IP Library › Granted Patent US 8,148,391

Granted Patent B2

US 8,148,391 · App. 12/162,851 · Granted Apr 3, 2012

Fused bicyclic derivatives of 2,4-diaminopyrimidine as ALK and c-Met inhibitors

Assignee: Cephalon, Inc.

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Patent No.: US 8,148,391
App. No.: 12/162,851
Granted: Apr 3, 2012
Kind: B2

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Abstract

The present invention provides a compound of formula I or II or a pharmaceutically acceptable salt form thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , A 1 , A 2 , A 3 , A 4 , and A 5 , are as defined herein. The compounds of formula I or II have ALK and/or c-Met inhibitory activity, and may be used to treat proliferative disorders.

Claims (258)

1. A compound of formula I or II

or a pharmaceutically acceptable salt form thereof,

wherein

R 1 is H, halogen, —NO 2 , —OR 10 , —C(═O)R 10 , —C(═O)OR 10 , —C(═O)NR 12 R 13 , —NR 10 R 11 , C 1-6 -alkyl, —C 1-6 -alkyl-OR 10 , —C 1-6 -alkyl-NR 12 R 13 , C 1-6 -haloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 6-15 -aryl, 5-15 membered heteroaryl, C 3-10 cycloalkyl, 3-15 membered heterocycloalkyl, pseudohalogen, —S(═O) n R 10 , —S(═O) 2 NR 12 R 13 , —OCH 2 F, —OCHF 2 , —OCF 3 , —NHOH, —OC(═O)R 10 , —OC(═O)NR 12 R 13 , —NR 10 C(═O)R 11 , —NR 10 C(═O)OR 11 , —NR 10 S(═O) 2 R 11 , —NR 10 C(═O)NR 12 R 13 , —NR 10 S(═O) 2 NR 12 R 13 , or —SCF 3 ;

R 2 is a group chosen from C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 6-15 -aryl, C 3-10 -cycloalkyl, 3-15 membered heterocycloalkyl, and 5-15 membered heteroaryl, wherein the R 2 group is optionally substituted by one or more members independently chosen from halogen, —NO 2 , —OR 20 , ═O, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NR 20 R 21 , C 1-6 -alkyl-(R 25 ) x , C 6-15 -aryl-(R 25 ) x , 5-15 membered heteroaryl-(R 25 ) x , C 3-10 cycloalkyl-(R 25 ) x , 3-15 membered heterocycloalkyl-(R 25 ) x , pseudohalogen, —S(═O) n R 20 , —S(═O) 2 NR 22 R 23 , —OCH 2 F, —OCHF 2 , —OCF 3 , —NHOH, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —NR 20 C(═O)R 21 , —NR 20 C(═O)OR 21 , —NR 20 S(═O) 2 R 21 , —NR 20 C(═O)NR 22 R 23 , —NR 20 S(═O) 2 NR 22 R 23 , and —SCF 3 ;

R 3 , R 4 , and R 5 are independently chosen from H, halogen, —NO 2 , —OR 30 , —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 30 R 31 , C 1-6 -alkyl-(R 35 ) x , C 6-15 -aryl-(R 35 ) x , 5-15 membered heteroaryl-(R 35 ) x , C 3-10 cycloalkyl-(R 35 ) x , 3-15 membered heterocycloalkyl-(R 35 ) x , pseudohalogen, —S(═O)R 30 , —S(═O) 2 NR 32 R 33 , —OCH 2 F, —OCHF 2 , —OCF 3 , —NHOH, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —NR 30 C(═O)R 31 , —NR 30 C(═O)OR 31 , —NR 30 S(═O) 2 R 31 , —NR 30 C(═O)NR 32 R 33 , —NR 30 S(═O) 2 NR 32 R 33 , and —SCF 3 ;

A 1 , A 2 , A 3 , A 4 , and A 5 are each independently —CZ 1 Z 2 —, wherein:

(a) when any two of Z 1 and Z 2 are located on adjacent atoms, they may form a bond between the atoms,

