ES2279162T3 - Nuevos purin- o pirrolo(2,3-d)pirimidin-2-carbonitrilos para tratar enfermedades asociadas con actividad de cisteina proteasa. - Google Patents
Nuevos purin- o pirrolo(2,3-d)pirimidin-2-carbonitrilos para tratar enfermedades asociadas con actividad de cisteina proteasa. Download PDFInfo
- Publication number
- ES2279162T3 ES2279162T3 ES03761002T ES03761002T ES2279162T3 ES 2279162 T3 ES2279162 T3 ES 2279162T3 ES 03761002 T ES03761002 T ES 03761002T ES 03761002 T ES03761002 T ES 03761002T ES 2279162 T3 ES2279162 T3 ES 2279162T3
- Authority
- ES
- Spain
- Prior art keywords
- carbonitrile
- purin
- chlorophenyl
- alkyl
- hydrogen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 201000010099 disease Diseases 0.000 title description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 6
- 108010005843 Cysteine Proteases Proteins 0.000 title description 5
- 102000005927 Cysteine Proteases Human genes 0.000 title description 5
- 230000000694 effects Effects 0.000 title description 5
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 48
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 39
- 239000001257 hydrogen Substances 0.000 claims abstract description 38
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 28
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 28
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 26
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 20
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 17
- -1 amino, hydroxy Chemical group 0.000 claims abstract description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 14
- 125000003118 aryl group Chemical group 0.000 claims abstract description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 13
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 9
- 125000004429 atom Chemical group 0.000 claims abstract description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 4
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 3
- 239000012453 solvate Substances 0.000 claims abstract description 3
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 3
- 125000005843 halogen group Chemical group 0.000 claims abstract 6
- CDLFCUGNXCSXKZ-UHFFFAOYSA-N 7-(4-chlorophenyl)-4-morpholin-4-ylpyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1N1C2=NC(C#N)=NC(N3CCOCC3)=C2C=C1 CDLFCUGNXCSXKZ-UHFFFAOYSA-N 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 8
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- OHYNGDSTLQYXLP-UHFFFAOYSA-N 4-(4-chloroanilino)-7-ethylpyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C2N(CC)C=CC2=C1NC1=CC=C(Cl)C=C1 OHYNGDSTLQYXLP-UHFFFAOYSA-N 0.000 claims description 4
- KJGSMDDJESIJNG-UHFFFAOYSA-N 6-(4-chloroanilino)-9-ethylpurine-2-carbonitrile Chemical compound N1=C(C#N)N=C2N(CC)C=NC2=C1NC1=CC=C(Cl)C=C1 KJGSMDDJESIJNG-UHFFFAOYSA-N 0.000 claims description 4
- BWHVBFJJBFQDHY-UHFFFAOYSA-N 9-(2-chlorophenyl)-6-morpholin-4-ylpurine-2-carbonitrile Chemical compound ClC1=CC=CC=C1N1C2=NC(C#N)=NC(N3CCOCC3)=C2N=C1 BWHVBFJJBFQDHY-UHFFFAOYSA-N 0.000 claims description 4
- XUIHMMWMTLPFOD-UHFFFAOYSA-N 9-(4-chlorophenyl)-6-morpholin-4-ylpurine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1N1C2=NC(C#N)=NC(N3CCOCC3)=C2N=C1 XUIHMMWMTLPFOD-UHFFFAOYSA-N 0.000 claims description 4
