SK283869B6 - Tricyklické triazolobenzazepínové deriváty, spôsob ich prípravy a antialergické prostriedky - Google Patents
Tricyklické triazolobenzazepínové deriváty, spôsob ich prípravy a antialergické prostriedky Download PDFInfo
- Publication number
- SK283869B6 SK283869B6 SK425-2000A SK4252000A SK283869B6 SK 283869 B6 SK283869 B6 SK 283869B6 SK 4252000 A SK4252000 A SK 4252000A SK 283869 B6 SK283869 B6 SK 283869B6
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- SK
- Slovakia
- Prior art keywords
- compound
- formula
- alkyl
- substituted
- alkoxy
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 42
- 230000008569 process Effects 0.000 title claims description 16
- 238000004519 manufacturing process Methods 0.000 title claims 4
- QDEVEJYEXBFIJD-UHFFFAOYSA-N triazolo[4,5-i][1]benzazepine Chemical class C1=CC2=CC=CC=NC2=C2C1=NN=N2 QDEVEJYEXBFIJD-UHFFFAOYSA-N 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 312
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 134
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 88
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 49
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 46
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 125000005843 halogen group Chemical group 0.000 claims abstract description 29
- 239000012453 solvate Substances 0.000 claims abstract description 28
- 239000001257 hydrogen Substances 0.000 claims abstract description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 14
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 3
- 125000003884 phenylalkyl group Chemical group 0.000 claims abstract 2
- -1 1-imidazolyl Chemical group 0.000 claims description 202
- 238000006243 chemical reaction Methods 0.000 claims description 66
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 53
- 229920006395 saturated elastomer Polymers 0.000 claims description 53
- 125000000623 heterocyclic group Chemical group 0.000 claims description 44
- 150000002367 halogens Chemical class 0.000 claims description 43
- OSDBJMYIUDLIRI-UHFFFAOYSA-N oxo-[[1-[[4-[[4-(oxoazaniumylmethylidene)pyridin-1-yl]methoxy]cyclohexyl]oxymethyl]pyridin-4-ylidene]methyl]azanium;dichloride Chemical compound [Cl-].[Cl-].C1=CC(=C[NH+]=O)C=CN1COC1CCC(OCN2C=CC(=C[NH+]=O)C=C2)CC1 OSDBJMYIUDLIRI-UHFFFAOYSA-N 0.000 claims description 39
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 35
- MNLAVFKVRUQAKW-UHFFFAOYSA-N VR nerve agent Chemical compound CCN(CC)CCSP(C)(=O)OCC(C)C MNLAVFKVRUQAKW-UHFFFAOYSA-N 0.000 claims description 32
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 17
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 229910001516 alkali metal iodide Inorganic materials 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical group [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 6
- 208000026935 allergic disease Diseases 0.000 claims description 6
- KPWJBEFBFLRCLH-UHFFFAOYSA-L cadmium bromide Chemical group Br[Cd]Br KPWJBEFBFLRCLH-UHFFFAOYSA-L 0.000 claims description 6
- OKIIEJOIXGHUKX-UHFFFAOYSA-L cadmium iodide Chemical compound [Cd+2].[I-].[I-] OKIIEJOIXGHUKX-UHFFFAOYSA-L 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical group Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 claims description 6
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical group I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 150000007529 inorganic bases Chemical class 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000002619 bicyclic group Chemical group 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 3
- 150000008041 alkali metal carbonates Chemical class 0.000 claims description 3
- 229940075417 cadmium iodide Drugs 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 229910052802 copper Inorganic materials 0.000 claims description 3
- 239000010949 copper Substances 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical group [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 claims description 3
- 229910001623 magnesium bromide Inorganic materials 0.000 claims description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 3
- BLQJIBCZHWBKSL-UHFFFAOYSA-L magnesium iodide Chemical group [Mg+2].[I-].[I-] BLQJIBCZHWBKSL-UHFFFAOYSA-L 0.000 claims description 3
