IP Library Granted Patent US 8,993,604
Granted Patent B2
US 8,993,604 · App. 13/379,776 · Granted Mar 31, 2015

Treatment and prevention of dengue virus infections

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Quick Facts
Patent No.
US 8,993,604
App. No.
13/379,776
Granted
Mar 31, 2015
Kind
B2
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.

Claims (17)

1. A method for the treatment of a Dengue virus infection, 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 S;

Ar is substituted or unsubstituted aryl or heteroaryl; and

A, B, D, and E are independently N or C—R 1 , C—R 2 , C—R 3 and C—R 4 , respectively, wherein R 1 , 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 1 and R 2 together with the carbons they are attached to may form a substituted or unsubstituted ring, 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 nonaromatic and may include one or more heteroatoms in the ring and may be fused with an aromatic or aliphatic ring.

2. The method of claim 1 , wherein Ar is a substituted aryl.

3. The method of claim 1 , wherein each of A, B, D and E is C—H.

4. The method of claim 1 , wherein each of A, B and E is C—H and D is C—CH 3 .

5. The method of claim 1 , wherein the compound of Formula I is selected from the group consisting of: N-(4-Benzothiazol-2-yl-3-hydroxy-phenyl)-4-methoxy-benzamide; 2,3-Dihydro-benzo[1,4]dioxine-6-carboxylic acid (4-benzothiazol-2-yl-phenyl)-amide; 2,4-Dimethoxy-N-[4-(6-methyl-benzothiazol-2-yl)-phenyl]-benzamide; N-(3-Benzothiazol-2-yl-phenyl)-2-methoxy-benz amide; N-(4-Benzothiazol-2-yl-3-chloro-phenyl)-3,4-dimethoxy-benzamide; N-(4-Benzothiazol-2-yl-3-chloro-phenyl)-4-methoxy-benzamide; 4-Dimethylamino-N-[4-(6-methyl-benzothiazol-2-yl)-phenyl]-benzamide; 4-Methyl-N-[4-(6-methyl-benzothiazol-2-yl)-phenyl]-phthalamic acid; N-[4-(6-Methyl-benzothiazol-2-yl)-phenyl]-3-(4-methyl-piperazine-1-sulfonyl)-benzamide; N-(4-Benzothiazol-2-yl-phenyl)-2-dimethylamino-benzamide; and N-(4-Benzothiazol-2-yl-3-chloro-phenyl)-2-methoxy-benzamide.

6. The method of claim 5 , wherein the compound of Formula I is 2,4-Dimethoxy-N-[4-(6-methyl-benzothiazol-2-yl)-phenyl]-benzamide.

7. The method of claim 1 , wherein the mammal is a human.

8. The method of claim 1 , wherein said Dengue virus is selected from the group consisting of DEN-1, DEN-2, DEN-3, and DEN-4.

9. The method of claim 1 , wherein said viral infection is associated with Dengue fever.

10. The method of claim 9 , wherein said Dengue fever is selected from the group consisting of classical dengue fever, dengue hemorrhagic fever syndrome, and dengue shock syndrome.

11. The method of claim 1 , which further comprises co-administration of at least one agent selected from the group consisting of antiviral agent, vaccine, and interferon.

12. The method of claim 11 , wherein said antiviral agent is Ribavirin.

13. The method of claim 11 , wherein said antiviral agent is cidofovir.

14. The method of claim 11 , wherein said interferon is pegylated.

Assignments (6)
RELEASE OF SECURITY INTEREST IN INTELLECTUAL PROPERTY AT REEL/FRAME NO. 40349/0219 Recorded Mar 13, 2020
From: CORTLAND CAPITAL MARKET SERVICES LLC
To: SIGA TECHNOLOGIES, INC.
Reel/Frame 052163/0014 →
SECURITY INTEREST Recorded Nov 16, 2016
From: SIGA TECHNOLOGIES, INC.
To: CORTLAND CAPITAL MARKET SERVICES, LLC
Reel/Frame 040349/0219 →
RELEASE OF SECURITY INTEREST Recorded Apr 2, 2015
From: GENERAL ELECTRIC CAPITAL CORPORATION, AS AGENT
To: SIGA TECHNOLOGIES, INC.
Reel/Frame 035319/0001 →
SECURITY AGREEMENT Recorded Dec 31, 2012
From: SIGA TECHNOLOGIES, INC.
To: GE CAPITAL EQUITY INVESTMENTS, INC. C/O GE HEALTHCARE FINANCIAL SERVICES, INC.
Reel/Frame 029557/0771 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 23, 2012
From: BYRD, CHELSEA M.; DAI, DONGCHENG; JORDAN, ROBERT; HRUBY, DENNIS E.
To: SIGA TECHNOLOGIES, INC.
Reel/Frame 027748/0711 →
CONFIRMATORY LICENSE Recorded Jan 10, 2012
From: SIGA TECHNOLOGIES, INC.
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 027505/0319 →