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US 8,076,482 B2Granted
3,3′-spiroindolinone derivatives
AssigneeHoffmann-La Roche Inc.
InventorsLi Chen, Xingchun Han, Song Yang, Zhuming Zhang
Life of this patent
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Abstract
There are provided compounds of the formula or a pharmaceutically acceptable salt or ester thereof wherein X, Y, W, W′, V, V′, V″, R1, R2 and R3 are as herein described. The compounds have utility as antiproliferative agents, especially, as anticancer agents.
Claims4
A compound of the formula
- wherein
- X is Cl,
- Y is hydrogen,
- V is F or Cl,
- V′ is hydrogen or F,
- V″ is hydrogen,
- W is Cl,
- W′ is hydrogen,
- R1 and R2 are methyl or ethyl,
- or R1 and R2 may link to form a cyclic structure selected from a substituted or unsubstituted cycloalkyl
- R3 is NHS(═O)2R″,
- R′, R″ is selected independently from the group consisting of lower alkyl, substituted alkyl, cycloalkyl and substituted cycloalkyl
- and the pharmaceutically acceptable salts and esters and enantiomers thereof.
10 more elements
A compound selected from the group consisting of
- chiral (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(1-hydroxycarbonyl-1-methyl-ethoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one,
- racemic (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(1-methoxycarbonyl-1-methyl-ethoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one,
- chiral (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(1-methoxycarbonyl-1-methyl-ethoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one,
- chiral (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(2-methanesulfonylamino-1,1-diethyl-2-oxo-ethoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one,
- chiral (2′R, 3R, 4′S)-6-chloro-4′-[5-chloro-2-(2-methanesulfonylamino-1,1-diethyl-2-oxo-ethoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one,
- chiral (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(2-methanesulfonylamino-1,1-diethyl-2-oxo-ethoxy)-phenyl]-2′-(5-chloro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one,
- racemic (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro2-(1-ethoxycarbonyl-1-propyl-butoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one,
- chiral (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(2-cyclopropanesulfonylamino-1,1-dimethyl-2-oxo-ethoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one and
- racemic (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(1-methoxycarbonyl-cyclobutoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one.
6 more elements
A compound selected from the group consisting of
- racemic (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(2-methoxycarbonyl-methoxy)-phenyl]-2′-[5-difluoro-2-methyl-phenyl]-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1 H)-one,
- racemic (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(1-methoxycarbonyl-1-methyl-ethoxy)-phenyl]-2′-(4,5-difluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one,
- racemic (2′R, 3R, 4′S)-6-chloro-4′-[5-chloro-4-fluoro-2-methoxy-phenyl]-2′-(5-fluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1 H)-one,
- racemic (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(1-methoxycarbonyl-1-methyl-ethoxy)-phenyl]-2′-(5,6-difluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one,
- racemic (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-4-fluoro-2-(1-methoxycarbonyl-1-methyl-ethoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one,
- racemic (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(1-methoxylcarbamoyl-1-methyl-ethoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one and
- racemic (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(1-methoxylcarbamoyl-1-ethyl-propoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)-6′-thioxo spiro[3H-indole-3,3′-piperidine]-2(1H)-one.
4 more elements
A pharmaceutical composition comprising a compound of the formula
- wherein
- X is Cl,
- Y is hydrogen,
- V is F or Cl,
- V′ is hydrogen,
- V″ is hydrogen or F,
- W is Cl,
- W is hydrogen,
- R1 and R2 are methyl or ethyl,
- R3 is NHS(═O)2R″,
- R′, R″ is selected independently from the group consisting of lower alkyl, substituted alkyl, cycloalkyl and substituted cycloalkyl
- and the pharmaceutically acceptable salts and esters and enantiomers thereof together with a pharmaceutically acceptable excipient or carrier.
9 more elements
Dependencies are inferred from the claim text.