US 12,012,411 B2
Viral replication inhibitors
Dorothée Bardiot, Leuven (BE); Gunter Carlens, Leuven (BE); Kai Dallmeier, Leuven (BE); Suzanne Kaptein, Leuven (BE); Michael McNaughton, Leuven (BE); Arnaud Marchand, Leuven (BE); Johan Neyts, Leuven (BE); Wim Smets, Leuven (BE); and Mohamed Koukni, Leuven (BE)
Assigned to Katholieke Universiteit Leuven, Leuven (BE)
Filed by Katholieke Universiteit Leuven, Leuven (BE)
Filed on Nov. 30, 2021, as Appl. No. 17/538,532.
Application 16/515,272 is a division of application No. 14/346,777, granted, now 10,550,123, issued on Feb. 4, 2020, previously published as PCT/EP2012/069007, filed on Sep. 26, 2012.
Application 17/538,532 is a continuation of application No. 16/515,272, filed on Jul. 18, 2019, granted, now 11,279,704.
Claims priority of provisional application 61/626,410, filed on Sep. 26, 2011.
Claims priority of application No. 1116559 (GB), filed on Sep. 26, 2011.
Prior Publication US 2022/0106321 A1, Apr. 7, 2022
Int. Cl. C07D 487/04 (2006.01); C07D 209/14 (2006.01); C07D 401/06 (2006.01); C07D 401/08 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 403/06 (2006.01); C07D 403/08 (2006.01); C07D 403/10 (2006.01); C07D 403/12 (2006.01); C07D 405/06 (2006.01); C07D 405/12 (2006.01); C07D 409/06 (2006.01); C07D 409/08 (2006.01); C07D 409/12 (2006.01); C07D 413/06 (2006.01); C07D 413/08 (2006.01); C07D 413/12 (2006.01); C07D 417/14 (2006.01); C07D 471/04 (2006.01); C07D 495/04 (2006.01); C07D 498/04 (2006.01); C07D 513/04 (2006.01)
CPC C07D 487/04 (2013.01) [C07D 209/14 (2013.01); C07D 401/06 (2013.01); C07D 401/08 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/06 (2013.01); C07D 403/08 (2013.01); C07D 403/10 (2013.01); C07D 403/12 (2013.01); C07D 405/06 (2013.01); C07D 405/12 (2013.01); C07D 409/06 (2013.01); C07D 409/08 (2013.01); C07D 409/12 (2013.01); C07D 413/06 (2013.01); C07D 413/08 (2013.01); C07D 413/12 (2013.01); C07D 417/14 (2013.01); C07D 471/04 (2013.01); C07D 495/04 (2013.01); C07D 498/04 (2013.01); C07D 513/04 (2013.01)] 18 Claims
 
1. A method of treatment of Dengue virus or yellow fever virus, by the administration of an effective amount of a compound of formula B:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, optionally in combination with one or more other medicines, to a human patient in need thereof,
wherein
the moiety

OG Complex Work Unit Chemistry
is

OG Complex Work Unit Chemistry
wherein the wavy line (custom character) indicates the point of attachment to the carbonyl of the main formula (B); wherein said moiety is substituted with one or more Z1;
cycle B is

OG Complex Work Unit Chemistry
wherein the wavy line (custom character) indicates the point of attachment to the carbon atom of the main formula (B), and wherein the depicted cycles are substituted with one, two, or three Z1a;
R1 is phenyl; wherein said phenyl is substituted with one, two, or three Z1b;
R2 is hydrogen;
each Z1 and Z1a is independently selected from the group consisting of halogen, hydroxyl, —OZ2, —O—C(═O)Z3, ═O, —S(═O)2Z3, —S(═O)2NZ4Z5, trifluoromethyl, trifluoromethoxy, —NZ4Z5, —NZ4C(═O)Z2, —NZ4C(═O)OZ2, cyano, —C(═O)Z3, —C(═O)OZ2, —C(═O)NZ4Z5, C1-6alkyl, heteroC1-6alkyl, aryl, heterocycle, and heterocycle-C1-6alkyl;
and wherein said C1-6alkyl, heteroC1-6alkyl, aryl, heterocycle, and heterocycle-C1-6alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, ═O, halogen, trifluoromethyl, —OCF3, —O—C(O)Me, cyano, nitro, —C(O)OH, —C(O)OC1-6alkyl, —NH2, —NHCH3; —N(CH3)2, —NH—C(═O)O—C1-4alkyl, —S(O)2C1-4alkyl, and —O—C1-6alkyl;
each Z1b is independently selected from the group consisting of hydroxyl, —OZ2, —O—C(═O)Z3, ═O, —S(═O)2Z3, —S(═O)2NZ4Z5, trifluoromethyl, trifluoromethoxy, —NZ4Z5, —NZ4C(═O)Z2, —NZ4C(═O)OZ2, cyano, —C(═O)Z3, —C(═O)OZ2, —C(═O)NZ4Z5, C3-6alkyl, heteroC1-6alkyl, aryl, heterocycle, and heterocycle-C1-6alkyl;
and wherein said C3-6alkyl, heteroC1-6alkyl, aryl, heterocycle, and heterocycle-C1-6alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, ═O, halogen, trifluoromethyl, —OCF3, —O—C(O)Me, cyano, nitro, —C(O)OH, —C(O)OC1-6alkyl, —NH2, —NHCH3; —N(CH3)2, —NH—C(═O)O—C1-4alkyl, —S(O)2C1-4alkyl, and —O—C1-6alkyl;
each Z2 is independently selected from C1-6alkyl, aryl, heterocycle, and heterocycle-C1-6alkyl;
wherein said C1-6alkyl, aryl, heterocycle, and heterocycle-C1-6alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, ═O, halogen, trifluoromethyl, difluoromethyl, —O—C1-6alkyl, —OCF3, —S(═O)2C1-4alkyl, cyano, —C(═O)OH, —C(═O)O—C1-4alkyl, —NH2, —N(CH3)2, pyrrolidinyl, piperidinyl, and piperazinyl, wherein said C1-6alkyl is not substituted with hydroxyl;
each Z3 is independently selected from hydroxyl, aryl, and heterocycle;
wherein said aryl and heterocycle are optionally substituted with one, two, or three substituents selected from C1-6alkyl and —N(CH3)2;
each Z4 and Z5 is independently selected from hydrogen, C1-6alkyl, aryl, C3-7cycloalkyl, and heterocycle;
or an isomer thereof, or a solvate thereof, or a salt thereof, or a prodrug thereof;
wherein the term “heterocycle” means a saturated, unsaturated, or aromatic ring system of 3 to 18 atoms including at least one N, O, S, or P.