JP2003522189A5 - - Google Patents
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- JP2003522189A5 JP2003522189A5 JP2001558051A JP2001558051A JP2003522189A5 JP 2003522189 A5 JP2003522189 A5 JP 2003522189A5 JP 2001558051 A JP2001558051 A JP 2001558051A JP 2001558051 A JP2001558051 A JP 2001558051A JP 2003522189 A5 JP2003522189 A5 JP 2003522189A5
- Authority
- JP
- Japan
- Prior art keywords
- amino
- thio
- methyl
- product
- purin
- 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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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 51
- 150000001875 compounds Chemical class 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 38
- 239000000047 product Substances 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 35
- 239000000243 solution Substances 0.000 description 28
- 239000007787 solid Substances 0.000 description 24
- 239000000203 mixture Substances 0.000 description 21
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 17
- 125000005843 halogen group Chemical group 0.000 description 17
- 125000001424 substituent group Chemical group 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 125000000217 alkyl group Chemical group 0.000 description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 10
- 239000012453 solvate Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 206010039083 rhinitis Diseases 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- -1 2,3-difluorophenyl Chemical group 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 206010025135 lupus erythematosus Diseases 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- BKMMTJMQCTUHRP-GSVOUGTGSA-N (2r)-2-aminopropan-1-ol Chemical compound C[C@@H](N)CO BKMMTJMQCTUHRP-GSVOUGTGSA-N 0.000 description 3
- 0 CCOC(Nc([n]1)nc(c(*)n2)c1nc2S)=O Chemical compound CCOC(Nc([n]1)nc(c(*)n2)c1nc2S)=O 0.000 description 3
- 102000009410 Chemokine receptor Human genes 0.000 description 3
- 108050000299 Chemokine receptor Proteins 0.000 description 3
- 108010012236 Chemokines Proteins 0.000 description 3
- 102000019034 Chemokines Human genes 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- ADEMRMNQYDVKRV-SECBINFHSA-N (2r)-2-[[8-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]butan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)CC)=NC=1SCC1=CC=CC(F)=C1F ADEMRMNQYDVKRV-SECBINFHSA-N 0.000 description 2
- VNGOAGLZSGVQHX-SSDOTTSWSA-N (2r)-2-[[8-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F VNGOAGLZSGVQHX-SSDOTTSWSA-N 0.000 description 2
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
- FTBSGSZZESQDBM-UHFFFAOYSA-N 1-(bromomethyl)-2,3-difluorobenzene Chemical compound FC1=CC=CC(CBr)=C1F FTBSGSZZESQDBM-UHFFFAOYSA-N 0.000 description 2
- MCBMLPDEXRAKDO-MRVPVSSYSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one Chemical compound N=1C=2NC(=O)CC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F MCBMLPDEXRAKDO-MRVPVSSYSA-N 0.000 description 2
- JKVINFJVZJHNLK-UHFFFAOYSA-N 2-[[8-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]-2-methylpropan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(NC(C)(CO)C)=NC=1SCC1=CC=CC(F)=C1F JKVINFJVZJHNLK-UHFFFAOYSA-N 0.000 description 2