- 229910001641 magnesium iodide Inorganic materials 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 229940102001 zinc bromide Drugs 0.000 claims description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
- 125000001425 triazolyl group Chemical group 0.000 claims 1
- 229940002612 prodrug Drugs 0.000 abstract description 3
- 239000000651 prodrug Substances 0.000 abstract description 3
- 125000000547 substituted alkyl group Chemical group 0.000 abstract description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 125
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 120
- 239000000243 solution Substances 0.000 description 117
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 115
- 239000000203 mixture Substances 0.000 description 99
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 77
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 58
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- 230000015572 biosynthetic process Effects 0.000 description 51
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
- 238000003786 synthesis reaction Methods 0.000 description 50
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- 239000000843 powder Substances 0.000 description 41
- 239000002904 solvent Substances 0.000 description 39
- 239000003921 oil Substances 0.000 description 35
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 33
- 239000000543 intermediate Substances 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- IHPFHZXEOBSXIH-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-2h-triazole-4-carboxylate Chemical compound N1=NNC(C(=O)C=2C(=CC(OC)=C(OC)C=2)[N+]([O-])=O)=C1C(=O)OCC IHPFHZXEOBSXIH-UHFFFAOYSA-N 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- 230000002829 reductive effect Effects 0.000 description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 238000010898 silica gel chromatography Methods 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 19
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 17
- 239000006260 foam Substances 0.000 description 17
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 16
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000000926 separation method Methods 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 239000012300 argon atmosphere Substances 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 14
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 150000003852 triazoles Chemical class 0.000 description 11
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 description 8
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 8
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 229930040373 Paraformaldehyde Natural products 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000008187 granular material Substances 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- IAKGGJYLHBHSQD-UHFFFAOYSA-N 1-(azidomethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CN=[N+]=[N-])C=C1 IAKGGJYLHBHSQD-UHFFFAOYSA-N 0.000 description 6
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 238000006396 nitration reaction Methods 0.000 description 6
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 235000009518 sodium iodide Nutrition 0.000 description 6
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 206010020751 Hypersensitivity Diseases 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000003111 delayed effect Effects 0.000 description 5
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- 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 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 150000001540 azides Chemical class 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- KFTQWOBRKGHZAP-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(2-methylpropanoyloxymethyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(COC(=O)C(C)C)N=C1C(=O)C1=CC(OC)=C(OC)C=C1N KFTQWOBRKGHZAP-UHFFFAOYSA-N 0.000 description 4
- SJAKKHIITAZTNR-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-1-[(4-methoxyphenyl)methyl]triazole-4-carboxylate Chemical compound C=1C(OC)=C(OC)C=C([N+]([O-])=O)C=1C(=O)C1=C(C(=O)OCC)N=NN1CC1=CC=C(OC)C=C1 SJAKKHIITAZTNR-UHFFFAOYSA-N 0.000 description 4
