US2007049618A1PendingUtilityA1
Isoindole-imide compounds and compositions comprising and methods of using the same
Est. expiryAug 31, 2025(expired)· nominal 20-yr term from priority
A61P 9/00A61P 9/10A61P 7/06A61P 37/02A61P 43/00A61P 25/20A61P 29/00A61P 35/00A61P 27/02A61P 25/28A61P 33/00A61P 25/04A61P 25/00A61P 31/00A61P 11/00A61P 17/00A61P 19/02C07D 401/14C07D 417/14C07D 409/14C07D 401/04C07D 413/14C07D 405/14A61K 31/45
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Claims
Abstract
This invention relates to isoindole-imide compounds, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.
Claims
exact text as granted — not AI-modified1 . A compound of formula (I):
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
X is O or S;
R 1 is H or methyl;
R 2 is: (C 2 -C 6 )alkyl, excluding cycloalkyl; (C 4 -C 6 )cycloalkyl; (C 1 -C 4 )alkoxy;
(C 1 -C 6 )alkyl, substituted with (C 1 -C 4 )alkoxy;
(C 1 -C 6 )alkyl-phenyl, wherein the phenyl is optionally substituted with one or more of halogen, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkyl, or cyano;
(C 0 -C 1 )alkyl-(5 to 6 membered heteroaryl), wherein the heteroaryl is optionally substituted with one or more of (C 1 -C 4 )alkyl or halogen; or
(C 0 -C 3 )alkyl-NR 3 R 4 ;
R 3 and R 4 are each independently:
H; (C 1 -C 6 )alkyl; (C 3 -C 6 )cycloalkyl;
(C 0 -C 1 )alkyl-(C 6 -C 10 )aryl, wherein the aryl is optionally substituted with one or more of (C 1 -C 4 )alkoxy, halogen, methyl, cyano, or —O—CH 2 —O—;
(C 0 -C 1 )alkyl-(5 to 10 membered heteroaryl), wherein the heteroaryl is substituted with one or more of (C 1 -C 4 )alkoxy, halogen, or methyl; or C(O)R 5 ; and
R 5 is (C 1 -C 4 )alkoxy or (C 1 -C 2 )alkyl-O—(C 1 -C 2 )alkyl;
with the proviso that if one of R 3 and R 4 is H, then the other is not ethyl.
2 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein X is O.
3 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein X is S.
4 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 2 is phenyl, optionally substituted with one or more halogen.
5 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 2 is NHR 4 .
6 . The compound of claim 5 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 4 is (C 6 -C 10 )aryl or 5 to 10 membered heteroaryl, both optionally substituted with one or more of (C 1 -C 4 )alkoxy, halogen, or methyl.
7 . The compound of claim 6 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein the aryl or heteroaryl is phenyl, pyridyl, or naphthyl.
