Treatment and prevention of dengue disease
The present invention relates to the use of substituted indole derivatives and substituted indoline derivatives in the manufacture of a medicament for the treatment of dengue disease in an individual infected by dengue virus or the prevention of dengue disease in an individual at risk of being infected by Dengue virus. The invention further provides a method for the treatment or the prevention of dengue in an individual at risk of being infected by Dengue virus.
1 . A method for the prevention of dengue in an individual at risk of being infected by Dengue virus or for the treatment of dengue disease in an individual infected by Dengue virus, comprising the step of administering to said individual a medicament comprising compound of formula I, wherein the first administration of the medicament occurs at least 24 hours prior to viral infection to at most 5 days after being infected, and wherein the formula I corresponds to
a stereo-isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof; said compound is selected from the group wherein:
R 1 is H, R 2 is F and R 3 is H or CH 3 ,
R 1 is H, CH 3 or F, R 2 is OCH 3 and R 3 is H,
R 1 is H, R 2 is OCH 3 and R 3 is CH 3 ,
R 1 is CH 3 , R 2 is F and R 3 is H,
R 1 is CF 3 or OCF 3 , R 2 is H and R 3 is H,
R 1 is OCF 3 , R 2 is OCH 3 and R 3 is H,
R 1 is OCF 3 , R 2 is H and R 3 is CH 3 .
2 . The method according to claim 1 , wherein the medicament is administered intermittently at least once every 24 hours.
3 . The method according to claim 1 , wherein the medicament comprises an effective amount of compound of formula I, said effective amount is selected such that dengue virus viral load in blood is kept at a level equal to or under 15 log 10 copies/mL.
4 . The method according to claim 1 , wherein the effective amount of the compound is from 0.05 mg/kg to 500 mg/kg body weight.
5 . The method according to claim 1 , wherein the medicament is administered orally, subcutaneously, intramuscularly, or intravenously.
6 . The method according to claim 1 , wherein the medicament is administered intermittently at least once every week.
7 . The method according to claim 1 , wherein the medicament is administered intermittently at least once every two weeks.
8 . The method according to claim 1 , wherein the medicament is administered intermittently at least once every month.
9 . The method according to claim 1 , wherein the medicament is administered intermittently at least once every 6 months.
10 . The method according to claim 1 , wherein the medicament comprises an effective amount of compound of formula I, said effective amount is selected such that dengue viral load in blood is kept at a level equal to or under 10 log 10 copies/mL.
11 . The method according to claim 1 , wherein the medicament comprises an effective amount of compound of formula I, said effective amount is selected such that dengue viral load in blood is kept at a level equal to or under 7 log 10 copies/mL.
12 . The method according to claim 1 , wherein the medicament comprises an effective amount of compound of formula I, said effective amount is selected such that dengue viral load in blood is kept at a level equal to or under 5 log 10 copies/mL.
13 . The method according to claim 1 , wherein the medicament comprises an effective amount of compound of formula I, said effective amount is selected such that dengue viral load in blood is kept at a level equal to or under 3 log 10 copies/mL.
14 . The method according to claim 1 , wherein the medicament comprises an effective amount of compound of formula I, said effective amount is selected such that dengue viral load in blood is kept at a level equal to or under 2 log 10 copies/mL.
15 . The method according to claim 1 , wherein the compound is
16 . The method according to claim 15 , wherein the compound is the (S)-enantiomer of the compound of formula (a).