- DJMDVHJVOTYDHB-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-3-[(4-methoxyphenyl)methyl]triazole-4-carboxylate Chemical compound CCOC(=O)C1=C(C(=O)C=2C(=CC(OC)=C(OC)C=2)[N+]([O-])=O)N=NN1CC1=CC=C(OC)C=C1 DJMDVHJVOTYDHB-UHFFFAOYSA-N 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 229920002866 paraformaldehyde Polymers 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 4
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- 125000001478 1-chloroethyl group Chemical group [H]C([H])([H])C([H])(Cl)* 0.000 description 3
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- SFOCXODYDZTUOT-UHFFFAOYSA-N diethyl 1-[(4-methoxyphenyl)methyl]triazole-4,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C(=O)OCC)N=NN1CC1=CC=C(OC)C=C1 SFOCXODYDZTUOT-UHFFFAOYSA-N 0.000 description 2
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- UZRLXARQFDGSTL-UHFFFAOYSA-N ethyl 2,3-dibromo-4-(3,4-dimethoxyphenyl)-4-oxobutanoate Chemical compound CCOC(=O)C(Br)C(Br)C(=O)C1=CC=C(OC)C(OC)=C1 UZRLXARQFDGSTL-UHFFFAOYSA-N 0.000 description 2
- IWYHQRRWJCJBDL-UHFFFAOYSA-N ethyl 2-(4-chlorobutanoyloxymethyl)-5-(4,5-dimethoxy-2-nitrobenzoyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(COC(=O)CCCCl)N=C1C(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O IWYHQRRWJCJBDL-UHFFFAOYSA-N 0.000 description 2
- VIAGMECHANXFFW-UHFFFAOYSA-N ethyl 2-(acetyloxymethyl)-5-(2-amino-4,5-dimethoxybenzoyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(COC(C)=O)N=C1C(=O)C1=CC(OC)=C(OC)C=C1N VIAGMECHANXFFW-UHFFFAOYSA-N 0.000 description 2
- IWTHUZQDTVMCJY-UHFFFAOYSA-N ethyl 2-(butoxycarbonyloxymethyl)-5-(4,5-dimethoxy-2-nitrobenzoyl)triazole-4-carboxylate Chemical compound CCCCOC(=O)OCN1N=C(C(=O)OCC)C(C(=O)C=2C(=CC(OC)=C(OC)C=2)[N+]([O-])=O)=N1 IWTHUZQDTVMCJY-UHFFFAOYSA-N 0.000 description 2
- JORRLPLHHODMSY-UHFFFAOYSA-N ethyl 2-(chloromethyl)-5-(4,5-dimethoxy-2-nitrobenzoyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(CCl)N=C1C(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O JORRLPLHHODMSY-UHFFFAOYSA-N 0.000 description 2
- ACMWIWSSYYKGOD-UHFFFAOYSA-N ethyl 2-[1-(1,3-diethoxypropan-2-yloxycarbonyloxy)-2-methylpropyl]-5-(4-methoxy-2-nitro-5-propan-2-yloxybenzoyl)triazole-4-carboxylate Chemical compound CCOCC(COCC)OC(=O)OC(C(C)C)N1N=C(C(=O)OCC)C(C(=O)C=2C(=CC(OC)=C(OC(C)C)C=2)[N+]([O-])=O)=N1 ACMWIWSSYYKGOD-UHFFFAOYSA-N 0.000 description 2
- DKJJVAFKNQRYKP-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(butoxycarbonyloxymethyl)triazole-4-carboxylate Chemical compound CCCCOC(=O)OCN1N=C(C(=O)OCC)C(C(=O)C=2C(=CC(OC)=C(OC)C=2)N)=N1 DKJJVAFKNQRYKP-UHFFFAOYSA-N 0.000 description 2
- HLHSZTSCYUYNKZ-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(chloromethyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(CCl)N=C1C(=O)C1=CC(OC)=C(OC)C=C1N HLHSZTSCYUYNKZ-UHFFFAOYSA-N 0.000 description 2
- REUXKVMWLIOTHQ-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(dodecanoyloxymethyl)triazole-4-carboxylate Chemical compound CCCCCCCCCCCC(=O)OCN1N=C(C(=O)OCC)C(C(=O)C=2C(=CC(OC)=C(OC)C=2)N)=N1 REUXKVMWLIOTHQ-UHFFFAOYSA-N 0.000 description 2
- IKDVDACKAACLSZ-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(ethoxycarbonyloxymethyl)triazole-4-carboxylate Chemical compound CCOC(=O)OCN1N=C(C(=O)OCC)C(C(=O)C=2C(=CC(OC)=C(OC)C=2)N)=N1 IKDVDACKAACLSZ-UHFFFAOYSA-N 0.000 description 2
- GDQLUNRELMXPTJ-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(ethoxymethyl)triazole-4-carboxylate Chemical compound CCOCN1N=C(C(=O)OCC)C(C(=O)C=2C(=CC(OC)=C(OC)C=2)N)=N1 GDQLUNRELMXPTJ-UHFFFAOYSA-N 0.000 description 2
- WYXHMMJSKZUNAQ-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(hexadecanoyloxymethyl)triazole-4-carboxylate Chemical compound CCCCCCCCCCCCCCCC(=O)OCN1N=C(C(=O)OCC)C(C(=O)C=2C(=CC(OC)=C(OC)C=2)N)=N1 WYXHMMJSKZUNAQ-UHFFFAOYSA-N 0.000 description 2
- LVAKCSQYHRPZPF-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(hexoxycarbonyloxymethyl)triazole-4-carboxylate Chemical compound CCCCCCOC(=O)OCN1N=C(C(=O)OCC)C(C(=O)C=2C(=CC(OC)=C(OC)C=2)N)=N1 LVAKCSQYHRPZPF-UHFFFAOYSA-N 0.000 description 2
- YESPBXGTYJEDSU-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(propan-2-yloxymethyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(COC(C)C)N=C1C(=O)C1=CC(OC)=C(OC)C=C1N YESPBXGTYJEDSU-UHFFFAOYSA-N 0.000 description 2