8 . The compound of claim 1 , which is:
1
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo2,3-dihydro-1H- isoindol-4-ylmethyl]-2- phenyl-acetamide
2
1-Cyclohexyl-3-[2-(2,6- dioxo-piperidin-3-yl)-1- oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-urea
3
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]- benzamide
4
Furan-2-carboxylic acid[2- (2,6-dioxo-piperidin-3-yl)- 1-oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-amide
5
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]- butyramide
6
3-Chloro-N-[2-(2,6-dioxo- piperidin-3-yl)-1-oxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-benzamide
7
1-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]-3- propyl-urea
8
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]- nicotinamide
9
1-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]-3- phenyl-urea
10
[2-(2,6-Dioxo-piperidin-3- yl)-1-oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]- carbamic acid tert-butyl ester
11
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]-3- methoxy-benzamide
12
3-Cyano-N-[2-(2,6-dioxo- piperidin-3-yl)-1-oxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-benzamide
13
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]-4- methoxy-benzamide
14
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]-2- methoxy-benzamide
15
1-[2-(2,6-Dioxo-pipderidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]-3- (3-methoxy-phenyl)-urea
16
1-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]-3- (4-methoxy-phenyl)-urea
17
1-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]-3- (2-methoxy-phenyl)-urea
18
1-(3-Cyano-phenyl)-3-[2- (2,6-dioxo-piperidin-3-yl)- 1-oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-urea
19
1-(3-Chloro-phenyl)-3-[2- (2,6-dioxo-piperidin-3-yl)- 1-oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-urea
20
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]- isonicotinamide
21
Pyridine-2-carboxylic acid [2-(2,6-dioxo-piperidin-3- yl)-1-oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-amide
22
1-Benzyl-3-[2-(2,6-dioxo- piperidin-3-yl)-1-oxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-urea
23
1-(3,4-Dichloro-phenyl)-3- [2-(2,6-dioxo-piperidin-3- yl)-1-oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-urea
24
1-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]-3- pyridin-3-yl-urea
25
3-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]- 1,1-dimethyl-urea
26
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]-3- methyl-benzamide
27
(2-{[2-(2,6-Dioxo- piperidin-3-yl)-1-oxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-carbamoyl}- ethyl)-carbamic acid t-butyl ester
28
3-Amino-N-[2-(2,6-dioxo- piperidin-3-yl)-1-oxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-propionamide Hydrochloride
29
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1-oxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]-2- methoxy-acetamide
30
2-Dimethylamino-N-[2- (2,6-dioxo-piperidin-3-yl)- 1-oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]- acetamide Hydrochloride
31
(3-{[2-(2,6-Dioxo- piperidin-3-yl)-1-oxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-carbamoyl}- propyl)-carbamic acid t- butyl ester
32
4-Amino-[2-(2,6-dioxo- piperidin-3-yl)-1-oxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-butyramide hydrochloride
33
1-(4-Chloro-phenyl)-3-[2- (2,6-dioxo-piperidin-3-yl)- 1-oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-urea
34
1-(3,4-Dimethyl-phenyl)-3- [2-(2,6-dioxo-piperidin-3- yl)-1-oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-urea
35
1-Cyclohexyl-3-[2-(2,6- dioxo-piperidin-3-yl)-1- oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]- thiourea
36
3,4-Dichloro-N-[2-(2,6- dioxo-piperidin-3-yl)-1- oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]- benzamide
37
1-(3-Chloro-4- methylphenyl)-3-[2-(2,6- dioxo-piperidin-3-yl)-1- oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]urea
38
1-[2-(2,6-Dioxopiperidin-3- yl)-1-oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-3- naphthalen-1-yl-urea
39
1-[2-(2,6-Dioxopiperidin-3- yl)-1-oxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-3- naphthalen-2-yl-urea.
9 . A compound of formula (II):
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 1 is H or methyl; and
R 2 is: (C 6 -C 10 )aryl, optionally substituted with one or more of: (C 1 -C 8 )alkyl, optionally substituted with NH 2 , NH(CH 3 ), or N(CH 3 ) 2 ; (C 1 -C 4 )alkoxy, optionally substituted with NH 2 , NH(CH 3 ), N(CH 3 ) 2 , or 3 to 6 membered heterocycloalkyl; (C 3 -C 6 )cycloalkyl; (C 5 -C 10 )aryloxy; hydroxy; NH 2 ;
NH(CH 3 ); N(CH 3 ) 2 ; —CH 2 —CH 2 —CH 2 —; halogen; or —O—CH 2 —O—;
(C 3 -C 6 )alkyl, optionally substituted with one or more of (C 1 -C 4 )alkoxy;
(C 1 -C 2 )alkyl, optionally substituted with carboxyl;
(C 1 -C 6 )alkyl-(C 3 -C 6 )cycloalkyl; or
5 to 10 membered heterocycle;
with the proviso that if R 2 is pentyl, then R 1 is methyl.
10 . The compound of claim 9 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 2 is phenyl, optionally substituted with one or more of (C 1 -C 4 )alkoxy or —O—CH 2 —O—.