- 208000002193 Pain Diseases 0.000 claims description 4
- DBYOJBZTUZLETB-UHFFFAOYSA-N 1-(4-methylphenyl)-4-morpholin-4-ylpyrazolo[3,4-d]pyrimidine-6-carbonitrile Chemical compound C1=CC(C)=CC=C1N1C2=NC(C#N)=NC(N3CCOCC3)=C2C=N1 DBYOJBZTUZLETB-UHFFFAOYSA-N 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- HIZRIHSRKDKKSH-UHFFFAOYSA-N 6-morpholin-4-yl-9-(4-propan-2-ylphenyl)purine-2-carbonitrile Chemical compound C1=CC(C(C)C)=CC=C1N1C2=NC(C#N)=NC(N3CCOCC3)=C2N=C1 HIZRIHSRKDKKSH-UHFFFAOYSA-N 0.000 claims description 3
- PCLZMBYSLWKOAK-UHFFFAOYSA-N 7-(4-chlorophenyl)-4-(ethylamino)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1=CC=2C(NCC)=NC(C#N)=NC=2N1C1=CC=C(Cl)C=C1 PCLZMBYSLWKOAK-UHFFFAOYSA-N 0.000 claims description 3
- TUXPZXDUIDXMKS-UHFFFAOYSA-N 7-(4-methoxyphenyl)-4-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1=CC(OC)=CC=C1N1C(N=C(N=C2N3CCOCC3)C#N)=C2CC1 TUXPZXDUIDXMKS-UHFFFAOYSA-N 0.000 claims description 3
- XNGFLKZGUISSFI-UHFFFAOYSA-N 7-(4-methoxyphenyl)-4-pyrrolidin-1-yl-5,6-dihydropyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1=CC(OC)=CC=C1N1C(N=C(N=C2N3CCCC3)C#N)=C2CC1 XNGFLKZGUISSFI-UHFFFAOYSA-N 0.000 claims description 3
- SADXVLLLVZNAIE-UHFFFAOYSA-N 8-amino-6-(4-chloroanilino)-9-ethylpurine-2-carbonitrile Chemical compound N1=C(C#N)N=C2N(CC)C(N)=NC2=C1NC1=CC=C(Cl)C=C1 SADXVLLLVZNAIE-UHFFFAOYSA-N 0.000 claims description 3
- YMNMAQWGBPDRTK-UHFFFAOYSA-N 8-amino-9-(4-chlorophenyl)-6-morpholin-4-ylpurine-2-carbonitrile Chemical compound NC1=NC2=C(N3CCOCC3)N=C(C#N)N=C2N1C1=CC=C(Cl)C=C1 YMNMAQWGBPDRTK-UHFFFAOYSA-N 0.000 claims description 3
- MVVBRPYXMOZGKI-UHFFFAOYSA-N 9-(3,4-difluorophenyl)-6-morpholin-4-ylpurine-2-carbonitrile Chemical compound C1=C(F)C(F)=CC=C1N1C2=NC(C#N)=NC(N3CCOCC3)=C2N=C1 MVVBRPYXMOZGKI-UHFFFAOYSA-N 0.000 claims description 3
- VBGBBKIHTJHISX-UHFFFAOYSA-N 9-(3-chlorophenyl)-6-morpholin-4-ylpurine-2-carbonitrile Chemical compound ClC1=CC=CC(N2C3=NC(=NC(=C3N=C2)N2CCOCC2)C#N)=C1 VBGBBKIHTJHISX-UHFFFAOYSA-N 0.000 claims description 3
- IUNJCEDNJBYIJD-UHFFFAOYSA-N 9-(4-chlorophenyl)-6-(4-pyrrolidin-1-ylpiperidin-1-yl)purine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1N1C2=NC(C#N)=NC(N3CCC(CC3)N3CCCC3)=C2N=C1 IUNJCEDNJBYIJD-UHFFFAOYSA-N 0.000 claims description 3
- CDHQZBPHQBCKQV-UHFFFAOYSA-N 9-(4-chlorophenyl)-6-(dimethylamino)purine-2-carbonitrile Chemical compound C1=NC=2C(N(C)C)=NC(C#N)=NC=2N1C1=CC=C(Cl)C=C1 CDHQZBPHQBCKQV-UHFFFAOYSA-N 0.000 claims description 3
- RFQMESZAJFZUBR-UHFFFAOYSA-N 9-(4-chlorophenyl)-6-(ethylamino)purine-2-carbonitrile Chemical compound C1=NC=2C(NCC)=NC(C#N)=NC=2N1C1=CC=C(Cl)C=C1 RFQMESZAJFZUBR-UHFFFAOYSA-N 0.000 claims description 3
- WMCPEBXOCLBPGC-UHFFFAOYSA-N 9-(4-chlorophenyl)-6-morpholin-4-yl-8-oxo-7h-purine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1N1C(=O)NC2=C(N3CCOCC3)N=C(C#N)N=C21 WMCPEBXOCLBPGC-UHFFFAOYSA-N 0.000 claims description 3
- UOMTYTKUUJJIBQ-UHFFFAOYSA-N 9-(4-chlorophenyl)-6-piperazin-1-ylpurine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1N1C2=NC(C#N)=NC(N3CCNCC3)=C2N=C1 UOMTYTKUUJJIBQ-UHFFFAOYSA-N 0.000 claims description 3
