Viral replication inhibitors

Patent metadata

Field	Value
Publication number	US-10633378-B2
Application number	US-201414777765-A
Country	US
Kind code	B2
Filing date	Mar 25, 2014
Priority date	Mar 25, 2013
Publication date	Apr 28, 2020
Grant date	Apr 28, 2020

Abstract

The present invention relates to a series of novel compounds, methods to prevent or treat viral infections in animals by using the novel compounds and to said novel compounds for use as a medicine, more preferably for use as a medicine to treat or prevent viral infections, particularly infections with RNA viruses, more particularly infections with viruses belonging to the family of the Flaviviridae, and yet more particularly infections with the Dengue virus. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of viral infections. The invention also relates to processes for preparation of the compounds.

First claim

The invention claimed is:

1. A compound of formula (A),

wherein,
cycle C is

wherein the wavy line ( ) indicates the point of attachment to the carbonyl of the main formula (A) and the hashed line ( ) indicates the point of attachment to the cycle A of the main formula (A);
cycle A is selected from

wherein the wavy line ( ) indicates the point of attachment to the atom of cycle C, and wherein the depicted cycles may be optionally substituted with one, two, or three substituents selected from alkyl, —OCH 3 , halogen, trifluoromethyl, —OCF 3 , or cyano;
cycle B is selected from

wherein the wavy line ( ) indicates the point of attachment to the carbon atom of the main formula (A), and wherein the depicted cycles may be optionally substituted with one, two, or three Z 1a ;
R 1 is selected from, aryl, and heterocycle,
and wherein said, aryl, and heterocycle are optionally substituted with one, two, or three Z 1b ;

R 2 is hydrogen;
R 12 is hydrogen;
R 15 is selected from hydrogen; C 1-6 alkyl; and C 3-7 cycloalkyl;
each Z 1a and Z 1b is independently selected from the group consisting of halogen, hydroxyl, —OZ 2 , ═O, —S(═O) 2 Z 3 , —S(═O) 2 NZ 4 Z 5 , trifluoromethyl, trifluoromethoxy, —NZ 4 C(═O)Z 2 , cyano, C(═O)OZ 2 , C 1-6 alkyl, heteroC 1-6 alkyl, aryl, and heterocycle;
and wherein said C 1-6 alkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from C 1-6 alkyl, hydroxyl, ═O, halogen, trifluoromethyl, —OCF 3 , and —C(O)OH;

each Z 2 is C 1-6 alkyl;
each Z 3 is independently selected from hydroxyl, and C 1-6 alkyl;
each Z 4 and Z 5 is independently selected from hydrogen, and C 1-6 alkyl;
or an isomer, solvate, or salt thereof;
wherein the term “heterocycle” as used herein means a saturated, unsaturated or aromatic ring system of 3 to 18 atoms including at least one N, O, or S.

2. A pharmaceutical composition comprising a pharmaceutically acceptable carrier, and as active ingredient an effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein the compound has structure according to formula (E1)

wherein each of cycle A, cycle B, R 12 , R 15 and Z 1b is as described for formula (A) in claim 1 .

4. The compound of claim 1 , wherein the isomer is a stereo-isomer or a tautomer.

5. The compound of claim 1 , wherein the salt is a pharmaceutically acceptable salt.

Assignees

• Univ Leuven Kath
• Univ Leuven Kath

Inventors

• Bardiot Dorothée
• Carlens Gunter
• Dallmeier Kai
• Kaptein Suzanne
• Koukni Mohamed
• Marchand Arnaud
• Neyts Johan
• Smets Wim

Classifications

• C07D207/323

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atoms · CPC title

• C07D265/30

  not condensed with other rings · CPC title

• C07D241/04

  having no double bonds between ring members or between ring members and non-ring members · CPC title

• C07D271/04

  1,2,3-Oxadiazoles; Hydrogenated 1,2,3-oxadiazoles · CPC title

• C07D285/10

  1,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles · CPC title