Thienopyridine Derivatives for the Treatment and Prevention of Dengue Virus Infections
Methods and pharmaceutical compositions for treating viral infections, by administering certain thienopyridine derivative compounds in therapeutically effective amounts are disclosed. Methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment 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.
1 . A compound having the following general Formula III 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 groups 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;
R is selected from the group consisting of halogen, cyano, isocyano, nitro, amino, alkylamino, dialkylamino, cycloalkylamino, heterocycloalkylamino, arylamino, heteroarylamino, acylamino, arylacylamino, heteroarylacylamino, alkylsulfonylamino, arylsulfonylamino, hydroxysulfonyl, aminosulfonyl, substituted aminosulfonyl, acyl, arylacyl, heteroarylacyl, carboxy, alkoxycarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, aminocarbonyl, and substituted aminocarbonyl;
B, D, and E are independently N or C—R 2 , C—R 3 and C—R 4 , respectively, wherein R 2 , R 3 and R 4 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 R 2 and R 3 or R 3 and R 4 together with the carbons they are attached to may form a substituted or unsubstituted ring, which may be aromatic or non-aromatic and may include one or more heteroatoms in the ring and may be fused with an aromatic or aliphatic ring; and
R 10 and R 11 are independently selected from the groups 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, provided that R 10 and R 11 can't both be hydrogen.
2 . The compound of claim 1 , wherein X is S.
3 . The compound of claim 1 , wherein B is C—H.
4 . The compound of claim 1 , wherein D is a C—H.
5 . The compound of claim 1 , wherein E is C—R 4 and R 4 is a heteroaryl.
6 . The compound of claim 1 , wherein D is C—R 3 and E is C—R 4 , and R 3 and R 4 form a ring.
7 . The compound of claim 1 , wherein R is a substituted aminocarbonyl.
8 . The compound of claim 1 being 3-[N-[3-amino-6-(2-thienyl)thieno[2,3-b]pyridine-2-carbonyl]-3-(trifluoromethyl)anilino]propanoic acid.
9 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the following general Formula III 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 groups 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;
R is selected from the group consisting of halogen, cyano, isocyano, nitro, amino, alkylamino, dialkylamino, cycloalkylamino, heterocycloalkylamino, arylamino, heteroarylamino, acylamino, arylacylamino, heteroarylacylamino, alkylsulfonylamino, arylsulfonylamino, hydroxysulfonyl, aminosulfonyl, substituted aminosulfonyl, acyl, arylacyl, heteroarylacyl, carboxy, alkoxycarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, aminocarbonyl, and substituted aminocarbonyl;
B, D, and E are independently N or C—R 2 , C—R 3 and C—R 4 , respectively, wherein R 2 , R 3 and R 4 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 R 2 and R 3 or R 3 and R 4 together with the carbons they are attached to may form a substituted or unsubstituted ring, which may be aromatic or non-aromatic and may include one or more heteroatoms in the ring and may be fused with an aromatic or aliphatic ring; and
R 10 and R 11 are independently selected from the groups 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, provided that R 10 and R 11 can't both be hydrogen,
wherein said composition is suitable for human or animal administration.
10 . The composition of claim 9 , wherein X is S.
11 . The composition of claim 9 , wherein B is C—H.
12 . The composition of claim 9 , wherein D is a C—H.
13 . The composition of claim 9 , wherein E is C—R 4 and R 4 is a heteroaryl.
14 . The composition of claim 9 , wherein D is C—R 3 and E is C—R 4 , and R 3 and R 4 form a ring.
15 . The composition of claim 9 , wherein R is a substituted aminocarbonyl.
16 . The composition of claim 9 , wherein said compound is 3-[N-[3-amino-6-(2-thienyl)thieno[2,3-b]pyridine-2-carbonyl]-3-(trifluoromethyl)anilino]propanoic acid.
17 . A method for the treatment of at least one type of a Dengue virus infection or disease associated therewith, comprising administering in a therapeutically effective amount to a mammal in need thereof, a compound of Formula III 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 groups 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;
R is selected from the group consisting of halogen, cyano, isocyano, nitro, amino, alkylamino, dialkylamino, cycloalkylamino, heterocycloalkylamino, arylamino, heteroarylamino, acylamino, arylacylamino, heteroarylacylamino, alkylsulfonylamino, arylsulfonylamino, hydroxysulfonyl, aminosulfonyl, substituted aminosulfonyl, acyl, arylacyl, heteroarylacyl, carboxy, alkoxycarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, aminocarbonyl, and substituted aminocarbonyl;
B, D, and E are independently N or C—R 2 , C—R 3 and C—R 4 , respectively, wherein R 2 , R 3 and R 4 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 R 2 and R 3 or R 3 and R 4 together with the carbons they are attached to may form a substituted or unsubstituted ring, which may be aromatic or non-aromatic and may include one or more heteroatoms in the ring and may be fused with an aromatic or aliphatic ring; and
R 10 and R 11 are independently selected from the groups 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, provided that R 10 and R 11 can't both be hydrogen.