- WIVBKPYLSWPJQG-UHFFFAOYSA-N 9-(4-chlorophenyl)-6-pyrrolidin-1-ylpurine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1N1C2=NC(C#N)=NC(N3CCCC3)=C2N=C1 WIVBKPYLSWPJQG-UHFFFAOYSA-N 0.000 claims description 3
- PJKVLYWRACWXQS-UHFFFAOYSA-N 9-(4-chlorophenyl)-8-(dimethylamino)-6-morpholin-4-ylpurine-2-carbonitrile Chemical compound CN(C)C1=NC2=C(N3CCOCC3)N=C(C#N)N=C2N1C1=CC=C(Cl)C=C1 PJKVLYWRACWXQS-UHFFFAOYSA-N 0.000 claims description 3
- SGVMUUDCZGWPHJ-UHFFFAOYSA-N 9-(4-methoxyphenyl)-6-morpholin-4-ylpurine-2-carbonitrile Chemical compound C1=CC(OC)=CC=C1N1C2=NC(C#N)=NC(N3CCOCC3)=C2N=C1 SGVMUUDCZGWPHJ-UHFFFAOYSA-N 0.000 claims description 3
- HOVKNKINGXLBAW-UHFFFAOYSA-N 9-(4-methoxyphenyl)-6-pyrrolidin-1-ylpurine-2-carbonitrile Chemical compound C1=CC(OC)=CC=C1N1C2=NC(C#N)=NC(N3CCCC3)=C2N=C1 HOVKNKINGXLBAW-UHFFFAOYSA-N 0.000 claims description 3
- ZGNVAGDTSYPAJB-UHFFFAOYSA-N 9-(4-methylphenyl)-6-pyrrolidin-1-ylpurine-2-carbonitrile Chemical compound C1=CC(C)=CC=C1N1C2=NC(C#N)=NC(N3CCCC3)=C2N=C1 ZGNVAGDTSYPAJB-UHFFFAOYSA-N 0.000 claims description 3
- GCLKFJUHXFRUKP-UHFFFAOYSA-N 9-(4-methylsulfonylphenyl)-6-morpholin-4-ylpurine-2-carbonitrile Chemical compound C1=CC(S(=O)(=O)C)=CC=C1N1C2=NC(C#N)=NC(N3CCOCC3)=C2N=C1 GCLKFJUHXFRUKP-UHFFFAOYSA-N 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 208000004296 neuralgia Diseases 0.000 claims description 3
- 208000021722 neuropathic pain Diseases 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- ILVKKBYDRWXMGO-UHFFFAOYSA-N 6-(2-aminoethylamino)-9-(4-chlorophenyl)purine-2-carbonitrile Chemical compound C1=NC=2C(NCCN)=NC(C#N)=NC=2N1C1=CC=C(Cl)C=C1 ILVKKBYDRWXMGO-UHFFFAOYSA-N 0.000 claims description 2
- IJLSEYBZVOUGOY-UHFFFAOYSA-N 6-(4-aminopiperidin-1-yl)-9-(4-chlorophenyl)purine-2-carbonitrile Chemical compound C1CC(N)CCN1C1=NC(C#N)=NC2=C1N=CN2C1=CC=C(Cl)C=C1 IJLSEYBZVOUGOY-UHFFFAOYSA-N 0.000 claims description 2
- JQODVNYFMAKYFL-UHFFFAOYSA-N 9-(4-chlorophenyl)-6-(3-pyrrolidin-1-ylpropylamino)purine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1N1C2=NC(C#N)=NC(NCCCN3CCCC3)=C2N=C1 JQODVNYFMAKYFL-UHFFFAOYSA-N 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 10
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 2
- VKVJIWVUYNTBEZ-UHFFFAOYSA-N 1,3-bis(3,5-dichlorophenyl)urea Chemical compound ClC1=CC(Cl)=CC(NC(=O)NC=2C=C(Cl)C=C(Cl)C=2)=C1 VKVJIWVUYNTBEZ-UHFFFAOYSA-N 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 60
- 239000000203 mixture Substances 0.000 description 57
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
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- 239000000047 product Substances 0.000 description 33
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 30
- 235000019341 magnesium sulphate Nutrition 0.000 description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000004587 chromatography analysis Methods 0.000 description 17
- 239000000377 silicon dioxide Substances 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 13
- 229910052708 sodium Inorganic materials 0.000 description 13
- 239000011734 sodium Substances 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
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- 239000002904 solvent Substances 0.000 description 11
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- 108090000613 Cathepsin S Proteins 0.000 description 8
