Treatment and Prevention of Dengue Virus Infections
AssigneeSiga Technologies, Inc.
InventorsChelsea M. Byrd, Dongcheng Dai, Robert Jordan, Dennis E. Hruby
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Abstract
Methods and pharmaceutical compositions for treating viral infections, by administering certain 2-aryl-benzothiazole or 2-heteroaryl-benzothiazole derivative compounds in therapeutically effective amounts are disclosed. Methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by flavivirus is disclosed, i.e., including but not limited to, Dengue virus, West Nile virus, yellow fever virus, Japanese encephalitis virus, and tick-borne encephalitis virus.
Claims26
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the following general Formula I or a pharmaceutically acceptable salt thereof:
- wherein X is selected from the groups consisting of O, S and N—R′, wherein R′ is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, arylalkyl, aryl, heteroaryl, acyl, arylacyl, heteroarylacyl, sulfonyl, aminosulfonyl, substituted aminosulfonyl, alkoxycarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, carbamoyl and substituted carbamoyl;
- Ar is substituted or unsubstituted aryl or heteroaryl;
- and
- A, B, D, and E are independently N or C—R1, C—R2, C—R3 and C—R4, respectively, wherein R1, R2, R3 and R4 are independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, arylalkyl, aryl, heteroaryl, hydroxy, alkyloxy, aryloxy, heteroaryloxy, acyloxy, arylacyloxy, heteroarylacyloxy, alkylsulfonyloxy, arylsulfonyloxy, thio, alkylthio, arylthio, amino, alkylamino, dialkylamino, cycloalkylamino, heterocycloalkylamino, arylamino, heteroarylamino, acylamino, arylacylamino, heteroarylacylamino, alkylsulfonylamino, arylsulfonylamino, acyl, arylacyl, heteroarylacyl, alkylsulfinyl, arylsulfinyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, substituted aminosulfonyl, carboxy, alkoxycarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, carbamoyl, substituted carbamoyl, halogen, cyano, isocyano and nitro;
- or R1 and R2 together with the carbons they are attached to may form a substituted or unsubstituted ring, or R2 and R3 or R3 and R4 together with the carbons they are attached to may form a substituted or unsubstituted ring, which may be aromatic or nonaromatic and may include one or more heteroatoms in the ring and may be fused with an aromatic or aliphatic ring.
A method for the treatment or prophylaxis of a viral infection or disease associated therewith, comprising administering in a therapeutically effective amount to a mammal in need thereof, a compound of Formula I below or a pharmaceutically acceptable salt thereof:
- wherein X is selected from the groups consisting of O, S and N—R′, wherein R′ is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, arylalkyl, aryl, heteroaryl, acyl, arylacyl, heteroarylacyl, sulfonyl, aminosulfonyl, substituted aminosulfonyl, alkoxycarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, carbamoyl and substituted carbamoyl;
- Ar is substituted or unsubstituted aryl or heteroaryl;
- and
- A, B, D, and E are independently N or C—R1, C—R2, C—R3 and C—R4, respectively, wherein R1, R2, R3 and R4 are independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, arylalkyl, aryl, heteroaryl, hydroxy, alkyloxy, aryloxy, heteroaryloxy, acyloxy, arylacyloxy, heteroarylacyloxy, alkylsulfonyloxy, arylsulfonyloxy, thio, alkylthio, arylthio, amino, alkylamino, dialkylamino, cycloalkylamino, heterocycloalkylamino, arylamino, heteroarylamino, acylamino, arylacylamino, heteroarylacylamino, alkylsulfonylamino, arylsulfonylamino, acyl, arylacyl, heteroarylacyl, alkylsulfinyl, arylsulfinyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, substituted aminosulfonyl, carboxy, alkoxycarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, carbamoyl, substituted carbamoyl, halogen, cyano, isocyano and nitro;
- or R1 and R2 together with the carbons they are attached to may form a substituted or unsubstituted ring, or R2 and R3 or R3 and R4 together with the carbons they are attached to may form a substituted or unsubstituted ring, which may be aromatic or nonaromatic and may include one or more heteroatoms in the ring and may be fused with an aromatic or aliphatic ring.
Dependencies are inferred from the claim text.