Patent
Therapeutically active fused pyrimidine derivatives
| العنوان: | Therapeutically active fused pyrimidine derivatives |
|---|---|
| Patent Number: | 9,227,984 |
| تاريخ النشر: | January 05, 2016 |
| Appl. No: | 14/239406 |
| Application Filed: | August 15, 2012 |
| مستخلص: | A series of monocyclic or bicyclic diamine-substituted thieno[2,3-d]pyrimidine and isothiazolo[5,4-d]pyrimidine derivatives are beneficial in the treatment and/or prevention of various human ailments, including inflammatory, autoimmune and oncological disorders; viral diseases; and organ and cell transplant rejection. |
| Inventors: | Brookings, Daniel Christopher (Slough, GB); Ford, Daniel James (Slough, GB); Ghawalkar, Anant Ramrao (Hyderabad, IN); Herman, Jean (Heverlee, BE); Huang, Qiuya (Leuven, BE); Kulisa, Claire Louise (Slough, GB); Louat, Thierry (Heverlee, BE); Neuss, Judi Charlotte (Slough, GB); Reuberson, James Thomas (Slough, GB); Vanderhoydonck, Bart (Diest, BE) |
| Assignees: | UCB Pharma S.A. (Brussels, BE), Katholieke Universiteit Leuven, K.U.Leuven R&D (Leuven, BE) |
| Claim: | 1. A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof: [chemical expression included] wherein Q represents a group of formula (Qa) or (Qb): [chemical expression included] in which the asterisk (*) represents the point of attachment to the remainder of the molecule; V represents —CH 2 —, —CH 2 CH 2 — or —CH 2 CH 2 CH 2 —; X represents C—R 3 or N; Y represents a covalent bond, or a linker group selected from —C(O)—, —S(O)—, —S(O) 2 —, —C(O)O—, —C(O)N(R 4)— and —S(O) 2 N(R 4)—; Z represents hydrogen; or C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6)alkyl, aryl, aryl(C 1-6)alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6)alkyl, heteroaryl or heteroaryl(C 1-6)alkyl, any of which groups may be optionally substituted by one or more substituents; A represents hydrogen or trifluoromethyl; or C 1-6 alkyl, optionally substituted by one or more substituents independently selected from —OR a and —NR b R c ; R 1 is —NH 2 ; R 2 represents halogen, cyano, nitro, hydroxy, trifluoromethyl, trifluoromethoxy, —OR a , —SR a , —SOR a , —SO 2 R a , —NR b R c , —CH 2 NR b R c , —NR c COR d , —CH 2 NR c COR d , —NR c CO 2 R d , —NHCONR b R c , —NR c SO 2 R e , —N(SO 2 R e) 2 , —NHSO 2 NR b R c , —COR d , —CO 2 R d , —CONR b R c , —CON(OR a)R b or —SO 2 NR b R c ; or C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6)alkyl, aryl, aryl(C 1-6)alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6)alkyl, heteroaryl or heteroaryl(C 1-6)alkyl, any of which groups may be optionally substituted by one or more substituents; R 3 and R 4 independently represent hydrogen; or C 1-6 alkyl, optionally substituted by one or more substituents independently selected from —OR a and —NR b R c ; R a represents hydrogen; or R a represents C 1-6 alkyl, aryl, aryl(C 1-6)alkyl, heteroaryl or heteroaryl(C 1-6)alkyl, any of which groups may be optionally substituted by one or more substituents; R b and R c independently represent hydrogen or trifluoromethyl; or C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6)alkyl, aryl, aryl(C 1-6)alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6)alkyl, heteroaryl or heteroaryl(C 1-6)alkyl, any of which groups may be optionally substituted by one or more substituents; or R b and R c , when taken together with the nitrogen atom to which they are both attached, represent azetidin-1-yl, pyrrolidin-1-yl, oxazolidin-3-yl, isoxazolidin-2-yl, thiazolidin-3-yl, isothiazolidin-2-yl, piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, piperazin-1-yl, homopiperidin-1-yl, homomorpholin-4-yl or homopiperazin-1-yl, any of which groups may be optionally substituted by one or more sub stituents; R d represents hydrogen; or C 1-6 alkyl, C 3-7 cycloalkyl, aryl, C 3-7 heterocycloalkyl or heteroaryl, any of which groups may be optionally substituted by one or more sub stituents; and R e represents C 1-6 alkyl, aryl or heteroaryl, any of which groups may be optionally substituted by one or more substituents. |
| Claim: | 2. The compound as claimed in claim 1 wherein R 2 represents cyano, hydroxy, trifluoromethyl, —NR c CO 2 R d , —CO 2 R d , —CONR b R c or —CON(OR a)R b ; or R 2 represents C 1-6 alkyl, C 3-7 cycloalkyl, aryl or heteroaryl, any of which groups may be optionally substituted by one or two substituents independently selected from halogen, C 1-6 alkyl, hydroxy and C 1-6 alkoxy. |
