IP Library › Granted Patent US 9,206,166

Granted Patent B2

US 9,206,166 · App. 14/071,953 · Granted Dec 8, 2015

Certain protein kinase inhibitors

Inventors: Weibo Wang (Moraga, CA); Meiyu Geng (Shanghai, CN); Jian Ding (Shanghai, CN); Xingdong Zhao (Moraga, CA); Jing Ai (Shanghai, CN); Qiang Tian (Chongqing, CN); Xia Peng (Shanghai, CN); Weipeng Zhang (Chongqing, CN); Hongbin Liu (Chongqing, CN); Haohan Tan (Chongqing, CN); Ling Chen (Chongqing, CN)

Assignees: Shanghai Institute of Materia Medica Academy of Sciences; Shanghai Fochon Pharmaceutical Co., LTD

C07D405/12 A61K31/506 A61K31/519 A61K31/5377 A61K45/06 C07D405/14 C07D487/04

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Quick Facts

Patent No.: US 9,206,166
App. No.: 14/071,953
Granted: Dec 8, 2015
Kind: B2

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Abstract

Disclosed herein are protein kinase inhibitors, more particularly novel pyrimidine derivatives and pharmaceutical compositions thereof, and method of use thereof.

Claims (281)

1. At least one compound of formula (I):

or at least one pharmaceutically acceptable salt thereof, wherein:

each R 1 is independently:

hydrogen,

halogen,

hydroxyl,

C 1-10 alkyl,

C 3-10 cycloalkyl,

C 3-10 cycloalkyl-alkyl,

heterocyclyl,

heterocyclylalkyl

aryl,

arylalkyl,

heteroaryl, or

heteroarylalkyl,

wherein alkyl, cycloalkyl, and heterocyclyl are each unsubstituted or substituted with at least one substituent independently selected from R 6a , and wherein aryl and heteroaryl are each unsubstituted or substituted with at least one substituent independently selected from R 6b ;

each R 2 is independently:

C 1-10 alkyl or piperidinyl,

wherein alkyl and piperidinyl are each unsubstituted or substituted with at least one substituent independently selected from R 6a ;

each R 3 is independently:

hydrogen,

halogen,

—CN,

—NR 7 R 8 , or

C 1-10 alkyl;

wherein alkyl is unsubstituted or substituted with at least one substituent independently selected from R 6a ;

each R 4 is independently:

hydrogen,

halogen,

—CN,

C 1-10 alkyl,

C 2-10 alkenyl,

C 2-10 alkynyl, or

C 3-10 cycloalkyl;

wherein C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, and C 3-10 cycloalkyl are each unsubstituted or substituted with at least one substituent independently selected from R 6a ;

or R 3 and R 4 together with the carbon atoms to which they are attached form a 5-6 membered ring containing 0, 1, 2 or 3 heteroatoms independently selected from the group consisting of oxygen, sulfur and nitrogen, and optionally substituted with 1-2 R 6b groups;

each R 5 is independently:

C 1-10 alkyl,

C 2-10 alkenyl,

C 2-10 alkynyl,

C 3-10 cycloalkyl,

—OR 8 ,

—NR 7 S(O) r R 8 ,

—NO 2 ,

halogen,

—S(O) r R 7 ,

—SR 8 ,

—S(O) 2 OR 7 ,

—OS(O) 2 R 8 ,

—S(O) r NR 7 R 8 ,

—NR 7 R 8 ,

—O(CR 9 R 10 ) t NR 7 R 8 ,

—C(O)R 7 ,

—CO 2 R 8 ,

—CO 2 (CR 9 R 10 ) t CONR 7 R 8 ,

—OC(O)R 7 ,

—CN,

—C(O)NR 7 R 8 ,

—NR 7 C(O)R 8 ,

—OC(O)NR 7 R 8 ,

—NR 7 C(O)OR 8 ,

—NR 7 C(O)NR 7 R 8 ,

—CR 7 (N—OR 8 ),

—CHF 2 ,

—CF 3 ,

—OCHF 2 , or

—OCF 3 ;

wherein C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, and C 3-10 cycloalkyl are each unsubstituted or substituted with at least one substituent independently selected from R 6a ;

each R 6a is independently:

