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US 8,440,720 B2Granted
Methods of use of antiviral compounds
AssigneeInflumedix, Inc.
InventorsJizhou Wang, Xiaodong Fan, Lidia Cristian
Life of this patent
Estimating the term…
Abstract
The present invention relates, in part, to methods of treatment, prevention, and inhibition of viral disorders. In one aspect, the present invention relates to inhibition of the M2 proton channel of influenza viruses (e.g. influenza A virus) and other similar viroporins (e.g., VP24 of Ebola and Marburg viruses; and NS3 protein of Bluetongue). The present invention further relates, inter alia, to compounds which have been shown to possess antiviral activity, in particular, inhibiting the M2 proton channel of influenza viruses.
Claims26
A method for treating an influenza virus-affected disease state or infection comprising the step of administering to a subject in need thereof a composition comprising a compound of formula I:
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is amino, amino(C1-C3)alkyl, nitro, nitro(C1-C3)alkyl, formamidinyl, guanidinyl, —CH(OH)CH2NO2, (C1-C3)alkylamino, or a five- or six-membered heterocyclic ring;
- R2a and R2b are independently hydrogen, hydroxyl, (C1-C3)alkyl optionally substituted with halo, (C1-C3)alkoxy, or halo;
- or, R1 together with R2a or R2b forms a five- or six-membered optionally substituted carbocyclic or heterocyclic ring;
- R3 is hydrogen, halo, hydroxyl, (C1-C3)alkoxy, thiol, or thio(C1-C3)alkyl;
- and,
- R4a and R4b are independently hydrogen, hydroxyl, halo, thiol, thionyl, cyano, (C1-C3)alkyl optionally substituted with halo, (C1-C3)alkoxy, oxo, oxime, hydroxy(C1-C3)alkyl, or R4a and R4b together with the carbon atom to which they are both attached form a three- to six-membered carbocyclic or heterocyclic ring,
- wherein:
- at least one of R2a or R2b;
- R3;
- or R4a and R4b are other than hydrogen,
- or,
- R1 includes or is involved in forming a five- or six-membered heterocyclic or carbocyclic ring that is directly bound to the carbon atom to which R1 is attached wherein the compound is not 3-fluoroadamantan-1-amine.
10 more elements
A compound according to formula II:
- or a pharmaceutically acceptable salt thereof, wherein
- (a)
- R5 is guanidinyl;
- R6a and R6b are independently hydrogen, hydroxyl, or (C1-C3)alkyl optionally substituted with halo;
- or, R5 together with R6a or R6b forms a five- or six-membered optionally substituted carbocyclic or heterocyclic ring;
- R7 is hydrogen or halo;
- and,
- R8a and R8b are independently hydrogen, hydroxyl, halo, cyano, (C1-C3)alkyl optionally substituted with halo, (C1-C3)alkoxy, thiol, thionyl, oxime, or R8a and R8b together with the carbon atom to which they are both attached form a three- to six-membered carbocyclic ring,
- or,
- (b)
- R5 is amino;
- R6a and R6b are independently hydrogen, hydroxyl, or (C1-C3)alkyl optionally substituted with halo;
- or, R5 together with R6a or R6b forms a five- or six-membered optionally substituted carbocyclic or heterocyclic ring;
- R7 is hydrogen or halo;
- and,
- R8a is hydroxyl, halo, cyano, (C1-C3)alkyl optionally substituted with halo, (C1-C3)alkoxy, thiol, thionyl, or oxime;
- R8b is hydroxyl, cyano, (C1-C3)alkyl optionally with halo, (C1-C3)alkoxy, thiol, thionyl, or oxime;
- or, R8a and R8b together with the carbon atom to which they are both attached form a three- to six-membered carbocyclic ring,
- or,
- (c)
