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US 2008/0188506 A1Published application
Spiroindolinone derivatives
OwnerQingjie Ding, Jin-Jun Liu +1inventors
InventorsQingjie Ding, Jin-Jun Liu, Zhuming Zhang
Life of this patent
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Abstract
There are provided spiroindolinones of the formula and enantiomers and pharmaceutically acceptable salts and esters thereof which have utility as antiproliferative agents, especially, as anticancer agents.
Claims12
A compound selected from the group consisting of
- wherein
- X is selected from the group consisting of hydrogen, halogen, cyano, nitro, ethynyl, cyclopropyl, methyl, ethyl, isopropyl, methoxy, and vinyl,
- Y is hydrogen or fluorine,
- R4, R5 are selected from the group consisting of hydrogen and lower alkyl, one of R1 and R8 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, cycloalkenyl, and substituted cycloalkenyl and the other is hydrogen,
- one of R6 and R7 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, cycloalkenyl, and substituted cycloalkenyl and the other is hydrogen, lower alkyl or cyano
- R2 is selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, C(═O)R9, C(═O)NHR9, C(═O)NR9R9′ and C(═O)OR9,
- R3 is selected from the group consisting of NHR9, SR9, and NR9R9,
- R9 is selected from the group consisting of lower alkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl and substituted cycloalkyl,
- R9′ is selected from the group consisting of lower alkyl and substituted lower alkyl
- and in the case of R9 and R9′ they may independently link to form a cyclic structure selected from heterocycle or substituted heterocycle and
- R10 is selected from the group consisting of hydrogen, hydroxyl and lower alkyl and the pharmaceutically acceptable salts and esters thereof.
8 more elements
A compound of the formula
- wherein
- X is Cl or Br,
- Y is hydrogen,
- R1 is hydrogen,
- R4 and R5 are both hydrogen,
- R6 is hydrogen,
- R7 is a substituted phenyl or substituted heteroaryl selected from group consisting of
- R8 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, cycloalkenyl and substituted cycloalkenyl,
- R3 is selected from the group consisting of NHR9 and NR9R9′,
- R9 is selected from the group consisting of lower alkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl and substituted cycloalkyl,
- R9′ is selected from the group consisting of lower alkyl and substituted lower alkyl
- and in the case of R9 and R9′ they may independently link to form a cyclic structure selected from heterocycle or substituted heterocycle and the pharmaceutically acceptable salts and esters thereof.
9 more elements
A compound of the formula
- Wherein
- X is Cl or Br,
- Y is hydrogen,
- R1 is hydrogen,
- R4 and R5 are both hydrogen,
- R6 is hydrogen,
- R7 is a substituted phenyl or substituted heteroaryl selected from group consisting of
- R8 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, cycloalkenyl and substituted cycloalkenyl,
- R10 is selected from the group consisting of hydrogen, hydroxyl, and methyl and the pharmaceutically acceptable salts and esters thereof.
6 more elements
A compound of the formula
- wherein
- X is Cl or Br
- Y is hydrogen,
- R1 is hydrogen,
- R4 and R5 are both hydrogen,
- R6 is hydrogen,
- R7 is a substituted phenyl or substituted heteroaryl selected from group consisting of
- R8 is selected from the group consisting of lower alkyl, substituted alkyl, lower alkenyl, substituted lower alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, cycloalkenyl and substituted cycloalkenyl,
- R2 is selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, C(═O)R9, C(═O)NHR9, C(═O)NR9R9′ and C(═O)OR9,
- R9 is selected from the group consisting of lower alkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, cycloalkyl and substituted cycloalkyl,
- R9′ is selected from the group consisting of lower alkyl and substituted lower alkyl
- and in the case of R9 and R9′ they may independently link to form a cyclic structure selected from heterocycle and substituted heterocycle and the pharmaceutically acceptable salts and esters thereof.
9 more elements
A compound of the formula
- Wherein
- X is Cl or Br,
- Y is hydrogen,
- R1 is hydrogen,
- R4 and R5 are both hydrogen,
- R6 is hydrogen,
- R8 is a substituted phenyl selected from group consisting of
- R7 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, cycloalkenyl and substituted cycloalkenyl.
- R2 is selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, C(═O)R9, C(═O)NHR9, C(═O)NR9R9′ and C(═O)OR9,
- R9 is selected from the group consisting of lower alkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, cycloalkyl and substituted cycloalkyl,
- R9′ is selected from the group consisting of lower alkyl and substituted lower alkyl
- and in the case of R9 and R9′ they may independently link to form a cyclic structure selected from heterocycle and substituted heterocycle and the pharmaceutically acceptable salts and esters thereof.
9 more elements
A pharmaceutical formulation comprising a compound of the formula
- wherein
- X is selected from the group consisting of hydrogen, halogen, cyano, nitro, ethynyl, cyclopropyl, methyl, ethyl, isopropyl, methoxy, and vinyl,
- Y is hydrogen or fluorine,
- R4, R5 are selected from the group consisting of hydrogen and lower alkyl one of R1 and R8 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, cycloalkenyl, and substituted cycloalkenyl and the other is hydrogen,
- one of R6 and R7 is selected from the group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, cycloalkenyl, and substituted cycloalkenyl and the other is hydrogen, lower alkyl or cyano
- R2 is selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, C(═O)R9, C(═O)NHR9, C(═O)NR9R9′ and C(═O)OR9,
- R3 is selected from the group consisting of NHR9, SR9, and NR9R9′,
- R9 is selected from the group consisting of lower alkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl and substituted cycloalkyl,
- R9′ is selected from the group consisting of lower alkyl and substituted lower alkyl
- and in the case of R9 and R9′ they may independently link to form a cyclic structure selected from heterocycle or substituted heterocycle,
- R10 is selected from the group consisting of hydrogen, hydroxyl and lower alkyl and the pharmaceutically acceptable salts and esters thereof together with a pharmaceutically acceptable carrier or excipient.
8 more elements
Dependencies are inferred from the claim text.