C 1-10 alkyl,

C 2-10 alkenyl,

C 2-10 alkynyl,

C 3-10 cycloalkyl,

—OR 8 ,

—NR 7 S(O) r R 8 ,

—NO 2 ,

halogen,

—S(O) r R 7 ,

—SR 8 ,

—S(O) 2 OR 7 ,

—OS(O) 2 R 8 ,

—S(O) r NR 7 R 8 ,

—NR 7 R 8 ,

—(CR 9 R 10 ) t OR 8 ,

—(CR 9 R 10 ) t NR 7 R 8 ,

—(CR 9 R 10 ) t SR 8 ,

—(CR 9 R 10 ) t S(O) r R 8 ,

—(CR 9 R 10 ) t CO 2 R 8 ,

—(CR 9 R 10 ) t CONR 7 R 8 ,

—(CR 9 R 10 ) t NR 7 CO 2 R 8 ,

—(CR 9 R 10 ) t OCONR 7 R 8 ,

—(CR 9 R 10 ) t NR 7 CONR 7 R 8 ,

—(CR 9 R 10 ) t NR 7 SO 2 NR 7 R 8 ,

—O(CR 9 R 10 ) t NR 7 R 8 ,

—C(O)R 7 ,

—C(O)(CR 9 R 10 ) t OR 8 ,

—C(O)(CR 9 R 10 ) t NR 7 R 8 ,

—C(O)(CR 9 R 10 ) t SR 8 ,

—C(O)(CR 9 R 10 ) t S(O) r R 8 ,

—CO 2 R 8 ,

—CO 2 (CR 9 R 10 ) t CONR 7 R 8 ,

—OC(O)R 7 ,

—CN,

—C(O)NR 7 R 8 ,

—NR 7 C(O)R 8 ,

—OC(O)NR 7 R 8 ,

—NR 7 C(O)OR 8 ,

—NR 7 C(O)NR 7 R 8 ,

—CR 7 (N—OR 8 ),

—CHF 2 ,

—CF 3 ,

—OCHF 2 , or

—OCF 3 ;

each R 6b is independently:

R 6a ,

aryl,

aryl-C 1-4 alkyl,

heteroaryl, or

heteroaryl-C 1-4 alkyl;

each R 7 and each Ware independently:

hydrogen,

C 1-10 alkyl,

C 2-10 alkenyl,

C 2-10 alkynyl,

C 3-10 cycloalkyl,

cycloalkyl-C 1-10 alkyl;

heterocyclyl,

heterocyclyl-C 1-10 alkyl,

aryl,

heteroaryl,

aryl-C 1-10 alkyl, or

heteroaryl-C 1-10 alkyl;

wherein alkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclyl are each unsubstituted or substituted with at least one substituent independently selected from R 6a , and aryl and heteroaryl are each unsubstituted or substituted with at least one substituent independently selected from R 6b ; or

R 7 and R 8 together with the atom(s) to which they are attached form a heterocyclic ring of 4 to 7 members containing 0, 1, or 2 additional heteroatoms independently selected from the group consisting of oxygen, sulfur and NR 11 , each R 7 and R 8 may be unsubstituted or substituted on a carbon or nitrogen atom with at least one substituent independently selected from R 12 ;

each R 9 and each R 10 are independently:

hydrogen,

C 1-10 alkyl,

C 2-10 alkenyl,

C 2-10 alkynyl,

C 3-10 cycloalkyl,

cycloalkyl-C 1-10 alkyl,

heterocyclyl,

heterocyclyl-C 1-10 alkyl,

aryl,

heteroaryl,

aryl-C 1-10 alkyl, or

heteroaryl-C 1-10 alkyl; or

R 9 and R 19 together with the carbon to which they are attached form a ring of 3 to 7 members containing 0, 1, or 2 heteroatoms independently selected from the group consisting of oxygen, sulfur and nitrogen;