| Claim: | 3. The compound as claimed in claim 1 represented by formula (IIA), or a pharmaceutically acceptable salt or solvate thereof: [chemical expression included] wherein W represents C—R 11 or N; R 11 represents hydrogen, halogen, cyano, C 1-6 alkyl, trifluoromethyl, hydroxy, C 1-6 alkoxy, trifluoromethoxy or C 1-6 alkylaminosulphonyl; and R 12 represents hydrogen, halogen, cyano, nitro, C 1-6 alkyl, trifluoromethyl, hydroxy, C 1-6 alkoxy, trifluoromethoxy, C 1-6 alkylthio, C 1-6 alkylsulphonyl, amino or di(C 1-6)alkylamino. |
| Claim: | 4. The compound as claimed in claim 1 represented by formula (IIB), or a pharmaceutically acceptable salt or solvate thereof: [chemical expression included] wherein R 22 represents —R d , —OR d , —NR b R c or —N(OR a)R b . |
| Claim: | 5. The compound as claimed in claim 1 wherein Z represents C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6)alkyl, aryl, aryl(C 1-6)alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl(C 1-6)alkyl, heteroaryl or heteroaryl(C 1-6)alkyl, any of which groups may be optionally substituted by one or two substituents independently selected from halogen, cyano, C 1-6 alkyl, aryl, (C 1-6)alkoxyaryl, (C 1-6)alkyl(C 3-7)-heterocycloalkyl, (C 3-7)heterocycloalkyl(C 1-6)alkyl, hydroxy, hydroxy(C 1-6)alkyl, C 1-6 alkoxy, difluoromethoxy, trifluoromethoxy, aryloxy, haloaryloxy, (C 1-6)alkoxyaryloxy, (C 1-3)alkylenedioxy, C 1-6 alkylamino, di(C 1-6)alkylamino, N—[(C 2-6)-alkoxycarbonyl]-N—[(C 1-6)alkyl]amino and C 2-6 alkoxycarbonyl. |
| Claim: | 6. The compound as claimed in claim 1 wherein A represents hydrogen; or A represents C 1-6 alkyl, optionally substituted by —OR a . |
| Claim: | 7. The compound as claimed in claim 1 represented by formula (IIC), or a pharmaceutically acceptable salt or solvate thereof: [chemical expression included] wherein R 32 represents cyano or —CO 2 R d . |
| Claim: | 8. The compound as claimed in claim 7 wherein Q represents a group of formula (Qa-1): [chemical expression included] in which the asterisk (*) represents the point of attachment to the remainder of the molecule. |
| Claim: | 9. A compound that is 1 2-Amino-5-(4-fluorophenyl)-4-(piperazin-1-yl)thieno[2,3-d]pyrimidine, 2 1{4-[2-amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]piperazin-1-y}-2-(4-chlorophenoxy)ethanone, 3 {4-[2-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]piperazin-1-yl}-(cyclopropyl)methanone, 4 4-[2-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(m-tolyl)piperazine-1-carboxamide, 5 4-[2-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-methoxyphenyl)-piperazine-1-carboxamide, 6 4-[2-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-isopropylphenyl)-piperazine-1-carboxamide, 7 4-[2-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-cyanophenyl)-piperazine-1-carboxamide, 8 4-[2-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-chlorophenyl)-piperazine-1-carboxamide, 9 4-[2-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-[4-(dimethylamino)-phenyl]piperazine-1-carboxamide, 10 2-Amino-4-(piperazin-1-yl)-5-(pyridin-3-yl)thieno[2,3d]pyrimidine, 11 2-Amino-6-methyl-5-phenyl-4-(piperazin-1-yl)thieno[2,3-d]pyrimidine, 12 4-[2-Amino-5-(pyridin-3-yl)thieno[2,3-d]pyrimidin-4-yl]-N-(2-methoxyphenyl)-piperazine-1-carboxamide, 13 4-(2-Amino-6-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxyphenyl)-piperazine-1-carboxamide, 14 3-(4- Fluorophenyl)-4-(4-methylpiperazin-1-yl)isothiazolo[5,4-d]pyrimidine, 15 3-(4-Fluorophenyl)-4-(piperazin-1-yl)isothiazolo[5,4-d]pyrimidin-6-amine, 16 3-(4-Fluorophenyl)-4-(4-methylpiperazin-1-yl)isothiazolo[5,4-d]pyrimidin-6-amine, 17 4-[6-Amino-3-(4-fluorophenyl)isothiazolo[5,4-d]pyrimidin-4-yl]-N-(p -tolyl)piperazine-1-carboxamide, 18 4-[6-Amino-3-(4-fluorophenyl)isothiazolo[5,4-d]pyrimidin-4-yl]-N-(4-isopropylphenyl)-piperazine-1-carboxamide, 19 1-{4-[6-Amino-3-(4-fluorophenyl)isothiazolo[5,4-d]pyrimidin-4-yl]piperazin-1-yl}-2-(4-chlorophenoxy)ethanone, 20 2-Amino-5-(ethoxycarbonyl)-4-(piperazin-1-yl)thieno[2,3-d]pyrimidine, 21 4-[2-Amino-5-(ethoxycarbonyl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-methoxyphenyl)-piperazine-1-carboxamide, 22 2-Amino-5-methyl-4-(piperazin-1-yl)thieno[2,3-d]pyrimidine, 23 2-Amino-5-isobutyl-4-(piperazin-1-yl)thieno[2,3-d]pyrimidine, 24 4-[2-Amino-5-methylthieno[2,3-d]pyrimidin-4-yl]-N-[4-(dimethylamino)phenyl]-piperazine-1-carboxamide, 25 4-[2-Amino-5-isobutylthieno[2,3-d]pyrimidin-4-yl]-N-[4-dimethylamino)phenyl]-piperazine-1-carboxamide, 26 2-Amino-4-[4-(4-methoxyphenylcarbamoyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylic acid, 27 2-Amino-4-[4-(4-methoxyphenylcarbamoyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylic acid methylamide, 28 