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- 102100035654 Cathepsin S Human genes 0.000 description 7
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 6
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- 230000005764 inhibitory process Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 150000002367 halogens Chemical group 0.000 description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 4
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- 238000004090 dissolution Methods 0.000 description 4
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- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 3
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
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- 230000007170 pathology Effects 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Pulmonology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0201980A SE0201980D0 (sv) | 2002-06-24 | 2002-06-24 | Novel compounds |
| SE0201980 | 2002-06-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2279162T3 true ES2279162T3 (es) | 2007-08-16 |
Family
ID=20288336
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES03761002T Expired - Lifetime ES2279162T3 (es) | 2002-06-24 | 2003-06-23 | Nuevos purin- o pirrolo(2,3-d)pirimidin-2-carbonitrilos para tratar enfermedades asociadas con actividad de cisteina proteasa. |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US7439240B2 (https=) |
| EP (1) | EP1532148B1 (https=) |
| JP (1) | JP2005533804A (https=) |
| AU (1) | AU2003243096A1 (https=) |
| DE (1) | DE60311272T2 (https=) |
| ES (1) | ES2279162T3 (https=) |
| SE (1) | SE0201980D0 (https=) |
| WO (1) | WO2004000843A1 (https=) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0117396D0 (en) | 2001-07-17 | 2001-09-05 | Glaxo Group Ltd | Chemical compounds |
| AR036375A1 (es) | 2001-08-30 | 2004-09-01 | Novartis Ag | Compuestos pirrolo [2,3-d] pirimidina -2- carbonitrilo, un proceso para su preparacion, una composicion farmaceutica y el uso de dichos compuestos para la preparacion de medicamentos |
| SE0201980D0 (sv) * | 2002-06-24 | 2002-06-24 | Astrazeneca Ab | Novel compounds |
| MXPA05007485A (es) * | 2003-01-14 | 2006-01-30 | Arena Pharm Inc | Derivados de arilo y heteroarilo 1,2,3-trisubstituidos como moduladores del metabolismo y la profilaxis y tratamiento de trastornos relacionados con ello tales como diabetes e hiperglicemia. |
| SI1599468T1 (sl) | 2003-01-14 | 2008-02-29 | Arena Pharm Inc | 1,2,3-trisubstituirani arilni in heteroarilni derivati kot modulatorji metabolizma ter profilaksa in zdravljenje motenj v zvezi z njim, kot diabetesain hiperglikemije |
| GB0308208D0 (en) | 2003-04-09 | 2003-05-14 | Glaxo Group Ltd | Chemical compounds |
| AR045047A1 (es) | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
| US7132426B2 (en) * | 2003-07-14 | 2006-11-07 | Arena Pharmaceuticals, Inc. | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
| WO2005085210A1 (ja) * | 2004-03-10 | 2005-09-15 | Ono Pharmaceutical Co., Ltd. | ニトリル化合物およびその化合物を有効成分として含有する医薬組成物 |
| TW200614993A (en) | 2004-06-11 | 2006-05-16 | Akzo Nobel Nv | 4-phenyl-pyrimidine-2-carbonitrile derivatives |
