JP2005533804A - システイン・プロテアーゼ活性に関係する疾患を処置するための新規プリン−もしくはピロール−［２，３−ｄ］ピリミジン−２−カルボニトリル - Google Patents
システイン・プロテアーゼ活性に関係する疾患を処置するための新規プリン−もしくはピロール−［２，３−ｄ］ピリミジン−２−カルボニトリル Download PDFInfo
- Publication number
- JP2005533804A JP2005533804A JP2004515329A JP2004515329A JP2005533804A JP 2005533804 A JP2005533804 A JP 2005533804A JP 2004515329 A JP2004515329 A JP 2004515329A JP 2004515329 A JP2004515329 A JP 2004515329A JP 2005533804 A JP2005533804 A JP 2005533804A
- Authority
- JP
- Japan
- Prior art keywords
- carbonitrile
- chlorophenyl
- purine
- alkyl
- morpholin
- 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.)
- Pending
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- 108010005843 Cysteine Proteases Proteins 0.000 title claims abstract description 13
- 102000005927 Cysteine Proteases Human genes 0.000 title claims abstract description 13
- 201000010099 disease Diseases 0.000 title abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 8
- 230000000694 effects Effects 0.000 title abstract description 5
- IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 51
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 21
- 108090000613 Cathepsin S Proteins 0.000 claims abstract description 11
- 102100035654 Cathepsin S Human genes 0.000 claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 26
- -1 amino, hydroxy Chemical group 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 13
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 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
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 7
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 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
- 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
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 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
- 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 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
- 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 3
- 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 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
- 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 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
- 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 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
- 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
- 241000124008 Mammalia Species 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 208000004296 neuralgia Diseases 0.000 claims description 3
- 208000021722 neuropathic pain Diseases 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 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 55
- 239000003112 inhibitor Substances 0.000 abstract description 4
- 229910052700 potassium Inorganic materials 0.000 abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 abstract description 2
- 239000013037 reversible inhibitor Substances 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 60
- 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 45
- 239000000243 solution Substances 0.000 description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 34
- 238000005160 1H NMR spectroscopy Methods 0.000 description 33
- 239000000047 product Substances 0.000 description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 239000012044 organic layer Substances 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 7
- 229940001584 sodium metabisulfite Drugs 0.000 description 7
- 235000010262 sodium metabisulphite Nutrition 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
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- 238000003756 stirring Methods 0.000 description 6
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 5
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
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- 238000001990 intravenous administration Methods 0.000 description 3
- FEONFRLLHYXTEZ-UHFFFAOYSA-N methyl 2,2-diethoxyacetate Chemical compound CCOC(OCC)C(=O)OC FEONFRLLHYXTEZ-UHFFFAOYSA-N 0.000 description 3
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- 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 2
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- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
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- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
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- 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
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- 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
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- 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 |
| PCT/SE2003/001079 WO2004000843A1 (en) | 2002-06-24 | 2003-06-23 | NOVEL PURINE- OR PYRROLOL[2,3-d]PYRIMIDINE-2-CARBONITILES FOR TREATING DISEASES ASSOCIATED WITH CYSTEINE PROTEASE ACTIVITY |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005533804A true JP2005533804A (ja) | 2005-11-10 |
| JP2005533804A5 JP2005533804A5 (https=) | 2006-08-10 |
Family
ID=20288336
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004515329A Pending JP2005533804A (ja) | 2002-06-24 | 2003-06-23 | システイン・プロテアーゼ活性に関係する疾患を処置するための新規プリン−もしくはピロール−［２，３−ｄ］ピリミジン−２−カルボニトリル |
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=) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009523717A (ja) * | 2006-01-16 | 2009-06-25 | ナームローゼ・フエンノートチヤツプ・オルガノン | カテプシンＫおよびＳの阻害剤としての６−フェニル−ＩＨ−イミダゾ［４，５−ｃ］ピリジン−４−カルボニトリル誘導体 |
| 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 |
| JP2010533675A (ja) * | 2007-07-16 | 2010-10-28 | ナームローゼ・フエンノートチヤツプ・オルガノン | カテプシン阻害剤としての６−フェニル−１Ｈ−イミダゾ［４，５−ｃ］ピリジン−４−カルボニトリル誘導体 |
| WO2013157562A1 (ja) * | 2012-04-17 | 2013-10-24 | アステラス製薬株式会社 | 含窒素二環式芳香族へテロ環化合物 |
| KR20190073673A (ko) * | 2017-12-19 | 2019-06-27 | 한림제약(주) | 피롤로[2,3-d]피리미딘 유도체 또는 이의 염 및 이를 포함하는 약학 조성물 |
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| 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 |
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| TW201035094A (en) | 2009-01-16 | 2010-10-01 | Organon Nv | 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives |
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| 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 |
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| 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 |
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| 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 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002000676A1 (en) * | 2000-06-27 | 2002-01-03 | Pfizer Limited | Purine derivatives |
Family Cites Families (15)
| 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 |
| 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
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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
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002000676A1 (en) * | 2000-06-27 | 2002-01-03 | Pfizer Limited | Purine derivatives |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009523717A (ja) * | 2006-01-16 | 2009-06-25 | ナームローゼ・フエンノートチヤツプ・オルガノン | カテプシンＫおよびＳの阻害剤としての６−フェニル−ＩＨ−イミダゾ［４，５−ｃ］ピリジン−４−カルボニトリル誘導体 |
| JP2010533675A (ja) * | 2007-07-16 | 2010-10-28 | ナームローゼ・フエンノートチヤツプ・オルガノン | カテプシン阻害剤としての６−フェニル−１Ｈ−イミダゾ［４，５−ｃ］ピリジン−４−カルボニトリル誘導体 |
| 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 |
| WO2013157562A1 (ja) * | 2012-04-17 | 2013-10-24 | アステラス製薬株式会社 | 含窒素二環式芳香族へテロ環化合物 |
| JPWO2013157562A1 (ja) * | 2012-04-17 | 2015-12-21 | アステラス製薬株式会社 | 含窒素二環式芳香族へテロ環化合物 |
| US9328118B2 (en) | 2012-04-17 | 2016-05-03 | Astellas Pharma Inc. | Nitrogen-containing bicyclic aromatic heterocyclic compound |
| EA026088B1 (ru) * | 2012-04-17 | 2017-02-28 | Астеллас Фарма Инк. | Азотсодержащее бициклическое ароматическое гетероциклическое соединение |
| US9585889B2 (en) | 2012-04-17 | 2017-03-07 | Astellas Pharma Inc. | Nitrogen-containing bicyclic aromatic heterocyclic compound |
| KR20190073673A (ko) * | 2017-12-19 | 2019-06-27 | 한림제약(주) | 피롤로[2,3-d]피리미딘 유도체 또는 이의 염 및 이를 포함하는 약학 조성물 |
| KR102054910B1 (ko) | 2017-12-19 | 2019-12-12 | 한림제약(주) | 피롤로[2,3-d]피리미딘 유도체 또는 이의 염 및 이를 포함하는 약학 조성물 |
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 |
| US20050203107A1 (en) | 2005-09-15 |
| EP1532148A1 (en) | 2005-05-25 |
| ES2279162T3 (es) | 2007-08-16 |
| DE60311272D1 (de) | 2007-03-08 |
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