2-Amino-4-[4-(4-methoxyphenylcarbamoyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylic acid N-methoxy-N-methylamide, 29 2-Amino-4-[4-(4-methoxyphenylcarbamoyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylic acid amide, 30 Benzyl 4-[2-amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]piperazine-1-carboxylate , 31 4-Methoxyphenyl 4-[2-amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]piperazine-1-carboxylate, 32 5-(4-Fluorophenyl)-4-[4-(3-methylbenzylsulfonyl)piperazin-1-yl]thieno[2,3-d]pyrimidin-2-amine, 33 5-(4-Fluorophenyl)-4-[4-(2-methyl-1H-imidazol-1-ylsulfonyl)piperazin-1-yl]thieno[2,3-d]pyrimidin-2-amine, 34 4-[2-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-methoxyphenyl)-piperazine-1-sulfonamide, 35 4-[2-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-[3-(morpholin-4-ylmethyl)phenyl]piperazine-1-carboxamide, 36 4-[2-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-[4-(4-methylpiperazin-1-yl)phenyl]piperazine-1-carboxamide, 37 4-[2-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-fluorophenyl)-piperazine-1-carboxamide, 38 4-[2-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(2,4-dimethoxyphenyl)-piperazine-1-carboxamide, 39 4-[2-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-[4-(piperidin-1-ylmethyl)-phenyl]piperazine-1-carboxamide, 40 4-[2-Amino-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(2,4-difluorophenyl)-piperazine-1-carboxamide, 41 4-[2-Amino-5-(pyridin-3-yl)thieno[2,3-d]pyrimidin-4-yl]-N-[4-(dimethylamino)phenyl]-piperazine-1-carboxamide, 42 4-[2-Amino-5-(pyridin-3-yl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-methoxyphenyl)-piperazine-1-carboxamide, 43 4-[2-Amino-5-(pyridin-3-yl)thieno[2,3-d]pyrimidin-4-yl]-N-(3-methylphenyl)piperazine-1-carboxamide, 44 4-[2-Amino-5-(pyridin-3-yl)thieno[2,3-d]pyrimidin-4-yl]-N-[3-(morpholin-4-ylmethyl)-phenyl]piperazine-1-carboxamide, 45 4-[2-Amino-5-(pyridin-3-yl)thieno[2,3-d]pyrimidin-4-yl]-N-[4-(piperidin-1-ylmethyl)-phenyl]piperazine-1-carboxamide, 46 4-[2-Amino-5-(4-methoxyphenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-methoxyphenyl)-piperazine-1-carboxamide, 47 4-[2-Amino-5-(4-methoxyphenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(3-methylphenyl)-piperazine-1-carboxamide, 48 4-[2-Amino-5-(4-methoxyphenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(2-methoxyphenyl)-piperazine-1-carboxamide, 49 4-[2-Amino-5-(4-methoxyphenyl)thieno[2,3-d]pyrimidin-4-yl]-N-[4-(dimethylamino)-phenyl]piperazine-1-carboxamide, 50 4-[2-Amino-5-(4-chlorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-methoxyphenyl)-piperazine-1-carboxamide, 51 4-[2-Amino-5-(4-chlorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-[4-(dimethylamino)-phenyl]piperazine-1-carboxamide, 52 4-[2-Amino-5-(4-chlorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(2-methoxyphenyl)-piperazine-1-carboxamide, 53 4-[2-Amino-5-(4-chlorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(3-methylphenyl)-piperazine-1-carboxamide, 54 4-[2-Amino-5-(3-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-[4-(dimethylamino)-phenyl]piperazine-1-carboxamide, 55 4-[2-Amino-5-(2-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-[4-(dimethylamino)-phenyl]piperazine-1-carboxamide, 56 4-[2-Amino-5-(2-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-[4-(4-methylpiperazin-1-yl)phenyl]piperazine-1-carboxamide, 57 4-[2-Amino-5-(2-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-methoxyphenyl)-piperazine-1-carboxamide, 58 4-(2-Amino-6-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)-N-[4-(dimethylamino)-phenyl]piperazine-1-carboxamide, 59 4-(2-Amino-6-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)-N-(2-methoxyphenyl)-piperazine-1-carboxamide, 60 4-(2-Amino-6-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)-N-[3-(morpholin-4-yl-methyl)phenyl]piperazine-1-carboxamide, 61 4-(2-Amino-6-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)-N-(3-methylphenyl)-piperazine-1-carboxamide, 62 4-[2-Amino-5-(4-fluorophenyl)-6-methylthieno[2,3-d]pyrimidin-4-yl]-N-[4-(4-methyl-piperazin-1-yl)phenyl]piperazine-1-carboxamide, 63 4-[2-Amino-5-(4-fluorophenyl)-6-methylthieno[2,3-d]pyrimidin-4-yl]-N-[4-(dimethyl-amino)phenyl]piperazine-1-carboxamide, 64 4-[2-Amino-5-(4-fluorophenyl)-6-methylthieno[2,3-d]pyrimidin-4-yl]-N-(4-methoxy-phenyl)piperazine-1-carboxamide, 65 4-(2-Amino-5-methylthieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxy-2-methylphenyl)-piperazine-1-carboxamide, 66 4-(2-Amino-5-methylthieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxyphenyl)piperazine-1-carboxamide, 