| TW200745055A (en) * | 2005-09-23 | 2007-12-16 | Organon Nv | 4-Phenyl-6-substituted-pyrimidine-2-carbonitrile derivatives |
| US7326715B2 (en) | 2005-09-23 | 2008-02-05 | N.V. Organon | 4-Phenyl-6-substituted-pyrimidine-2-carbonitrile derivatives |
| TW200734338A (en) * | 2006-01-16 | 2007-09-16 | Organon Nv | 6-Phenyl-1H-imidazo [4,5-c] pyridine-4-carbonitrile derivatives |
| US7687515B2 (en) | 2006-01-17 | 2010-03-30 | N.V. Organon | 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives |
| US20090227579A1 (en) * | 2006-06-23 | 2009-09-10 | Astrazeneca Ab | Pteridine Derivatives and their Use as Cathespin Inhibitors |
| US20090099157A1 (en) * | 2007-02-15 | 2009-04-16 | Ameriks Michael K | Tetrahydro-pyrazolo-pyridine thioether modulators of cathepsin s |
| US20080200454A1 (en) * | 2007-02-15 | 2008-08-21 | Ameriks Michael K | Carbon-linked tetrahydro-pyrazolo-pyridine modulators of cathepsin s |
| US20080207683A1 (en) * | 2007-02-15 | 2008-08-28 | Darin Allen | Biaryl-substituted tetrahydro-pyrazolo-pyridine modulators of cathepsin s |
| US20090118274A1 (en) * | 2007-02-15 | 2009-05-07 | Darin Allen | Monocyclic aminopropyl tetrahydro-pyrazolo-pyridine modulators of cathepsin s |
| US20080269241A1 (en) * | 2007-02-15 | 2008-10-30 | Darin Allen | Bicyclic aminopropyl tetrahydro-pyrazolo-pyridine modulators of cathepsin s |
| EP2118106A1 (en) * | 2007-03-02 | 2009-11-18 | Glaxo Group Limited | Purines as cysteine protease inhibitors |
| EP1972630A1 (en) * | 2007-03-02 | 2008-09-24 | Glaxo Group Limited | Purines as cysteine protease inhibitors |
| TW200911803A (en) * | 2007-07-16 | 2009-03-16 | Organon Nv | 6-phenyl-1H-imidazo [4,5-c] pyridine-4-carbonitrile derivatives |
| US7932251B2 (en) | 2007-07-16 | 2011-04-26 | N.V. Organon | 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives |
| WO2009107767A1 (ja) * | 2008-02-29 | 2009-09-03 | 大日本住友製薬株式会社 | Ｈ４受容体アンタゴニスト作用を有する新規２環性ピリミジン誘導体 |
| US8193202B2 (en) | 2008-04-21 | 2012-06-05 | Lexicon Pharmaceuticals, Inc. | LIMK2 inhibitors, compositions comprising them, and methods of their use |
| WO2010059418A1 (en) * | 2008-11-19 | 2010-05-27 | The Government Of The U.S.A. As Represented By The Secretary Of The Dept. Of Health & Human Services | Substituted triazine and purine compounds, methods of inhibiting cruzain and rhodesain and methods of treating chagas disease and african trypanosomiasis |
| TW201035094A (en) | 2009-01-16 | 2010-10-01 | Organon Nv | 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives |
| US8026236B2 (en) | 2009-01-16 | 2011-09-27 | N.V. Organon | 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives |
| GB0917934D0 (en) | 2009-10-13 | 2009-11-25 | Syngenta Ltd | Herbicidal compounds |
| WO2011086125A1 (en) | 2010-01-15 | 2011-07-21 | N.V. Organon | 1H-[1,2,3]TRIAZOLO[4,5-c]PYRIDINE-4-CARBONITRILE DERIVATIVES |
| PH12013500547A1 (en) | 2010-09-22 | 2013-06-10 | Arena Pharm Inc | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| CN108192972B (zh) | 2010-10-06 | 2022-09-09 | 生物医学研究机构基金会 | 用于乳腺癌转移的诊断、预后和治疗的方法 |
| EP2650682A1 (en) | 2012-04-09 | 2013-10-16 | Fundació Privada Institut de Recerca Biomèdica | Method for the prognosis and treatment of cancer metastasis |
| ES2644965T3 (es) * | 2012-04-17 | 2017-12-01 | Astellas Pharma Inc. | Compuesto heterocíclico aromático bicíclico nitrogenado |