each R 11 is independently:

hydrogen,

C 1-10 alkyl,

C 3-10 cycloalkyl,

C 3-10 cycloalkyl-C 1-4 alkyl,

heterocyclyl,

heterocyclyl-C 1-4 alkyl,

aryl,

aryl-C 1-4 alkyl,

heteroaryl,

heteroaryl-C 1-4 alkyl,

—S(O) r R 7 ,

—C(O)R 7 ,

—CO 2 R 7 ,

—CO 2 (CR 9 R 10 ) t CONR 7 R 8 , or

—C(O)NR 7 R 8 ;

each R 12 is independently:

halogen,

C 1-10 alkyl,

C 3-10 cycloalkyl,

C 3-10 cycloalkylalkyl,

heterocyclyl,

heterocyclylalkyl,

aryl,

aryl-C 1-4 alkyl,

heteroaryl,

heteroaryl-C 1-4 alkyl,

—OR 7 ,

—NR 7 S(O) r R 8 ,

—S(O) r R 7 ,

—SR 7 ,

—S(O) 2 OR 7 ,

—OS(O) 2 R 7 ,

—S(O) r NR 7 R 8 ,

—NR 7 R 8 ,

—O(CR 9 R 10 ) t NR 7 R 8 ,

—C(O)R 7 ,

—CO 2 R 8 ,

—CO 2 (CR 9 R 10 ) t CONR 7 R 8 ,

—OC(O)R 7 ,

—CN,

—C(O)NR 7 R 8 ,

—NR 7 C(O)R 8 ,

—OC(O)NR 7 R 8 ,

—NR 7 C(O)OR 8 ,

—NR 7 C(O)NR 7 R 8 ,

—CHF 2 ,

—CF 3 ,

—OCHF 2 , or

—OCF 3 ;

each m is independently 0, 1, or 2;

each n is independently 1, 2, or 3;

each p is independently 2;

each q is independently 0, 1, 2, or 3;

each r is independently 1 or 2;

each t is independently 1, 2, or 3.

2. At least one compound of claim 1 or at least one pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen or C 1-10 alkyl, wherein alkyl is unsubstituted or substituted with at least one substituent independently selected from the group consisting of hydroxyl and C 1-10 alkoxy.

3. At least one compound of claim 1 or at least one pharmaceutically acceptable salt thereof, wherein m is 0.

4. At least one compound of claim 1 or at least one pharmaceutically acceptable salt thereof, wherein R 1 is C 1-10 alkyl, wherein alkyl is unsubstituted or substituted with at least one substituent independently selected from the group consisting of hydroxyl and C 1-10 alkoxy.

5. At least one compound of claim 1 or at least one pharmaceutically acceptable salt thereof, wherein m is 1.

6. At least one compound of claim 5 or at least one pharmaceutically acceptable salt thereof, wherein R 1 is methyl, hydroxymethyl, or methoxymethyl.

7. At least one compound of claim 1 or at least one pharmaceutically acceptable salt thereof, wherein each R 2 is independently selected from the group consisting of methyl and 4-piperidinyl.

8. At least one compound of claim 7 or at least one pharmaceutically acceptable salt thereof, wherein each R 2 is independently methyl or 4-piperidinyl, wherein 4-piperidinyl is unsubstituted or substituted with at least one substituent independently selected from R 6a , wherein R 6a is independently selected from the group consisting of C 1-10 alkyl, —C(O)R 7 , —S(O) r R 7 , —(CR 9 R 10 ) t CO 2 R 8 , —C(O)(CR 9 R 10 ) t OR 8 , —C(O)(CR 9 R 10 ) t NR 7 R 8 , —(CR 9 R 10 ) t OR 8 , —(CR 9 R 10 ) t CONR 7 R 8 , —(CR 9 R 10 ) t S(O) r R 8 , —CO 2 R 8 , —C(O)NR 7 R 8 , and —(CR 9 R 10 ) t OR 8 .