- PYMFWZQOVMSEJK-UHFFFAOYSA-N 2-[[8-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]-2-methylpropane-1,3-diol Chemical compound N=1C=2NC(N)=NC=2C(NC(CO)(CO)C)=NC=1SCC1=CC=CC(F)=C1F PYMFWZQOVMSEJK-UHFFFAOYSA-N 0.000 description 2
- KSTLGFMLCSREDG-UHFFFAOYSA-N 2-[[8-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]propane-1,3-diol Chemical compound N1=C2NC(N)=NC2=C(NC(CO)CO)N=C1SCC1=CC=CC(F)=C1F KSTLGFMLCSREDG-UHFFFAOYSA-N 0.000 description 2
- RURRPCNSHIMRGD-SECBINFHSA-N 2-benzylsulfanyl-6-[[(2r)-1-hydroxypropan-2-yl]amino]-7,9-dihydropurin-8-one Chemical compound N=1C=2NC(=O)NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC=C1 RURRPCNSHIMRGD-SECBINFHSA-N 0.000 description 2
- UUQYSXBFJGFLKV-UHFFFAOYSA-N 4-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one Chemical compound N=1C=2NC(=O)CC=2C(N)=NC=1SCC1=CC=CC(F)=C1F UUQYSXBFJGFLKV-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 201000008283 Atrophic Rhinitis Diseases 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 102000002791 Interleukin-8B Receptors Human genes 0.000 description 2
- 108010018951 Interleukin-8B Receptors Proteins 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- 206010039088 Rhinitis atrophic Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- KJOWSAVFSCSBMZ-UHFFFAOYSA-N (2,4-dimethoxyphenyl)methylazanium;chloride Chemical compound Cl.COC1=CC=C(CN)C(OC)=C1 KJOWSAVFSCSBMZ-UHFFFAOYSA-N 0.000 description 1
- HNISIXROLNYCDM-SECBINFHSA-N (2r)-2-[(8-amino-2-benzylsulfanyl-7h-purin-6-yl)amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC=C1 HNISIXROLNYCDM-SECBINFHSA-N 0.000 description 1
- GDTREHIOQWBWJN-SECBINFHSA-N (2r)-2-[[6-amino-2-[(2-fluorophenyl)methylsulfanyl]pyrimidin-4-yl]amino]propan-1-ol Chemical compound OC[C@@H](C)NC1=CC(N)=NC(SCC=2C(=CC=CC=2)F)=N1 GDTREHIOQWBWJN-SECBINFHSA-N 0.000 description 1
- MKLKVMAYCTWMMU-MRVPVSSYSA-N (2r)-2-[[8-amino-2-(1,3-benzodioxol-4-ylmethylsulfanyl)-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC2=C1OCO2 MKLKVMAYCTWMMU-MRVPVSSYSA-N 0.000 description 1
- QVHDGKCBQUZUBN-MRVPVSSYSA-N (2r)-2-[[8-amino-2-[(2-bromophenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC=C1Br QVHDGKCBQUZUBN-MRVPVSSYSA-N 0.000 description 1
- PKZKDRUQEOVESZ-MRVPVSSYSA-N (2r)-2-[[8-amino-2-[(2-fluorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC=C1F PKZKDRUQEOVESZ-MRVPVSSYSA-N 0.000 description 1
- NYPVTAVIUQXVBD-SNVBAGLBSA-N (2r)-2-[[8-amino-2-[(2-methylphenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC=C1C NYPVTAVIUQXVBD-SNVBAGLBSA-N 0.000 description 1
- ROEMIMZCSNFQTP-SSDOTTSWSA-N (2r)-2-[[8-amino-2-[(3-chloro-2-fluorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(Cl)=C1F ROEMIMZCSNFQTP-SSDOTTSWSA-N 0.000 description 1
- YWPYWSARFFOWGB-MRVPVSSYSA-N (2r)-2-[[8-amino-2-[(3-chloro-4-methoxyphenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound C1=C(Cl)C(OC)=CC=C1CSC1=NC(N[C@H](C)CO)=C(N=C(N)N2)C2=N1 YWPYWSARFFOWGB-MRVPVSSYSA-N 0.000 description 1
- FYJXTHIJKZOBDD-MRVPVSSYSA-N (2r)-2-[[8-amino-2-[(3-chlorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(Cl)=C1 FYJXTHIJKZOBDD-MRVPVSSYSA-N 0.000 description 1
