Isoindolinones, pharmaceutical compositions, and therapeutic applications
Provided herein are isoindolinones, e.g., a compound of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a disorder, disease, or condition mediated by a zinc-figure protein, casein kinase 1α, GSPT1, or PDE6D.
1 . A compound of Formula (I):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, or a mixture of two or more tautomers thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein:
R 1 is hydrogen or C 1-6 alkyl;
R 2 is hydrogen;
R 3 is hydrogen or fluoro;
R 4 is
R 5 is absent;
R 6 is:
(i) ethyl, propyl, isopropyl, isobutyl, trifluoromethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 3-chloropropyl, cyclobutylmethyl, cyclopentyl-methyl, cyclohexylmethyl, (3-methylphenoxy)methyl, benzyl, 2-phenyl-ethyl, 3-phenylpropyl, 2-(3-bromophenyl)ethyl, 2-methyl-2-phenylpropyl, 2-(3-trifluoromethylphenyl)ethyl, 2-(2-methoxyphenyl)ethyl, 2-benzoxy-ethyl, 2-(5-methylfuran-2-yl)ethyl, pyrazol-1-ylmethyl, pyrrol-2-ylmethyl, 2-(pyrrol-2-yl)ethyl, 1,2,3-triazol-1-ylmethyl, pyrimidin-2-ylmethyl, pyrimidin-5-ylmethyl, 2-methoxypyridin-3-ylmethyl, 2-(pyridin-2-yl)-ethyl, 2-(pyridin-3-yl)ethyl, 2-(quinolin-6-yl)ethyl, pyrrolidin-1-ylmethyl, tetrahydropyran-4-ylmethyl, piperidin-1-ylmethyl, 1-benzoxycarbonyl-piperidin-4-ylmethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 2-(1-(tert-butoxycarbonyl)piperidin-4-yl) prop-2-yl, 4-(tert-butoxycarbonyl)-piperazin-1-ylmethyl, morpholinomethyl, 3-hydroxy-2-methylprop-2-yl, benzoxymethyl, 2-benzoxyethyl, methylaminomethyl, or (tert-butoxy-carbonyl)aminomethyl;
(ii) cyclopropyl, cyclobutyl, 3,3-dimethylcyclobut-1-yl, cyclopentyl, cyclo-hexyl, adamantan-1-yl, 1-fluorocyclopropyl, 4,4-difluorocyclohexyl, 3,3-dimethylcyclobutyl, 4-hydroxybicyclo[2.2.2]octan-1-yl, 1-aminocyclo-butyl, 4-(tert-butoxycarbonylamino)cyclohexyl, or 4-(tert-butoxy-carbonylaminomethyl)cyclohexyl;
(iii) phenyl, optionally substituted with one, two, or three substituents, each of which is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxycarbonylamino)-methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxy-phenyl, benzyl, 5-methylfuran-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methylpyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxycarbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)-piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxycarbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, amino-carbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylamino-carbonyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methyl-phenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yloxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonylamino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl;
(iv) bicyclo[4.2.0]octa-1 (6),2,4-trien-3-yl, naphthalen-1-yl, naphthalen-2-yl, 5-(dimethylamino)naphthalen-1-yl, 6-(dimethylamino)naphthalen-2-yl, 5,6,7,8-tetrahydronaphthalen-1-yl, or 5,6,7,8-tetrahydronaphthalen-2-yl;
(v) benzyl, 2-cyanobenzyl, 3-cyanobenzyl, 4-cyanobenzyl, 4-fluorobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methyl-benzyl, 4-trifluoromethylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 2-phenylethyl, 3-phenylpropyl, 2-phenylprop-2-yl, 2-(3-bromophenyl)ethyl, 2-methyl-2-phenylpropyl, 2-(3-trifluoromethyl-phenyl)ethyl, or 2-(2-methoxyphenyl)ethyl;
(vi) furanyl, imidazolyl, oxazolyl, pyrazolyl, pyrrolyl, thiazolyl, thienyl, 1,2,4-triazolyl, tetrazolyl, pyridinyl, 1,2-dihydropyridinyl, 1,6-dihydropyridinyl, pyridazinyl, or pyrimidinyl, each optionally substituted with one, two, or three substituents, each of which is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, isobutyl, tert-butyl, trifluoromethyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxy-carbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoromethyl-phenyl, 2-methoxyphenyl, benzyl, 5-methylfuran-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methyl-pyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxycarbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxy-carbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylamino-carbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoro-methoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yl-oxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)-(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonyl-amino, methylsulfonylamino, methylthio, methylsulfonyl, or ethyl-sulfonyl;