67 4-(2-Amino-5-cyclohexylthieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxy-2-methylphenyl)-piperazine-1-carboxamide, 68 4-(2-Amino-5-cyclohexylthieno[2,3-d]pyrimidin-4-yl)-N-[4-(dimethylamino)phenyl]-piperazine-1-carboxamide, 69 4-(2-Amino-5-cyclohexylthieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxyphenyl)piperazine-1-carboxamide, 70 4-[2-Amino-5-(3-chloropropyl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-methoxy-2-methyl-phenyl)piperazine-1-carboxamide, 71 4-[2-Amino-5-(3-chloropropyl)thieno[2, 3-d]pyrimidin-4-yl]-N-(4-methoxyphenyl)-piperazine-1-carboxamide, 72 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-[4-(dimethylamino)phenyl]piperazine-1-carboxamide, 73 4-[2-Amino-5-(ethoxycarbonyl)thieno[2,3-d]pyrimidin-4-yl]-N-[4-(dimethylamino)-phenyl]piperazine-1-carboxamide, 74 4-[2-Amino-5-(ethoxycarbonyl)thieno[2,3-d]pyrimidin-4-yl]-N-(2,4-difluorophenyl)-piperazine-1-carboxamide, 75 Ethyl 2-amino-4-{4-[4-(4-methylpiperazin-1-yl)phenylcarbamoyl]piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 76 4-[2-Amino-5-(ethoxycarbonyl)thieno[2,3-d]pyrimidin-4-yl]-N-(2,4-dimethoxyphenyl)-piperazine-1-carboxamide, 77 4-[2-Amino-5-(ethoxycarbonyl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-methoxy-2-methyl-phenyl)piperazine-1-carboxamide, 78 4-[2-Amino-5-(hydroxymethyl)thieno[2,3-d]pyrimidin-4-yl]-N-[4-(dimethylamino)-phenyl]piperazine-1-carboxamide, 79 Ethyl 2-amino-4-{4-[4-(dimethylamino)phenylcarbamoyl]piperazin-1-yl}thieno[2,3-d]-pyrimidin-5-ylcarbamate, 80 2-Amino-4-[4-(4-methoxy-2-methylphenylcarbamoyl)piperazin-1-yl]thieno[2,3-d]-pyrimidine-5-carboxylic acid (2-hydroxy-1,1-dimethylethyl)amide, 81 4-[2-Amino-5-(trifluoromethyl)thieno[2,3-d]pyrimidin-4-yl]piperazine-1-carboxylic acid (4-methoxyphenyl)amide, 82 4-[2-Amino-5-(trifluoromethyl)thieno[2,3-d]pyrimidin-4-yl]piperazine-1-carboxylic acid (4-methoxy-2-methylphenyl)amide, 83 2-Amino-4-[4-(4-methoxyphenylcarbamoyl)piperazin-1-yl]isothiazolo[5,4-d]pyrimidine, 84 2-Amino-4-[4-(4-methoxy-2-methylphenylcarbamoyl)piperazin-1-yl]isothiazolo[5,4-d]-pyrimidine, 85 2-Amino-4-[4-(4-methoxyphenylcarbamoyl)-2-(S)-methylpiperazin-1-yl]isothiazolo[5,4-d]pyrimidine, 86 2-Amino-4-[4-(4-methoxy-2-methylphenylcarbamoyl)-2-(S)-methylpiperazin-1-yl]-isothiazolo[5,4-d]pyrimidine, 87 4-(2-Amino-5-cyanothieno[2,3-d]pyrimidin-4-yl)piperazine-1-carboxylic acid (4-methoxyphenyl)amide, 88 4-(2-Amino-5-oxo-5,6-dihydrothieno[2,3-d]pyrimidin-4-yl)piperazine-1-carboxylic acid (4-methoxy-2- methylphenyl)amide, 89 Ethyl 2-amino-4-{4-[(3-chloro-4-methoxyphenyl)-carbamoyl]piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 90 Ethyl 2-amino-4-{4-[(4-ethoxyphenyl)carbamoyl]-piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 91 Ethyl 2-amino-4-[4-(o-tolylcarbamoyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 92 Ethyl 2-amino-4-[4-(m-tolylcarbamoyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 93 Ethyl 2-amino-4-[4-(benzo[d][1,3]dioxol-5-yl-carbamoyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 94 Ethyl 2-amino-4-(4-{[4-(trifluoromethoxy)phenyl]-carbamoyl}piperazin-1-yl)thieno[2,3-d]pyrimidine-5-carboxylate, 95 Ethyl 2-amino-4-(4-{[4-(difluoromethoxy)phenyl]-carbamoyl}piperazin-1-yl)thieno[2,3-d]pyrimidine-5-carboxylate, 96 Ethyl 2-amino-4-[4-(phenylcarbamoyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 97 Ethyl 2-amino-4-(4-{2-[4-(dimethylamino)phenyl]-acetyl}piperazin-1-yl)thieno[2,3-d]pyrimidine-5-carboxylate, 98 Ethyl 2-amino-4-[4-(benzylcarbamoyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 99 Ethyl 2-amino-4-{4-[2-(pyridin-4-yl)acetyl]-piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 100 Ethyl 2-amino-4-[4-(pyridin-3-ylmethyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 101 Ethyl 2-amino-4-{4-[(4-methoxybenzyl)-carbamoyl]piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 102 Ethyl 2-amino-4-[4-(5-methyl-1H-pyrazole-3-carbonyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 103 Ethyl 2-amino-4-[4-(2-phenoxyacetyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 104 Ethyl 2-amino-4-[4-(imidazo[1,2-a]pyridine-2-carbonyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 105 Ethyl 2-amino-4-[4-(pyridin-2-ylmethyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 106 Ethyl 2-amino-4-(4-nicotinoylpiperazin-1-yl)-thieno[2,3-d]pyrimidine-5-carboxylate, 107 Ethyl 2-amino-4-{4-[2-(3,4-dimethoxyphenyl)-acetyl]piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 108 (S)-Ethyl 2-amino-4-[4-(1,2,3,4-tetrahydro-isoquinoline-3-carbonyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 