- ANEZWBQXYCKHBF-SECBINFHSA-N (2r)-2-[[8-amino-2-[(3-methoxyphenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound COC1=CC=CC(CSC=2N=C3NC(N)=NC3=C(N[C@H](C)CO)N=2)=C1 ANEZWBQXYCKHBF-SECBINFHSA-N 0.000 description 1
- TUZBVXBBJUMRKH-SNVBAGLBSA-N (2r)-2-[[8-amino-2-[(3-methylphenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(C)=C1 TUZBVXBBJUMRKH-SNVBAGLBSA-N 0.000 description 1
- UHMAUIOYRZTETM-SNVBAGLBSA-N (2r)-2-[[8-amino-2-[(4-methylphenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=C(C)C=C1 UHMAUIOYRZTETM-SNVBAGLBSA-N 0.000 description 1
- JCBPETKZIGVZRE-SCSAIBSYSA-N (2r)-2-aminobutan-1-ol Chemical compound CC[C@@H](N)CO JCBPETKZIGVZRE-SCSAIBSYSA-N 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- BKMMTJMQCTUHRP-VKHMYHEASA-N (S)-2-aminopropan-1-ol Chemical compound C[C@H](N)CO BKMMTJMQCTUHRP-VKHMYHEASA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- UUSHWADNFWAUQP-UHFFFAOYSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-5-nitrosopyrimidine-4,6-diamine Chemical compound NC1=C(N=O)C(N)=NC(SCC=2C(=C(F)C=CC=2)F)=N1 UUSHWADNFWAUQP-UHFFFAOYSA-N 0.000 description 1
- SYZOJSBWVZKNNP-UHFFFAOYSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]pyrimidine-4,5,6-triamine Chemical compound NC1=C(N)C(N)=NC(SCC=2C(=C(F)C=CC=2)F)=N1 SYZOJSBWVZKNNP-UHFFFAOYSA-N 0.000 description 1
- QDUYLZMCFOXYAB-UHFFFAOYSA-N 2-[2-[(2,3-difluorophenyl)methylsulfanyl]-4-hydroxy-6-oxo-1h-pyrimidin-5-yl]acetic acid Chemical compound N1=C(O)C(CC(=O)O)=C(O)N=C1SCC1=CC=CC(F)=C1F QDUYLZMCFOXYAB-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- JWTXBTQLUWRAGK-UHFFFAOYSA-N 2-[4-chloro-2-[(2,3-difluorophenyl)methylsulfanyl]-6-[(2,4-dimethoxyphenyl)methylamino]pyrimidin-5-yl]acetic acid Chemical compound COC1=CC(OC)=CC=C1CNC1=NC(SCC=2C(=C(F)C=CC=2)F)=NC(Cl)=C1CC(O)=O JWTXBTQLUWRAGK-UHFFFAOYSA-N 0.000 description 1
- VOUCOPWIMWCBPG-UHFFFAOYSA-N 2-[[8-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]ethanol Chemical compound N1=C2NC(N)=NC2=C(NCCO)N=C1SCC1=CC=CC(F)=C1F VOUCOPWIMWCBPG-UHFFFAOYSA-N 0.000 description 1
- 229940058020 2-amino-2-methyl-1-propanol Drugs 0.000 description 1
- UXFQFBNBSPQBJW-UHFFFAOYSA-N 2-amino-2-methylpropane-1,3-diol Chemical compound OCC(N)(C)CO UXFQFBNBSPQBJW-UHFFFAOYSA-N 0.000 description 1
- KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 description 1
- FONJIJWCXJZLND-UHFFFAOYSA-N 2-benzylsulfanyl-4,6-dichloro-5-nitropyrimidine Chemical compound N1=C(Cl)C([N+](=O)[O-])=C(Cl)N=C1SCC1=CC=CC=C1 FONJIJWCXJZLND-UHFFFAOYSA-N 0.000 description 1
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| GB2359081A (en) | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active thiazolopyrimidines |
| DE60101372T2 (de) * | 2000-02-11 | 2004-10-14 | Astrazeneca Ab | Pyrimidinverbindungen und ihre verwendung als modulatoren der chemokin-rezeptor-aktivität |
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| SE0102716D0 (sv) * | 2001-08-14 | 2001-08-14 | Astrazeneca Ab | Novel compounds |
| EP2402310A1 (en) * | 2002-05-24 | 2012-01-04 | Millennium Pharmaceuticals, Inc. | CCR9 inhibitors and methods of use thereof |
| GB0217431D0 (en) | 2002-07-27 | 2002-09-04 | Astrazeneca Ab | Novel compounds |
| DE60318219T2 (de) | 2002-08-24 | 2009-01-15 | Astrazeneca Ab | PYRIMIDINDERIVATE ALS MODULATOREN DER AKTIVITuT VON CHEMOKINREZEPTOREN |