9. At least one compound of claim 1 or at least one pharmaceutically acceptable salt thereof, wherein R 3 is hydrogen.

10. At least one compound of claim 1 or at least one pharmaceutically acceptable salt thereof, wherein R 4 is independently hydrogen, C 1-10 alkyl, or halogen.

11. At least one compound of claim 10 or at least one pharmaceutically acceptable salt thereof, wherein R 4 is independently selected from halogen.

12. At least one compound of claim 11 or at least one pharmaceutically acceptable salt thereof, wherein R 4 is chlorine.

13. At least one compound of claim 1 or at least one pharmaceutically acceptable salt thereof, wherein R 3 and R 4 together with the carbon atoms to which they are attached form a 5 membered ring containing 2 nitrogen atoms, wherein the 5-membered ring is optionally substituted with 1-2 C 1-10 alkyl.

14. At least one compound of claim 1 or at least one pharmaceutically acceptable salt thereof, wherein R 3 and R 4 together with the carbon atoms to which they are attached form pyrazolo.

15. At least one compound of claim 1 or at least one pharmaceutically acceptable salt thereof, wherein R 5 is —S(O) r R 7 .

16. At least one compound of claim 15 or at least one pharmaceutically acceptable salt thereof, wherein R 5 is —S(O) 2 R 7 , wherein R 7 is C 1-10 alkyl, and q is 1.

17. At least one compound of claim 16 or at least one pharmaceutically acceptable salt thereof, wherein R 5 is —S(O) 2 R 7 , wherein R 7 is isopropyl.

18. At least one compound of claim 1 or at least one pharmaceutically acceptable salt thereof, wherein n is 1.

19. At least one compound selected from the group consisting of:

N-4-(2-(isopropylsulfonyl)phenyl)-3-methyl-N-6-(5-methyl-4-(piperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;

N-4-(2-(isopropylsulfonyl)phenyl)-3-methyl-N-6-(5-methyl-4-(1-methylpiperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;

(R)—N-6-(2,5-dimethyl-4-(piperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;

(R)—N-6-(2,5-dimethyl-4-(1-methylpiperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;

(S)—N-6-(2,5-dimethyl-4-(piperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;

(S)—N-6-(2,5-dimethyl-4-(1-methylpiperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;

(7-(4-(2-(isopropylsulfonyl)phenylamino)-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)-5-methyl-4-(piperidin-4-yl)-2,3-dihydrobenzofuran-2-yl)methanol;

N-4-(2-(isopropylsulfonyl)phenyl)-N-6-(2-(methoxymethyl)-5-methyl-4-(piperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;

(R)-5-chloro-N-2-(2,5-dimethyl-4-(piperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;

(R)-5-chloro-N-2-(2,5-dimethyl-4-(1-methylpiperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;

(S)-5-chloro-N-2-(2,5-dimethyl-4-(piperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;

(S)-5-chloro-N-2-(2,5-dimethyl-4-(1-methylpiperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;

5-chloro-N-4-(2-(isopropylsulfonyl)phenyl)-N-2-(5-methyl-4-(piperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)pyrimidine-2,4-diamine;

5-chloro-N-4-(2-(isopropylsulfonyl)phenyl)-N-2-(5-methyl-4-(1-methylpiperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)pyrimidine-2,4-diamine;

(S)-1-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)ethanone;

(R)-1-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)ethanone;

(S)-5-chloro-N-2-(2,5-dimethyl-4-(1-(methylsulfonyl)piperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;

(R)-5-chloro-N-2-(2,5-dimethyl-4-(1-(methylsulfonyl)piperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;

(S)-2-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)acetic acid;

(R)-2-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)acetic acid;

(S)-2-amino-1-(4-((S)-7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)propan-1-one;

(S)-2-amino-1-(4-((R)-7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)propan-1-one;