(vii) benzo[d][1,3]dioxolyl, benzofuranyl, benzo[d]imidazolyl, benzo[d]oxazol-yl, benzo[d]thiazolyl, benzo[b]thienyl, chromanyl, 2,3-dihydrobenzo[b]-[1,4]dioxinyl, 2,3-dihydrobenzofuranyl, 2,3-dihydro[1,4]dioxino[2,3-b]-pyridinyl, 5,6-dihydroimidazo[2,1-c][1,4]oxazinyl, 3,4-dihydropyrano-[2,3-c]pyridinyl, furo[2,3-c]pyridinyl, imidazo[1,2-a]pyridinyl, imidazo-[1,5-a]pyridinyl, imidazo[4,5-b]pyridinyl, imidazo[1,2-a]pyrimidinyl, indazolyl, indolyl, indolinyl, indolizinyl, isoindolinyl, isoquinolinyl, 1,8-naphthyridinyl, pyrazolo[1,5-a]pyridinyl, pyrrolo[2,3-b]pyrazinyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-b]pyridinyl, quinazolinyl, quinolinyl, quinoxalinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, thieno[2,3-b]pyridinyl, thieno[3,2-c]-pyridinyl, or [1,2,4]triazolo[1,5-a]pyridinyl, each optionally substituted with one, two, or three substituents, each of which is independently cyano, fluoro, chloro, bromo, oxo, methyl, ethyl, isopropyl, tert-butyl, trifluoro-methyl, morpholinomethyl, hydroxymethyl, (dimethylamino)methyl, (tert-butoxycarbonylamino)methyl, ethynyl, cyclopropyl, cyclobutyl, cyclo-pentyl, cyclohexyl, phenyl, 3-bromophenyl, 4-methylphenyl, 3-trifluoro-methylphenyl, 2-methoxyphenyl, benzyl, 5-methylfuran-2-yl, imidazol-1-yl, oxazol-5-yl, pyrazol-1-yl, pyrrol-2-yl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridin-3-yl, pyridin-4-yl, 4-methyl-pyridin-2-yl, 2-methoxypyridin-3-yl, quinolin-6-yl, pyrrolidin-1-yl, morpholino, piperidin-1-yl, 1-benzoxycarbonyl-piperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 4-methylpiperazin-1-yl, 4-(tert-butoxy-carbonyl)piperazin-1-yl, 2,2,2-trifluoroacetyl, benzoxycarbonyl, tert-butoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylamino-carbonyl, isopropylaminocarbonyl, hydroxyl, methoxy, ethoxy, difluoro-methoxy, trifluoromethoxy, cyclohexylmethoxy, cyclopentoxy, phenoxy, 4-cyanophenoxy, 3-methylphenoxy, 4-trifluoromethylphenoxy, 4-cyano-2-fluorophenoxy, benzoxy, 4-cyanobenzoxy, pyridin-2-yloxy, pyridin-3-yl-oxy, amino, methylamino, ethylamino, dimethylamino, (2-hydroxyethyl)-(methyl)amino), acetamido, benzoxycarbonylamino, tert-butoxycarbonyl-amino, methylsulfonylamino, methylthio, methylsulfonyl, or ethylsulfonyl; or
(viii) 1-methylazetidin-3-yl, oxetan-3-yl, 3-methyloxetan-3-yl, tetrahydro-pyran-4-yl, ethylpiperidin-4-yl, 1-benzylpiperidin-4-yl, 1-benzoxy-carbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 1-(ethyl-sulfonyl)piperidin-4-yl, 1-(tert-butoxycarbonyl)-4-fluoropiperidin-4-yl, or 4-(tert-butoxycarbonyl)piperazin-1-yl;
A is N;
X is —(CH 2 ) n —, —C(O)—, —S(O)—, or —S(O 2 )—; wherein n is an integer of 1, 2, 3, 4, or 5; and
c and d are:
(i) c and d are each independently an integer of 1; and
e and f are each independently an integer of 0 or 1; or
(ii) c and d are each independently an integer of 0 or 1; and
e and f are each independently an integer of 1.
2 . The compound of claim 1 , having the structure of Formula (XI):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, or a mixture of two or more tautomers thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.
3 . The compound of claim 1 , having the structure of Formula (XII):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, or a mixture of two or more tautomers thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.
4 . The compound of claim 1 , having the structure of
or an enantiomer, a mixture or enantiomers, a diastereomer, a mixture or two or more diastereomers, a tautomer, or a mixture of two or more tautomers thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.
5 . The compound of claim 1 , having the structure of Formula (XIII):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, or a mixture of two or more tautomers thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.
6 . The compound of claim 1 , having the structure of Formula (XVII):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, or a mixture of two or more tautomers thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.
7 . The compound of claim 1 , wherein R 1 is hydrogen.
8 . The compound of claim 1 , wherein X is —C(O)—.
9 . The compound of claim 1 , wherein X is —S(O 2 )—.
10 . The compound of claim 1 , wherein R 6 is ethyl, propyl, isopropyl, isobutyl, trifluoromethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 3-chloropropyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, (3-methylphenoxy)methyl, benzyl, 2-phenylethyl, 3-phenylpropyl, 2-(3-bromophenyl)ethyl, 2-methyl-2-phenylpropyl, 2-(3-trifluoro-methylphenyl)ethyl, 2-(2-methoxyphenyl)ethyl, 2-benzoxyethyl, 2-(5-methylfuran-2-yl)ethyl, pyrazol-1-ylmethyl, pyrrol-2-ylmethyl, 2-(pyrrol-2-yl)ethyl, 1,2,3-triazol-1-ylmethyl, pyrimidin-2-yl-methyl, pyrimidin-5-ylmethyl, 2-methoxypyridin-3-ylmethyl, 2-(pyridin-2-yl)ethyl, 2-(pyridin-3-yl)ethyl, 2-(quinolin-6-yl)ethyl, pyrrolidin-1-ylmethyl, tetrahydropyran-4-ylmethyl, piperidin-1-ylmethyl, 1-benzoxycarbonylpiperidin-4-ylmethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 2-(1-(tert-butoxycarbonyl)piperidin-4-yl) prop-2-yl, 4-(tert-butoxycarbonyl)-piperazin-1-yl-methyl, morpholinomethyl, 3-hydroxy-2-methylprop-2-yl, benzoxymethyl, 2-benzoxyethyl, methylaminomethyl, or (tert-butoxycarbonyl)aminomethyl.
11 . The compound of claim 1 , wherein R 6 is cyclopropyl, cyclobutyl, 3,3-dimethylcyclobut-1-yl, cyclopentyl, cyclohexyl, adamantan-1-yl, 1-fluorocyclo-propyl, 4,4-difluorocyclohexyl, 3,3-dimethylcyclobutyl, 4-hydroxybicyclo[2.2.2]octan-1-yl, 1-aminocyclobutyl, 4-(tert-butoxycarbonylamino)cyclohexyl, or 4-(tert-butoxycarbonylamino-methyl)cyclohexyl.