109 Ethyl 2-amino-4-[4-(1-methyl-1H-imidazole-5-carbonyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 110 Ethyl 4-[4-(1H-indazole-3-carbonyl)piperazin-1-yl]-2-aminothieno[2,3-d]pyrimidine-5-carboxylate, 111 Ethyl 2-amino-4-{4-[6-(hydroxymethyl)picolinoyl]-piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 112 Ethyl 2-amino-4-[4-(quinoxaline-2-carbonyl)-piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 113 Ethyl 2-amino-4-[4-(isoquinoline-3-carbonyl)-piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 114 Ethyl 2-amino-4-{4-[3-(2-methyl-1H-imidazol-1-yl)propanoyl]piperazin-1-yl}thieno[2,3-d]-pyrimidine-5-carboxylate, 115 Ethyl 2-amino-4-{4-[1-(tert-butoxycarbonyl)-piperidine-4-carbonyl]piperazin-1-yl}thieno[2,3-d]-pyrimidine-5-carboxylate, 116 Ethyl 2-amino-4-{4-[(1-phenylethyl)carbamoyl]-piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 117 rac-(R)- Ethyl 2-amino-4-[4-(3-hydroxy-3-phenyl-propanoyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 118 Ethyl 4-[4-(1H-pyrazole-3-carbonyl)piperazin-1-yl]-2-aminothieno[2,3-d]pyrimidine-5-carboxylate, 119 Ethyl 2-amino-4-{4-[2-(morpholin-4-yl)acetyl]-piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 120 Ethyl 2-amino-4-[4-(1-methyl-1H-imidazole-2-carbonyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 121 Ethyl 2-amino-4-{4-[2-(thien-3-yl)acetyl]piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 122 Ethyl 2-amino-4-[4-(pyrazine-2-carbonyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 123 Ethyl 2-amino-4-(4-picolinoylpiperazin-1-yl)-thieno[2,3-d]pyrimidine-5-carboxylate, 124 Ethyl 2-amino-4-{4-[3-(pyridin-3-yl)propanoyl]-piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 125 Ethyl 2-amino-4-(4-benzylpiperazin-1-yl)-thieno[2,3-d]pyrimidine-5-carboxylate, 126 Ethyl 2-amino-4-[4-(imidazo[1,2-a]pyridine-3-carbonyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 127 Ethyl 2-amino-4-{4-[3-(morpholin-4-yl)propanoyl]-piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 128 Ethyl 2-amino-4-{4-[3-(4-methoxyphenyl)-propanoyl]piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 129 Ethyl 2-amino-4-{4-[3-(3-methoxyphenyl)-propanoyl]piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 130 Ethyl 4-4-{4-[3-(1H-benzo [d]imidazol-2 -yl)-propanoyl]piperazin-1-yl}-2-aminothieno[2,3-d]-pyrimidine-5-carboxylate, 131 Ethyl 2-amino-4-[4-(2-phenylethyl)piperazin-1-yl]-thieno[2,3-d]pyrimidine-5-carboxylate, 132 Ethyl 2-amino-4-{4-[3-(2-methoxyphenyl)-propanoyl]piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 133 Ethyl 2-amino-4-[4-(1,2,3,4-tetrahydronaphthalene-2-carbonyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 134 Ethyl 2-amino-4-{4-[3-(furan-2-yl)propanoyl]-piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 135 Ethyl 2-amino-4-(4-benzoylpiperazin-1-yl)-thieno[2,3-d]pyrimidine-5-carboxylate, 136 Ethyl 2-amino-4-[4-(3-cyclopentylpropanoyl)-piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 137 Ethyl 2-amino-4-[4-(isoquinoline-1-carbonyl)-piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 138 Ethyl 2-amino-4-{4-[3-(3-chloro-4-methoxy-phenyl)propanoyl]piperazin-1-yl}thieno[2,3-d]-pyrimidine-5-carboxylate, 139 Ethyl 2-amino-4-[4-(quinoline-2-carbonyl)-piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 140 Ethyl 2-amino-4-{4-[3-(4-fluorophenyl)propanoyl]-piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 141 Ethyl 2-amino-4-{4-[3-(p-tolyl)propanoyl]-piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 142 Ethyl 4-[4-(1H-benzo [d]imidazole-2-carbonyl)-piperazin-1-yl]-2-aminothieno[2,3-d]pyrimidine-5-carboxylate, 143 Ethyl 2-amino-4-{4-[3-(4-methylpiperazin-1-yl)-propanoyl]piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 144 Ethyl 2-amino-4-{4-[2-(dimethylamino)acetyl]-piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 145 Ethyl 2-amino-4-{4-[3-(o-tolyl)propanoyl]-piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 146 Ethyl 4-[4-(1H-indole-2-carbonyl)piperazin-1-yl]-2-aminothieno[2,3-d]pyrimidine-5-carboxylate, 147 (S)-Ethyl 2-amino-4-{4-[2-(methylamino)-2-phenylacetyl]piperazin-1-yl}thieno[2,3-d]-pyrimidine-5-carboxylate, 148 Ethyl 2-amino-4-{4-[1-(4-methoxyphenyl)-cyclopropanecarbonyl]piperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 149 Ethyl 2-amino-4-[4-(2-methyl-3-phenylpropanoyl)-piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 150 Ethyl 2-amino-4-[4-(2-phenylcyclopropane-carbonyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 151 Ethyl 2-amino-4-[4-(3-phenylbutyl)piperazin-1-yl]-thieno[2,3-d]pyrimidine-5-carboxylate, 152 (S)-Ethyl 