11 . The compound of claim 9 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 2 is (C 3 -C 6 )alkyl, optionally substituted with one or more of (C 1 -C 4 )alkoxy.
12 . The compound of claim 9 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 2 is phenyl, substituted with one or more (C 1 -C 4 )alkyl, which is substituted with N(CH 3 ) 2 .
13 . The compound of claim 10 , which is:
40
2-(2,6-Dioxopiperidin-3-yl)-4- phenylaminoisoindole-1,3- dione
41
2-(2,6-Dioxopiperidin-3-yl)-4- (3,4- methylenedioxyphenylamino) isoindole-1,3-dione
42
2-(2,6-Dioxopiperidin-3-yl)-4- (3,4- dimethoxyphenylamino)isoin- dole-1,3-dione
43
2-(3-Methyl-2,6- dioxopiperidin-3-yl)-4- pentylaminoisoindole-1,3- dione
44
4-(Cyclopropylmethylamino)- 2-(2,6-dioxopiperidin-3- yl)isoindole-1,3-dione
45
[2-(2,6-Dioxopiperidin-3-yl)- 1,3-dioxo-2,3-dihydro-1H- isoindol-4-yl-amino]acetic acid
46
2-(2,6-Dioxopiperidin-3-yl)-4- (2-methoxy-1- methylethylamino)isoindole- 1,3-dione
47
4-(4-tert-Butylphenylamino)- 2-(2,6-dioxopiperidin-3- yl)isoindole-1,3-dione
48
4-(4-Isopropylphenylamino)-2- (2,6-dioxopiperidin-3- yl)isoindole-1,3-dione
49
2-(2,6-Dioxo-piperidin-3-yl)- 4-(indan-5-ylamino)-isoindole- 1,3-dione
50
4-(2,4- Dimethoxyphenylamino)-2- (2,6-dioxopiperidin-3- yl)isoindole-1,3-dione
51
2-(2,6-Dioxopiperidin-3-yl)-4- (4-methoxyphenylamino) isoindole-1,3-dione
52
2-(2,6-Dioxopiperidin-3-yl)-4- (3-ethoxy-4- methoxyphenylamino)- isoindole-1,3-dione
53
2-(2,6-Dioxopiperidin-3-yl)-4- (3-hydroxy-4- methoxyphenylamino)- isoindole-1,3-dione
54
2-(2,6-Dioxopiperidin-3-yl)-4- (naphthalen-2-ylamino) isoindole-1,3-dione
55
4-(4-Cyclohexylphenylamino)- 2-(2,6-dioxopiperidin-3- yl)isoindole-1,3-dione
56
4-(2-Methoxyphenylamino)-2- (2,6-dioxopiperidin-3- yl)isoindole-1,3-dione
57
4-(2,5- Dimethoxyphenylamino)-2- (2,6-dioxopiperidin-3- yl)isoindole-1,3-dione
58
4-(2-Phenoxyphenylamino)-2- (2,6-dioxopiperidin-3-yl) isoindole-1,3-dione
59
4-(4- Dimethylaminophenylamino)- 2-(2,6-dioxopiperidin-3- yl)isoindole-1,3-dione
60
4-[4-(2- Dimethylaminoethoxy)-2- methoxyphenylamino]-2-(2,6- dioxo-piperidin-3-yl)- isoindole-1,3-dione
61
4-[4-(2- Dimethylaminoethoxy)-2- methoxyphenylamino]-2-(2,6- dioxo-piperidin-3-yl)- isoindole-1,3-dione hydrochloride
62
4-{2-(2-Dimethylaminoethoxy)- 4-methoxyphenylamino]-2- (2,6-dioxopiperidin-3- yl)isoindole-1,3-dione hydrochloride
63
2-(2,6-Dioxopiperidin-3-yl)-4- [2-methoxy-4-(2-morpholin-4- ylethoxy)phenylamino]- isoindole-1,3-dione hydrochloride
64
4-(4-Dimethylaminomethyl-2- methoxyphenylamino)-2-(2,6- dioxopiperidin-3-yl)isoindole- 1,3-dione
65