12 . The compound of claim 1 , wherein R 6 is 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromo-phenyl, 3-bromophenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-isopropylphenyl, 4-isopropylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3-hydroxymethyl-phenyl, 4-hydroxymethylphenyl, 4-((dimethylamino)methyl)phenyl, 2-ethynyl-phenyl, 3-ethynylphenyl, 4-ethynylphenyl, 2-cyclopropylphenyl, 4-cyclopropylphenyl, 4-phenyl-phenyl, 4-benzylphenyl, 3-(imidazol-1-yl)phenyl, 4-(imidazol-1-yl)phenyl, 4-(oxazol-5-yl)-phenyl, 4-(pyrazol-1-yl)phenyl, 2-(1,2,4-triazol-1-yl)phenyl, 3-(1,2,4-triazol-1-yl)phenyl, 4-(1,2,4-triazol-1-yl)phenyl, 3-(pyridin-4-yl)phenyl, 3-(pyrrolidin-1-yl)phenyl, 4-(pyrrolidin-1-yl)-phenyl, 2-(morpholino)phenyl, 3-(morpholino)phenyl, 4-(morpholino)phenyl, 3-aminocarbonyl-phenyl, 4-aminocarbonylphenyl, 4-(methylaminocarbonyl)phenyl, 2-(dimethylaminocarbonyl)-phenyl, 4-(isopropylaminocarbonyl)phenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 2-methoxy-phenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-difluoromethoxyphenyl, 2-trifluoromethoxyphenyl, 4-cyclopentoxyphenyl, 3-(cyclohexylmethoxy)phenyl, 3-phenoxy-phenyl, 4-phenoxyphenyl, 3-(4-cyanophenoxy)phenyl, 4-(4-cyanophenoxy)phenyl, 4-(4-trifluoromethylphenoxy)phenyl, 4-(4-cyano-2-fluorophenoxy)phenyl, 3-benzoxyphenyl, 4-benzoxyphenyl, 3-(4-cyanobenzoxy)phenyl, 4-(4-cyanobenzoxy)phenyl, 2-(pyridin-2-yloxy)-phenyl, 4-(pyridin-2-yl-oxy)phenyl, 4-(pyridin-3-yloxy)phenyl, 3-morpholinophenyl, 4-morpho-linophenyl, 2-aminophenyl, 4-aminophenyl, 2-methylaminophenyl, 4-ethylaminophenyl, 2-(dimethylamino)phenyl, 3-(dimethylamino)phenyl, 4-(dimethylamino)phenyl, 4-(2-hydroxy-ethyl)(methyl)amino)phenyl, 3-acetamidophenyl, 4-acetamidophenyl, 4-benzoxycarbonylamino-phenyl, 4-methylsulfonylaminophenyl, 2-methylsulfonylaminophenyl, 3-methylsulfonylamino-phenyl, or 4-(ethylsulfonyl)phenyl.
13 . The compound of claim 1 , wherein R 6 is 2-amino-3-chlorophenyl, 2-amino-4-chlorophenyl, 2-amino-6-chlorophenyl, 2-amino-5-fluorophenyl, 2-benzoxy-4-methylphenyl, 4-benzoxy-2-methylphenyl, 2-bromo-4-(4-cyanophenoxy)phenyl, 2-bromo-5-(4-cyanophenoxy)phenyl, 3-bromo-4-(4-methylpiperazin-1-yl)phenyl, 3-bromo-4-morpholinophenyl, 2-chloro-4-cyanophenyl, 3-chloro-4-cyanophenyl, 3-chloro-5-cyanophenyl, 4-chloro-3-cyanophenyl, 2-chloro-6-methylphenyl, 3-chloro-4-methylphenyl, 2-chloro-4-morpholinophenyl, 3-chloro-4-morpholinophenyl, 2-chloro-4-trifluoromethylphenyl, 2-chloro-5-trifluoromethylphenyl, 3-chloro-4-trifluoromethylphenyl, 4-chloro-2-trifluoromethylphenyl, 5-chloro-2-trifluoromethylphenyl, 2-cyano-4-fluorophenyl, 2-cyano-5-fluorophenyl, 3-cyano-4-fluorophenyl, 3-cyano-5-fluorophenyl, 4-cyano-3-fluorophenyl, 4-cyano-2-fluorophenyl, 5-cyano-2-fluorophenyl, 3-cyano-4-(4-methylimidazol-1-yl)phenyl, 3-cyano-4-hydroxyphenyl, 4-cyano-2-hydroxyphenyl, 2-cyano-4-methoxyphenyl, 4-cyano-2-methoxyphenyl, 4-cyano-3-methoxyphenyl, 4-cyano-3-methoxyphenyl, 2-cyano-3-methylphenyl, 2-cyano-4-methylphenyl, 3-cyano-2-methylphenyl, 3-cyano-5-methylphenyl, 4-cyano-2-methylphenyl, 2,4-dichloro-phenyl, 2,5-dichlorophenyl, 2,4-difluorophenyl, 2,5-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 4-(dimethylamino)-3-methylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,5-dimethylphenyl, 2-ethynyl-4-fluorophenyl, 3-fluoro-4-methoxyphenyl, 5-fluoro-2-methoxyphenyl, 2-fluoro-4-methylphenyl, 2-fluoro-5-methylphenyl, 3-fluoro-2-methylphenyl, 3-fluoro-4-methylphenyl, 3-fluoro-5-methylphenyl, 4-fluoro-2-methylphenyl, 4-fluoro-3-methylphenyl, 5-fluoro-2-methylphenyl, 2-hydroxy-4-methyl-phenyl, 3-hydroxy-5-methylphenyl, 2-methoxy-3-methylphenyl, 2-methoxy-4-methylphenyl, 2-methoxy-6-methylphenyl, 3-methoxy-2-methylphenyl, 3-methoxy-4-methylphenyl, 3-methoxy-5-methylphenyl, 4-methoxy-2-methylphenyl, or 4-methoxy-3-methylphenyl.