- AHPSGKYZIXKRTN-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-2-(1-pentan-3-yloxycarbonyloxypropyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(C(CC)OC(=O)OC(CC)CC)N=C1C(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O AHPSGKYZIXKRTN-UHFFFAOYSA-N 0.000 description 2
- CLCKMZLARNBLHV-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-2-(2-methylpropanoyloxymethyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(COC(=O)C(C)C)N=C1C(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O CLCKMZLARNBLHV-UHFFFAOYSA-N 0.000 description 2
- AKHCCWOLOOXHRC-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-2-(3-methoxypentan-3-yl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(C(CC)(CC)OC)N=C1C(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O AKHCCWOLOOXHRC-UHFFFAOYSA-N 0.000 description 2
- SDOIBUJUSQMAIJ-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-2-(4-ethoxyheptan-4-yl)triazole-4-carboxylate Chemical compound CCCC(CCC)(OCC)N1N=C(C(=O)OCC)C(C(=O)C=2C(=CC(OC)=C(OC)C=2)[N+]([O-])=O)=N1 SDOIBUJUSQMAIJ-UHFFFAOYSA-N 0.000 description 2
- BFWDRMDPWOMBHE-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-2-(dodecanoyloxymethyl)triazole-4-carboxylate Chemical compound CCCCCCCCCCCC(=O)OCN1N=C(C(=O)OCC)C(C(=O)C=2C(=CC(OC)=C(OC)C=2)[N+]([O-])=O)=N1 BFWDRMDPWOMBHE-UHFFFAOYSA-N 0.000 description 2
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- 125000004432 carbon atom Chemical group C* 0.000 description 1
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- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
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- 125000004122 cyclic group Chemical group 0.000 description 1
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- RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 1
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- 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 description 1
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- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
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- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
- NQGIJDNPUZEBRU-UHFFFAOYSA-N dodecanoyl chloride Chemical compound CCCCCCCCCCCC(Cl)=O NQGIJDNPUZEBRU-UHFFFAOYSA-N 0.000 description 1
- 239000012374 esterification agent Substances 0.000 description 1
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- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- KLKFAASOGCDTDT-UHFFFAOYSA-N ethoxymethoxyethane Chemical compound CCOCOCC KLKFAASOGCDTDT-UHFFFAOYSA-N 0.000 description 1
- WWAQSVGFVNIDMS-UHFFFAOYSA-N ethyl 2,3-dibromo-4-(4,5-dimethoxy-2-nitrophenyl)-4-oxobutanoate Chemical compound CCOC(=O)C(Br)C(Br)C(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O WWAQSVGFVNIDMS-UHFFFAOYSA-N 0.000 description 1
- VHNIIYYKZAFDKF-UHFFFAOYSA-N ethyl 2-(1-chloroethyl)-5-(4,5-dimethoxy-2-nitrobenzoyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(C(C)Cl)N=C1C(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O VHNIIYYKZAFDKF-UHFFFAOYSA-N 0.000 description 1
- SIFHWJYUSOUPMT-UHFFFAOYSA-N ethyl 2-(acetyloxymethyl)-5-(4,5-dimethoxy-2-nitrobenzoyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(COC(C)=O)N=C1C(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O SIFHWJYUSOUPMT-UHFFFAOYSA-N 0.000 description 1
- SAEFKHVNAALQSA-UHFFFAOYSA-N ethyl 2-(benzoyloxymethyl)-5-(4,5-dimethoxy-2-nitrobenzoyl)triazole-4-carboxylate Chemical compound N1=C(C(=O)C=2C(=CC(OC)=C(OC)C=2)[N+]([O-])=O)C(C(=O)OCC)=NN1COC(=O)C1=CC=CC=C1 SAEFKHVNAALQSA-UHFFFAOYSA-N 0.000 description 1
- QNPDPTUQKZJXHS-UHFFFAOYSA-N ethyl 2-(cyclohexanecarbonyloxymethyl)-5-(4,5-dimethoxy-2-nitrobenzoyl)triazole-4-carboxylate Chemical compound N1=C(C(=O)C=2C(=CC(OC)=C(OC)C=2)[N+]([O-])=O)C(C(=O)OCC)=NN1COC(=O)C1CCCCC1 QNPDPTUQKZJXHS-UHFFFAOYSA-N 0.000 description 1
- OFWQMEIAVINULN-UHFFFAOYSA-N ethyl 2-(diethoxyphosphoryloxymethyl)-5-(4,5-dimethoxy-2-nitrobenzoyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(COP(=O)(OCC)OCC)N=C1C(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O OFWQMEIAVINULN-UHFFFAOYSA-N 0.000 description 1