| BR112014030750A2 (pt) | 2012-06-06 | 2017-08-22 | Inst Catalana Recerca Estudis Avancats | Método para diagnóstico, prognóstico e tratamento da metástase do câncer pulmonar |
| ES2906586T3 (es) | 2012-10-12 | 2022-04-19 | Inbiomotion Sl | Método para el diagnóstico, pronóstico y tratamiento de metástasis de cáncer de próstata |
| US10119171B2 (en) | 2012-10-12 | 2018-11-06 | Inbiomotion S.L. | Method for the diagnosis, prognosis and treatment of prostate cancer metastasis |
| MD20150037A2 (ro) | 2012-11-08 | 2015-11-30 | Pfizer Inc. | Compuşi heteroaromatici şi utilizarea lor ca liganzi de dopamină D1 |
| CA2906394A1 (en) | 2013-03-15 | 2014-09-18 | Fundacio Institut De Recerca Biomedica (Irb Barcelona) | Method for the prognosis and treatment of cancer metastasis |
| WO2014184679A2 (en) | 2013-03-15 | 2014-11-20 | Inbiomotion S.L. | Method for the prognosis and treatment of renal cell carcinoma metastasis |
| DK3055429T3 (en) | 2013-10-09 | 2019-04-23 | Fundacio Inst De Recerca Biomedica Irb Barcelona | Procedure for the prognosis and treatment of metastatic bone cancer resulting from breast cancer |
| EP3137469B1 (en) | 2014-04-28 | 2019-10-09 | Pfizer Inc | Heterocyclic compounds and their use as dopamine d1 ligands |
| HRP20220522T1 (hr) | 2014-08-04 | 2022-06-10 | Nuevolution A/S | Proizvoljno kondenzirani heterociklil-supstituirani derivati pirimidina koji su korisni za liječenje upalnih, metaboličkih, onkoloških i autoimunih bolesti |
| KR20170093182A (ko) | 2014-12-11 | 2017-08-14 | 인바이오모션 에스.엘. | 인간 c-maf에 대한 결합 구성원 |
| MX386419B (es) | 2015-01-06 | 2025-03-18 | Arena Pharm Inc | Metodos de condiciones de tratamiento relacionadas con el receptor s1p1. |
| EP3939965A1 (en) | 2015-06-22 | 2022-01-19 | Arena Pharmaceuticals, Inc. | Crystalline l-arginine salt of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl)acetic acid for use in sipi receptor-associated disorders |
| US11596642B2 (en) | 2016-05-25 | 2023-03-07 | Inbiomotion S.L. | Therapeutic treatment of breast cancer based on c-MAF status |
| MA47504A (fr) | 2017-02-16 | 2019-12-25 | Arena Pharm Inc | Composés et méthodes de traitement de l'angiocholite biliaire primitive |
| KR20200104298A (ko) | 2017-11-22 | 2020-09-03 | 인바이오모션 에스.엘. | c-MAF 상태에 기반한 유방암의 요법 치료 |
| KR102054910B1 (ko) * | 2017-12-19 | 2019-12-12 | 한림제약(주) | 피롤로[2,3-d]피리미딘 유도체 또는 이의 염 및 이를 포함하는 약학 조성물 |
| ES2987794T3 (es) | 2018-06-06 | 2024-11-18 | Arena Pharm Inc | Procedimientos de tratamiento de afecciones relacionadas con el receptor S1P1 |
| AU2020250933A1 (en) | 2019-04-05 | 2021-10-28 | Centre Hospitalier Régional Et Universitaire De Brest | Protease-activated receptor-2 inhibitors for the treatment of sensory neuropathy induced by a marine neurotoxic poisoning |
| MX2022007265A (es) | 2019-12-20 | 2022-09-09 | Nuevolution As | Compuestos activos frente a receptores nucleares. |
| US11685727B2 (en) | 2019-12-20 | 2023-06-27 | Nuevolution A/S | Compounds active towards nuclear receptors |
| CA3174176A1 (en) | 2020-03-31 | 2021-10-07 | Sanne Schroder Glad | Compounds active towards nuclear receptors |
| EP4126874A1 (en) | 2020-03-31 | 2023-02-08 | Nuevolution A/S | Compounds active towards nuclear receptors |