4-(4-Dimethylaminomethyl-2- methoxyphenylamino)-2-(2,6- dioxopiperidin-3-yl)isoindole- 1,3-dione hydrochloride
66
4-[4-(3- Dimethylaminopropoxy)-2- methoxyphenylamino]-2-(2,6- dioxopiperidin-3-yl)isoindole- 1,3-dione hydrochloride
67
4-[4-(2-Dimethylamino- ethoxy)-phenylamino]-2-(2,6- dioxo-piperidin-3-yl)- isoindole-1,3-dione
68
4-[4-(2-Dimethylamino- ethoxy)-2-isopropoxy- phenylamino]-2-(2,6-dioxo- piperidin-3-yl)-isoindole-1,3- dione
69
2-(2,6-Dioxo-piperidin-3-yl)- 4-(4-methoxy-2-phenoxy- phenylamino)-isoindole-1,3- dione
70
4-[4-(2-Dimethylamino- ethoxy)-2-phenoxy- phenylamino]-2-(2,6-dioxo- piperidin-3-yl)-isoindole-1,3- dione
71
2-(2,6-Dioxo-piperidin-3-yl)- 4-[4-(2-morpholin-4-yl- ethoxy)-phenylamino]- isoindole-1,3-dione
72
2-(2,6-Dioxo-piperidin-3-yl)- 4-[3-(2-morpholin-4-yl- ethoxy)-phenylamino]- isoindole-1,3-dione
73
2-(2,6-Dioxo-piperidin-3-yl)- 4-[2-methoxy-4-(2-piperidin- 1-yl-ethoxy)-phenylamino]- isoindole-1,3-dione
74
2-(2,6-Dioxo-piperidin-3-yl)- 4-[2-methoxy-4-(2-pyrrolidin- 1-yl-ethoxy)-phenylamino]- isoindole-1,3-dione
75
2-(2,6-Dioxo-piperidin-3-yl)- 4-[2-fluoro-4-(2-morpholin-4- yl-ethoxy)-phenylamino]- isoindole-1,3-dione
76
4-(2,4-Dimethoxy- phenylamino)-2-[(3S)-3- methyl-2,6-dioxo-piperidin-3- yl]-isoindole-1,3-dione
77
4-(Indan-5-ylamino)-2-[(3S)- 3-methyl-2,6-dioxo-piperidin- 3-yl]-isoindole-1,3-dione
78
2-(2,6-Dioxo-piperidin-3-yl)- 4-(3-methoxy-phenylamino)- isoindole-1,3-dione.
14 . A compound of formula (III):
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 1 is H or methyl; and
R 2 is: amino, optionally substituted with one or more of (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, or phenyl; 3 to 6 membered heterocycloalkyl; or (C 1 -C 4 )alkoxy.
15 . The compound of claim 14 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 2 is —NH(CH 3 ) or —N(CH 3 ) 2 .
16 . The compound of claim 14 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 2 is (C 3 -C 6 )cycloalkyl.
17 . The compound of claim 14 , which is:
79
2-[2-(2,6-Dioxopiperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H-isoindol-4- ylamino]-N-methylacetamide
80
[2-(2,6-Dioxopiperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H-isoindol-4- ylamino]acetic acid methyl ester
81
2-[2-(2,6-Dioxopiperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H-isoindol-4- ylamino]-N-methylacetamide
82
N-Cyclopropyl-2-[2-(2,6- dioxopiperidin-3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylamino]acetamide
83
4-(2-(Azetidin-1-yl)-2- oxoethylamino)-2-(2,6-dioxo piperidin-3-yl)isoindoline-1,3- dione
84
2-[2-(2,6-Dioxopiperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H-isoindol-4- ylamino]-N-phenyl-acetamide.