(b) any of Z 1 and Z 2 may be independently chosen from H, halogen, —NO 2 , —OR 40 , —C(═O)R 40 , —C(═O)OR 40 , —C(═O)NR 42 R 43 , —NR 40 R 41 , C 1-6 -alkyl-(R 45 ) x , C 6-15 -aryl-(R 45 ) x , 5-15 membered heteroaryl-(R 45 ) x , C 3-10 cycloalkyl-(R 45 ) x , 3-15 membered heterocycloalkyl-(R 45 ) x , C 2-6 -alkenyl-(R 45 ) x , C 2-6 -alkynyl-(R 45 ) x , pseudohalogen, —S(═O) n R 40 , —S(═O) 2 NR 42 R 43 , —OCH 2 F, —OCHF 2 , —OCF 3 , —NHOH, —OC(═O)R 40 , —OC(═O)NR 42 R 43 , —NR 40 C(═O)R 41 , —NR 40 C(═O)OR 41 , —NR 40 S(═O) 2 R 41 , —NR 40 C(═O)NR 42 R 43 , —NR 40 S(═O) 2 NR 42 R 43 , and —SCF 3 , and

wherein A 6 , A 7 , A 8 , A 9 , and A 10 are independently chosen from a bond, —CZ 4 Z 5 —, —C(═O)—, —NZ 6 —, —S—, —S(═O)—, —S(═O) 2 —, or —O—, wherein:

(i) when any two of Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , and Z 6 are located on adjacent atoms, they may form a bond between the atoms, and

(ii) any of Z 4 , Z 5 , and Z 6 may be independently chosen from H, halogen, —NO 2 , —OR 50 , —C(═O)R 50 , —C(═O)OR 50 , —C(═O)NR 52 R 53 , —NR 50 R 51 , C 1-6 -alkyl-(R 55 ) x , C 6-15 -aryl-(R 55 ) x , 5-15 membered heteroaryl-(R 55 ) x , C 3-10 cycloalkyl-(R 55 ) x , 3-15 membered heterocycloalkyl-(R 55 ) x , pseudohalogen, —S(═O) n R 50 , —S(═O) 2 NR 52 R 53 , —OCH 2 F, —OCHF 2 , —OCF 3 , —NHOH, —OC(═O)R 50 , —OC(═O)NR 52 R 53 , —NR 50 C(═O)R 51 , —NR 50 C(═O)OR 51 , —NR 50 S(═O) 2 R 51 , —NR 50 C(═O)NR 52 R 53 , —NR 50 S(═O) 2 NR 52 R 53 , and —SCF 3 ;

R 25 , R 35 , R 45 , and R 55 at each occurrence are independently chosen from halogen, —NO 2 , —OR 60 , ═O, —C(═O)R 60 , —C(═O)OR 60 , —C(═O)NR 62 R 63 , —NR 60 R 61 , C 1-6 -alkyl, C 1-6 -haloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 6-15 -aryl, 5-15 membered heteroaryl, C 3-10 cycloalkyl, 3-15 membered heterocycloalkyl, pseudohalogen, —S(═O) n R 60 , —S(═O) 2 NR 62 R 63 , —OCH 2 F, —OCHF 2 , —OCF 3 , —NHOH, —OC(═O)R 60 —OC(═O)NR 62 R 63 , —OP(═O)(OH) 2 , —NR 60 C(═O)R 61 , —NR 60 C(═O)OR 61 , —NR 60 S(═O) 2 R 61 , —NR 60 C(═O)NR 62 R 63 , —NR 60 S(═O) 2 NR 62 R 63 , and —SCF 3 , in which said C 1-6 -alkyl, C 1-6 -haloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 6-15 -aryl, 5-15 membered heteroaryl, C 3-10 cycloalkyl, and 3-15 membered heterocycloalkyl groups are optionally substituted by one or more substituents independently chosen from C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, halogen, cyano, C 3-10 cycloalkyl, phenyl, 5-10 membered heteroaryl-(R 79 ) x , 3-10 membered heterocycloalkyl, —N(R 76 ) 2 , —C(═O)OR 76 , —C(═O)N(R 76 ) 2 , ═O, and —OR 76 ;