| WO2024105159A1 (en) * | 2022-11-16 | 2024-05-23 | University Of Zurich | Ligands of the m6a-rna readers |
| CN121652156A (zh) * | 2024-09-13 | 2026-03-13 | 常州强力电子新材料股份有限公司 | 一种氮杂腺嘌呤化合物及其制备方法与应用 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1362947A (zh) | 1999-03-15 | 2002-08-07 | Axys药物公司 | 用作蛋白酶抑制剂的n－氰基甲基酰胺 |
| JP2001011037A (ja) * | 1999-07-01 | 2001-01-16 | Kissei Pharmaceut Co Ltd | シクロアルカンカルボン酸アミド誘導体 |
| US20020103161A1 (en) * | 1999-12-17 | 2002-08-01 | Manfred Weigele | Novel heterocycles |
| EP1252154A1 (en) * | 2000-02-04 | 2002-10-30 | Pfizer Products Inc. | Heterocyclic amide derivatives |
| US6921753B2 (en) * | 2000-06-27 | 2005-07-26 | Pfizer Inc | Purine derivatives |
| GB0015727D0 (en) * | 2000-06-27 | 2000-08-16 | Pfizer Ltd | Purine derivatives |
| EP1326848A1 (en) | 2000-10-19 | 2003-07-16 | Naeja Pharmaceutical Inc. | Dihydropyrimidine derivatives as cysteine protease inhibitors |
| AR036375A1 (es) | 2001-08-30 | 2004-09-01 | Novartis Ag | Compuestos pirrolo [2,3-d] pirimidina -2- carbonitrilo, un proceso para su preparacion, una composicion farmaceutica y el uso de dichos compuestos para la preparacion de medicamentos |
| GB0121033D0 (en) | 2001-08-30 | 2001-10-24 | Novartis Ag | Organic compounds |
| SE0201980D0 (sv) * | 2002-06-24 | 2002-06-24 | Astrazeneca Ab | Novel compounds |
| SE0201976D0 (sv) * | 2002-06-24 | 2002-06-24 | Astrazeneca Ab | Novel compounds |
| GB0220187D0 (en) * | 2002-08-30 | 2002-10-09 | Novartis Ag | Organic compounds |
| AR043692A1 (es) | 2003-02-06 | 2005-08-10 | Novartis Ag | 2-cianopirrolopirimidinas y sus usos farmaceuticos |
| GB0304640D0 (en) | 2003-02-28 | 2003-04-02 | Novartis Ag | Organic compounds |
| WO2005085210A1 (ja) | 2004-03-10 | 2005-09-15 | Ono Pharmaceutical Co., Ltd. | ニトリル化合物およびその化合物を有効成分として含有する医薬組成物 |
| WO2006040300A1 (en) | 2004-10-12 | 2006-04-20 | N.V. Organon | 4-cycloalkyl-pyrimidine-2-carbonitrile derivatives |
-
2002
- 2002-06-24 SE SE0201980A patent/SE0201980D0/xx unknown
-
2003
- 2003-06-23 DE DE60311272T patent/DE60311272T2/de not_active Expired - Fee Related
- 2003-06-23 JP JP2004515329A patent/JP2005533804A/ja active Pending
- 2003-06-23 AU AU2003243096A patent/AU2003243096A1/en not_active Abandoned
- 2003-06-23 US US10/518,815 patent/US7439240B2/en not_active Expired - Fee Related
- 2003-06-23 ES ES03761002T patent/ES2279162T3/es not_active Expired - Lifetime
- 2003-06-23 EP EP03761002A patent/EP1532148B1/en not_active Expired - Lifetime
- 2003-06-23 WO PCT/SE2003/001079 patent/WO2004000843A1/en not_active Ceased
-
2008
- 2008-02-01 US US12/024,375 patent/US20080125426A1/en not_active Abandoned
- 2008-02-01 US US12/024,423 patent/US20080119469A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20080125426A1 (en) | 2008-05-29 |
| WO2004000843A1 (en) | 2003-12-31 |
| AU2003243096A1 (en) | 2004-01-06 |
| US7439240B2 (en) | 2008-10-21 |
| EP1532148B1 (en) | 2007-01-17 |
| US20080119469A1 (en) | 2008-05-22 |
| SE0201980D0 (sv) | 2002-06-24 |
| DE60311272T2 (de) | 2007-11-15 |
| JP2005533804A (ja) | 2005-11-10 |
| US20050203107A1 (en) | 2005-09-15 |
| EP1532148A1 (en) | 2005-05-25 |
| DE60311272D1 (de) | 2007-03-08 |
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