14 . The compound of claim 1 , wherein R 6 is 4-hydroxy-3,5-dimethylphenyl or 2,4,6-trimethylphenyl.
15 . The compound of claim 1 , wherein R 6 is bicyclo[4.2.0]-octa-1(6),2,4-trien-3-yl, naphthalen-1-yl, naphthalen-2-yl, 5-(dimethylamino)naphthalen-1-yl, 6-(dimethylamino)naphthalen-2-yl, 5,6,7,8-tetrahydronaphthalen-1-yl, or 5,6,7,8-tetrahydro-naphthalen-2-yl.
16 . The compound of claim 1 , wherein R 6 is benzyl, 2-cyanobenzyl, 3-cyanobenzyl, 4-cyanobenzyl, 4-fluorobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 4-trifluoromethylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 2-phenylethyl, 3-phenylpropyl, 2-phenylprop-2-yl, 2-(3-bromophenyl)ethyl, 2-methyl-2-phenylpropyl, 2-(3-trifluoromethylphenyl)ethyl, or 2-(2-methoxyphenyl)ethyl.
17 . The compound of claim 1 , wherein R 6 is furan-2-yl, furan-3-yl, 5-methylfuran-2-yl, 4-isopropylfuran-2-yl, 5-(morpholinomethyl)furan-2-yl, 5-(hydroxymethyl)furan-2-yl, 3-methoxyfuran-2-yl, imidazol-4-yl, 1-methylimidazol-2-yl, 1-methylimidazol-4-yl, 1-methylimidazol-5-yl, 2-methylimidazol-4-yl, 2,5-dimethylimidazol-4-yl, 2-phenylimidazol-4-yl, 4-phenylimidazol-2-yl, oxazol-2-yl, 2-methyloxazol-4-yl, 2-methyl-oxazol-5-yl, 4-methyloxazol-5-yl, pyrazol-3-yl, pyrazol-4-yl, 1-methylpyrazol-3-yl, 1-methyl-pyrazol-4-yl, 1-methylpyrazol-5-yl, 5-methylpyrazol-3-yl, 1-isopropylpyrazol-4-yl, 1-isobutyl-pyrazol-4-yl, 5-amino-1-methylpyrazol-4-yl, 4-chloro-1-methylpyrazol-3-yl, 2-cyano-1-methyl-pyrazol-4-yl, 1,4-dimethylpyrazol-5-yl, 1-phenylpyrazol-3-yl, 1-(2-methylphenyl)pyrazol-4-yl, pyrrol-2-yl, pyrrol-3-yl, 3-cyanopyrrol-2-yl, 4-cyanopyrrol-2-yl, 1-methylpyrrol-2-yl, 3-methyl-pyrrol-2-yl, 5-methylpyrrol-2-yl, 5-(hydroxymethyl)pyrrol-2-yl, 5-(tert-butyl)pyrrol-2-yl, 2-cyano-1-methylpyrrol-4-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, 2-methylthiazol-5-yl, 4-methylthiazol-5-yl, 5-methylthiazol-2-yl, 2-cyclopropylthiazol-5-yl, 2-(morpholino)thiazol-5-yl, thien-2-yl, thien-3-yl, 2-chlorothien-3-yl, 5-chlorothien-2-yl, 5-cyanothien-2-yl, 5-cyanothien-3-yl, 3-methylthien-2-yl, 5-(dimethylamino)thien-2-yl, 5-methyl-1,2,4-triazol-3-yl, 1-(tert-butyl)-1,2,3-triazol-4-yl, 1-(1-tert-butoxycarbonylpiperidin-4-yl)-1,2,3-triazol-4-yl, 2-methyltetrazol-5-yl, chloropyrazin-2-yl, 3-methylpyrazin-2-yl, 5-methylpyrazin-2-yl, 5-methoxypyrazin-2-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 4-cyanopyridin-2-yl, 5-cyanopyridin-2-yl, 5-cyano-pyridin-3-yl, 6-cyanopyridin-2-yl, 6-cyanopyridin-3-yl, 3-fluoropyridin-4-yl, 4-fluoropyridin-2-yl, 5-fluoropyridin-2-yl, 5-fluoropyridin-3-yl, 6-fluoropyridin-2-yl, 6-fluoropyridin-3-yl, 3-chloropyridin-4-yl, 6-chloro-pyridin-2-yl, 2-methylpyridin-3-yl, 2-methylpyridin-4-yl, 3-methyl-pyridin-2-yl, 4-methylpyridin-2-yl, 4-methylpyridin-3-yl, 5-methylpyridin-2-yl, 5-methyl-pyridin-3-yl, 6-methylpyridin-2-yl, 5-isopropylpyridin-3-yl, 2-trifluoromethylpyridin-5-yl, 6-(trifluoromethyl)pyridin-3-yl, 2-(tert-butyl)pyridin-4-yl, 5-ethynylpyridin-2-yl, 6-(4-methyl-phenyl)pyridin-3-yl, 6-(pyrrolidin-1-yl)pyridin-3-yl, 2-(4-methylpyridin-2-yl)pyridine-4-yl, 2-hydroxypyridin-3-yl, 2-methoxypyridin-3-yl, 2-methoxypyridin-4-yl, 3-methoxypyridin-2-yl, 3-methoxypyridin-4-yl, 4-methoxypyridin-2-yl, 4-methoxypyridin-3-yl, 5-methoxypyridin-2-yl, 5-methoxypyridin-3-yl, 6-methoxypyridin-2-yl, 6-methoxypyridin-3-yl, 6-phenoxypyridin-3-yl, 2-aminopyridin-3-yl, 3-aminopyridin-4-yl, 6-(methylsulfonyl)pyridin-2-yl, 2-amino-5-cyano-pyridin-3-yl, 2-amino-5-methylpyridin-3-yl, 5-chloro-2-methoxypyridin-3-yl, 2,6-dimethyl-pyridin-4-yl, 5-fluoro-2-oxo-1,2-dihydropyridin-3-yl, 1-methyl-2-oxo-1,2-dihydropyridin-4-yl, 1-methyl-6-oxo-1,6-dihydropyridin-2-yl, pyridazin-4-yl, pyrimidin-4-yl, pyrimidin-5-yl, 2-methylpyrimidin-4-yl, 2-methylpyrimidin-5-yl, 2-methoxypyrimidin-4-yl, 2-(methylthio)-pyrimidin-4-yl, or 2-chloro-4-(morpholino)pyrimidin-5-yl.
