US 11,851,422 B2
Anti-viral compounds
Koen Vandyck, Paal (BE); Dorothée Alice Marie-Eve Bardiot, Leuven (BE); Pierre Jean-Marie Bernard Raboisson, Wavre (BE); Leonid Beigelman, San Mateo, CA (US); Antitsa Dimitrova Stoycheva, Half Moon Bay, CA (US); Sandro Boland, Leuven (BE); and Arnaud Didier Marie Marchand, Leuven (BE)
Assigned to Aligos Therapeutics, Inc.; and Katholieke Universiteit Leuven, Leuven (BE)
Filed by Aligos Therapeutics, Inc., South San Francisco, CA (US); and Katholieke Universiteit Leuven, Leuven (BE)
Filed on Jul. 6, 2022, as Appl. No. 17/811,008.
Claims priority of provisional application 63/268,052, filed on Feb. 15, 2022.
Claims priority of provisional application 63/265,479, filed on Dec. 15, 2021.
Claims priority of provisional application 63/264,212, filed on Nov. 17, 2021.
Claims priority of provisional application 63/261,480, filed on Sep. 22, 2021.
Claims priority of provisional application 63/203,135, filed on Jul. 9, 2021.
Prior Publication US 2023/0093249 A1, Mar. 23, 2023
Int. Cl. C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 403/12 (2006.01); C07D 403/14 (2006.01); C07D 405/14 (2006.01); C07D 413/12 (2006.01); C07D 413/14 (2006.01); C07D 487/04 (2006.01); C07D 491/04 (2006.01); C07D 491/107 (2006.01); C07D 498/04 (2006.01); A61P 31/14 (2006.01); A61K 31/403 (2006.01); A61K 31/422 (2006.01); A61K 31/4439 (2006.01); A61K 31/497 (2006.01); A61K 31/519 (2006.01); A61K 31/437 (2006.01); A61K 31/4709 (2006.01); A61K 31/407 (2006.01); A61K 31/4155 (2006.01); A61K 31/538 (2006.01); A61K 31/5377 (2006.01); A61K 31/4245 (2006.01); A61K 31/553 (2006.01); A61K 31/4192 (2006.01)
CPC C07D 403/12 (2013.01) [C07D 403/14 (2013.01); C07D 405/14 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01); C07D 487/04 (2013.01); C07D 491/107 (2013.01); C07D 498/04 (2013.01)] 61 Claims
 
1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure:
wherein:

OG Complex Work Unit Chemistry
Ring A1 is selected from the group consisting of

OG Complex Work Unit Chemistry
and wherein Ring A1 is optionally substituted with one or more moieties independently selected from the group consisting of ═O, ═CH2, deuterium, halogen, hydroxy, an unsubstituted C1-4 alkyl, an unsubstituted C1-4 haloalkyl, an unsubstituted C2-4 alkenyl and an unsubstituted or a substituted C3-6 monocyclic cycloalkyl, wherein the C3-6 monocyclic cycloalkyl is connected in a spiro-fashion;
R1 is selected from the group consisting of cyano, an unsubstituted or a substituted C2-5 alkynyl, an unsubstituted or a substituted acyl, an unsubstituted or a substituted ketoamide, —CH(OH)((P═O)(OR6)2) and —C(═O)CH2—O—((P═O)(OR7)2);
each R6 and each R7 re independently hydrogen, an unsubstituted C1-6 alkyl, an unsubstituted C2-6 alkenyl, an unsubstituted C1-6 haloalkyl, an unsubstituted or a substituted aryl or an unsubstituted or a substituted aryl(C1-4 alkyl);
R2 is hydrogen, deuterium or halogen;
R3 is an unsubstituted or a substituted monocyclic nitrogen-containing heterocyclyl(C1-4 alkyl), an unsubstituted or a substituted bicyclic nitrogen-containing heterocyclyl(C1-4 alkyl) or an unsubstituted or a substituted monocyclic nitrogen-containing heteroaryl(C1-4 alkyl);
R4 is hydrogen, deuterium or halogen;
R5 is