R 10 , R 11 , R 20 , R 21 , R 30 , R 31 , R 40 , R 41 , R 50 , R 51 , R 60 , R 61 at each occurrence are independently chosen from H, C 1-6 -alkyl, C 2-6 -alkynyl, C 1-6 -haloalkyl, C 6-15 -aryl, 5-15 membered heteroaryl, C 3-10 cycloalkyl, and 3-15 membered heterocycloalkyl, in which said C 1-6 -alkyl, C 2-6 -alkynyl, C 1-6 -haloalkyl, C 6-15 -aryl, 5-15 membered heteroaryl, C 3-10 cycloalkyl, and 3-15 membered heterocycloalkyl groups are optionally substituted by one or more substituents independently chosen from C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, halogen, cyano, phenyl, 5-10 membered heteroaryl-(R 79 ) x , 3-10 membered heterocycloalkyl, —N(R 76 ) 2 , —C(═O)OR 76 , —C(═O)N(R 76 ) 2 , ═O, and —OR 76 ;

R 12 , R 13 , R 22 , R 23 , R 32 , R 33 , R 42 , R 43 , R 52 , R 53 , R 62 , and R 63 at each occurrence are independently chosen from H, C 1-6 -alkyl, C 2-6 -alkynyl, C 1-6 -haloalkyl, C 6-15 -aryl, 5-15 membered heteroaryl, C 3-10 cycloalkyl, and 3-15 membered heterocycloalkyl, in which said C 1-6 -alkyl, C 2-6 -alkynyl, C 1-6 -haloalkyl, C 6-15 -aryl, 5-15 membered heteroaryl, C 3-10 cycloalkyl, and 3-15 membered heterocycloalkyl groups are optionally substituted by one or more substitutents independently chosen from C 1-6 -alkyl, halogen, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl-(R 87 ) x , —N(R 86 ) 2 , cyano, C 2-6 -alkynyl, ═O, and —OR 86 ;

or R 12 and R 13 , R 22 and R 23 , R 32 and R 33 , R 42 and R 43 , R 52 and R 53 , or R 62 and R 63 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl group or a 5-15 membered heteroaryl group, in which said 3-15 membered heterocycloalkyl group or 5-15 membered heteroaryl group is optionally substituted by one or more substituents independently chosen from C 1-6 -alkyl, halogen, and —OH;

R 76 and R 86 at each occurrence are independently chosen from H, C 1-6 -alkyl-(R 78 ) x , and —C(═O)—C 1-6 -alkyl;

R 78 at each occurrence is independently chosen from ═O and phenyl;

R 79 at each occurrence is ═O;

R 87 at each occurrence is independently chosen from C 1-6 -alkyl;

n at each occurrence is independently chosen from 0, 1, and 2; and

x at each occurrence is independently chosen from 0, 1, 2, 3, 4, 5, and 6;

with the proviso that the compound is not:

(a)

2. A pharmaceutical composition comprising a compound as defined in claim 1 and at least one pharmaceutically acceptable carrier, diluent, or excipient therefor.

3. A pharmaceutical composition as defined in claim 2 , wherein the compound is a compound of formula I or a pharmaceutically acceptable salt thereof.

4. A pharmaceutical composition as defined in claim 2 , wherein the compound is a compound of formula II or a pharmaceutically acceptable salt thereof.

5. A compound of formula I as defined in claim 1 , wherein said compound is:

4-[5-Chloro-4-(2-methylcarbamoyl-phenylamino)-pyrimidin-2-ylamino]-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-12-carboxylic acid ethyl ester;

2-{5-Chloro-2-[12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;

2-[5-Chloro-2-(12-prop-2-ynyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;

2-[5-Chloro-2-(12-cyclopropanecarbonyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;

N-{(1R,2R)-2-[5-Chloro-2-(12-ethyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;

N-{2-[5-Chloro-2-(12-ethyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-phenyl}-methanesulfonamide;

2-[5-Chloro-2-(3-chloro-12-ethyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;

5-Chloro-4-[5-chloro-4-(2-methylcarbamoyl-phenylamino)-pyrimidin-2-ylamino]-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-12-carboxylic acid ethyl ester;

3-Chloro-4-[5-chloro-4-(2-methylcarbamoyl-phenylamino)-pyrimidin-2-ylamino]-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-12-carboxylic acid ethyl ester;