(R)-1-(4-((R)-7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)propan-2-ol;

(S)-1-(4-((R)-7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)propan-2-ol;

(S)-2-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)acetamide;

(R)-2-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)acetamide;

(S)-2-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)-N,N-dimethylacetamide;

(R)-2-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)-N,N-dimethylacetamide;

(S)-5-chloro-N-2-(2,5-dimethyl-4-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;

(R)-5-chloro-N-2-(2,5-dimethyl-4-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;

(S)-5-chloro-N-4-(2-(isopropylsulfonyl)phenyl)-N-2-(4-(1-(2-methoxyethyl)piperidin-4-yl)-2,5-dimethyl-2,3-dihydrobenzofuran-7-yl)pyrimidine-2,4-diamine;

(R)-5-chloro-N-4-(2-(isopropylsulfonyl)phenyl)-N-2-(4-(1-(2-methoxyethyl)piperidin-4-yl)-2,5-dimethyl-2,3-dihydrobenzofuran-7-yl)pyrimidine-2,4-diamine;

(R)-2-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)ethanol;

(S)-2-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)ethanol;

(R)-1-(4-((S)-7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)propan-2-ol;

(S)-1-(4-((S)-7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)propan-2-ol;

(R)-1-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)-2-hydroxyethanone;

(S)-1-(4-((R)-7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)-2-hydroxypropan-1-one;

(R)-1-(4-((R)-7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)-2-hydroxypropan-1-one;

(S)-methyl 4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidine-1-carboxylate;

(S)-ethyl 2-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)acetate;

(S)-2-amino-1-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)ethanone;

(S)-4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidine-1-carboxamide;

(S)-1-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)-2-(methylamino)ethanone;

(S)-1-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)-2-(dimethylamino)ethanone;

(S)-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)(piperazin-1-yl)methanone;

(S)-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)(4-methylpiperazin-1-yl)methanone;

(S)-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)(morpholino)methanone;

(R)-1-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)propan-1-one;

(R)-1-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)-2-methylpropan-1-one;

(R)-(4-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)(cyclopropyl)methanone;

(R)-5-chloro-N-2-(4-(1-(ethylsulfonyl)piperidin-4-yl)-2,5-dimethyl-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;

(R)-5-chloro-N-4-(2-(isopropylsulfonyl)phenyl)-N-2-(4-(1-(isopropylsulfonyl)piperidin-4-yl)-2,5-dimethyl-2,3-dihydrobenzofuran-7-yl)pyrimidine-2,4-diamine;

(R)-5-chloro-N-2-(4-(1-(cyclopropylsulfonyl)piperidin-4-yl)-2,5-dimethyl-2,3-dihydrobenzofuran-7-yl)-N-4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;

(R)-1-(4-((S)-7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)-2-methoxypropan-1-one;

(R)-1-(4-((R)-7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)-2-methoxypropan-1-one;

(S)-1-(4-((R)-7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)-2-methoxypropan-1-one;

(S)-1-(4-((S)-7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-2,5-dimethyl-2,3-dihydrobenzofuran-4-yl)piperidin-1-yl)-2-methoxypropan-1-one; and pharmaceutically acceptable salts thereof.

20. A pharmaceutical composition, comprising at least one compound of claim 1 , or at least one pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 9, 2014

From: WANG, WEIBO; GENG, MEIYU; DING, JIAN; ZHAO, XINGDONG; AL, JING; TIAN, QIANG; PENG, XIA; ZHANG, WEIPENG; LIU, HONGBIN; TAN, HAOHAN; CHEN, LING

To: SHANGHAI FOCHON PHARMACEUTICAL CO. LTD.; SHANGHAI INSTITUTE OF MATERIA MEDICA CHINESE ACADEMYOF SCIENCES

Reel/Frame 031928/0862 →

Continuity (2)

Provisional Application 61723099 · Nov 6, 2012

Related Publication 20140128387A1 · May 8, 2014