- WDPODKMALKHKFF-UHFFFAOYSA-N ethyl 2-[(4-aminobenzoyl)oxymethyl]-5-(2-amino-4,5-dimethoxybenzoyl)triazole-4-carboxylate Chemical compound N1=C(C(=O)C=2C(=CC(OC)=C(OC)C=2)N)C(C(=O)OCC)=NN1COC(=O)C1=CC=C(N)C=C1 WDPODKMALKHKFF-UHFFFAOYSA-N 0.000 description 1
- HYQOKOHTDDAMMI-UHFFFAOYSA-N ethyl 2-[1-(1,3-diethoxypropan-2-yloxycarbonyloxy)-2-methylpropyl]-5-(3,4-dimethoxybenzoyl)triazole-4-carboxylate Chemical compound CCOCC(COCC)OC(=O)OC(C(C)C)N1N=C(C(=O)OCC)C(C(=O)C=2C=C(OC)C(OC)=CC=2)=N1 HYQOKOHTDDAMMI-UHFFFAOYSA-N 0.000 description 1
- UVEPRDADPAKTSE-UHFFFAOYSA-N ethyl 2-[1-(1,3-diethoxypropan-2-yloxycarbonyloxy)-2-methylpropyl]-5-(4,5-dimethoxy-2-nitrobenzoyl)triazole-4-carboxylate Chemical compound CCOCC(COCC)OC(=O)OC(C(C)C)N1N=C(C(=O)OCC)C(C(=O)C=2C(=CC(OC)=C(OC)C=2)[N+]([O-])=O)=N1 UVEPRDADPAKTSE-UHFFFAOYSA-N 0.000 description 1
- DQJBEYQDAGBISH-UHFFFAOYSA-N ethyl 2-[1-(1,3-diethoxypropan-2-yloxycarbonyloxy)-2-methylpropyl]-5-(4-methoxy-3-propan-2-yloxybenzoyl)triazole-4-carboxylate Chemical compound CCOCC(COCC)OC(=O)OC(C(C)C)N1N=C(C(=O)OCC)C(C(=O)C=2C=C(OC(C)C)C(OC)=CC=2)=N1 DQJBEYQDAGBISH-UHFFFAOYSA-N 0.000 description 1
- WXFQMQWBEXMWOA-UHFFFAOYSA-N ethyl 4-(3,4-dimethoxyphenyl)-4-oxobut-2-enoate Chemical compound CCOC(=O)C=CC(=O)C1=CC=C(OC)C(OC)=C1 WXFQMQWBEXMWOA-UHFFFAOYSA-N 0.000 description 1
- HRKQNGUQJKPAIB-UHFFFAOYSA-N ethyl 4-(4,5-dimethoxy-2-nitrophenyl)-4-oxobut-2-enoate Chemical compound CCOC(=O)C=CC(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O HRKQNGUQJKPAIB-UHFFFAOYSA-N 0.000 description 1
- GGXHUOFQQHNZOK-UHFFFAOYSA-N ethyl 4-(4-methoxy-2-nitro-5-propan-2-yloxyphenyl)-4-oxobut-2-ynoate Chemical compound CCOC(=O)C#CC(=O)C1=CC(OC(C)C)=C(OC)C=C1[N+]([O-])=O GGXHUOFQQHNZOK-UHFFFAOYSA-N 0.000 description 1
- ASEYTPDDGDRESF-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(1-chloroethyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(C(C)Cl)N=C1C(=O)C1=CC(OC)=C(OC)C=C1N ASEYTPDDGDRESF-UHFFFAOYSA-N 0.000 description 1
- ARCOCRHVMWBEIH-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(2-methyl-1-propan-2-yloxycarbonyloxypropyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(C(OC(=O)OC(C)C)C(C)C)N=C1C(=O)C1=CC(OC)=C(OC)C=C1N ARCOCRHVMWBEIH-UHFFFAOYSA-N 0.000 description 1
- PCVPTZNGKIUBTK-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(3-methoxypentan-3-yl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(C(CC)(CC)OC)N=C1C(=O)C1=CC(OC)=C(OC)C=C1N PCVPTZNGKIUBTK-UHFFFAOYSA-N 0.000 description 1
- QDUXMJNBUIHRNM-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(4-chlorobutanoyloxymethyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(COC(=O)CCCCl)N=C1C(=O)C1=CC(OC)=C(OC)C=C1N QDUXMJNBUIHRNM-UHFFFAOYSA-N 0.000 description 1
- FQWJUZUFUOPTIL-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(benzoyloxymethyl)triazole-4-carboxylate Chemical compound N1=C(C(=O)C=2C(=CC(OC)=C(OC)C=2)N)C(C(=O)OCC)=NN1COC(=O)C1=CC=CC=C1 FQWJUZUFUOPTIL-UHFFFAOYSA-N 0.000 description 1
- PYOWQJDGMJGIAZ-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-(propan-2-yloxycarbonyloxymethyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(COC(=O)OC(C)C)N=C1C(=O)C1=CC(OC)=C(OC)C=C1N PYOWQJDGMJGIAZ-UHFFFAOYSA-N 0.000 description 1
- YLOJPYNYPUUTCN-UHFFFAOYSA-N ethyl 5-(2-amino-4,5-dimethoxybenzoyl)-2-[[2-(4-methoxyphenyl)acetyl]oxymethyl]triazole-4-carboxylate Chemical compound N1=C(C(=O)C=2C(=CC(OC)=C(OC)C=2)N)C(C(=O)OCC)=NN1COC(=O)CC1=CC=C(OC)C=C1 YLOJPYNYPUUTCN-UHFFFAOYSA-N 0.000 description 1
- BCCIDBQPLKZQSC-UHFFFAOYSA-N ethyl 5-(2-amino-4-methoxy-5-propan-2-yloxybenzoyl)-2-(2-methyl-1-propan-2-yloxycarbonyloxypropyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(C(OC(=O)OC(C)C)C(C)C)N=C1C(=O)C1=CC(OC(C)C)=C(OC)C=C1N BCCIDBQPLKZQSC-UHFFFAOYSA-N 0.000 description 1
- HTYTXAGPUTZLEU-UHFFFAOYSA-N ethyl 5-(2-amino-4-methoxy-5-propan-2-yloxybenzoyl)-2-[1-(1,3-diethoxypropan-2-yloxycarbonyloxy)-2-methylpropyl]triazole-4-carboxylate Chemical compound CCOCC(COCC)OC(=O)OC(C(C)C)N1N=C(C(=O)OCC)C(C(=O)C=2C(=CC(OC)=C(OC(C)C)C=2)N)=N1 HTYTXAGPUTZLEU-UHFFFAOYSA-N 0.000 description 1
- HFLJBGRYKIVLHA-UHFFFAOYSA-N ethyl 5-(3,4-dimethoxybenzoyl)-1-[(4-methoxyphenyl)methyl]triazole-4-carboxylate Chemical compound C=1C=C(OC)C(OC)=CC=1C(=O)C1=C(C(=O)OCC)N=NN1CC1=CC=C(OC)C=C1 HFLJBGRYKIVLHA-UHFFFAOYSA-N 0.000 description 1