- R5 is amino(C1-C3)alkyl, nitro(C1-C3)alkyl, or guanidinyl;
- R6a and R6b are independently hydrogen, hydroxyl, or (C1-C3)alkyl optionally substituted with halo;
- or, R5 together with R6a or R6b forms a five- or six-membered optionally substituted carbocyclic or heterocyclic ring;
- R7 is hydrogen or halo;
- R8a is hydrogen or R8a and R8b together with the carbon atom to which they are both attached form a three- to six-membered carbocyclic ring;
- and,
- R8b is hydroxyl, cyano, (C1-C3)alkyl optionally substituted with halo, (C1-C3)alkoxy, thiol, thionyl, oxime, or R8a and R8b together with the carbon atom to which they are both attached form a three- to six-membered carbocyclic ring;
- or,
- (d)
- R5 is amino(C1-C3)alkyl or guanidinyl;
- R6a and R6b are independently hydrogen, hydroxyl, or (C1-C3)alkyl optionally substituted with halo;
- or, R5 together with R6a or R6b forms a five- or six-membered optionally substituted carbocyclic or heterocyclic ring;
- R7 is hydrogen;
- and,
- R8a and R8b are independently hydrogen, hydroxyl, halo, cyano, (C1-C3)alkyl optionally substituted with halo, (C1-C3)alkoxy, thiol, thionyl, oxime, or R8a and R8b together with the carbon atom to which they are both attached form a three- to six-membered carbocyclic ring,
- or,
- (e)
- R5 is amino(C1-C3)alkyl or guanidinyl;
- R6a and R6b are independently hydrogen, hydroxyl, or (C1-C3)alkyl optionally substituted with halo;
- or, R5 together with R6a or R6b forms a five- or six-membered optionally substituted carbocyclic or heterocyclic ring;
- R7 is hydrogen or halo;
- and,
- R8a is hydrogen, hydroxyl, halo, cyano, (C1-C3)alkyl optionally substituted with halo, (C1-C3)alkoxy, thiol, thionyl, oxime;
- R8b is hydroxyl, halo, cyano, (C1-C3)alkyl optionally substituted with halo, (C1-C3)alkoxy, thiol, thionyl, oxime;
- or, R8a and R8b together with the carbon atom to which they are both attached form a three- to six-membered carbocyclic ring,
- or,
- (f)
- R5 is nitro(C1-C3)alkyl;
- R6a and R6b are independently hydrogen, hydroxyl, or (C1-C3)alkyl optionally substituted with halo;
- or, R5 together with R6a or R6b forms a five- or six-membered optionally substituted carbocyclic or heterocyclic ring;
- R7 is hydrogen or halo;
- and,
- R8a and R8b are independently hydrogen, hydroxyl, cyano, (C1-C3)alkyl optionally substituted with halo, (C1-C3)alkoxy, thiol, thionyl, or oxime;
- or R8a and R8b are both halo;
- or R8a and R8b together with the carbon atom to which they are both attached form a three- to six-membered carbocyclic ring,
- or,
- (g)
- R5 is amino;
- R6a and R6b are independently hydrogen, hydroxyl, or (C1-C3)alkyl optionally substituted with halo;
- or, R5 together with R6a or R6b forms a five- or six-membered optionally substituted carbocyclic or heterocyclic ring;
- R7 is hydrogen or halo;
- R8a is hydrogen or R8a and R8b together with the carbon atom to which they are both attached form a three- to six-membered carbocyclic ring;
- and,
- R8b is hydroxyl, cyano, (C1-C3)alkyl optionally substituted with halo, thiol, thionyl, oxime, or R8a and R8b together with the carbon atom to which they are both attached form a three- to six-membered carbocyclic ring;
- wherein said compound is substituted at two or more positions, and
- wherein if R5 includes an —NH2 group, and one of R6a and R6b, or one of R8a and R8b is hydroxyl, then the other of R6a and R6b or the other of R8a and R8b are not hydrogen.
63 more elements
Dependencies are inferred from the claim text.