IP Library › Granted Patent US 8,110,572
Granted Patent B2
US 8,110,572 · App. 12/174,334 · Granted Feb 7, 2012

Inhibitors of protein kinases

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Quick Facts
Patent No.
US 8,110,572
App. No.
12/174,334
Granted
Feb 7, 2012
Kind
B2
Abstract

Compounds that inhibit Aurora-kinases, compositions containing the compounds and methods of treating diseases using the compounds are disclosed.

Claims (191)

1. A compound having Formula I

or a therapeutically acceptable salt thereof, wherein

X is S, O or NG 1 ;

G 1 is H or is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one, two, three, four or five of independently selected R 6 , OR 6 , NH 2 , NHR 6 , N(R 6 ) 2 , OH or (O);

A 1 is C(O)NHR 1 ;

B 1 , C 1 , and D 1 are H;

R 1 is R 2 ;

R 2 is phenyl;

wherein R 2 is substituted with one or two or three or four or five of independently selected R 10 , OR 10 , SR 10 , S(O)R 10 , SO 2 R 10 , C(O)R 10 , CO(O)R 10 , OC(O)R 10 , OC(O)OR 10 , NH 2 , NHR 10 , N(R 10 ) 2 , NHC(O)R 10 , NR 10 C(O)R 10 , NHS(O) 2 R 10 , NR 10 S(O) 2 R 10 , NHC(O)OR 10 , NR 10 C(O)OR 10 , NHC(O)NH 2 , NHC(O)NHR 10 ,)NHC(O)N(R 10 ) 2 , NR 10 C(O)NHR 10 ,)NR 10 C(O)N(R 10 ) 2 , C(O)NH 2 , C(O)NHR 10 , C(O)N(R 10 ) 2 )C(O)NHOH, C(O)NHOR 10 , C(O)NHSO 2 R 10 , C(O)NR 10 SO 2 R 10 , SO 2 NH 2 , SO 2 NHR 10 ,)SO 2 N(R 10 ) 2 , C(O)H, C(O)OH, C(N)NH 2 , C(N)NHR 10 , C(N)N(R 10 ) 2 , CNOH, CNOCH 3 , OH, (O), CN, N 3 , NO 2 , CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , F, Cl, Br or I;

R 10 is R 11 , R 12 , R 13 or R 14 ;

R 11 is phenyl which is unfused or fused with benzene, heteroarene or R 11A ; R 11A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R 12 is heteroaryl which is unfused or fused with benzene, heteroarene or R 12A ; R 12A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R 13 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R 13A ; R 13A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R 14 is alkyl, alkenyl or alkenyl, each of which is unsubstituted or substituted with one, two, three, four or five of independently selected R 15 , OR 15 , SR 15 , S(O)R 15 , SO 2 R 15 , CO(O)R 15 , OC(O)R 15 , OC(O)OR 15 , NH 2 , NHR 15 , N(R 15 ) 2 , NHC(O)R 15 , NR 15 C(O)R 15 , NHS(O) 2 R 15 , NR 15 S(O) 2 R 15 , NHC(O)OR 15 , NR 15 C(O)OR 15 , NHC(O)NH 2 , NHC(O)NHR 15 , NHC(O)N(R 15 ) 2 , NR 15 C(O)NHR 15 , NR 15 C(O)N(R 15 ) 2 , C(O)NH 2 , C(O)NHR 15 , C(O)N(R 15 ) 2 , C(O)NHOH, C(O)NHOR 15 , C(O)NHSO 2 R 15 , C(O)NR 15 SO 2 R 15 , SO 2 NH 2 , SO 2 NHR 15 , SO 2 N(R 15 ) 2 , C(O)OH, C(N)NH 2 , C(N)NHR 15 , C(N)N(R 15 ) 2 , CNOH, CNOCH 3 , OH, (O), CN, N 3 , NO 2 , CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , F, Cl, Br or I;

R 15 is R 16 , R 17 , R 18 or R 19 ;

R 16 is phenyl which is unfused or fused with benzene, heteroarene or R 16A ; R 16A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R 17 is heteroaryl which is unfused or fused with benzene, heteroarene or R 17A ; R 17A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R 18 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R 18A ; R 18A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;

R 19 is alkyl, alkenyl or alkenyl, each of which is unsubstituted or substituted with R 20 ;