2-amino-4-[4-(1-methylpyrrolidine-2-carbonyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 153 Ethyl 4-{4-[3-(1H-indo1-3-yl)propanoyl]piperazin-1-yl}2-aminothieno[2,3-d]pyrimidine-5-carboxylate, 154 Ethyl 2-amino-4-[4-(3-phenylpropanoyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 155 Ethyl 2-amino-4-[4-(3-phenylpropyl)piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 156 Ethyl 2-amino-4-{4-[(4-methoxyphenyl)-carbamoyl]-3-methylpiperazin-1-yl}thieno[2,3-d]-pyrimidine-5-carboxylate, 157 Ethyl 2-amino-4-{4-[(4-methoxyphenyl)-carbamoyl]-2-methylpiperazin-1-yl}thieno[2,3-d]-pyrimidine-5-carboxylate, 158 Ethyl 2-amino-4-{4-[2-(3-methoxyphenoxy)acetyl]-3-methylpiperazin-1-yl}thieno[2,3-d] p yrimidine-5-carboxylate, 159 Ethyl 2-amino-4-{4-[2-(4-methoxyphenoxy)acetyl]-3-methylpiperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 160 Ethyl 2-amino-4-[2-methyl-4-(p-tolylcarbamoyl)-piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 161 Ethyl 2-amino-4-4-{4-[(3-methoxyphenyl)-carbamoyl]-2-methylpiperazin-1-yl}thieno[2,3-d]-pyrimidine-5-carboxylate, 162 Ethyl 2-amino-4-4-{4-[(3-methoxyphenyl)-carbamoyl]-3-methylpiperazin-1-yl}thieno[2,3-d]-pyrimidine-5-carboxylate, 163 Ethyl 2-amino-4-[3-methyl-4-(p-tolylcarbamoyl)-piperazin-1-yl]thieno[2,3-d]pyrimidine-5-carboxylate, 164 Ethyl 2-amino-4-4-{4-[2-(3-methoxyphenoxy)acetyl]-2-methylpiperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 165 Ethyl 2-amino-4-{4-[2-(4-methoxyphenoxy)acetyl]-2-methylpiperazin-1-yl}thieno[2,3-d]pyrimidine-5-carboxylate, 166 Ethyl 2-amino-4-4-{4-[3-(4-methoxyphenyl)-propanoyl]-3-methylpiperazin-1-yl}thieno[2,3-d]-pyrimidine-5-carboxylate, 167 Ethyl 2-amino-4-4-{4-[3-(4-methoxyphenyl)-propanoyl]-2-methylpiperazin-1-yl}thieno[2,3-d]-pyrimidine-5-carboxylate, 168 Ethyl 2-amino-4-4-{5-[2-(3-methoxyphenoxy)acetyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl}thieno[2,3-d]-pyrimidine-5-carboxylate, 169 Ethyl 2-amino-4-4-{5-[(3-methoxyphenyl)-carbamoyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl}-thieno[2,3-d]pyrimidine-5-carboxylate, 170 Ethyl 2-amino-4-[5-(p-tolylcarbamoyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]thieno[2,3-d]-pyrimidine-5-carboxylate, 171 Ethyl 2-amino-4-{5-[(4-methoxyphenyl)-carbamoyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl}-thieno[2,3-d]pyrimidine-5-carboxylate, 172 Ethyl 2-amino-4-{5-[3-(4-methoxyphenyl)-propanoyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl}-thieno[2,3-d]pyrimidine-5-carboxylate, 173 Ethyl 2-amino-4-{5-[2-(4-methoxyphenoxy)acetyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl}thieno[2,3-d]-pyrimidine-5-carboxylate, 174 Ethyl 2-amino-4-{4-[(4-methoxy-2-methylphenyl)-carbamoyl]-2-methylpiperazin-1-yl}thieno[2,3-d]-pyrimidine-5-carboxylate, 175 Ethyl 2-amino-4-{(2S)-4-[(4-methoxy-2-methyl-phenyl)carbamoyl]-2-methylpiperazin-1-yl]-thieno[2,3 -d]pyrimidine-5-carboxylate, 176 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(3-chloro-4-methoxyphenyl)piperazine-1-carboxamide, 177 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(o-tolyl)piperazine-1-carboxamide, 178 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxyphenyl)piperazine-1-carboxamide, 179 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(4-ethoxyphenyl)piperazine-1-carboxamide, 180 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(benzo[d][1,3]dioxo1-5-yl)piperazine-1-carboxamide, 181 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-[4-(trifluoromethoxy)phenyl]piperazine-1-carboxamide, 182 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(m-tolyl)piperazine-1-carboxamide, 183 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-[4-(difluoromethoxy)phenyl]piperazine-1-carboxamide, 184 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-phenoxyethanone, 185 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](1H-pyrazol-3-yl)methanone, 186 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-phenyl-piperazine-1-carboxamide, 187 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](5-methyl-1H-pyrazol-3-yl)methanone, 188 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](imidazo[1,2-alpyridin-2-yl)methanone, 189 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](isoquinolin-3-yl)methanone, 190 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-benzyl-piperazine-1-carboxamide, 191 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-(4-methoxyphenyl)propan-1-one, 192 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxybenzyl)piperazine-1-carboxamide, 193 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](pyrazin-2-yl)methanone, 