- CPDZQJAZWCFEBD-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-2-(2-methyl-1-propan-2-yloxycarbonyloxypropyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(C(OC(=O)OC(C)C)C(C)C)N=C1C(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O CPDZQJAZWCFEBD-UHFFFAOYSA-N 0.000 description 1
- JPTAPOGSMWRIPY-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-2-(2-methylpropoxycarbonyloxymethyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(COC(=O)OCC(C)C)N=C1C(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O JPTAPOGSMWRIPY-UHFFFAOYSA-N 0.000 description 1
- QTPQKXMSCLOOFZ-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-2-(ethoxymethyl)triazole-4-carboxylate Chemical compound CCOCN1N=C(C(=O)OCC)C(C(=O)C=2C(=CC(OC)=C(OC)C=2)[N+]([O-])=O)=N1 QTPQKXMSCLOOFZ-UHFFFAOYSA-N 0.000 description 1
- NEABHENBWMHAHJ-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-2-(hexoxycarbonyloxymethyl)triazole-4-carboxylate Chemical compound CCCCCCOC(=O)OCN1N=C(C(=O)OCC)C(C(=O)C=2C(=CC(OC)=C(OC)C=2)[N+]([O-])=O)=N1 NEABHENBWMHAHJ-UHFFFAOYSA-N 0.000 description 1
- KNNUIBNXACNTHF-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-2-(propan-2-yloxycarbonyloxymethyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(COC(=O)OC(C)C)N=C1C(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O KNNUIBNXACNTHF-UHFFFAOYSA-N 0.000 description 1
- JOSHSKKQDYMEDW-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-2-[1-(1h-imidazole-2-carbonyloxy)propyl]triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(C(CC)OC(=O)C=2NC=CN=2)N=C1C(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O JOSHSKKQDYMEDW-UHFFFAOYSA-N 0.000 description 1
- XHVAKIOSOUSFIQ-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-2-[1-[2-(2-methoxyethoxy)ethoxycarbonyloxy]-2-methylpropyl]triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(C(OC(=O)OCCOCCOC)C(C)C)N=C1C(=O)C1=CC(OC)=C(OC)C=C1[N+]([O-])=O XHVAKIOSOUSFIQ-UHFFFAOYSA-N 0.000 description 1
- GYWJDCDXOAITJZ-UHFFFAOYSA-N ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-2-[[2-(4-methoxyphenyl)acetyl]oxymethyl]triazole-4-carboxylate Chemical compound N1=C(C(=O)C=2C(=CC(OC)=C(OC)C=2)[N+]([O-])=O)C(C(=O)OCC)=NN1COC(=O)CC1=CC=C(OC)C=C1 GYWJDCDXOAITJZ-UHFFFAOYSA-N 0.000 description 1
- HNCAOZXLNLYZHW-UHFFFAOYSA-N ethyl 5-(4-methoxy-2-nitro-5-propan-2-yloxybenzoyl)-2h-triazole-4-carboxylate Chemical compound N1=NNC(C(=O)C=2C(=CC(OC)=C(OC(C)C)C=2)[N+]([O-])=O)=C1C(=O)OCC HNCAOZXLNLYZHW-UHFFFAOYSA-N 0.000 description 1
- JOOVEFZUMDHLFB-UHFFFAOYSA-N ethyl 5-(4-methoxy-3-propan-2-yloxybenzoyl)-2-(2-methyl-1-propan-2-yloxycarbonyloxypropyl)triazole-4-carboxylate Chemical compound CCOC(=O)C1=NN(C(OC(=O)OC(C)C)C(C)C)N=C1C(=O)C1=CC=C(OC)C(OC(C)C)=C1 JOOVEFZUMDHLFB-UHFFFAOYSA-N 0.000 description 1
- VVFQKXBDILRLIL-UHFFFAOYSA-N ethyl 5-(4-methoxy-3-propan-2-yloxybenzoyl)-2h-triazole-4-carboxylate Chemical compound N1=NNC(C(=O)C=2C=C(OC(C)C)C(OC)=CC=2)=C1C(=O)OCC VVFQKXBDILRLIL-UHFFFAOYSA-N 0.000 description 1
- HKKZLDQMWRNXOW-UHFFFAOYSA-N ethyl 5-[(4,5-dimethoxy-2-nitrophenyl)-hydroxymethyl]-1-[(4-methoxyphenyl)methyl]triazole-4-carboxylate Chemical compound C=1C(OC)=C(OC)C=C([N+]([O-])=O)C=1C(O)C1=C(C(=O)OCC)N=NN1CC1=CC=C(OC)C=C1 HKKZLDQMWRNXOW-UHFFFAOYSA-N 0.000 description 1
- BGCXLCFAOUGMKG-UHFFFAOYSA-N ethyl 5-[hydroxy-(4-methoxy-2-nitro-5-propan-2-yloxyphenyl)methyl]-1-[(4-methoxyphenyl)methyl]triazole-4-carboxylate Chemical compound C=1C(OC(C)C)=C(OC)C=C([N+]([O-])=O)C=1C(O)C1=C(C(=O)OCC)N=NN1CC1=CC=C(OC)C=C1 BGCXLCFAOUGMKG-UHFFFAOYSA-N 0.000 description 1
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- ARBOVOVUTSQWSS-UHFFFAOYSA-N hexadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCC(Cl)=O ARBOVOVUTSQWSS-UHFFFAOYSA-N 0.000 description 1
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- 150000004677 hydrates Chemical class 0.000 description 1
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- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
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- RHGZVXXMXLZIJI-UHFFFAOYSA-N methyl 4-(3,4-dimethoxybenzoyl)-3-[(4-methoxyphenyl)methyl]-1,2-dihydrotriazole-5-carboxylate Chemical compound N1NC(C(=O)OC)=C(C(=O)C=2C=C(OC)C(OC)=CC=2)N1CC1=CC=C(OC)C=C1 RHGZVXXMXLZIJI-UHFFFAOYSA-N 0.000 description 1