OG Complex Work Unit Chemistry
a substituted monocyclic C3-6 cycloalkyl or a substituted 4- to 6-membered monocyclic heterocyclyl, wherein the monocyclic C3-6 cycloalkyl and the 4- to 6-membered monocyclic heterocyclyl are independently substituted 1, 2 or 3 times with a moiety selected from the group consisting of deuterium, halogen, an unsubstituted C1-6 alkyl, an unsubstituted C1-6 haloalkyl and an unsubstituted C1-6 alkoxy, or independently substituted in a spiro-fashion by an unsubstituted or a substituted bicyclic cycloalkenyl or an unsubstituted or a substituted bicyclic heterocyclyl;
R8 and R10 are independently selected from the group consisting of an unsubstituted or a substituted C2-6 alkyl, an unsubstituted or a substituted C2-6 alkenyl, an unsubstituted or a substituted C2-6 alkynyl, an unsubstituted or a substituted monocyclic C3-6 cycloalkyl, an unsubstituted or a substituted bicyclic C5-8 cycloalkyl, an unsubstituted or a substituted monocyclic 4- to 6-membered heterocyclyl and an unsubstituted monocyclic C3-6 cycloalkyl(CH2)—,
wherein when the C2-6 alkyl is substituted, the C2-6 alkyl is substituted 1, 2, 3 or 4 times with a substituent independently selected from the group consisting of halogen, cyano, an unsubstituted or a substituted monocyclic C3-6 cycloalkyl, an unsubstituted C1-4 alkoxy and an unsubstituted C1-4 haloalkoxy, or the C2-6 alkyl is substituted 1 to 13 times with deuterium;
wherein when the C2-6 alkenyl, the C2-6 alkynyl, the monocyclic C3-6 cycloalkyl, the bicyclic C5-8 cycloalkyl and the monocyclic 4- to 6-membered heterocyclyl are substituted, the C2-6 alkenyl, the C2-6 alkynyl, the monocyclic C3-6 cycloalkyl, the bicyclic C5-8 cycloalkyl and the monocyclic 4- to 6-membered heterocyclyl are substituted 1, 2, 3 or 4 times with a substituent independently selected from the group consisting of halogen, an unsubstituted C1-4 alkyl, an unsubstituted C2-4 alkenyl, an unsubstituted C2-4 alkynyl, an unsubstituted C1-4 haloalkyl, an unsubstituted or a substituted monocyclic C3-6 cycloalkyl and an unsubstituted C1-4 alkoxy; and
R9 is selected from the group consisting of an unsubstituted or a substituted C1-6 alkyl, an unsubstituted or a substituted C1-6 haloalkyl, a substituted monocyclic C3-6 cycloalkyl, an unsubstituted or a substituted bicyclic C5-6 cycloalkyl, an unsubstituted or a substituted monocyclic heteroaryl and an unsubstituted or a substituted monocyclic heterocyclyl, wherein the substituted C1-6 alkyl is substituted 1 or 2 times with an unsubstituted C1-4 alkoxy, wherein the substituted monocyclic C3-6 cycloalkyl is substituted 1, 2, 3 or 4 times with a substituent independently selected from the group consisting of halogen, an unsubstituted C1-4 alkyl, an unsubstituted C1-4 alkoxy, an unsubstituted C1-4 haloalkyl and an unsubstituted monocyclic C3-6 cycloalkyl, and wherein the substituted C1-6 haloalkyl is substituted 1 or 2 times with an unsubstituted C1-4 alkoxy; and
R11 is selected from the group consisting of an optionally substituted monocyclic 4- to 6-membered heterocyclyl, —(NH)m-an optionally substituted 5- to 6-membered monocyclic heteroaryl, —O-an optionally substituted C1-6 alkyl, —O-an optionally substituted C3-8 cycloalkyl and —O-an optionally substituted C3-8 cycloalkyl(C1-4 alkyl), wherein m is 0 or 1.