18 . A compound of formula (IV):
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 1 is H or methyl; and R 2 is 5 to 6 membered heteroaryl;
with the proviso that if R 2 is furan or thiophene, then R 1 is methyl; and
with the proviso that if R 2 is pyridine, then the pyridine is not connected to the core at the 3 position.
19 . The compound of claim 18 , which is:
85
2-(2,6-Dioxopiperidin-3-yl)-4- [(pyridin-2-yl- methyl)amino]isoindole-1,3-dione hydrochloride
86
2-(2,6-Dioxopiperidin-3-yl)-4- [(pyridin-4-yl- methyl)amino]isoindole-1,3-dione hydrochloride
87
4-[(Furan-2-ylmethyl)amino]-2- (3-methyl-2,6-dioxopiperidin-3- yl)isoindole-1,3-dione.
20 . A compound of formula (V):
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 1 is H or methyl; and
R 2 is: H; methyl; ethyl;
phenyl, substituted with one or more of (C 1 -C 6 )alkyl, halogen, (C 1 -C 4 )alkoxy, cyano, or —O—CH 2 —O—;
naphthyl, optionally substituted with one or more of (C 1 -C 6 )alkyl, halogen, (C 1 -C 4 )alkoxy, or cyano; or
5 to 10 membered heteroaryl, optionally substituted with one or more of (C 1 -C 6 )alkyl, halogen, (C 1 -C 4 )alkoxy, or cyano;
with the proviso that if R 2 is ethyl, then R 1 is methyl; and
with the proviso that if R 2 is pyridine, then the pyridine is not connected to the core at the 3 position.
21 . The compound of claim 20 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 2 is phenyl, optionally substituted with one or more of methyl, halogen, (C 1 -C 4 )alkoxy, cyano, or —O—CH 2 —O—.
22 . The compound of claim 20 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 2 is naphthyl.
23 . The compound of claim 20 , which is:
88
1-Ethyl-3-[2-(3-methyl- 2,6-dioxo-piperidin-3-yl)- 1,3-dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-urea
89
1-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3-(3-methoxy- phenyl)-urea
90
1-(3-Chloro-phenyl)-3-[2- (2,6-dioxo-piperidin-3-yl)- 1,3-dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-urea
91
1-(3-Cyano-phenyl)-3-[2- (2,6-dioxo-piperidin-3-yl)- 1,3-dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-urea
92
1-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3-(4-methoxy- phenyl)-urea
93
1-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3-(2-methoxy- phenyl)-urea
94
1-(3,4- Methylenedioxyphenyl)-3- [2-(2,6-dioxopiperidin-3- yl)-1,3-dioxo-2,3-dihydro- 1H-isoindol-4- ylmethyl]urea
95
1-(3-Chloro-4- methylphenyl)-3-[2-(2,6- dioxopiperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]urea
96
1-(3,4-dichlorophenyl)-3- [2-(2,6-dioxopiperidin-3- yl)-1,3-dioxo-2,3-dihydro- 1H-isoindol-4- ylmethyl]urea
97
1-[2-(2,6-Dioxopiperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3-naphthalen-1- yl-urea
98
1-[2-(2,6-Dioxopiperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3-naphthalen-2- yl-urea
99
1-(3,4-Dimethyl-phenyl)-3- [2-(2,6-dioxo-piperidin-3- yl)-1,3-dioxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]- urea
100
1-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3-m-tolyl-urea
101
1-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3-pyridin-2-yl- urea
102
1-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3-p-tolyl-urea
103
1-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3-o-tolyl-urea
104
[2-(2,6-Dioxo-piperidin-3- yl)-1,3-dioxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]- urea.