N-(2-{5-Chloro-2-[12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino}-phenyl)-methanesulfonamide;

N-((1R,2R)-2-{5-Chloro-2-[12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

2-[2-(12-Aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-N-methyl-benzamide;

2-[5-Chloro-2-(12-isopropyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;

2-[5-Chloro-2-(3-chloro-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;

N-{(1R,2R)-2-[2-(12-Aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;

N-{(1R,2R)-2-[5-Chloro-2-(12-isopropyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;

N-{(1R,2R)-2-[2-(12-sec-Butyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;

2-[5-Chloro-2-(3-chloro-12-isopropyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;

2-{5-Chloro-2-[3-chloro-12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;

2-{5-Chloro-2-[5-chloro-12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;

N-{(1R,2R)-2-[2-(12-sec-Butyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;

2-[2-(12-Aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-3-chloro-N-methyl-benzamide;

3-Chloro-2-{5-chloro-2-[12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;

N-{(1R,2R)-2-[5-Chloro-2-(3-methoxy-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;

N-{(1R,2R)-2-[5-Chloro-2-(12-ethyl-3-methoxy-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;

(+/−)-2-[5-Chloro-2-(12-ethyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;

(+/−)-2-[5-Chloro-2-(12-methanesulfonyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;

2-[5-Chloro-2-(7-oxo-6,7,8,9-tetrahydro-5H-benzocyclo-hepten-2-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;

(2-exo,3-exo)-3-[5-Chloro-2-(7-oxo-6,7,8,9-tetrahydro-5H-benzocyclo-hepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

N-{(1R,2R)-2-[5-Chloro-2-(7-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;

2-[5-Chloro-4-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyrimidin-2-ylamino]-5,6,8,9-tetrahydro-benzocyclohepten-7-one;

2-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;

N-{(1R,2R)-2-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;

2-[5-Chloro-2-(7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;

N-{(1R,2R)-2-[5-Chloro-2-(7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;

5-Chloro-N*2*-(7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4* -(2-methoxy-4-morpholin-4-yl-phenyl)-pyrimidine-2,4-diamine;

2-{5-Chloro-4-[2-(1-methyl-1H-imidazol-2-yl)-phenylamino]-pyrimidin-2-ylamino}-5,6,8,9-tetrahydro-benzocyclohepten-7-one;

5-Chloro-N*4*-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-N*2*-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-pyrimidine-2,4-diamine;

5-Chloro-N*2*-(7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-pyrimidine-2,4-diamine;

2-{5-Chloro-2-[12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0(2,7)]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-methyl-benzamide;

2-{5-Chloro-2-[12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0(2,7)]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino-}-3-fluoro-benzoic acid isopropyl ester;

5-Chloro-N*4*-(4-methoxy-2-pyrazol-1-yl-phenyl)-N*2*-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-pyrimidine-2,4-diamine;

2-[5-Chloro-4-(4-methoxy-2-pyrazol-1-yl-phenylamino)-pyrimidin-2-ylamino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol;

(2-exo-3-exo)-3-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid methylamide;

(2-exo-3-exo)-3-[5-Chloro-2-(7-hydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid methylamide;

(1S,2S,3R,4R)-3-[2-((S)-7-Acetylamino-1-methoxy-9-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-5-chloro-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

2-{5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;

5-Chloro-N*4*-(2-ethyl-4-morpholin-4-yl-phenyl)-N*2*-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-pyrimidine-2,4-diamine;

(1R,2R)-2-5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino-cyclohexanecarboxylic acid amide;

1S,2R,3S,4R)-3-{5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]heptane-2-carboxylic acid amide;

5-Chloro-N*4*-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-N*2*-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-pyrimidine-2,4-diamine;

N-((1R,2R)-2-{5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

5-Chloro-N*4*-[2-(3-methyl-pyridin-2-yl)-phenyl]-N*2*-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-pyrimidine-2,4-diamine;

5-Chloro-N*4*-(2-methoxy-phenyl)-N*2*-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-pyrimidine-2,4-diamine;

5-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-(2-methoxy-4-morpholin-4-yl-phenyl)-pyrimidine-2,4-diamine;

2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;

5-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-pyrimidine-2,4-diamine;