18 . The compound of claim 1 , wherein R 6 is benzo[d][1,3]-dioxol-4-yl, benzo[d][1,3]dioxol-5-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl, benzofuran-7-yl, 4-fluorobenzofuran-7-yl, benzo[d]imidazol-2-yl, benzo[d]imidazol-4-yl, 5-fluorobenzo[d]imidazol-2-yl, 1-methylbenzo[d]imidazol-2-yl, 2-hydroxybenzo[d]imidazol-6-yl, benzo[d]oxazol-5-yl, benzo[d]oxazol-6-yl, 2-methylbenzo[d]oxazol-6-yl, benzo[d]thiazol-4-yl, benzo[d]thiazol-6-yl, benzo[b]thien-2-yl, benzo[b]thien-3-yl, chroman-6-yl, 6-fluorochroman-8-yl, 2,3-dihydrobenzo[b][1,4]dioxin-6-yl, 2,3-dihydro[1,4]dioxino[2,3-b]pyridin-6-yl, 5,6-dihydroimidazo[2,1-c][1,4]oxazin-2-yl, 2,3-dihydrobenzofuran-5-yl, 2,3-dihydrobenzofuran-7-yl, 5,6-dihydroimidazo[2,1-c][1,4]oxazin-3-yl, 3,4-dihydropyrano[2,3-c]pyridin-6-yl, furo[2,3-c]pyridin-5-yl, imidazo[1,2-a]pyridin-2-yl, imidazo[1,2-a]pyridin-3-yl, imidazo[1,2-a]pyridin-5-yl, imidazo[1,2-a]pyridin-6-yl, imidazo[1,2-a]pyridin-7-yl, imidazo[1,2-a]pyridin-8-yl, 2-methylimidazo[1,2-a]pyridin-3-yl, 3-methylimidazo[1,2-a]pyridin-2-yl, 5-methylimidazo[1,2-a]-pyridin-3-yl, 6-methylimidazo[1,2-a]pyridin-2-yl, 7-methylimidazo[1,2-a]pyridin-3-yl, imidazo-[1,5-a]pyridin-1-yl, 1-methylimidazo[4,5-b]pyridin-2-yl, imidazo[1,2-a]pyrimidin-3-yl, imidazo-[1,2-a]pyrimidin-7-yl, indazol-6-yl, 1-methylindazol-4-yl, 1-methylindazol-6-yl, 2-methyl-indazol-3-yl, 2-methylindazol-5-yl, indol-2-yl, indol-3-yl, indol-5-yl, indol-6-yl, indol-7-yl, 6-cyanoindol-2-yl, 6-cyanoindol-3-yl, 1-methylindol-5-yl, 1-methylindol-6-yl, 2-methylindol-4-yl, 3-methylindol-2-yl, 4-methylindol-3-yl, 6-methylindol-3-yl, 7-methylindol-3-yl, 1-tert-butoxy-carbonylindolin-6-yl, indolizin-1-yl, 1,3-dioxoisoindolin-2-yl, 1-oxoisoindolin-5-yl, 3-oxo-isoindolin-5-yl, isoquinolin-3-yl, isoquinolin-4-yl, isoquinolin-5-yl, isoquinolin-8-yl, 1-chloro-isoquinolin-5-yl, 1,8-naphthyridin-2-yl, pyrazolo[1,5-a]pyridin-3-yl, pyrazolo[1,5-a]pyridin-7-yl, pyrrolo[2,3-b]pyrazin-7-yl, pyrrolo[2,3-b]pyridin-6-yl, 5-methylpyrrolo[2,3-b]pyridin-3-yl, pyrrolo[2,3-c]pyridin-3-yl, pyrrolo[3,2-b]pyridin-3-yl, pyrrolo[3,2-b]pyridin-6-yl, quinazolin-6-yl, quinolin-4-yl, quinolin-6-yl, quinolin-8-yl, quinoxalin-2-yl, quinoxalin-5-yl, quinoxalin-6-yl, 1,2,3,4-tetrahydroisoquinolin-7-yl, 2-(2,2,2-trifluoroacetyl)-1,2,3,4-tetrahydroisoquinolin-7-yl, 2-oxo-1,2,3,4-tetrahydroquinolin-6-yl, thieno[2,3-b]pyridin-2-yl, thieno[3,2-c]pyridin-2-yl, or [1,2,4]triazolo[1,5-a]pyridin-7-yl.