- HWFBZCHUTWPZIH-UHFFFAOYSA-N methyl 4-(3,4-dimethoxyphenyl)-4-oxobut-2-enoate Chemical compound COC(=O)C=CC(=O)C1=CC=C(OC)C(OC)=C1 HWFBZCHUTWPZIH-UHFFFAOYSA-N 0.000 description 1
- UDPCFPDALSEQFD-UHFFFAOYSA-N methyl 5-(3,4-dimethoxybenzoyl)-1-[(4-methoxyphenyl)methyl]triazole-4-carboxylate Chemical compound C=1C=C(OC)C(OC)=CC=1C(=O)C1=C(C(=O)OC)N=NN1CC1=CC=C(OC)C=C1 UDPCFPDALSEQFD-UHFFFAOYSA-N 0.000 description 1
- DFYCWORLSDLMDV-UHFFFAOYSA-N methyl 5-(3,4-dimethoxybenzoyl)-2h-triazole-4-carboxylate Chemical compound N1=NNC(C(=O)C=2C=C(OC)C(OC)=CC=2)=C1C(=O)OC DFYCWORLSDLMDV-UHFFFAOYSA-N 0.000 description 1
- NJEIEZKKLUYBGX-UHFFFAOYSA-N methyl 5-(4-methoxy-3-propan-2-yloxybenzoyl)-2h-triazole-4-carboxylate Chemical compound N1=NNC(C(=O)C=2C=C(OC(C)C)C(OC)=CC=2)=C1C(=O)OC NJEIEZKKLUYBGX-UHFFFAOYSA-N 0.000 description 1
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- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
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- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 125000005544 phthalimido group Chemical group 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical class OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical class OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- RKBCYCFRFCNLTO-UHFFFAOYSA-N triisopropylamine Chemical compound CC(C)N(C(C)C)C(C)C RKBCYCFRFCNLTO-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- 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
-
- 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
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pulmonology (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26461197 | 1997-09-29 | ||
| JP5206398 | 1998-03-04 | ||
| PCT/JP1998/004363 WO1999016770A1 (fr) | 1997-09-29 | 1998-09-29 | Derives de triazolobenzazepine tricyclique, leur procede de production et antiallergique |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK4252000A3 SK4252000A3 (en) | 2000-10-09 |
| SK283869B6 true SK283869B6 (sk) | 2004-03-02 |
Family
ID=26392670
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK425-2000A SK283869B6 (sk) | 1997-09-29 | 1998-09-29 | Tricyklické triazolobenzazepínové deriváty, spôsob ich prípravy a antialergické prostriedky |
Country Status (25)
| Country | Link |
|---|---|
| US (3) | US6372735B1 (zh) |
| EP (1) | EP1026167B1 (zh) |
| JP (1) | JP3188482B2 (zh) |
| KR (1) | KR100389140B1 (zh) |
| CN (2) | CN1155599C (zh) |
| AT (1) | ATE233764T1 (zh) |
| AU (1) | AU744636B2 (zh) |
| BR (1) | BR9814055B1 (zh) |
| CA (1) | CA2305307C (zh) |
| DE (1) | DE69811930T2 (zh) |
| DK (1) | DK1026167T3 (zh) |
| ES (1) | ES2191963T3 (zh) |
| HK (1) | HK1032782A1 (zh) |
| HU (1) | HUP0004020A3 (zh) |
| ID (1) | ID24101A (zh) |
| IL (1) | IL135303A0 (zh) |
| NO (2) | NO319542B1 (zh) |
| NZ (1) | NZ503601A (zh) |
| PL (1) | PL339544A1 (zh) |
| PT (1) | PT1026167E (zh) |
| RU (1) | RU2198885C2 (zh) |
| SK (1) | SK283869B6 (zh) |
| TR (1) | TR200000808T2 (zh) |
| TW (1) | TW510902B (zh) |
| WO (1) | WO1999016770A1 (zh) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE469902T1 (de) * | 2001-12-26 | 2010-06-15 | Meiji Seika Kaisha | Amorphe substanz eines tricyclischen triazolobenzazepinderivats |
| ATE359277T1 (de) * | 2002-02-01 | 2007-05-15 | Meiji Seika Kaisha | Verfahren zur herstellung einer 1,2,3- triazolverbindung |
| JP4579681B2 (ja) | 2002-07-09 | 2010-11-10 | ブリストル−マイヤーズ スクイブ カンパニー | 抗糖尿病薬および抗肥満薬として有用な置換ヘテロシクロ誘導体および方法 |
| MXPA05000279A (es) | 2002-07-09 | 2005-03-31 | Squibb Bristol Myers Co | Derivados heterociclicos sustituidos utiles como agentes antidiabeticos y antiobesidad y metodo. |
| EP1642900A1 (en) * | 2003-06-19 | 2006-04-05 | Meiji Seika Kaisha Ltd. | Tricyclic triazolobenzazepine derivative produced as novel crystalline substance |
| JP4391475B2 (ja) * | 2003-06-20 | 2009-12-24 | 明治製菓株式会社 | 難水溶性物質と水溶性高分子との共沈物の製造方法 |
| ES2540987T3 (es) | 2004-05-14 | 2015-07-15 | Millennium Pharmaceuticals, Inc. | Métodos para preparar inhibidores de la aurora cinasa |
| CA2644810A1 (en) * | 2006-03-02 | 2007-09-07 | Meiji Seika Kaisha, Ltd. | Prophylactic or therapeutic agents for allergic ophthalmic diseases or allergic nasal diseases, comprising tricyclic triazolobenzazepine derivative |