| GB0221828D0 (en) * | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| GB0221829D0 (en) * | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| GB0328243D0 (en) | 2003-12-05 | 2004-01-07 | Astrazeneca Ab | Methods |
| GB0401269D0 (en) * | 2004-01-21 | 2004-02-25 | Astrazeneca Ab | Compounds |
| DE602004009166T2 (de) * | 2004-06-29 | 2008-08-21 | Grünenthal GmbH | Neue Analoga von Nitrobenzylthioinosin |
| BRPI0514735B8 (pt) | 2004-08-28 | 2021-05-25 | Astrazeneca Ab | derivados de pirimidino sulfonamida como moduladores do receptor de quimiocina. |
| AU2008305633B2 (en) * | 2007-09-25 | 2013-09-12 | Actimis Pharmaceuticals, Inc. | 2-S-benzyl substituted pyrimidines as CRTH2 antagonists |
| ATE547407T1 (de) | 2007-09-25 | 2012-03-15 | Actimis Pharmaceuticals Inc | Alkylthiopyrimidine als crth2-antagonisten |
| EP2373317B1 (en) * | 2008-11-25 | 2016-12-14 | Merck Sharp & Dohme Corp. | 4-amino-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one or 4-amino-5,8-dihydropyrido[2,3-d]pyrimidin-7(6H)-one derivatives as activators of the soluble guanylat cyclase for the treatment of cardiovascular diseases |
| PT2616444E (pt) * | 2010-09-14 | 2015-12-09 | Inst Biochemii I Biofizyki Pan | Compostos como moduladores de uma proteína cftr mutante e seu uso para tratar doenças associadas à disfunção da proteína cftr |
| CN109020882A (zh) * | 2018-08-09 | 2018-12-18 | 杭州华东医药集团浙江华义制药有限公司 | 3,5-二氯-2-氰基吡啶的合成方法 |
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| US3318900A (en) * | 1964-05-06 | 1967-05-09 | Janssen Pharmaceutica Nv | Derivatives of benzimidazolinyl piperidine |
| DE2331223C2 (de) | 1972-06-19 | 1984-11-22 | Kohjin Co., Ltd., Tokio / Tokyo | S-substituierte-2-Thioadenosine, deren 5'-Monophosphate, Verfahren zu deren Herstellung und Arzneimittel, welche diese enthalten |
| JPS5188994A (en) * | 1975-02-04 | 1976-08-04 | Shinkijichikan 88 aminoadeninjudotainoseizoho | |
| EG12406A (en) * | 1976-08-12 | 1979-03-31 | Janssen Pharmaceutica Nv | Process for preparing of novel n-aryl-n-(1-l-4-piperidinyl)-arylacetamides |
| FR2421899A1 (fr) * | 1978-01-16 | 1979-11-02 | Roussel Uclaf | Nouveaux derives du tetrahydropyridinyl-indole et leurs sels, le procede de preparation et l'application a titre de medicaments de ces nouveaux produits |
| US4410528A (en) * | 1980-05-16 | 1983-10-18 | Kyowa Hakko Kogyo Co., Ltd. | Hypotensive piperidine derivatives |
| CA1338012C (en) | 1987-04-27 | 1996-01-30 | John Michael Mccall | Pharmaceutically active amines |
| FR2659656B1 (fr) | 1990-03-15 | 1994-09-09 | Sanofi Sa | Derives de pyrimidinedione-2,4 et medicaments les contenant. |
| DE4119767A1 (de) | 1991-06-15 | 1992-12-17 | Dresden Arzneimittel | Verfahren zur herstellung von (pyrimid-2-yl-thio- bzw. seleno)-essigsaeurederivaten |
| US5521197A (en) * | 1994-12-01 | 1996-05-28 | Eli Lilly And Company | 3-<1-alkylenearyl>-4-<1,2,3,6-tetrahydropyridinyl>-and 3-<1-alkylenearyl>-4-piperidinyl-1h-indoles: new 5-HT1F agonists |
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| WO1997040035A1 (en) | 1996-04-19 | 1997-10-30 | Neurosearch A/S | 1-(4-piperidyl)-benzimidazoles having neurotrophic activity |