N-((1R,2R)-2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

5-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-(2-methoxy-phenyl)-pyrimidine-2,4-diamine;

2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-methyl-benzamide;

(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic;

(1S,2S,3R,4R)-3-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

N-((1R,2R)-2-[5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino-cyclohexyl)-methanesulfonamide;

N-((1R,2R)-2-[5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino-cyclohexyl)-methanesulfonamide;

(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

5-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-methyl-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;

(1S,2S,3R,4R)-3-{5-Chloro-2-[1-methoxy-7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

5-Chloro-N*2*-[1-methoxy-7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-methyl-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;

1S,2S,3R,4R)-3-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;

2-{5-Chloro-2-[1-methoxy-7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;

N-((1R,2R)-2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

N-((1R,2R)-2-{5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;

5-Chloro-N*2*-[1-methoxy-7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;

(1S,2S,3R,4R)-3-{5-Chloro-2-[1-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

N-((1R,2R)-2-{5-Chloro-2-[1-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

1-(2-{5-Chloro-2-[1-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzenesulfonyl)-pyrrolidin-3-ol;

1S,2S,3R,4R)-3-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

N-((1R,2R)-2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

(1S,2S,3R,4R)-3-(5-Chloro-2-{1-methoxy-7-[(2-methoxy-ethyl)-methyl-amino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino}-pyrimidin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

N-[(1R,2R)-2-(5-Chloro-2-{1-methoxy-7-[(2-methoxy-ethyl)-methyl-amino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino}-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide;

1-(2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzenesulfonyl)-pyrrolidin-3-ol;

2-(2-{5-Chloro-4-[2-(pyrrolidine-1-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ylamino)-ethanol;

2-{2-[5-Chloro-4-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyrimidin-2-ylamino]-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ylamino}-ethanol;

2-([5-[5-Chloro-2-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-2-fluoro-benzyl]-ethylamino)-ethanol;

6-{5-Chloro-2-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-4-methanesulfonyl-7-methoxy-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one;

5-Chloro-N*4*-(2-methoxy-4-morpholin-4-yl-phenyl)-N*2*-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-pyrimidine-2,4-diamine;

2-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N-ethyl-benzamide;

3-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

2-[5-Chloro-2-(1-methoxy-7-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;

(1S,2S,3R,4R)-3-[5-Chloro-2-(1-methoxy-7-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

(1S,2S,3R,4R)-3-[5-Chloro-2-((R)-1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

(1S,2S,3R,4R)-3-[5-Chloro-2-((S)-1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

5-Chloro-N*2*-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;

N-{(1R,2R)-2-[5-Chloro-2-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;

N-[(1R,2R)-2-(5-Chloro-2-{7-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino}-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide;

(1S,2S,3R,4R)-3-(5-Chloro-2-{7-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino}-pyrimidin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

N-((1R,2R)-2-{5-Chloro-2-[7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

2-[5-Chloro-2-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;

2-{5-Chloro-2-[7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;

5-Chloro-N*4*-(2-methoxy-phenyl)-N*2*-[7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-pyrimidine-2,4-diamine;

(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

(2-{5-Chloro-2-[7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-phenoxy)-acetonitrile;

5-Chloro-N*4*-(2-methoxy-4-morpholin-4-yl-phenyl)-N*2*-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-pyrimidine-2,4-diamine;

N-((1R,2R)-2-{5-Chloro-2-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

(1S,2S,3R,4R)-3-{5-Chloro-2-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

2-{5-Chloro-2-[7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-methyl-benzamide;

5-Chloro-N*2*-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-[2-(pyrrolidine-1-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;

5-Chloro-N*2*-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;

3-[5-Chloro-2-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-azepan-2-one;

(1S,3R,4R)-3-[5-Chloro-2-((S)-1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid 2-methoxy-ethyl ester;

1-{2-[5-Chloro-2-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-benzenesulfonyl}-pyrrolidin-3-ol;

2-{5-Chloro-2-[7-(3-hydroxy-piperidin-1-yl)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;

1-(2-{5-Chloro-4-[2-(pyrrolidine-1-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl)-piperidin-3-ol;

(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(3-hydroxy-piperidin-1-yl)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