19 . The compound of claim 1 , wherein Re is 1-methyl-azetidin-3-yl, oxetan-3-yl, 3-methyloxetan-3-yl, tetrahydropyran-4-yl, ethylpiperidin-4-yl, 1-benzylpiperidin-4-yl, 1-benzoxycarbonylpiperidin-4-yl, 1-(tert-butoxycarbonyl)piperidin-4-yl, 1-(ethylsulfonyl)-piperidin-4-yl, 1-(tert-butoxycarbonyl)-4-fluoropiperidin-4-yl, or 4-(tert-butoxy-carbonyl)-piperazin-1-yl.
20 . The compound of claim 1 , wherein c and d are each an integer of 1; and e and f are each an integer of 0.
21 . The compound of claim 1 , wherein c and d are each an integer of 0; and e and f are each an integer of 1.
22 . The compound of claim 1 , wherein the compound is:
3-(4-(7-(furan-2-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione E0001;
3-(4-(7-(furan-3-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione E0002;
3-(4-(7-(2-(1H-pyrrol-2-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindo-lin-2-yl)piperidine-2,6-dione E0003;
3-(4-(7-(2-(1H-pyrazol-1-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindo-lin-2-yl)piperidine-2,6-dione E0004;
3-(1-oxo-4-(7-(2-(pyrrolidin-1-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindo-lin-2-yl)piperidine-2,6-dione E0005;
3-(1-oxo-4-(7-(tetrahydro-2H-pyran-4-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-isoindolin-2-yl)piperidine-2,6-dione E0006;
3-(4-(7-(2-morpholinoacetyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E0007;
3-(2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-2,7-diazaspiro[3.5]-nonane-7-carbonyl)benzonitrile E0008;
3-(1-oxo-4-(7-(2-(m-tolyl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)-piperidine-2,6-dione E0009;
3-(1-oxo-4-(7-(3-phenylpropanoyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione E0010;
3-(1-oxo-4-(7-(3-(pyridin-2-yl)propanoyl)-2,7-diazaspiro[3.5]nonan-2-yl)iso-indolin-2-yl)piperidine-2,6-dione E0011;
3-(4-(7-(3-(hydroxymethyl)benzoyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoiso-indolin-2-yl)piperidine-2,6-dione E0012;
3-(4-(7-(1H-pyrrole-2-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E0013;
3-(1-oxo-4-(7-(2-(m-tolyloxy)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione E0014;
3-(4-(7-(2-(2-methoxypyridin-3-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxo-isoindolin-2-yl)piperidine-2,6-dione E0015;
2-chloro-5-(2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-2,7-diazaspiro-[3.5]nonane-7-carbonyl)benzonitrile E0016;
2-chloro-4-(2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-2,7-diazaspiro-[3.5]nonane-7-carbonyl)benzonitrile E0017;
3-(1-oxo-4-(7-(3-(pyridin-3-yl)propanoyl)-2,7-diazaspiro[3.5]nonan-2-yl)iso-indolin-2-yl)piperidine-2,6-dione E0018;
3-(4-(7-(2,6-difluorobenzoyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E0019;
3-(4-(7-(2,5-difluorobenzoyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E0020;
3-(4-(7-(3,5-difluorobenzoyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E0021;
3-(4-(7-(2-methyl-2-phenylpropanoyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoiso-indolin-2-yl)piperidine-2,6-dione E0022;
3-(1-oxo-4-(7-(pyrimidine-4-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione E0023;
3-(4-(7-(1-methyl-1H-pyrrole-2-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxo-isoindolin-2-yl)piperidine-2,6-dione E0024;
3-(4-(7-(2-methyl-1H-imidazole-5-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E0025;
3-(4-(7-(2-(1H-1,2,3-triazol-1-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxo-isoindolin-2-yl)piperidine-2,6-dione E0026;
3-(4-(7-(2-cyclopentylacetyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E0027;
5-(2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-2,7-diazaspiro[3.5]-nonane-7-carbonyl)-1H-pyrrole-2-carbonitrile E0028;
5-(2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-2,7-diazaspiro[3.5]-nonane-7-carbonyl)-1H-pyrrole-3-carbonitrile E0029;
3-(1-oxo-4-(7-(2-(pyrimidin-2-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindo-lin-2-yl)piperidine-2,6-dionee E0030;
3-(1-oxo-4-(7-(2-(pyrimidin-5-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindo-lin-2-yl)piperidine-2,6-dione E0031;
3-(4-(7-(3-(1H-pyrrol-2-yl)propanoyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoiso-indolin-2-yl)piperidine-2,6-dione E0032;
3-(4-(7-(1-methylpiperidine-4-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoiso-indolin-2-yl)piperidine-2,6-dione E0033;
3-(1-oxo-4-(7-(2-(piperidin-1-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindo-lin-2-yl)piperidine-2,6-dione E0034;
3-(1-oxo-4-(7-(2-(tetrahydro-2H-pyran-4-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione E0035;
3-(4-(7-benzyl-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E1001;
3-(1-oxo-4-(7-(pyridin-3-ylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione E1002;
3-(1-oxo-4-(7-(pyridin-4-ylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione E1003;
3-(1-oxo-4-(7-(pyridin-2-ylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione E1004;
3-(1-oxo-4-(7-(pyrimidin-5-ylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione E1005;
3-(4-(7-((1-methyl-1H-imidazol-5-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E1006;
3-(1-oxo-4-(7-phenethyl-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperi-dine-2,6-dione E1007;
3-((2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-2,7-diazaspiro[3.5]-nonan-7-yl)methyl)benzonitrile E1008;
2-((2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-2,7-diazaspiro[3.5]-nonan-7-yl)methyl)benzonitrile E1009;
6-((2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-2,7-diazaspiro[3.5]-nonan-7-yl)methyl) nicotinonitrile E1010;
3-(1-oxo-4-(7-(3-phenylpropyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)-piperidine-2,6-dione E1011;
3-(4-(7-(4-(hydroxymethyl)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindo-lin-2-yl)piperidine-2,6-dione E1012;