18 . The method of claim 17 , wherein X is S.
19 . The method of claim 17 , wherein B is C—H.
20 . The method of claim 17 , wherein D is a C—H.
21 . The method of claim 17 , wherein E is C—R 4 and R 4 is a heteroaryl.
22 . The method of claim 17 , wherein D is C—R 3 and E is C—R 4 , and R 3 and R 4 form a ring.
23 . The method of claim 17 , wherein R is a substituted aminocarbonyl.
24 . The method of claim 17 , wherein said compound is 3-[N-[3-amino-6-(2-thienyl)thieno[2,3-b]pyridine-2-carbonyl]-3-(trifluoromethyl)anilino]propanoic acid.
25 . The method of claim 17 , wherein the mammal is a human.
26 . The method of claim 17 , wherein said Dengue virus is selected from the group consisting of DEN-1, DEN-2, DEN-3, and DEN-4.
27 . The method of claim 17 , wherein said viral infection is associated with Dengue fever.
28 . The method of claim 27 , wherein said Dengue fever is selected from the group consisting of classical dengue fever and dengue hemorrhagic fever.
29 . The method of claim 17 , which further comprises co-administration of at least one agent selected from the group consisting of antiviral agent, vaccine, and interferon.
30 . The method of claim 29 , wherein said interferon is pegylated.
31 . A compound selected from the group consisting of: 3-amino-N-cyclohexyl-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-N-butyl-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-N-(tert-butyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-6-methyl-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-5-methyl-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-4-methoxy-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-4-methyl-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3,5-diamino-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-2-((5-phenyl-1,3,4-thiadiazol-2-yl)carbamoyl)thieno[2,3-b]pyridine-5-carboxylic acid; 3-amino-6-chloro-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-methyl-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-7,8-dihydro-5H-thieno[2,3-b][1,6]naphthyridine-2-carboxamide; 2-(thiophen-2-yl)-10-(3-(trifluoromethyl)phenyl)-7,8-dihydro-5H-pyrido[3′,2′:4,5]thieno[3,2-b][1,5]diazonine-6,9,11(10H)-trione; 7-(thiophen-2-yl)-3-(3-(trifluoromethyl)phenyl)pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione; 3-amino-6-(trifluoromethyl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(2,4-dimethylthiazol-5-yl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(2-thienyl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamidine; 8-(thiophen-2-yl)-4-(3-(trifluoromethyl)phenyl)-3,4-dihydro-1H-pyrido[3′,2′:4,5]thieno[3,2-e][1,4]diazepine-2,5-dione; 3-amino-N-methyl-6-(2-thienyl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(2-dimethylaminoethyl)-6-(2-thienyl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 6-acetamido-3-amino-N-(4-bromophenyl)-5-cyano-4-(2-furyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(4-bromophenyl)-5-cyano-4-(2-furyl)-6-hydroxy-thieno[2,3-b]pyridine-2-carboxamide; 2-[N-[3-amino-6-(2-thienyl)thieno[2,3-b]pyridine-2-carbonyl]-3-(trifluoromethyl)anilino]acetic acid; 3-[N-[3-amino-6-(2-thienyl)thieno[2,3-b]pyridine-2-carbonyl]-3-(trifluoromethyl)anilino]propanoic acid; 3-amino-5-oxo-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-5-hydroxy-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-5-fluoro-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-[4-(trifluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-[3-(trifluoromethoxy)phenyl]-N-[4-(trifluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N,6-bis(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 4-[[3-amino-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carbonyl]amino]benzoic acid; 3-amino-N-(5-bromo-2-pyridyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(6-bromo-3-pyridyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-[4-(difluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-[4-(1,1-difluoroethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-[3-(difluoromethoxy)phenyl]-N-[4-(trifluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-[4-(difluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(2-bromophenyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(3,4-dichlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(2,3-dichlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(3-chlorophenyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-[3-(difluoromethoxy)phenyl]-N-[4-(difluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 4-[[3-amino-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carbonyl]amino]benzenesulfonic acid; 3-amino-6-(4-chlorophenyl)-N-(2,5-dichlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(3,4-dimethylphenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(4-bromophenyl)-6-(5-chloro-2-pyridyl)thieno[2,3-b]pyridine-2-carboxamide; 3-(N-[3-amino-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carbonyl]-4-bromo-anilino)propanoic acid; 3-amino-6-(4-chlorophenyl)-N-[4-(2,2,2-trifluoroacetyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(5-chloro-2-pyridyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(6-chloro-3-pyridyl)thieno[2,3-b]pyridine-2-carboxamide; 3-[N-[3-amino-6-(3-methoxyphenyl)thieno[2,3-b]pyridine-2-carbonyl]-4-(trifluoromethoxy)anilino]propanoic acid; 3-(N-[3-amino-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carbonyl]-4-chloro-anilino)propanoic acid; 3-amino-6-(4-chlorophenyl)-N-(4-hydroxyphenyl)thieno[2,3-b]pyridine-2-carboxamide; and 3-amino-N-(4-pyridyl)-6-(2-thienyl)thieno[2,3-b]pyridine-2-carboxamide.