24 . A compound of formula (VI):
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 1 is H or methyl; and
R 2 is: N(CH 3 ) 2 ;
(C 0 -C 1 )alkyl-(C 6 -C 10 )aryl, substituted with one or more of: methyl, itself optionally substituted with one or more halogen; (C 1 -C 4 )alkoxy, itself optionally substituted with one or more halogen; or halogen;
(C 0 -C 1 )alkyl-(5 to 10 membered heteroaryl), optionally substituted with one or more of (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, or halogen; or
(5 to 6 membered heteroaryl)-phenyl, wherein the heteroaryl and phenyl are each independently optionally substituted with one or more of (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy;
with the proviso that R 2 is not unsubstituted pyridine, furan, or thiophene.
25 . The compound of claim 24 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 2 is phenyl, substituted with one or more of methyl, (C 1 -C 4 )alkoxy, or halogen.
26 . The compound of claim 24 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 2 is pyrazine, pyrimidine, quinoxaline, or isoquinoline, optionally substituted with one or more of (C 1 -C 4 )alkyl or halogen.
27 . The compound of claim 24 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R 2 is 5 membered heteroaryl, substituted with one of more (C 1 -C 4 )alkyl.
28 . The compound of claim 24 , which is:
105
3-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-1,1-dimethyl- urea
106
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-4-methoxy- benzamide
107
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3-methyl- benzamide
108
3,4-Dichloro-N-[2-(2,6- dioxopiperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-yl- methyl]benzamide
109
Isoquinoline-3-carboxylic acid [2-(2,6- dioxopiperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]amide
110
5-Butylpyridine-2- carboxylic acid [2-(2,6- dioxopiperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]amide
111
6-Bromopyridine-2- carboxylic acid [2-(2,6- dioxopiperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]amide
112
6-Methylpyridine-2- carboxylic acid [2-(2,6- dioxopiperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]amide
113
Pyrazine-2-carboxylic acid [2-(2,6-dioxopiperidin-3- yl)-1,3-dioxo-2,3-dihydro- 1H-isoindol-4-yl- methyl]amide
114
Quinoxaline-2-carboxylic acid [2-(2,6- dioxopiperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]amide
115
Pyrimidine-5-carboxylic acid [2-(2,6- dioxopiperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]amide
116
2,5-Dichloro-N-[2-(2,6- dioxopiperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-yl- methyl]nicotinamide
117
6-(3-Ethoxy-4- methoxyphenyl)pyridine-2- carboxylic acid [2-(2,6- dioxopiperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]amide
118
1H-Indole-2-carboxylic acid [2-(2,6-dioxo- piperidin-3-yl)-1,3-dioxo- 2,3-dihydro-1H-isoindol-4- ylmethyl]-amide
119
1,5-Dimethyl-1H-pyrazole- 3-carboxylic acid [2-(2,6- dioxo-piperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-amide
120
5-Methyl-isoxazole-3- carboxylic acid [2-(2,6- dioxo-piperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-amide
121
1-Methyl-1H-pyrrole-2- carboxylic acid [2-(2,6- dioxo-piperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-amide
122
3-Methyl-3H-imidazole-4- carboxylic acid [2-(2,6- dioxo-piperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-amide
123
N-[2-(2,6-dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-4- trifluoromethyl-benzamide
124
5-Phenyl- [1,3,4]oxadiazole-2- carboxylic acid [2-(2,6- dioxo-piperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethylamide
125
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3- trifluoromethyl-benzamide
126
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3,4-difluoro- benzamide
127
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3-fluoro- benzamide
128
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-4-methyl- benzamide
129