2-((2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-2,7-diazaspiro[3.5]-nonan-7-yl)methyl)-5-methoxybenzonitrile E1013;
3-chloro-5-((2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-2,7-diazaspiro-[3.5]nonan-7-yl)methyl)benzonitrile E1014;
2-chloro-4-((2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-2,7-diazaspiro-[3.5]nonan-7-yl)methyl)benzonitrile E1015;
3-(1-oxo-4-(7-((2-phenyl-1H-imidazol-5-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione E1016;
3-(1-oxo-4-(7-(4-(pyrrolidin-1-yl)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindo-lin-2-yl)piperidine-2,6-dione E1017;
3-(4-(7-(4-((2-hydroxyethyl)(methyl)amino)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E1018;
3-(4-(7-(4-(cyclopentyloxy)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindo-lin-2-yl)piperidine-2,6-dione E1019;
3-(4-(7-(4-morpholinobenzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E1020;
3-(4-(7-(3-morpholinobenzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E1021;
3-(4-(7-(4-benzylbenzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione E1022;
3-(1-oxo-4-(7-(4-(pyridin-3-yloxy)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)iso-indolin-2-yl)piperidine-2,6-dione E1023;
3-(1-oxo-4-(7-(pyrimidin-4-ylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione E1024;
3-(4-(7-(cyclohexylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione E1025;
3-(1-oxo-4-(7-((tetrahydro-2H-pyran-4-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione E1026;
3-(4-(7-(4-methoxybenzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione E1027;
3-(4-(7-(3-methoxybenzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione E1028;
3-(4-(7-((6-methoxypyridin-3-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxo-isoindolin-2-yl)piperidine-2,6-dione E1029;
3-(4-(7-((1H-indol-3-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E1030;
3-(4-(7-(2-methoxyphenethyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E1031;
3-(1-oxo-4-(7-((6-(pyrrolidin-1-yl)pyridin-3-yl)methyl)-2,7-diazaspiro[3.5]-nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione E1032;
3-(4-(7-((5-(morpholinomethyl)furan-2-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E1033;
3-(4-(7-((1-benzylpiperidin-4-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxo-isoindolin-2-yl)piperidine-2,6-dione E1034;
3-(4-(7-((4-(benzyloxy)pyridin-2-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione E1035;
3-(1-oxo-4-(7-(4-((pyridin-2-yloxy)methyl)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione E1036;
3-(4-(7-(2-chloro-4-morpholinobenzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoiso-indolin-2-yl)piperidine-2,6-dione E1037;
3-(4-(7-(furan-3-ylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione E1038;
3-(4-(7-(furan-2-ylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione E1039;
3-(4-(7-((1H-pyrazol-4-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindo-lin-2-yl)piperidine-2,6-dione E1040;
3-(5-(7-(furan-2-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione F0001;
3-(5-(7-(furan-3-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione F0002;
3-(5-(7-(2-(1H-pyrrol-2-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindo-lin-2-yl)piperidine-2,6-dione F0003;
3-(5-(7-(2-(1H-pyrazol-1-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindo-lin-2-yl)piperidine-2,6-dione F0004;
3-(1-oxo-5-(7-(2-(pyrrolidin-1-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)-isoindo-lin-2-yl)piperidine-2,6-dione F0005;
3-(1-pxo-5-(7-(tetrahydro-2H-pyran-4-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-isoindolin-2-yl)piperidine-2,6-dione F0006;
3-(5-(7-(2-morpholinoacetyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F0007;
3-(2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)-2,7-diazaspiro[3.5]-nonane-7-carbonyl)benzonitrile F0008;
3-(1-oxo-5-(7-(2-(m-tolyl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)-piperidine-2,6-dione F0009;
3-(1-oxo-5-(7-(3-phenylpropanoyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione F0010;
3-(1-oxo-5-(7-(3-(pyridin-2-yl)propanoyl)-2,7-diazaspiro[3.5]nonan-2-yl)iso-indolin-2-yl)piperidine-2,6-dione F0011;
3-(5-(7-(3-(hydroxymethyl)benzoyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoiso-indolin-2-yl)piperidine-2,6-dione F0012;
3-(5-(7-(1H-pyrrole-2-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F0013;
3-(1-oxo-5-(7-(2-(m-tolyloxy)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione F0014;
3-(5-(7-(2-(2-methoxypyridin-3-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxo-isoindolin-2-yl)piperidine-2,6-dione F0015;
2-chloro-5-(2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)-2,7-diazaspiro-[3.5]nonane-7-carbonyl)benzonitrile F0016;
2-chloro-4-(2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)-2,7-diazaspiro-[3.5]nonane-7-carbonyl)benzonitrile F0017;
3-(1-oxo-5-(7-(3-(pyridin-3-yl)propanoyl)-2,7-diazaspiro[3.5]nonan-2-yl)iso-indolin-2-yl)piperidine-2,6-dione F0018;
3-(5-(7-(2,6-difluorobenzoyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F0019;
3-(5-(7-(2,5-difluorobenzoyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F0020;
3-(5-(7-(3,5-difluorobenzoyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F0021;
3-(5-(7-(2-methyl-2-phenylpropanoyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoiso-indolin-2-yl)piperidine-2,6-dione F0022;
3-(1-oxo-5-(7-(pyrimidine-4-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione F0023;
3-(5-(7-(1-methyl-1H-pyrrole-2-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxo-isoindolin-2-yl)piperidine-2,6-dione F0024;
3-(5-(7-(2-methyl-1H-imidazole-5-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F0025;
3-(5-(7-(2-(1H-1,2,3-triazol-1-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxo-isoindolin-2-yl)piperidine-2,6-dione F0026;
