US 11,306,101 B2Granted

Substituted 1-oxo-isoindoline-5-carboxamide compounds, compositions thereof, and methods of treatment therewith

AssigneeCelgene Corporation

InventorsFrans Baculi, Katherine Northcote, Matthew D. Correa, Joshua Hansen, Laurie A. Lebrun, Chin-Chun Lu, Gang Lu, Mark A. Nagy, Sophie Peng, Sophie Perrin-Ninkovic

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Abstract

Provided herein are 1-oxo-isoindoline-5-carboxamide compounds having the following structure: wherein R1, R2, R3, R4 and n are as defined herein, compositions comprising an effective amount of a 1-oxo-isoindoline-5-carboxamide compound, and methods for treating or preventing disorders.

Claims35

Dependent claims

A compound of Formula (I)

or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof,
wherein:
R1 is C1-3 alkyl, or C1-3 fluoroalkyl;
R2 is substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C3-10 cycloalkyl, substituted or unsubstituted 3-6-membered heterocyclyl, substituted or unsubstituted C6-10 aryl, or substituted or unsubstituted 5-10-membered heteroaryl;
substituents on R2 when present, are selected from F, Cl, Br, CN, OH, OCH3, OCF3, OCH2CH3, O-n-propyl, O-isopropyl, O-n-butyl, O-sec-butyl, O-tert-butyl, O-cyclopropyl, O-cyclobutyl, O-phenyl, CH3, CH2CH3, CF3, CH2CF3, CH2NHCH3, CH2N(CH3)2, and a —(C0-3 alkyl)(3-6 membered heterocyclyl) selected from piperidyl, piperazinyl, morpholino, CH2-aziridyl, CH2-pyrrolidyl, CH2-piperazinyl, CH2-piperidyl, CH2-morpholinyl, and CH2(2-oxa-6-azaspiro[3.3]heptyl), wherein the —(C0-3 alkyl)(3-6 membered heterocyclyl) is optionally substituted with one or more F, Cl or CH3;
R3 is H;
R4 is halogen;
and
n is 0-3.