R 20 is phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl;

wherein the moieties represented by R 11 , R 12 ,R 13 , R 16 ,R 17 , R 18 and R 20 are independently unsubstituted or substituted with one or two or three of independently selected R 21 , OR 21 , SR 21 , S(O)R 21 , SO 2 R 21 , C(O)R 21 , CO(O)R 21 , OC(O)R 21 , OC(O)OR 21 , NH 2 , NHR 21 , N(R 21 ) 2 , NHC(O)R 21 , NR 21 C(O)R 21 , NHS(O) 2 R 21 , NR 21 S(O) 2 R 21 , NHC(O)OR 21 , NR 21 C(O)OR 21 , NHC(O)NH 2 , NHC(O)NHR 21 , NHC(O)N(R 21 ) 2 , NR 21 C(O)NHR 21 , NR 21 C(O)N(R 21 ) 2 , C(O)NH 2 , C(O)NHR 21 , C(O)N(R 21 ) 2 , C(O)NHOH, C(O)NHOR 21 , C(O)NHSO 2 R 21 , C(O)NR 21 SO 2 R 21 , SO 2 NH 2 , SO 2 NHR 21 , SO 2 N(R 21 ) 2 , C(O)H, C(O)OH, C(N)NH 2 , C(N)NHR 21 , C(N)N(R 21 ) 2 , CNOH, CNOCH 3 , OH, (O), CN, N 3 , NO 2 , CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , F, Cl, Br or I;

R 21 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R 22 , F, Cl, Br, I, OH, C(O)OH, NO 2 or NH 2 ; and

R 22 K is phenyl, heteroaryl, cycloalkyl, cycloalkenyl or heterocycloalkyl.

2. A compound of claim 1 which is

3-amino-N-(3-(((((3-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((2-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((anilinocarbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((4-(trifluoromethyl)phenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((4-methylphenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((2-fluoro-5-methylphenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((3-methoxyphenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((4-methoxyphenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((3,4-difluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((3,5-difluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((4-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-((((cyclopentylamino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-((((cyclohexylamino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-((((thien-2-ylamino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-((((thien-3-ylamino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((3-methylphenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((3,5-dimethylphenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((3-chlorophenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((2-(trifluoromethyl)phenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((3-methylbenzoyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-((benzoylamino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((phenylacetyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((3-fluorophenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((andinocarbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-(((thien-3-ylamino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-(4-((((4-methylphenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((3-methylphenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((2,4-difluorophenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((3,5-difluorophenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((3,4-difluorophenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((anilinocarbonyl)amino)phenyl)-7-methyl-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-(benzoylamino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((3-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisothiazole-4-carboxamide,

3-amino-N-(3-(((anilinocarbonyl)amino)methyl)phenyl)-1,2-benzisothiazole-4-carboxamide,

3-amino-N-(3-(((((4-(trifluoromethyl)phenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisothiazole-4-carboxamide,

3-amino-N-(4-((((3-fluorophenyl)amino)carbonyl)amino)phenyl)-1,2-benzisothiazole-4-carboxamide,

3-amino-N-(4-((anilinocarbonyl)amino)phenyl)-1,2-benzisothiazole-4-carboxamide,

3-amino-N-(4-((((3-(2-hydroxyethyl)phenyl)amino)carbonyl)amino)phenyl)-1,2-benzisothiazole-4-carboxamide,

3-amino-N-(4-((((3,4-dichlorophenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((3-methoxyphenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((4-bromophenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((4-fluorophenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((4-chlorophenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((4-methoxyphenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-(((benzylamino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((3-cyanophenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((3-(methylthio)phenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((4-(methylthio)phenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(4-((((3-chloro-4-fluorophenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((4-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole -4-carboxamide,

3-amino-N-(3-(((((3-chlorophenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(3-(((((4-(trifluoromethoxy)phenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(3-(((((3-methylphenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(3-(((((4-(trifluoromethyl)phenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(3-(((((3-(trifluoromethyl)phenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(3-(((((3-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(4-((anilinocarbonyl)amino)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(4-((((3-fluorophenyl)amino)carbonyl)amino)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(3-(1-((((3-fluorophenyl)amino)carbonyl)amino)ethyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((anilinocarbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(3-(((((4-chlorophenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(3-(((((4-chloro-2-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(3-(((((3-fluoro-4-methylphenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(3-(((((2-fluoro-5-methylphenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(3-(((((2-fluoro-5-(trifluoromethyl)phenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(3-(((((3,5-difluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(3-(((((3,4-difluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide,