2-{5-Chloro-2-[1-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;

1-{2-[5-Chloro-4-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyrimidin-2-ylamino]-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl}-piperidin-3-ol;

5-Chloro-N*2*-[1-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;

2-[5-Chloro-2-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;

(1S,2S,3R,4R)-3-{5-Chloro-2-[1-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

N-Methyl-2-[2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-benzamide;

4-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-3-methoxy-N-propyl-benzamide;

(1S,2S,3R,4R)-3-[2-(7-Morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

7-[5-Chloro-2-(7-hydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-4-methoxy-2-methyl-2,3-dihydro-isoindol-1-one;

7-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-4-methoxy-2-methyl-2,3-dihydro-isoindol-1-one;

(1S,2S,3R,4R)-3-[5-Chloro-2-(1-methoxy-6-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

2-[5-Chloro-2-(1-methoxy-6-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;

5-Chloro-N(2)-(1-methoxy-6-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N(4)-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;

2-[5-Chloro-2-(1-methoxy-6-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-benzoic acid isopropyl ester;

N-{(1R,2R)-2-[5-Chloro-2-(1-methoxy-6-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;

5-Chloro-N(4)-(2-methoxy-4-morpholin-4-yl-phenyl)-N(2)-(1-methoxy-6-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-pyrimidine-2,4-diamine;

(1S,2S,3R,4R)-3-{5-Chloro-2-[1-methoxy-6-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

2-{5-Chloro-2-[1-methoxy-6-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;

N-((1R,2R)-2-{5-Chloro-2-[1-methoxy-6-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

5-Chloro-N(2)-[1-methoxy-6-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N(4)-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;

(1S,2S,3R,4R)-3-{5-Chloro-2-[6-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

2-(2-{5-Chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-ylamino)-ethanol;

(R)-1-(2-{5-Chloro-2-[6-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzenesulfonyl)-pyrrolidin-3-ol;

(S)-1-(2-{5-Chloro-2-[6-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzenesulfonyl)-pyrrolidin-3-ol;

2-(2-{5-Chloro-4-[2-(pyrrolidine-1-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-ylamino)-ethanol;

N-((1R,2R)-2-{5-Chloro-2-[6-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

(1S,2S,3R,4R)-3-[5-Chloro-2-(7-hydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

5-Chloro-N*4*-[2-(3-methoxy-pyridin-2-yl)-phenyl]-N*2*-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-pyrimidine-2,4-diamine;

2-{5-Chloro-4-[2-(3-methoxy-pyridin-2-yl)-phenylamino]-pyrimidin-2-ylamino}-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol;

5-Chloro-N*4*-[2-(3-methyl-pyridin-2-yl)-phenyl]-N*2*-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-pyrimidine-2,4-diamine;

2-{5-Chloro-4-[2-(3-methyl-pyridin-2-yl)-phenylamino]-pyrimidin-2-ylamino}-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol;

2-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;

2-[5-Chloro-2-(7-hydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;

5-Chloro-N*2*-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;

2-[5-Chloro-4-(2-pyrazol-1-yl-phenylamino)-pyrimidin-2-ylamino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol;

5-Chloro-N*2*-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;

2-{5-Chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol;

(1S,2S,3R,4R)-3-[5-Chloro-2-(3-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

2-[5-Chloro-2-(3-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;

5-Chloro-N*2*-(3-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;

N-{(1R,2R)-2-[5-Chloro-2-(3-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;

5-Chloro-N*2*-(3-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;

(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acidamide;

2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;

5-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;

N-((1R,2R)-2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

5-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;

5-Chloro-N*2*-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-[2-(pyrrolidine-1-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;

1-(2-{5-Chloro-2-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzenesulfonyl)-pyrrolidin-3-ol;

2-{5-Chloro-2-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;

5-Chloro-N*2*-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;

5-Chloro-N*2*-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;

2-{5-Chloro-2-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;

2-(2-{5-Chloro-4-[2-(pyrrolidine-1-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ylamino)-ethanol;

1-(2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzenesulfonyl)-pyrrolidin-3-ol;

2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;

2-(2-{5-Chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ylamino)-ethanol;

