US 12,325,701 B2
YKL-40 inhibitors and their therapeutic
Łukasz Krzemiński, Warsaw (PL); Wojciech Czestkowski, Pabianice (PL); Marzena Mazur, Łódź (PL); Gleb Andryianau, Irvine, CA (US); Sylwia Olejniczak, Łódź (PL); Michal Czesław Piotrowicz, Łódź (PL); Robert Koralewski, Łódź (PL); Elżbieta Pluta, Dębe Wielkie (PL); Krzysztof Matyszewski, Łódź (PL); Michał Kowaiski, Godziszka (PL); Barbara Dymek, Warsaw (PL); Rafał Kozieł, Lesznowola (PL); Jacek Olozak, Łódź (PL); Adam Gołębiowski, Madison, CT (US); Agnieszka Bartoszewicz, Warsaw (PL); and Katarzyna Krysztofiak, Warsaw (PL)
Assigned to Molecure S.A., Warsaw (PL)
Filed by Molecure S.A., Warsaw (PL)
Filed on Mar. 3, 2023, as Appl. No. 18/117,193.
Claims priority of provisional application 63/316,477, filed on Mar. 4, 2022.
Claims priority of application No. 440558 (PL), filed on Mar. 4, 2022.
Prior Publication US 2023/0278996 A1, Sep. 7, 2023
Int. Cl. C07D 413/14 (2006.01); C07D 487/04 (2006.01); C07D 495/04 (2006.01); G01N 33/543 (2006.01); G01N 33/68 (2006.01)
CPC C07D 413/14 (2013.01) [C07D 487/04 (2013.01); C07D 495/04 (2013.01); G01N 33/5438 (2013.01); G01N 33/6893 (2013.01); G01N 2500/02 (2013.01)] 6 Claims
 
1. A compound represented by formula (I)

OG Complex Work Unit Chemistry
wherein:
X1 is —C(R4R5)—;
X2 is selected from the group consisting of —C(R6R7)—, —N(R8)—, and —O—;
X3 is —C(R9R10)—;
X4 is —CH2—;
Y is chloro;
Z is selected from the group consisting of pyridin-2-yl, 5-fluoro-pyridin-2-yl, 6-fluoro-pyridin-2-yl, 4-chloro-pyridin-2-yl, pyrazin-2-yl, 3-fluoro-pyridin-2-yl, 6-chloro-pyridin-2-yl, 2-fluoro-pyridin-4-yl, 3-methyl-pyridin-2-yl, 6-cyano-pyridin-2-yl, 5-cyano-pyridin-2-yl, 4-trifluoromethyl-pyridin-2-yl, 4-cyano-pyridin-2-yl, 3-cyano-pyridin-2-yl, 3-chloro-pyridin-2-yl, 6-fluoro-pyrimidin-4-yl, 3,5-difluoro-pyridin-2-yl, pyrimidin-4-yl, pyridin-3-yl, pyridin-4-yl, 4-methoxy-pyridin-2-yl, 4-methyl-pyridazin-6-yl, phenyl, 4-methyl-pyrimidin-2-yl, pyrimidin-2-yl, 5-fluoro-pyrimidin-2-yl, 3-cyano-4-methyl-pyridin-2-yl, 3-trifluoromethyl-pyridin-2-yl, 2-chloro-pyrimidin-4-yl, 2-amino-pyrimidin-4-yl, 4-fluoro-pyridin-2-yl, 4-bromo-pyridin-2-yl, 3-methoxycarbonyl-pyridin-2-yl, 2-cyano-6-fluoro-phenyl, 2-cyano-phenyl, 3-hydroxymethyl-pyridin-2-yl, 2-fluoro-4-methoxycarbonyl-pyridin-3-yl, 3-fluoro-4-methoxycarbonyl-pyridin-2-yl, 2-fluoro-4-hydroxycarbonyl-pyridin-3-yl, 2,6-difluorophenyl, 4-methoxycarbonyl-pyridin-2-yl, 4-hydroxy-carbonyl-pyridin-2-yl, 2-fluorophenyl, 3-fluorophenyl, 4-aminocarbonyl-pyridin-2-yl, 4-(hydroxymethyl)-pyridin-2-yl, 4-(2-hydroxyprop-2-yl)-pyridin-2-yl, pyrimidin-5-yl, 6-methyl-pyridin-2-yl, 5-methyl-pyridin-2-yl, 4-methyl-pyridin-2-yl, 4-trifluoromethyl-pyrimidin-6-yl, 2-trifluoromethyl-pyrazin-6-yl, 2-trifluoromethyl-pyrazin-5-yl, 3-methoxy-pyridin-2-yl, 4-hydroxy-pyridin-2-yl, 3-hydroxy-pyridin-2-yl, 2-amino-1,3,5-triazin-6-yl, 2-dimethylamino-1,3,5-triazin-6-yl, 2-methyl-1,3,5-triazin-6-yl, 2-methoxy-1,3,5-triazin-6-yl, 2-hydroxy-1,3,5-triazin-6-yl, 2-chloro-1,3,5-triazin-6-yl, and 2-cyano-1,3,5-triazin-6-yl;
R1 is hydrogen;
R2 is selected from the group consisting of hydrogen and methyl;
R3 is hydrogen;
R4 is hydrogen;
R5 is hydrogen;
R6 is selected from the group consisting of hydrogen and methyl;
R7 is selected from the group consisting of hydroxy and methoxy;
R8 is selected from the group consisting of methyl, isobutyl, and 2-hydroxypropyl;
R9 is selected from the group consisting of hydrogen, methyl, hydroxymethyl, 4-morpholino-methyl, 4-methyl-piperazinyl, dimethylaminocarboxymethyl, dimethylamino-ethyl(methyl)aminomethyl, acetylaminomethyl, phthalimidomethyl, succinimidomethyl, (2,5-dioxo-imidazolidin-1-yl)methyl, pyrrolidinylmethyl, isobutyl, methylsulfonylmethyl, isopropyl, and 1-hydroxyethyl;
or R8 and R9, taken together, represent —CH2CH2CH2—, optionally substituted with one or more substituents selected from hydroxy, methoxy, and fluoro;
R10 is hydrogen; and
wherein any occurrence of alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkylene, heterocyclyl, cycloalkyl, alkoxy, alkylthio, haloalkyl, or hydroxyalkyl is optionally substituted with one or more substituents independently selected from the group consisting of hydroxy and halo;
or a tautomer, stereoisomer, pharmaceutically acceptable salt, solvate, or polymorph thereof.