3-amino-N-(3-(((((3-fluoro-4-methylphenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((4-chlorophenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((3-bromophenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide,

3-amino-N-(3-(((((4-chloro-2-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(3-((((pyridin-3-ylamino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(4-((((3-fluorophenyl)amino)carbonyl)amino)-3-methylphenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(4-((((3-fluorophenyl)amino)carbonyl)amino)-3-methylphenyl)-7-methoxy-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(4-((((2-fluorophenyl)amino)carbonyl)amino)-3-methylphenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(4-((((2-fluorophenyl)amino)carbonyl)amino)-3-methylphenyl)-7-methoxy-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(3-methyl-4-((((4-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-7-methoxy-N-(3-methyl-4-((((4-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(3-(((((4-chlorophenyl)amino)carbonyl)amino)methyl)-4-fluorophenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(4-fluoro-3-(((((4-methylphenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(3-(((((4-(difluoromethoxy)phenyl)amino)carbonyl)amino)methyl)-4-fluorophenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(4-fluoro-3-(((((2-fluoro-5-methylphenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(3-(((((4-chloro-2-fluorophenyl)amino)carbonyl)amino)methyl)-4-fluorophenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(4-fluoro-3-(((((4-(trifluoromethyl)phenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(3-(((anilinocarbonyl)amino)methyl)-4-fluorophenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(4-fluoro-3-(((((4-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(4-fluoro-3-(((((3-(trifluoromethyl)phenyl)amino)carbonyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(3-(((((2,5-difluorophenyl)amino)carbonyl)amino)methyl)-4-fluorophenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(3-(((4-fluorobenzoyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(3(((3-fluorobenzoyl)amino)methyl)phenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(3-(((anilinocarbonyl)amino)methyl)-4-methylphenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(3-(aminomethyl)phenyl)-1,2-benzisoxazole-4-carboxamide;

3-amino-N-(3-(((((3-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1-methyl-1H-indazole-4-carboxamide;

3-amino-N-(3-(((((4-chloro-2-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1-methyl-1H-indazole-4-carboxamide;

3-amino-N-(3-(((((4-chlorophenyl)amino)carbonyl)amino)methyl)phenyl)-1-methyl-1H-indazole-4-carboxamide ;

3-amino-N-(3-(((((3-fluoro-4-methylphenyl)amino)carbonyl)amino)methyl)phenyl)-1-methyl-1H-indazole-4-carboxamide;

3-amino-N-(3-(((((3-chloro-4-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1-methyl-1H-indazole-4-carboxamide;

3-amino-1-methyl-N-(3-(((((3-(trifluoromethyl)phenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide;

3-amino-1-methyl-N-(3-(((((4-(trifluoromethyl)phenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide;

3-amino-N-(3-(((((4-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1-methyl-1H-indazole-4-carboxamide;

3-amino-N-(3-(((((2-chlorophenyl)amino)carbonyl)amino)methyl)phenyl)-1-methyl-1H-indazole-4-carboxamide;

3-amino-N-(3-(((((4-methylphenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide;

3-amino-N-(3-(((((2-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide;

3-amino-N-(3-(((((4-isopropylphenyl)amino)carbonyl)amino)methyl)phenyl)-1H-indazole-4-carboxamide;

or a therapeutically acceptable salt thereof.

3. A composition comprising an excipient and a therapeutically effective amount of a compound having Formula I of claim 1 .

4. The compound of claim 1 , wherein X is S.

5. The compound of claim 4 , wherein R 2 is substituted with NHC(O)NHR 10 ;

R 10 is R 11 or R 12 ;

R 11 is phenyl;

R 12 is heteroaryl;

wherein the moieties represented by R 11 and R 12 are independently unsubstituted or substituted with one or two or three of independently selected R 21 , OR 21 ; SR 21 , CN, CF 3 , OCF 3 , F, Cl, Br or I; and

R 21 is alkyl which is unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, or OH.