3-(5-(7-(2-cyclopentylacetyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F0027;
5-(2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)-2,7-diazaspiro[3.5]-nonane-7-carbonyl)-1H-pyrrole-2-carbonitrile F0028;
5-(2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)-2,7-diazaspiro[3.5]-nonane-7-carbonyl)-1H-pyrrole-3-carbonitrile F0029;
3-(1-oxo-5-(7-(2-(pyrimidin-2-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)iso-indolin-2-yl)piperidine-2,6-dione F0030;
3-(1-oxo-5-(7-(2-(pyrimidin-5-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)iso-indolin-2-yl)piperidine-2,6-dione F0031;
3-(5-(7-(3-(1H-pyrrol-2-yl)propanoyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxo-isoindolin-2-yl)piperidine-2,6-dione F0032;
3-(5-(7-(1-methylpiperidine-4-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxo-isoindolin-2-yl)piperidine-2,6-dione F0033;
3-(1-oxo-5-(7-(2-(piperidin-1-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindo-lin-2-yl)piperidine-2,6-dione F0034;
3-(1-oxo-5-(7-(2-(tetrahydro-2H-pyran-4-yl)acetyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione F0035;
3-(5-(7-benzyl-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F1001;
3-(1-oxo-5-(7-(pyridin-3-ylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione F1002;
3-(1-oxo-5-(7-(pyridin-4-ylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione F1003;
3-(1-oxo-5-(7-(pyridin-2-ylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione F1004;
3-(1-oxo-5-(7-(pyrimidin-5-ylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione F1005;
3-(5-(7-((1-methyl-1H-imidazol-5-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F1006;
3-(1-oxo-5-(7-phenethyl-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperi-dine-2,6-dione F1007;
3-((2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)-2,7-diazaspiro[3.5]-nonan-7-yl)methyl)benzonitrile F1008;
2-((2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)-2,7-diazaspiro[3.5]-nonan-7-yl)methyl)benzonitrile F1009;
6-((2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)-2,7-diazaspiro[3.5]-nonan-7-yl)methyl) nicotinonitrile F1010;
3-(1-oxo-5-(7-(3-phenylpropyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)-piperidine-2,6-dione F1011;
3-(5-(7-(4-(hydroxymethyl)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindo-lin-2-yl)piperidine-2,6-dione F1012;
2-((2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)-2,7-diazaspiro[3.5]-nonan-7-yl)methyl)-5-methoxybenzonitrile F1013;
3-chloro-5-((2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)-2,7-diazaspiro-[3.5]nonan-7-yl)methyl)benzonitrile F1014;
2-chloro-4-((2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)-2,7-diazaspiro-[3.5]nonan-7-yl)methyl)benzonitrile F1015;
3-(1-oxo-5-(7-((2-phenyl-1H-imidazol-5-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione F1016;
3-(1-oxo-5-(7-(4-(pyrrolidin-1-yl)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindo-lin-2-yl)piperidine-2,6-dione F1017;
3-(5-(7-(4-((2-hydroxyethyl)(methyl)amino)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F1018;
3-(5-(7-(4-(cyclopentyloxy)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindo-lin-2-yl)piperidine-2,6-dione F1019;
3-(5-(7-(4-morpholinobenzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F1020;
3-(5-(7-(3-morpholinobenzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F1021;
3-(5-(7-(4-benzylbenzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione F1022;
3-(1-oxo-5-(7-(4-(pyridin-3-yloxy)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)iso-indolin-2-yl)piperidine-2,6-dione F1023;
3-(1-oxo-5-(7-(pyrimidin-4-ylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione F1024;
3-(5-(7-(cyclohexylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione F1025;
3-(1-oxo-5-(7-((tetrahydro-2H-pyran-4-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione F1026;
3-(5-(7-(4-methoxybenzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione F1027;
3-(5-(7-(3-methoxybenzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione F1028;
3-(5-(7-((6-methoxypyridin-3-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxo-isoindolin-2-yl)piperidine-2,6-dione F1029;
3-(5-(7-((1H-indol-3-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F1030;
3-(5-(7-(2-methoxyphenethyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F1031;
3-(1-oxo-5-(7-((6-(pyrrolidin-1-yl)pyridin-3-yl)methyl)-2,7-diazaspiro[3.5]-nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione F1032;
3-(5-(7-((5-(morpholinomethyl)furan-2-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F1033;
3-(5-(7-((1-benzylpiperidin-4-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxo-isoindolin-2-yl)piperidine-2,6-dione F1034;
3-(5-(7-((4-(benzyloxy)pyridin-2-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione F1035;
3-(1-oxo-5-(7-(4-((pyridin-2-yloxy)methyl)benzyl)-2,7-diazaspiro[3.5]nonan-2-yl)isoindolin-2-yl)piperidine-2,6-dione F1036;
3-(5-(7-(2-chloro-4-morpholinobenzyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxo-isoindolin-2-yl)piperidine-2,6-dione F1037;
3-(5-(7-(furan-3-ylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione F1038;
3-(5-(7-(furan-2-ylmethyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione F1039; or
3-(5-(7-((1H-pyrazol-4-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1-oxoisoindo-lin-2-yl)piperidine-2,6-dione F1040;
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, or a mixture of two or more tautomers thereof, or a pharmaceutically acceptable salt, solvate, or hydrate thereof.
23 . A pharmaceutical composition comprising an effective amount of the compound of claim 1 , or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, or a mixture of two or more tautomers thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; and a pharmaceutically acceptable excipient.