6 more elements

A compound selected from the group consisting of

2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((S)-1-phenylethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-N-isopropyl-1-oxoisoindoline-5-carboxamide;
N—((S)-1-cyclopentylethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((S)-1-cyclohexylethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((S)-1-cyclopropylethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((S)-1-phenylpropyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((S)-1-p-tolylethyl)isoindoline-5-carboxamide;
N—((S)-1-(4-chlorophenyl)ethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((S)-1-cyclobutylethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((S)-1-(pyridin-2-yl)ethyl)isoindoline-5-carboxamide;
N—((S)-1-(3-cyanophenyl)ethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-N—((S)-1-(4-methoxyphenyl)ethyl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-N—((S)-1-(3-methoxyphenyl)ethyl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-N—((S)-1-(2-methoxyphenyl)ethyl)-1-oxoisoindoline-5-carboxamide;
N—((S)-1-(3-chlorophenyl)ethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-N—((S)-1-(4-fluorophenyl)ethyl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-N—((S)-1-(3-fluorophenyl)ethyl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-N—((S)-1-(2-fluorophenyl)ethyl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((S)-1-(pyridin-3-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((S)-1-o-tolylethyl)isoindoline-5-carboxamide;
N—((S)-1-(2-chlorophenyl)ethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-cyclohexylethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-cyclohexyl-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-phenylethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((S)-3,3,3-trifluoro-1-phenylpropyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((S)-1-(tetrahydro-2H-pyran-4-yl)ethyl)isoindoline-5-carboxamide;
N—((S)-1-cyclohexyl-2-methylpropyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-N—((S)-3-methylbutan-2-yl)-1-oxoisoindoline-5-carboxamide;
N—((S)-1-cyclohexyl-3,3,3-trifluoropropyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((S)-3,3-dimethylbutan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-1,1,1-trifluoro-3-methylbutan-2-yl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-methoxyphenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-1,1,1-trifluoro-3,3-dimethylbutan-2-yl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-methoxyphenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(tetrahydro-2H-pyran-4-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-fluorophenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(2-methoxyphenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(pyridin-4-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-(trifluoromethyl)phenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-(trifluoromethoxy)phenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(4-chlorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3-chlorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(2-(trifluoromethoxy)phenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(4,4-difluorocyclohexyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(4,4-dimethylcyclohexyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(2-(trifluoromethyl)phenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(pyridin-2-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(2-fluorophenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(2-chlorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((S)-1-(2,4-difluorophenyl)ethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-(trifluoromethyl)phenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N-((1R)-2,2,2-trifluoro-1-(spiro[3.5]nonan-7-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(pyridin-3-yl)ethyl)isoindoline-5-carboxamide;
N—((S)-1-(4-chloro-2-fluorophenyl)ethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-((1r,4R)-4-hydroxycyclohexyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(bicyclo[1.1.1]pentan-1-yl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-(trifluoromethoxy)phenyl)ethyl)isoindoline-5-carboxamide;
N—((S)-1-(2-chloro-4-fluorophenyl)ethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-((R)-2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-phenylethyl)isoindoline-5-carboxamide;
2-((S)-2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-phenylethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-((1s,4S)-4-hydroxycyclohexyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(4-cyanophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3-cyanophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(1-methyl-1H-pyrazol-3-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(pyrimidin-5-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-fluoro-2-methoxyphenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-N—((R)-1,1,1,4,4,4-hexafluoro-3,3-dimethylbutan-2-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(1-methyl-1H-pyrazol-5-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(1-methyl-1H-pyrazol-4-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N-((1R)-2,2,2-trifluoro-1-(4-(trifluoromethyl)cyclohexyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(2-chloro-4-fluorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3,4-difluorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(1-methylcyclobutyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(1-(trifluoromethyl)cyclopropyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(5-fluoropyridin-2-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-fluoro-2-(trifluoromethyl)phenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(1-methylcyclopropyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(4-chloro-2-fluorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(2,4-difluorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(1-methylpiperidin-4-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(pyrazin-2-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(1-methylcylopentyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-phenylethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxo-N—((S)-1-phenylethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-fluoro-2-(trifluoromethoxy)phenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-3-cyano-1,1,1-trifluoro-3-methylbutan-2-yl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-(2-(trifluoromethyl)phenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-phenylethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-(trifluoromethyl)phenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(4-chlorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(4-chlorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-methyloxetan-3-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-1,1,1-trifluoro-4-hydroxy-3,3-dimethylbutan-2-yl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-(trifluoromethyl)phenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-(2-(trifluoromethyl)phenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-(2-fluorophenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-(2-fluorophenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-hydroxyphenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-isopropoxyphenyl)ethyl)isoindoline-5-carboxamide;
2-((S)-2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)isoindoline-5-carboxamide;
2-((R)-2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(2,4-difluorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3-chloropyridin-2-yl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3-chlorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-fluorophenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(5-chloropyridin-2-yl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-fluoropyridin-2-yl)ethyl)isoindoline-5-carboxamide;