194 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-[4-(dimethylamino)phenyl]-ethanone, 195 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-(1H-benzo[d]imidazol-2-yl)-propan-1-one, 196 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](1-methyl-1H-imidazol-2-yl)methanone, 197 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(pyridin-4-yl)ethanone, 198 (S)-1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-hydroxy-3-phenylpropan-1-one, 199 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(thien-3-yl)ethanone, 200 4-[4-(Pyridin-3-ylmethyl)piperazin-1-yl)thieno[2,3-d]pyrimidin-2-amine, 201 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](1-methyl-1H-imidazol-5-yl)methanone, 202 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(3,4-dimethoxyphenyl)ethanone, 203 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](quinoxalin-2-yl)methanone, 204 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](1H-indazol-3-yl)methanone, 205 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(1-phenylethyl)piperazine-1-carboxamide, 206 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-phenylpropan-1-one 207 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](pyridin-3-yl)methanone, 208 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-(furan-2-yl)propan-1-one, 209 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl][6-(hydroxymethyl)pyridin-2-yl]methanone, 210 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](phenyl)methanone, 211 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-cyclopentylpropan-1-one, 212 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-(4-methylpiperazin-1-yl)propan-1-one, 213 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](quinolin-2-yl)methanone, 214 4-[4-(Pyridin-2-ylmethyl)piperazin-1-yl]thieno[2,3-d]pyrimidin-2-amine, 215 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-(3-methoxyphenyl)propan-1-one, 216 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-(o-tolyl)propan-1-one 217 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(morpholin-4-yl)ethanone, 218 4-[4-(3-Phenylbutyl)piperazin-1-yl]thieno[2,3-d]-pyrimidin-2-amine, 219 4-(4-Benzylpiperazin-1-yl)thieno[2,3-d]pyrimidin-2-amine, 220 4-[4-(2-Phenylethyl)piperazin-1-yl]thieno[2,3-d]-pyrimidin-2-amine, 221 4-[4-(3-Phenylpropyl)piperazin-1-yl]thieno[2,3-d]-pyrimidin-2-amine, 222 tert-Butyl 4-[4-(2-aminothieno[2,3-d]pyrimidin-4-yl)piperazine-1-carbonyl]piperidine-1-carboxylate, 223 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(dimethylamino)ethanone, 224 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-methyl-3-phenylpropan-1-one, 225 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-(4-fluorophenyl)propan-1-one, 226 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-(p-tolyl)propan-1-one 227 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-(1H-indol-3-yl)propan-1-one, 228 (S)-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl](1-methylpyrrolidin-2-yl)methanone, 229 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](1H-benzo[d]imidazol-2-yl)methanone, 230 (S)-1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(methylamino)-2-phenylethanone, 231 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl][1-(4-methoxyphenyl)cyclopropl]methanone, 232 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-(2-methyl-1H-imidazol-1-yl)-propan-1-one, 233 (S)-tert-Butyl N-{2-[4-(2-aminothieno[2,3-d]-pyrimidin-4-yl)piperazin-1-yl]-2-oxo-1-phenyl-ethal}-N-(methyl)carbamate, 234 (S)-tert-Butyl 3-[4-(2-aminothieno[2,3-d]pyrimidin-4-yl)piperazine-1-carbonyl]-3,4-dihydro-isoquinoline-2(1H)-carboxylate, 235 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](pyridin-2-yl)methanone, 236 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-(morpholin-4-yl)propan-1-one, 237 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-2-(4-methylpiperazin-1-yl)ethanone, 238 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](2-phenylcyclopropyl)methanone, 239 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-(3-chloro-4-methoxyphenyl)-propan-1-one, 240 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-(pyridin-3-yl)propan-1-one, 241 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-(2-methoxyphenyl)propan-1-one, 242 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](1H-indol-2-yl)methanone, 243 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](isoquinolin-1-yl)methanone, 244 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](1,2,3,4-tetrahydronaphthalen-2-yl)methanone, 245 [4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl](imidazo[1,2-α]pyridin-3-yl)methanone, 