2-{2-[5-Chloro-4-(2-pyrazol-1-yl-phenylamino)-pyrimidin-2-ylamino]-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ylamino}-ethanol;

2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;

2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzoic acid 2-methoxy-ethyl ester;

N-((1R,2R)-2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

1-(2-{5-Chloro-2-[3-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzenesulfonyl)-pyrrolidin-3-ol;

2-{5-Chloro-2-[3-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;

5-Chloro-N*2*-[3-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;

N-((1R,2R)-2-{5-Chloro-2-[3-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

(1S,2S,3R,4R)-3-{5-Chloro-2-[3-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

(1S,2S,3R,4R)-3-[5-Chloro-2-(1-methoxy-8-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

2-[5-Chloro-2-(1-methoxy-8-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;

[2-(5-Chloro-2-{7-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino}-pyrimidin-4-ylamino)-3-fluoro-phenoxy]-acetonitrile;

3-Chloro-2-(5-chloro-2-{7-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino}-pyrimidin-4-ylamino)-N-methyl-benzamide; or

N-{(1R,2R)-2-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-N-methyl-methanesulfonamide;

or a pharmaceutically acceptable salt form thereof.

6. A compound of formula II as defined in claim 1 , wherein said compound is:

tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-4,12-dicarboxylic acid 12-ethyl ester 4-methyl ester;

3-[5-Chloro-2-(4-methoxy-8-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;

2-[5-Chloro-2-(4-methoxy-8-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;

5-Chloro-N(2)-(4-methoxy-8-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-yl)-N(4)-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;

N-{(1R,2R)-2-[5-Chloro-2-(2-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;

5-Chloro-N*2*-(2-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-yl)-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;

2-[5-Chloro-2-(2-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;

2-[5-Chloro-2-(2-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;

N-((1R,2R)-2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-2-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;

5-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-2-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-yl]-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;

2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-2-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide; or

2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-2-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;

or a pharmaceutically acceptable salt form thereof.

7. A pharmaceutical composition comprising a compound as defined in claim 5 and at least one pharmaceutically acceptable carrier, diluent, or excipient therefor.

8. A pharmaceutical composition comprising a compound as defined in claim 6 and at least one pharmaceutically acceptable carrier, diluent, or excipient therefor.

Assignments (6)

CORRECTIVE ASSIGNMENT TO CORRECT THE TO CORRECT THE SPELLING OF THE "CITY" IN THE RECEIVING PARTY DATA SECTION FROM "CRANBERRY" TO --CRANBURY--. PREVIOUSLY RECORDED ON REEL 024157 FRAME 0174. ASSIGNOR(S) HEREBY CONFIRMS THE CHANGE OF NAME. Recorded Apr 5, 2010

From: PHARMACOPEIA, INC.

To: PHARMACOPEIA, LLC

Reel/Frame 024183/0619 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 30, 2010

From: BRESLIN, HENRY JOSEPH; BURKE, JASON; CURRY, MATTHEW A.; DIEBOLD, JAMES L.; DORSEY, BRUCE; DUGAN, BENJAMIN J.; GINGRICH, DIANE E.; LEARN, KEITH S.; LISKO, JOSEPH G.; MESAROS, EUGEN; MILKIEWICZ, KAREN; OTT, GREGORY R.; PARRISH, JONATHAN; THEROFF, JAY P.; THIEU, THO V.; TRIPATHY, RABINDRANATH; UNDERINER, THEODORE L.; WAGNER, JASON C.; WEINBERG, LINDA; WELLS, GREGORY J.; ZIFICSAK, CRAIG A.

To: CEPHALON, INC.

Reel/Frame 024156/0877 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 30, 2010

From: AHMED, GULZAR; BOHNSTEDT, ADOLPH; FENG, DAMING; GUO, TAO; HO, KOC-KAN; LIU, RONG-QIANG; YOU, MING

To: PHARMACOPEIA DRUG DISCOVERY, INC.

Reel/Frame 024157/0013 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 30, 2010

From: PHARMACOPEIA, LLC

To: CEPHALON, INC.

Reel/Frame 024157/0061 →

CHANGE OF NAME Recorded Mar 30, 2010

From: PHARMACOPEIA, INC.