32 . The compound of claim 31 being 3-amino-N,6-bis(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide.
33 . The compound of claim 31 being 3-amino-6-[3-(difluoromethoxy)phenyl]-N-[4-(difluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide.
34 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound selected from the group consisting of: 3-amino-N-cyclohexyl-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-N-butyl-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-N-(tert-butyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-6-methyl-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-5-methyl-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-4-methoxy-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-4-methyl-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3,5-diamino-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-2-((5-phenyl-1,3,4-thiadiazol-2-yl)carbamoyl)thieno[2,3-b]pyridine-5-carboxylic acid; 3-amino-6-chloro-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-methyl-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-7,8-dihydro-5H-thieno[2,3-b][1,6]naphthyridine-2-carboxamide; 2-(thiophen-2-yl)-10-(3-(trifluoromethyl)phenyl)-7,8-dihydro-5H-pyrido[3′,2′:4,5]thieno[3,2-b][1,5]diazonine-6,9,11(10H)-trione; 7-(thiophen-2-yl)-3-(3-(trifluoromethyl)phenyl)pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione; 3-amino-6-(trifluoromethyl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(2,4-dimethylthiazol-5-yl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(2-thienyl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamidine; 8-(thiophen-2-yl)-4-(3-(trifluoromethyl)phenyl)-3,4-dihydro-1H-pyrido[3′,2′:4,5]thieno[3,2-e][1,4]diazepine-2,5-dione; 3-amino-N-methyl-6-(2-thienyl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(2-dimethylaminoethyl)-6-(2-thienyl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 6-acetamido-3-amino-N-(4-bromophenyl)-5-cyano-4-(2-furyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(4-bromophenyl)-5-cyano-4-(2-furyl)-6-hydroxy-thieno[2,3-b]pyridine-2-carboxamide; 2-[N-[3-amino-6-(2-thienyl)thieno[2,3-b]pyridine-2-carbonyl]-3-(trifluoromethyl)anilino]acetic acid; 3-[N-[3-amino-6-(2-thienyl)thieno[2,3-b]pyridine-2-carbonyl]-3-(trifluoromethyl)anilino]propanoic acid; 3-amino-5-oxo-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-5-hydroxy-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-5-fluoro-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-[4-(trifluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-[3-(trifluoromethoxy)phenyl]-N-[4-(trifluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N,6-bis(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 4-[[3-amino-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carbonyl]amino]benzoic acid; 3-amino-N-(5-bromo-2-pyridyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(6-bromo-3-pyridyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-[4-(difluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-[4-(1,1-difluoroethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-[3-(difluoromethoxy)phenyl]-N-[4-(trifluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-[4-(difluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(2-bromophenyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(3,4-dichlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(2,3-dichlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(3-chlorophenyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-[3-(difluoromethoxy)phenyl]-N-[4-(difluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 4-[[3-amino-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carbonyl]amino]benzenesulfonic acid; 3-amino-6-(4-chlorophenyl)-N-(2,5-dichlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(3,4-dimethylphenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(4-bromophenyl)-6-(5-chloro-2-pyridyl)thieno[2,3-b]pyridine-2-carboxamide; 3-(N-[3-amino-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carbonyl]-4-bromo-anilino)propanoic acid; 3-amino-6-(4-chlorophenyl)-N-[4-(2,2,2-trifluoroacetyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(5-chloro-2-pyridyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(6-chloro-3-pyridyl)thieno[2,3-b]pyridine-2-carboxamide; 3-[N-[3-amino-6-(3-methoxyphenyl)thieno[2,3-b]pyridine-2-carbonyl]-4-(trifluoromethoxy)anilino]propanoic acid; 3-(N-[3-amino-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carbonyl]-4-chloro-anilino)propanoic acid; 3-amino-6-(4-chlorophenyl)-N-(4-hydroxyphenyl)thieno[2,3-b]pyridine-2-carboxamide; and 3-amino-N-(4-pyridyl)-6-(2-thienyl)thieno[2,3-b]pyridine-2-carboxamide, wherein said composition is suitable for human or animal administration.
35 . The composition of claim 34 , wherein said compound is 3-amino-N,6-bis(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide.
36 . The composition of claim 34 , wherein said compound is 3-amino-6-[3-(difluoromethoxy)phenyl]-N-[4-(difluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide.
37 . A method for the treatment of at least one type of a Dengue virus infection or disease associated therewith, comprising administering in a therapeutically effective amount to a mammal in need thereof, a compound or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the group consisting of: 3-amino-N-cyclohexyl-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-N-butyl-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-N-(tert-butyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-6-methyl-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-5-methyl-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-4-methoxy-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-4-methyl-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3,5-diamino-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-2-((5-phenyl-1,3,4-thiadiazol-2-yl)carbamoyl)thieno[2,3-b]pyridine-5-carboxylic acid; 3-amino-6-chloro-N-(5-phenyl-1,3,4-thiadiazol-2-yl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-methyl-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-7,8-dihydro-5H-thieno[2,3-b][1,6]naphthyridine-2-carboxamide; 2-(thiophen-2-yl)-10-(3-(trifluoromethyl)phenyl)-7,8-dihydro-5H-pyrido[3′,2′:4,5]thieno[3,2-b][1,5]diazonine-6,9,11(10H)-trione; 7-(thiophen-2-yl)-3-(3-(trifluoromethyl)phenyl)pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione; 3-amino-6-(trifluoromethyl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(2,4-dimethylthiazol-5-yl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(2-thienyl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamidine; 8-(thiophen-2-yl)-4-(3-(trifluoromethyl)phenyl)-3,4-dihydro-1H-pyrido[3′,2′:4,5]thieno[3,2-e][1,4]diazepine-2,5-dione; 3-amino-N-methyl-6-(2-thienyl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(2-dimethylaminoethyl)-6-(2-thienyl)-N-[3-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 6-acetamido-3-amino-N-(4-bromophenyl)-5-cyano-4-(2-furyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(4-bromophenyl)-5-cyano-4-(2-furyl)-6-hydroxy-thieno[2,3-b]pyridine-2-carboxamide; 2-[N-[3-amino-6-(2-thienyl)thieno[2,3-b]pyridine-2-carbonyl]-3-(trifluoromethyl)anilino]acetic acid; 3-[N-[3-amino-6-(2-thienyl)thieno[2,3-b]pyridine-2-carbonyl]-3-(trifluoromethyl)anilino]propanoic acid; 3-amino-5-oxo-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-5-hydroxy-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-5-fluoro-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]thieno[3,2-e]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-[4-(trifluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-[3-(trifluoromethoxy)phenyl]-N-[4-(trifluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N,6-bis(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 4-[[3-amino-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carbonyl]amino]benzoic acid; 3-amino-N-(5-bromo-2-pyridyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(6-bromo-3-pyridyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-[4-(difluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-[4-(1,1-difluoroethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-[3-(difluoromethoxy)phenyl]-N-[4-(trifluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-[4-(difluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(2-bromophenyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(3,4-dichlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(2,3-dichlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(3-chlorophenyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-[3-(difluoromethoxy)phenyl]-N-[4-(difluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 4-[[3-amino-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carbonyl]amino]benzenesulfonic acid; 3-amino-6-(4-chlorophenyl)-N-(2,5-dichlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(3,4-dimethylphenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(4-bromophenyl)-6-(5-chloro-2-pyridyl)thieno[2,3-b]pyridine-2-carboxamide; 3-(N-[3-amino-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carbonyl]-4-bromo-anilino)propanoic acid; 3-amino-6-(4-chlorophenyl)-N-[4-(2,2,2-trifluoroacetyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(5-chloro-2-pyridyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(4-chlorophenyl)-N-(6-chloro-3-pyridyl)thieno[2,3-b]pyridine-2-carboxamide; 3-[N-[3-amino-6-(3-methoxyphenyl)thieno[2,3-b]pyridine-2-carbonyl]-4-(trifluoromethoxy)anilino]propanoic acid; 3-(N-[3-amino-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carbonyl]-4-chloro-anilino)propanoic acid; 3-amino-6-(4-chlorophenyl)-N-(4-hydroxyphenyl)thieno[2,3-b]pyridine-2-carboxamide; and 3-amino-N-(4-pyridyl)-6-(2-thienyl)thieno[2,3-b]pyridine-2-carboxamide.