246 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxyphenyl)-3-methylpiperazine-1-carboxamide, 247 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide, 248 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(3-methoxyphenyl)-3-methylpiperazine-1-carboxamide, 249 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl]-2-(3-methoxyphenoxy)-ethanone, 250 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl]-2-(4-methoxyphenoxy)-ethanone, 251 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-3-(hydroxymethyl)-N-(p-tolyl)piperazine-1-carboxamide, 252 4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-3-(hydroxymethyl)-N-(4-methoxyphenyl)piperazine-1-carboxamide, 253 1-[4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-3-(hydroxymethyl)piperazin-1-yl]-2-(3-methoxy-phenoxy)ethanone, 254 (3S)-4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxyphenyl)-3methylpiperazine-1-carboxamide, 255 (3S)-4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide, 256 (3R)-4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxyphenyl)-3-methylpiperazine-1-carboxamide, 257 (3R)-4-(2-Aminothieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide, 258 4-(2-Amino-5-cyanothieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxyphenyl)-3-methyl-piperazine-1-carboxamide, 259 4-(2-Amino-5-cyanothieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide, 260 4-[2-Amino-5-(3-methyl-1,2,4-oxadiazol-5-yl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-methoxyphenyl)piperazine-1-carboxamide, 261 4-[2-Amino-5-(3-isopropyl-1,2,4-oxadiazol-5-yl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-methoxyphenyl)piperazine-1-carboxamide, or 262 4-[2-Amino-5-(3-tert-butyl-1,2,4-oxadiazol-5-yl)thieno[2,3-d]pyrimidin-4-yl]-N-(4-methoxyphenyl)piperazine-1-carboxamide, or a pharmaceutically acceptable salt thereof. |
| Claim: | 10. A pharmaceutical composition comprising a compound of formula (I) as defined in claim 1 , or a pharmaceutically acceptable salt or solvate thereof, in association with a pharmaceutically acceptable carrier. |
| Claim: | 11. A method for the treatment of a viral disease, or organ or cell transplant rejection, which comprises administering to a patient in need of such treatment an effective amount of a compound of formula (I) as defined in claim 1 , or a pharmaceutically acceptable salt or solvate thereof. |
| Patent References Cited: | 22 00 764 July 1973 01/46200 June 2001 03/022214 March 2003 2006/079916 August 2006 2006/100591 September 2006 2006/103544 October 2006 2006/103545 October 2006 2006/103555 October 2006 2007/146284 December 2007 2010/103130 September 2010 2011/029054 March 2011 |
| Other References: | Wolff et. al., “Burger's Medicinal Chemistry and Drug Discovery,” 5th Ed. Part 1, pp. 975-977 (1995). cited by examiner Banker, et. al., (1996), Modern Pharmaceuticals, p. 596. cited by examiner Darias, et. al., Chimica Therapeutica (1972), 7(3), 224-7. cited by examiner Kortum et al., “Thienopyrimidine-based P2Y12 platelet aggregation inhibitors”, Bioorganic & Medicinal Chemistry Letters, 2009, 19(20), 5919-5923. cited by applicant XP002685933, Database Registry Chemical Abstracts, 2004, 1 page. cited by applicant XP002685934, Database Registry Chemical Abstracts, 2011, 1 page. cited by applicant XP002685935, Database Registry Chemical Abstracts, 2011, 1 page. cited by applicant XP002685936, Database Registry Chemical Abstracts, 2011, 1 page. cited by applicant XP002685937, Database Registry Chemical Abstracts, 2011, 1 page. cited by applicant XP002685938, Database Registry Chemical Abstracts, 2011, 1 page. cited by applicant XP002685939, Database Registry Chemical Abstracts, 2011, 1 page. cited by applicant XP002685940, Database Registry Chemical Abstracts, 2011, 1 page. cited by applicant XP002685941, Database Registry Chemical Abstracts, 2011, 1 page. cited by applicant XP002685942, Database Registry Chemical Abstracts, 2011, 1 page. cited by applicant XP002685943, Database Registry Chemical Abstracts, 2011, 1 page. cited by applicant XP002685944, Database Registry Chemical Abstracts, 2011, 1 page. cited by applicant R. Böhm et al., Pharmazie, 1986, 41, 23-25 (Compounds in the figure at the bottom of the left column on p. 23, the compounds of Tables 1 and 2 on p. 24, and the figure at the top of p. 25). cited by applicant |
| Primary Examiner: | Murray, Jeffrey H |
| Attorney, Agent or Firm: | McDonnell Boehnen Hulbert & Berghoff LLP |
| رقم الانضمام: | edspgr.09227984 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |