalkyl, al kenyl, cycloalkenyl, alkynyl, aryl, heterocyclo, halogen such as F, Cl, Br, I; OH, NH2, NH-(C1-C6 alkyl, cycloalkyl, aryl, or heterocyclo; E= (CH2)HONHR 1; n is an integer from 0-6 and more typically 0-3; R1= aryl or heterocyclo; each of W, Y, R is individually selected from the group consisting of H; C1 -C6 alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, heterocyclo; ha logen such as F, Cl, Br, and I; O, OH, Oalkyl, Oaryl, NH2, NH-(C1-C6 alkyl, cycloalkyl, aryl, or heterocyclo); provided that at least one of W, Y, and R is other than H and wherein both W and Y together can be =O; and each D ind ividually is OH, Oalkyl, Oaryl, Fl and H;pharmaceutically acceptable salts t hereof, prodrugs thereof and mixtures thereof are provided. Compounds of thi s disclosure are useful as inhibitors of viral RNA and DNA polymerases such as, but not limited to, Influenza, Hantaan Virus, Crimean Congo hemorrhagic fever virus, hepatitis B, hepatitis C, Polio, Coxsackie A and B, Rhino, Echo , orthopoxvirus (small pox), HIV, Ebola, and West Nile virus polymerases; an especially orthopoxvirus, HIV, and hepatitis B.

Description

technical field

[0001] The present invention relates to azoles and especially diazines (such as pyrazoles and imidazoles), triazines and purines, which are useful as, but not limited to, influenza virus, Hantavirus (HTNV), Crimean - Congo Haemorrhagic Fever Virus (CCHF), Rift Valley Fever virus (RVFV), Hepatitis B virus, Hepatitis C virus, Poliovirus, Coxsackie virus A and B, Rhinovirus, Echovirus, orthopoxvirus (smallpox), HIV, Ebola virus and West Nile virus polymerase and especially influenza viruses and viruses such as Hantavirus, Crimean-Congo haemorrhagic fever virus and Rift Valley fever virus Viral RNA and DNA polymerase inhibitors of Bunyaviridae family viruses.

[0002] The present invention also relates to pharmaceutical compositions comprising the above compounds, and methods of using the compounds to inhibit viral RNA and DNA polymerases and to treat patients suffering from diseases caused by various RNA and DNA viruses and various cancers.

[0003] The present ...

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