| US8242105B2 (en) * | 2006-09-25 | 2012-08-14 | Forschungsverbund Berlin E.V. | Structural mimetics of proline-rich peptides and the pharmaceutical use thereof |
| CL2007003244A1 (es) | 2006-11-16 | 2008-04-04 | Millennium Pharm Inc | Compuestos derivados de pirimido[5,4-d][2]benzazepina; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento del cancer. |
| DK2123277T3 (da) * | 2007-12-18 | 2011-03-14 | Meiji Seika Kaisha | Forebyggende eller terapeutisk middel mod inflammatorisk tarmsygdom |
| MX2011006725A (es) | 2008-12-22 | 2011-09-15 | Millennium Pharm Inc | Combinacion de inhibidores de aurora cinasa y anticuerpos anti-cd20. |
| JO3635B1 (ar) | 2009-05-18 | 2020-08-27 | Millennium Pharm Inc | مركبات صيدلانية صلبة وطرق لانتاجها |
| US9107911B2 (en) | 2010-01-07 | 2015-08-18 | Alkermes Pharma Ireland Limited | Prodrugs of heteraromatic compounds |
| RU2012140021A (ru) | 2010-02-19 | 2014-03-27 | Миллениум Фармасьютикалз, Инк. | КРИСТАЛЛИЧЕСКИЕ ФОРМЫ 4-{[9-ХЛОР-7-(2-ФТОР-6-МЕТОКСИФЕНИЛ)-5Н-ПИРИМИДО[5,4-d][2]БЕНЗАЗЕПИН-2-ИЛ]АМИНО}-2-МЕТОКСИБЕНЗОАТА НАТРИЯ |
| US20130303519A1 (en) | 2012-03-20 | 2013-11-14 | Millennium Pharmaceuticals, Inc. | Methods of treating cancer using aurora kinase inhibitors |
| US9724354B2 (en) | 2013-03-22 | 2017-08-08 | Millennium Pharmaceuticals, Inc. | Combination of catalytic mTORC1/2 inhibitors and selective inhibitors of Aurora A kinase |
| JP2018524292A (ja) | 2015-07-21 | 2018-08-30 | ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | オーロラキナーゼインヒビターと化学療法剤の投与 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3290664B2 (ja) * | 1993-12-28 | 2002-06-10 | 明治製菓株式会社 | ３環性ベンゾアゼピンおよびベンゾチアゼピン誘導体 |
| WO1997000258A1 (fr) * | 1995-06-15 | 1997-01-03 | Meiji Seika Kabushiki Kaisha | Composes de benzazepine tricyclique |
| US6124281A (en) * | 1996-03-08 | 2000-09-26 | Zeneca Limited | Azolobenzazepine derivatives as neurologically active agents |
| US20070059533A1 (en) * | 2005-09-12 | 2007-03-15 | Burdette Steven R | Thermal reflow of glass and fused silica body |
-
1998
- 1998-09-29 TW TW087116198A patent/TW510902B/zh not_active IP Right Cessation
- 1998-09-29 JP JP51996999A patent/JP3188482B2/ja not_active Expired - Fee Related
- 1998-09-29 PL PL98339544A patent/PL339544A1/xx unknown
- 1998-09-29 HU HU0004020A patent/HUP0004020A3/hu unknown
- 1998-09-29 KR KR10-2000-7003362A patent/KR100389140B1/ko not_active IP Right Cessation
- 1998-09-29 CA CA002305307A patent/CA2305307C/en not_active Expired - Fee Related
- 1998-09-29 IL IL13530398A patent/IL135303A0/xx unknown
- 1998-09-29 ES ES98944289T patent/ES2191963T3/es not_active Expired - Lifetime
- 1998-09-29 DK DK98944289T patent/DK1026167T3/da active
- 1998-09-29 DE DE69811930T patent/DE69811930T2/de not_active Expired - Lifetime
- 1998-09-29 EP EP98944289A patent/EP1026167B1/en not_active Expired - Lifetime
- 1998-09-29 AU AU91869/98A patent/AU744636B2/en not_active Ceased
- 1998-09-29 NZ NZ503601A patent/NZ503601A/en unknown
- 1998-09-29 WO PCT/JP1998/004363 patent/WO1999016770A1/ja not_active Application Discontinuation
- 1998-09-29 AT AT98944289T patent/ATE233764T1/de active
- 1998-09-29 SK SK425-2000A patent/SK283869B6/sk unknown
- 1998-09-29 PT PT98944289T patent/PT1026167E/pt unknown
- 1998-09-29 RU RU2000111517/04A patent/RU2198885C2/ru not_active IP Right Cessation
- 1998-09-29 ID IDW20000808A patent/ID24101A/id unknown
- 1998-09-29 CN CNB98810735XA patent/CN1155599C/zh not_active Expired - Fee Related
- 1998-09-29 TR TR2000/00808T patent/TR200000808T2/xx unknown
- 1998-09-29 CN CNB2003101047539A patent/CN1312135C/zh not_active Expired - Fee Related
- 1998-09-29 US US09/509,494 patent/US6372735B1/en not_active Expired - Lifetime
- 1998-09-29 BR BRPI9814055-8A patent/BR9814055B1/pt not_active IP Right Cessation
-
2000
- 2000-03-23 NO NO20001500A patent/NO319542B1/no unknown
-
2001
- 2001-05-22 HK HK01103502A patent/HK1032782A1/xx not_active IP Right Cessation
-
2002
- 2002-02-13 US US10/073,326 patent/US7022860B2/en not_active Expired - Fee Related
-
2004
- 2004-09-08 NO NO20043765A patent/NO20043765L/no not_active Application Discontinuation
-
2005
- 2005-11-09 US US11/269,828 patent/US7238812B2/en not_active Expired - Fee Related
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