3,5-Dichloro-N-[2-(2,6- dioxo-piperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]- benzamide
130
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3,5-difluoro- benzamide
131
4-Chloro-N-[2-(2,6-dioxo- piperidin-3-yl)-1,3-dioxo- 2,3-dihydro-1H-isoindol-4- ylmethyl]-benzamide
132
2-Chloro-N-[2-(2,6-dioxo- piperidin-3-)-1,3-dioxo- 2,3-dihydro-1H-isoindol-4- ylmethyl]-benzamide
133
3-Chloro-N-[2-(2,6-dioxo- piperidin-3-yl)-1,3-dioxo- 2,3-dihydro-1H-isoindol-4- ylmethyl]-4-methyl- benzamide
134
Benzofuran-2-carboxylic acid [2-(2,6-dioxo- piperidin-3-yl)-1,3-dioxo- 2,3-dihydro-1H-isoindol-4- ylmethyl]-amide
135
2-(3,4-Dichloro-phenyl)-N- [2-(2,6-dioxopiperidin-3- yl)-1,3-dioxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]- acetamide
136
2-(3-Chloro-phenyl)-N-[2- (2,6-dioxo-piperidin-3-yl)- 1,3-dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]- acetamide
137
Benzo[1,3]dioxole-5- carboxylic acid [2-(2,6- dioxo-piperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-amide
138
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4-yl- methyl]-3,4-dimethoxy- benzamide
139
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-4- trifluoromethoxy- benzamide
140
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3- trifluoromethoxy- benzamide
141
4-Difluoromethoxy-N-[2- (2,6-dioxo-piperidin-3-yl)- 1,3-dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]- benzamide
142
3-Difluoromethoxy-N-[2- (2,6-dioxo-piperidin-3-yl)- 1,3-dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]- benzamide
143
2-Difluoromethoxy-N-[2- (2,6-dioxo-piperidin-3-yl)- 1,3-dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]- benzamide
144
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-4-fluoro- benzamide
145
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-(4-fluoro- phenyl)-acetamide
146
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-(3-fluoro- phenyl)-acetamide
147
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-(2-fluoro- phenyl)-acetamide
148
2-(3,5-Difluoro-phenyl)-N- [2-(2,6-dioxo-piperidin-3- yl)-1,3-dioxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]- acetamide
149
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-(4- trifluoromethoxy-phenyl)- acetamide
150
2-(3,5-Bis-trifluoromethyl- phenyl)-N-[2-(2,6-dioxo- piperidin-3-yl)-1,3-dioxo- 2,3-dihydro-1H-isoindol-4- ylmethyl]-acetamide
151
(N-[2-(2,6-Dioxo- piperidin-3-yl)-1,3-dioxo- 2,3-dihydro-1H-isoindol-4- ylmethyl]-2-(4- trifluoromethyl-phenyl)- acetamide
152
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-(3- trifluoromethyl-phenyl)- acetamide
153
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-(3- trifluoromethoxy-phenyl)- acetamide
154
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-(3-fluoro-4- methyl-phenyl)-acetamide
155
2-(3,5-Dimethoxy-phenyl)- N-[2-(2,6-dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-acetamide
156
2-(4-Chloro-phenyl)-N-[2- (2,6-dioxo-piperidin-3-yl)- 1,3-dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]- acetamide
157
2-Benzo[1,3]dioxo-5-yl-N- [2-(2,6-dioxo-piperidin-3- yl)-1,3-dioxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]- acetamide
158
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-pyridinyl-2-yl- acetamide
159
N-[2-(2,6-dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-pyridinyl-3-yl- acetamide
160
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-pyridin-4-yl- acetamide
161
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-naphthalen-1- yl-acetamide
162
2-(4,5-Dimethyl-furan-2- yl)-N-[2-(2,6-dioxo- piperidin-3-yl)-1,3-dioxo- 2,3-dihydro-1H-isoindol-4- ylmethyl]-acetamide
163
2-(2,5-Dimethyl-furan-3- yl)-N-[2-(2,6-dioxo- piperidin-3-yl)-1,3-dioxo- 2,3-dihydro-1H-isoindol-4- ylmethyl]-acetamide
164
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]2-(6-methoxy- benzofuran-3-yl)- acetamide
165
2-{2,5-Dimethyl-1,3- thiazol-4-yl)-N-[2-(2,6- dioxo-piperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]- acetamide
166