N—((R)-2,2-difluoro-1-(4-fluorophenyl)ethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-2,2-difluoro-1-(4-fluorophenyl)ethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3,4-difluorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(2-chlorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-(5-fluoropyridin-2-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-(trifluoromethyl)pyridin-2-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-fluoropyridin-2-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-1-phenylpropyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-(trifluoromethyl)pyridin-2-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-(trifluoromethoxy)phenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-cyclohexyl-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3-cyclopropoxyphenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((S)-3,3,3-trifluoro-1-(4-fluorophenyl)propyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-N—((R)-2-methyl-1-phenylpropyl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(6-(trifluoromethyl)pyridin-2-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(5-(trifluoromethyl)pyridin-2-yl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(5-chloro-3-fluoropyridin-2-yl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-o-tolylethyl)isoindoline-5-carboxamide;
N—((S)-1-(4-chlorophenyl)-3,3,3-trifluoropropyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(4-cyclopropoxyphenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(2-cyanophenyl)ethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-cyclopentylethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3,5-difluoropyridin-2-yl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-m-tolylethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-(trifluoromethoxy)phenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-(2-(trifluoromethoxy)phenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-cyclopentyl-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(bicyclo[1.1.1]pentan-1-yl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3-chloropyridin-2-yl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-(morpholinomethyl)phenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(4-((dimethylamino)methyl)phenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-(morpholinomethyl)phenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((R)-2,2,2-trifluoro-1-p-tolylethyl)isoindoline-5-carboxamide;
N—((R)-1-(2-chloro-4-fluorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxo-N—((S)-3,3,3-trifluoro-1-(3-fluorophenyl)propyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-phenoxyphenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(4-cyclopropoxyphenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((S)-1-(4-chlorophenyl)-3,3,3-trifluoropropyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3-((dimethylamino)methyl)phenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(2-chloro-6-fluorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(2-chloro-3-fluorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
4-chloro-2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-N—((S)-2-methyl-1-phenylpropyl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(2-(morpholinomethyl)phenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-((1r,4R)-4-hydroxy-4-methylcyclohexyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(2-cyclopropoxyphenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-phenoxyphenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(2-phenoxyphenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(2-chloro-5-fluorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(2-cyclopropoxyphenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((S)-3,3,3-trifluoro-1-(3-fluorophenyl)propyl)isoindoline-5-carboxamide;
N—((R)-1-(2,4-dichlorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(2,4-dichlorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-(2-hydroxypropan-2-yl)bicyclo[1.1.1]pentan-1-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N-((1R)-2,2,2-trifluoro-1-(spiro[2.5]octan-6-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-N—((S)-1-(2-fluorophenyl)-2-methylpropyl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-((1s,4S)-4-hydroxy-4-methylcyclohexyl)ethyl)isoindoline-5-carboxamide;
N—((S)-1-(2-chlorophenyl)-2-methylpropyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-N—((S)-1-(4-fluorophenyl)-2-methylpropyl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3-chloropyridin-2-yl)-2-methylpropyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((S)-1-(3-chloropyridin-2-yl)-2-methylpropyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3-chloropyridin-2-yl)-2,2,2-trifluoroethyl)-2-((S)-2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N-(2,2-difluoro-1-(4-fluorophenyl)propyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3-chloro-5-fluoropyridin-2-yl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N-(2,2,2-trifluoro-1-(2-hydroxyspiro[3.5]nonan-7-yl)ethyl)isoindoline-5-carboxamide;
N—((S)-1-(4-chlorophenyl)-2-methylpropyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3,5-dichloropyridin-2-yl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
N-((1R)-1-(4-(2-oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-(pyrrolidin-1-ylmethyl)phenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N-(2,2,2-trifluoro-1-(2-hydroxyspiro[3.5]nonan-7-yl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(3-chloropyridin-2-yl)-2,2,2-trifluoroethyl)-2-((R)-2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3-chloro-5-fluoropyridin-2-yl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3,5-dichloropyridin-2-yl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-((4-methylpiperazin-1-yl)methyl)phenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(4-((dimethylamino)methyl)phenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-4-fluoro-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-3,3,3-trifluoro-1-phenylpropyl)isoindoline-5-carboxamide;
N—((R)-1-(4-((3,3-difluoroazetidin-1-yl)methyl)phenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(4-(azetidin-1-ylmethyl)phenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-3,3,3-trifluoro-1-(3-fluorophenyl)propyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-3,3,3-trifluoro-1-(4-fluorophenyl)propyl)isoindoline-5-carboxamide;
N—((R)-1-(2-((dimethylamino)methyl)phenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(5-chloro-3-fluoropyridin-2-yl)-2,2,2-trifluoroethyl)-2-((S)-2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(3-chlorophenyl)-3,3,3-trifluoropropyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-3,3,3-trifluoro-1-(2-fluorophenyl)propyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-3,3,3-trifluoro-1-o-tolylpropyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((S)-2,2,2-trifluoro-1-(2-fluorophenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(2-chloro-4-((dimethylamino)methyl)phenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-methylpyridin-2-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-methoxypyridin-2-yl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-morpholinophenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(3-chloro-5-((dimethylamino)methyl)pyridin-2-yl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
N—((R)-1-(2-chloro-4,6-difluorophenyl)-2,2,2-trifluoroethyl)-2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-morpholinophenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(2-morpholinophenyl)ethyl)isoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(2-(4-methylpiperazin-1-yl)phenyl)ethyl)isoindoline-5-carboxamide;
N—((R)-1-(3,5-dichloropyridin-2-yl)-2,2,2-trifluoroethyl)-2-((S)-2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxamide;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(4-(4-methylpiperazin-1-yl)phenyl)ethyl)isoindoline-5-carboxamide and;
2-(2,6-dioxopiperidin-3-yl)-1-oxo-N—((R)-2,2,2-trifluoro-1-(3-(4-methylpiperazin-1-yl)phenyl)ethyl)isoindoline-5-carboxamide;
or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof.

207 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/887,766Filed 29 May 2020 · us provisional application
Priority: 31 May 2019
Published: US 2020/0377512 A13 Dec 2020
Granted: 19 Apr 2022
Term ends: Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07D 491/107
Spiro-condensed systems: with only one oxygen atom as ring hetero atom in the oxygen-containing ring
A61P 35/02
Antineoplastic agents: specific for leukemia
C07D 401/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…

Family

Application62/855,619Us provisional application · filed 31 May 2019
US 2020/0377512 A1Pre-grant publication · published 3 Dec 2020
US 11,306,101 B2This patent

From the US filing history. Foreign family members aren’t listed.

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