6. The compound of claim 4 , wherein R 2 is substituted with R 10 ,

R 10 is R 14 ;

R 14 is alkyl which is substituted with NHC(O)R 15 or NHC(O)NHR 15 ;

R 15 is R 16 ;

R 16 is phenyl;

wherein R 16 is unsubstituted or substituted with one or two or three of independently selected R 21 , OR 21 , SR 21 , CN, CF 3 , OCF 3 , F, Cl, Br or I; and

R 21 is alkyl which is unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, or OH.

7. The compound of claim 4 , wherein R 2 is substituted with NHC(O)R 10 ;

R 10 is R 11 or R 12 ;

R 11 is phenyl;

R 12 is heteroaryl;

wherein the moieties represented by R 11 and R 12 are independently unsubstituted or substituted with one or two or three of independently selected R 21 , OR 21 , SR 21 , CN, CF 3 , OCF 3 , F, Cl, Br or I; and

R 21 is alkyl which is unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, or OH.

8. The compound of claim 1 , wherein X is O.

9. The compound of claim 8 , wherein R 2 is substituted with NHC(O)NHR 10 ;

R 10 is R 11 or R 12 ;

R 11 is phenyl;

R 12 is heteroaryl;

wherein the moieties represented by R 11 and R 12 are independently unsubstituted or substituted with one or two or three of independently selected R 21 , OR 21 , SR 21 , CN, CF 3 , OCF 3 , F, Cl, Br or I; and

R 21 is alkyl which is unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, or OH.

10. The compound of claim 8 , wherein R 2 is substituted with R 10 ,

R 10 is R 14 ;

R 14 is alkyl which is substituted with NHC(O)R 15 or NHC(O)NHR 15 ;

R 15 is R 16 ;

R 16 is phenyl;

wherein R 16 is unsubstituted or substituted with one or two or three of independently selected R 21 , OR 21 , SR 21 , CN, CF 3 , OCF 3 , F, Cl, Br or I; and

R 21 is alkyl which is unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, or OH.

11. The compound of claim 8 , wherein R 2 is substituted with NHC(O)R 10 ;

R 10 is R 11 or R 12 ;

R 11 is phenyl;

R 12 is heteroaryl;

wherein the moieties represented by R 11 and R 12 are independently unsubstituted or substituted with one or two or three of independently selected R 21 , OR 21 , SR 21 , CN, CF 3 , OCF 3 , F, Cl, Br or I; and

R 21 is alkyl which is unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, or OH.

12. The compound of claim 1 , wherein X is NG 1 , and G 1 is H or alkyl.

13. The compound of claim 12 , wherein R 2 is substituted with NHC(O)NHR 10 ;

R 10 is R 11 or R 12 ;

R 11 is phenyl;

R 12 is heteroaryl;

wherein the moieties represented by R 11 and R 12 are independently unsubstituted or substituted with one or two or three of independently selected R 21 , OR 21 , SR 21 , CN, CF 3 , OCF 3 , F, Cl, Br or I; and

R 21 is alkyl which is unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, or OH.

14. The compound of claim 12 , wherein R 2 is substituted with R 10 ,

R 10 is R 14 ;

R 14 is alkyl which is substituted with NHC(O)R 15 or NHC(O)NHR 15 ;

R 15 is R 16 ;

R 16 is phenyl;

wherein R 16 is unsubstituted or substituted with one or two or three of independently selected R 21 , OR 21 , SR 21 , CN, CF 3 , OCF 3 , F, Cl, Br or I; and

R 21 is alkyl which is unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, or OH.

15. The compound of claim 12 , wherein R 2 is substituted with NHC(O)R 10 ;

R 10 is R 11 or R 12 ;

R 11 is phenyl;

R 12 is heteroaryl;

wherein the moieties represented by R 11 and R 12 are independently unsubstituted or substituted with one or two or three of independently selected R 21 , OR 21 , SR 21 , CN, CF 3 , OCF 3 , F, Cl, Br or I; and

R 21 is alkyl which is unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, or OH.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 17, 2013
From: ABBOTT LABORATORIES
To: ABBVIE INC.
Reel/Frame 030237/0588 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 27, 2008
From: DAI, YUJIA; JI, ZHIQIN; MICHAELIDES, MICHAEL R.
To: ABBOTT LABORATORIES
Reel/Frame 021739/0013 →