N-[2-(2,6-Dioxopiperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-(3-methyl- isoxazol-5-yl)-acetamide
167
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-(1-methyl-1H- indol-3-yl)-acetamide
168
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3-thiophen-2-yl- acetamide
169
N-[2-(2.6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-thiophen-2-yl- acetamide
170
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-3-fluoro-4- trifluoromethyl-benzamide
171
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-fluoro-4- trifluoromethyl-benzamide
172
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-4-fluoro-3- trifluoromethyl-benzamide
173
N-[2-(2,6-Dioxo-piperidin- 3-yl)-1,3-dioxo-2,3- dihydro-1H-isoindol-4- ylmethyl]-2-fluoro-3- trifluoromethyl-benzamide
174
Bnezo[b]thiophene-5- carboxylic acid [2-(2,6- dioxo-piperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-amide
175
4-Methyl-oxazole-5- carboxylic acid [2-(2,6- dioxo-piperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-amide
176
4-Methyl-2-phenyl- thiazole-5-carboxylic acid [2-(2,6-dioxopiperidin-3- yl)-1,3-dioxo-2,3-dihydro- 1H-isoindol-4- ylmethylamide
177
Isoxazole-5-carboxylic acid [2-(2,6-dioxo- piperidin-3-yl)-1,3-dioxo- 2,3-dihydro-1H-isoindol-4- ylmethyl]-amide
178
Thiazole-2-carboxylic acid [2-(2,6-dioxo-piperidin-3- yl)-1,3-dioxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]- amide
179
Benzo[c]isoxazole-3- carboxylic acid [2-(2,6- dioxo-piperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-ylmethyl]-amide.
29 . A compound of formula, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:
180
cyclopropanecarboxylic acid [2-(2,6-dioxo-piperidin-3- yl)-1,3-dioxo-2,3-dihydro- 1H-isoindol-4-ylmethyl]- amide
181
2-amino-N-[2-(3-methyl-2,6- dioxo-piperidin-3-yl)-1,3- dioxo-2,3-dihydro-1H- isoindol-4-yl)-acetamide
182
3-[4-[(Benzofuran-2- ylmethyl)-amino]-1-oxo-1,3- dihydro-isoindol-2-yl}- piperidine-2,6-dione
183
3-{4-[(4,5-Dimethyl-furan-2- ylmethyl)-amino]-1-oxo-1,3- dihydro-isoindol-2-yl}- piperidine-2,6-dione
184
3-{4-[(5-Methyl-furan-2- ylmethyl)-amino]-1-oxo-1,3- dihydro-isoindol-2-yl}- piperidine-2,6-dione.
30 . The compound of formula 29, or a pharmaceutically acceptable salt or solvate thereof, which is a stereomerically pure (R) isomer, a stereomerically pure (S) isomer, or a racemic mixture thereof.
31 . A pharmaceutical composition comprising a compound of claim 1 , 9 , 14 , 18 , 20 , 24 , or 29 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
32 . A method of treating, managing or preventing a disease or disorder which comprises administering to a patient in need of such treatment, management or prevention a therapeutically or prophylactically effective amount of a compound of claim 1 , 9 , 14 , 18 , 20 , 24 , or 29 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein the disease or disorder is cancer, a disorder associated with angiogenesis, pain, macular degeneration or a related syndrome, a skin disease, a pulmonary disorder, an asbestos-related disorder, a parasitic disease, an immunodeficiency disorder, a CNS disorder, CNS injury, atherosclerosis or a related disorder, dysfunctional sleep or a related disorder, hemoglobinopathy or a related disorder, or a TNFα related disorder.
33 . The method of claim 32 , which further comprises administration of one or more additional active agents.
34 . The method of claim 32 , wherein the compound, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, is administered orally or parenterally.
35 . A single unit dosage form comprising a compound of claim 1 , 9 , 14 , 18 , 20 , 24 , or 29 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
36 . The single unit dosage form of claim 35 , which is suitable for oral or parenteral administration.
37 . The single unit dosage form of claim 36 , which is suitable for oral administration.
38 . The single unit dosage form of claim 37 , which is a tablet or a capsule.Cited by (0)
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