| BR9711970A (pt) * | 1996-08-28 | 1999-08-24 | Pfizer | Derivados 6,5-substitu¡do-heterobic¡clicos |
| AU5522498A (en) * | 1996-12-13 | 1998-07-03 | Merck & Co., Inc. | Substituted aryl piperazines as modulators of chemokine receptor activity |
| JP2002510327A (ja) | 1997-07-25 | 2002-04-02 | メルク エンド カンパニー インコーポレーテッド | 環状アミンケモカイン受容体活性調節剤 |
| AR013669A1 (es) | 1997-10-07 | 2001-01-10 | Smithkline Beecham Corp | Compuestos y metodos |
| KR100613634B1 (ko) * | 1997-11-28 | 2006-08-18 | 다이닛본 스미토모 세이야꾸 가부시끼가이샤 | 신규한 복소환 화합물 |
| DK1049689T3 (da) | 1998-01-19 | 2002-07-22 | Pfizer | 4-(2-keto-1-benzimidazolinyl)piperidinderivater som ORL1-receptoragonister |
| CN1166665C (zh) * | 1998-03-19 | 2004-09-15 | 日本农药株式会社 | 芳基哌啶衍生物及其用途 |
| WO1999051608A1 (en) * | 1998-04-03 | 1999-10-14 | Du Pont Pharmaceuticals Company | THIAZOLO[4,5-d]PYRIMIDINES AND PYRIDINES AS CORTICOTROPIN RELEASING FACTOR (CRF) ANTAGONISTS |
| MA26659A1 (fr) | 1998-08-06 | 2004-12-20 | Pfizer | Dérivés de benzimidazole nouveaux, compositions pharmaceutiques les contenant et procédé pour leur préparation. |
| SE9802729D0 (sv) * | 1998-08-13 | 1998-08-13 | Astra Pharma Prod | Novel Compounds |
| PE20001420A1 (es) | 1998-12-23 | 2000-12-18 | Pfizer | Moduladores de ccr5 |
| AU770551B2 (en) | 1998-12-28 | 2004-02-26 | 4-Aza Bioscience Nv | Immunosuppressive effects of pteridine derivatives |
| WO2000045800A2 (en) | 1999-02-02 | 2000-08-10 | K.U. Leuven Research & Development | Immunosurpressive effects of pteridine derivatives |
| US6248755B1 (en) | 1999-04-06 | 2001-06-19 | Merck & Co., Inc. | Pyrrolidine modulators of chemokine receptor activity |
| US6432981B1 (en) * | 1999-06-11 | 2002-08-13 | Merck & Co., Inc. | Cyclopentyl modulators of chemokine receptor activity |
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| CA2393896A1 (en) | 1999-09-15 | 2001-03-22 | Warner-Lambert Company | Pteridinones as kinase inhibitors |
| SE9903544D0 (sv) | 1999-10-01 | 1999-10-01 | Astra Pharma Prod | Novel compounds |
| PE20010628A1 (es) | 1999-10-01 | 2001-06-18 | Takeda Chemical Industries Ltd | Compuestos de amina ciclica, su produccion y su uso |
| EP1122257B1 (en) | 2000-01-05 | 2005-10-12 | Pfizer Inc. | Benzimidazole compounds as ORL1-receptor agonists |
| DE60101372T2 (de) * | 2000-02-11 | 2004-10-14 | Astrazeneca Ab | Pyrimidinverbindungen und ihre verwendung als modulatoren der chemokin-rezeptor-aktivität |
| GB2359081A (en) * | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active thiazolopyrimidines |
| GB2359079A (en) * | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| GB2359551A (en) | 2000-02-23 | 2001-08-29 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| GB0005642D0 (en) * | 2000-03-10 | 2000-05-03 | Astrazeneca Uk Ltd | Chemical compounds |
| SE0101322D0 (sv) * | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | Novel compounds |
| SE0102716D0 (sv) | 2001-08-14 | 2001-08-14 | Astrazeneca Ab | Novel compounds |
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2000
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2001
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2005
- 2005-01-14 US US11/036,682 patent/US20050234077A1/en not_active Abandoned
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