38 . The method of claim 37 , wherein said compound is 3-amino-N,6-bis(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide.
39 . The method of claim 37 , wherein said compound is 3-amino-6-[3-(difluoromethoxy)phenyl]-N-[4-(difluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide.
40 . The method of claim 37 , wherein the mammal is a human.
41 . The method of claim 37 , wherein said Dengue virus is selected from the group consisting of DEN-1, DEN-2, DEN-3, and DEN-4.
42 . The method of claim 37 , wherein said viral infection is associated with Dengue fever.
43 . The method of claim 42 , wherein said Dengue fever is selected from the group consisting of classical dengue fever and dengue hemorrhagic fever.
44 . The method of claim 37 , which further comprises co-administration of at least one agent selected from the group consisting of antiviral agent, vaccine, and interferon.
45 . The method of claim 44 , wherein said interferon is pegylated.
46 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the group consisting of: 3-amino-N-(4-bromophenyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(3-methoxyphenyl)-N-[4-(trifluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(2,5-dichlorophenyl)-6-(2-thienyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(2,3-dichlorophenyl)-6-(2-thienyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(4-bromophenyl)-6-(3-methoxyphenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(1,3-benzodioxol-5-yl)-N-(2-bromo-4-methyl-phenyl)thieno[2,3-b]pyridine-2-carboxamide; and 3-amino-6-(3-methoxyphenyl)-N-(2-phenoxyphenyl)thieno[2,3-b]pyridine-2-carboxamide, wherein said composition is suitable for human or animal administration.
47 . The composition of claim 46 , wherein said compound is 3-amino-N-(4-bromophenyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide.
48 . The composition of claim 46 , wherein said compound is 3-amino-6-(3-methoxyphenyl)-N-[4-(trifluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide.
49 . A method for the treatment of at least one type of a Dengue virus infection or disease associated therewith, comprising administering in a therapeutically effective amount to a mammal in need thereof, a compound or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the group consisting of: 3-amino-N-(4-bromophenyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(3-methoxyphenyl)-N-[4-(trifluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(2,5-dichlorophenyl)-6-(2-thienyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(2,3-dichlorophenyl)-6-(2-thienyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-N-(4-bromophenyl)-6-(3-methoxyphenyl)thieno[2,3-b]pyridine-2-carboxamide; 3-amino-6-(1,3-benzodioxol-5-yl)-N-(2-bromo-4-methyl-phenyl)thieno[2,3-b]pyridine-2-carboxamide; and 3-amino-6-(3-methoxyphenyl)-N-(2-phenoxyphenyl)thieno[2,3-b]pyridine-2-carboxamide.
50 . The method of claim 49 , wherein said compound is 3-amino-N-(4-bromophenyl)-6-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide.
51 . The method of claim 49 , wherein said compound is 3-amino-6-(3-methoxyphenyl)-N-[4-(trifluoromethoxy)phenyl]thieno[2,3-b]pyridine-2-carboxamide.
52 . The method of claim 49 , wherein the mammal is a human.
53 . The method of claim 49 , wherein said Dengue virus is selected from the group consisting of DEN-1, DEN-2, DEN-3, and DEN-4.
54 . The method of claim 53 , wherein said viral infection is associated with Dengue fever.
55 . The method of claim 54 , wherein said Dengue fever is selected from the group consisting of classical dengue fever and dengue hemorrhagic fever.
56 . The method of claim 49 , which further comprises co-administration of at least one agent selected from the group consisting of antiviral agent, vaccine, and interferon.
57 . The method of claim 56 , wherein said interferon is pegylated.