US 12,258,323 B2
Dihydrooxadiazinones
Manuel Ellermann, Berlin (DE); Stefan Nikolaus Gradl, Berlin (DE); Charlotte Christine Kopitz, Falkenesee (DE); Martin Lange, Berlin (DE); Adrian Tersteegen, Wuppertal (DE); Philip Lienau, Berlin (DE); Christa Hegele-Hartung, Mülheim an der Ruhr (DE); Detlev Sülzle, Berlin (DE); Timothy A. Lewis, Cambridge, MA (US); Heidi Greulich, Cambridge, MA (US); Xiaoyun Wu, Cambridge, MA (US); Matthew Meyerson, Boston, MA (US); and Alex Burgin, Cambridge, MA (US)
Assigned to Bayer Aktiengesellschaft, Leverkusen (DE); Bayer Pharma Aktiengesellschaft, Berlin (DE); The Broad Institute, Inc., Cambridge, MA (US); and Dana-Farber Cancer Institute, Inc., Boston, MA (US)
Filed by Bayer Aktiengesellschaft, Leverkusen (DE); Bayer Pharma Aktiengesellschaft, Berlin (DE); The Broad Institute, Inc., Cambridge, MA (US); and Dana-Farber Cancer Institute, Inc., Boston, MA (US)
Filed on Jul. 11, 2022, as Appl. No. 17/862,255.
Application 17/862,255 is a division of application No. 16/635,504, granted, now 11,427,553, previously published as PCT/EP2018/071039, filed on Aug. 2, 2018.
Claims priority of provisional application 62/541,627, filed on Aug. 4, 2017.
Prior Publication US 2023/0017200 A1, Jan. 19, 2023
Int. Cl. C07D 273/04 (2006.01); C07D 413/10 (2006.01); C07D 413/12 (2006.01); C07D 417/10 (2006.01); C07D 471/04 (2006.01); C07D 491/107 (2006.01); C07D 495/10 (2006.01)
CPC C07D 273/04 (2013.01) [C07D 413/10 (2013.01); C07D 413/12 (2013.01); C07D 417/10 (2013.01); C07D 471/04 (2013.01); C07D 491/107 (2013.01); C07D 495/10 (2013.01)] 15 Claims
 
1. A compound of formula (I)

OG Complex Work Unit Chemistry
where
R1 is selected from a hydrogen atom, a halogen atom, a cyano group, a C1-C3-alkyl group, a C1-C3-haloalkyl group, and a C1-C3-haloalkoxy group;
R2 is selected from a hydrogen atom and a halogen atom;
R3 is selected from,
a C1-C6-alkyl group which is substituted with one or two substituents and each substituent is independently selected from a hydroxy group, a C1-C4-alkoxy group and a 3-to 7-membered heterocycloalkyl group;
a C2-C6-alkenyl group which is optionally substituted with an C1-C4-alkoxy group;
a C3-C9-cycloalkyl group, which is optionally substituted with a hydroxy group;
a C5-C9-cycloalkenyl group, which is optionally substituted with a hydroxy group;
a 3- to 9-membered heterocycloalkyl group, comprising one, two or three heteroatoms which are independently selected from —O—, —S—, —S(O)—, S(O)2, and —NR9—,
and said heterocycloalkyl group optionally further comprising a bridging group selected from —O—, —NR9—, —CH2—, —CH2—CH2—, —O—CH2—, —CH2—O—, —NR9—CH2—, and —CH2—NR9—;
and said heterocycloalkyl group is optionally substituted with one, two or three substituents and each substituent is independently selected from
a halogen atom;
a oxo (═O) group;
a cyano group;
a hydroxy group;
a C1-C3-alkyl group which is optionally further substituted with a hydroxy group;
a C1-C3-haloalkyl group;
a C1-C3-alkoxy group;
a C1-C3-haloalkoxy group;
a C(O)NR5R6 group
and a NR5R6 group;
a 5- to 9-membered heterocycloalkyl group which is partially unsaturated and optionally substituted with one, two or three substituents and each substituent is independently selected from an oxo group (═O), a C1-C3-alkyl group, a —C(O)R5R6 group and a halogen atom;
an aryl group which is optionally substituted with one, two, three or four substituents and each substituent is independently selected from a halogen atom, a hydroxy group, a cyano group, a C1-C3-alkyl group, a C1-C3-haloalkyl group, a C1-C3-alkoxy group, a C1-C3-haloalkoxy group, and a NR5R6 group;
a mono- or bicyclic heteroaryl group which is optionally substituted with one, two or three substituents and each substituent is independently selected from a halogen atom, a C1-C3-alkyl group, a cyano group, a C1-C3-haloalkyl group, a C1-C3-hydroxalkyl group, a C1-C3-alkoxy group, a hydroxy group, and a NR5R6 group, with the proviso that said monocyclic heteroaryl group is not 4-pyridyl;
and a NR7R8 group;
R4 is selected from a hydrogen atom, and a C1-C3-alkyl group;
R5/R6 are independently selected from a hydrogen atom, a C1-C6-alkyl group, a —C1-C5-alkylene-O—C1-C5-alkyl group, a —C1-C5-alkylene-S—C1-C5-alkyl group, C3-C6-cycloalkyl group, and a C3-C5-heterocycloalkyl group;
R7/R8 are independently selected from a hydrogen atom, with the proviso that R7=R8=hydrogen is excluded,
a C1-C6-alkyl group,
which is substituted with one, two, three or four substituents and said substituent is independently selected from
a halogen atom,
a cyano group,
a hydroxy group,
a C(O)NR5R6 group,
a NR5R6 group,
a C1-C3-alkoxy group,
a C3-C7-cycloalkyl group which is optionally substituted with one or two substituents and said substituents are independently selected from a C1-C3-alkyl group, a oxo (═O) group, a hydroxy group, and a C1-C3-hydroxyalkyl group;
a 3- to 7-membered heterocycloalkyl group which itself is optionally substituted with, a C1-C3-alkyl group or an oxo (═O) group;
a heteroaryl group, which itself is optionally substituted with a C1-C3-alkyl group;
a —C1-C5-alkylene-O—C1-C5-alkyl group;
a —C1-C5-alkylene-S—C1-C5-alkyl group;
a —C1-C5-alkylene-NR5-C1-C5-alkyl group;
a C3-C6-cycloalkyl group which is optionally substituted with a hydroxy group; and
a 3- to 6-membered heterocycloalkyl group, which is optionally substituted with one or two substituents, said substituent independently selected from C1-C3-alkyl group and a hydroxy group;
R9 is a hydrogen atom or a C1-C3-alkyl group or a bond;
or a stereoisomer, a tautomer, an N-oxide, or a salt thereof, or a mixture of same.