DD254001A5 - Verfahren zur herstellung von heterocyclischen oxophtalazinylessigsaeuren - Google Patents
Verfahren zur herstellung von heterocyclischen oxophtalazinylessigsaeurenInfo
- Publication number
- DD254001A5 DD254001A5 DD29601286A DD29601286A DD254001A5 DD 254001 A5 DD254001 A5 DD 254001A5 DD 29601286 A DD29601286 A DD 29601286A DD 29601286 A DD29601286 A DD 29601286A DD 254001 A5 DD254001 A5 DD 254001A5
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- substituted
- chloro
- methyl
- group
- phenyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 33
- 238000002360 preparation method Methods 0.000 title description 12
- 230000008569 process Effects 0.000 title description 5
- -1 Z is a covalent bond Chemical group 0.000 claims abstract description 108
- 150000001875 compounds Chemical class 0.000 claims abstract description 106
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 19
- 229910052717 sulfur Chemical group 0.000 claims abstract description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
- 239000001257 hydrogen Substances 0.000 claims abstract description 17
- 239000001301 oxygen Substances 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 239000002253 acid Substances 0.000 claims abstract description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000011593 sulfur Substances 0.000 claims abstract description 11
- 239000000651 prodrug Chemical group 0.000 claims abstract description 9
- 229940002612 prodrug Drugs 0.000 claims abstract description 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 78
- 239000000460 chlorine Substances 0.000 claims description 29
- 238000006243 chemical reaction Methods 0.000 claims description 27
- 125000001246 bromo group Chemical group Br* 0.000 claims description 23
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 125000005605 benzo group Chemical group 0.000 claims description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000001449 isopropyl group Chemical class [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 6
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 5
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 4
- 159000000000 sodium salts Chemical class 0.000 claims description 4
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 125000000956 methoxy group Chemical class [H]C([H])([H])O* 0.000 claims description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 3
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 3
- 229930192474 thiophene Natural products 0.000 claims description 3
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- KXNQKOAQSGJCQU-UHFFFAOYSA-N benzo[e][1,3]benzothiazole Chemical compound C1=CC=C2C(N=CS3)=C3C=CC2=C1 KXNQKOAQSGJCQU-UHFFFAOYSA-N 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- 150000001804 chlorine Chemical class 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 abstract description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 10
- 102000016912 Aldehyde Reductase Human genes 0.000 abstract description 9
- 108010053754 Aldehyde reductase Proteins 0.000 abstract description 9
- 125000003282 alkyl amino group Chemical group 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- OLPXAVJPVMMDQO-UHFFFAOYSA-N 2-oxo-2-phthalazin-1-ylacetic acid Chemical compound C1=CC=C2C(C(=O)C(=O)O)=NN=CC2=C1 OLPXAVJPVMMDQO-UHFFFAOYSA-N 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 80
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 75
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 60
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- 239000000203 mixture Substances 0.000 description 41
- 239000007787 solid Substances 0.000 description 40
- 239000000047 product Substances 0.000 description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 26
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 239000000284 extract Substances 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 239000012312 sodium hydride Substances 0.000 description 11
- 239000006185 dispersion Substances 0.000 description 10
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- 239000002904 solvent Substances 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 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 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
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- 206010012601 diabetes mellitus Diseases 0.000 description 8
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- 239000005457 ice water Substances 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
- 230000001684 chronic effect Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 6
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- URFKLQSFBXBOQU-UHFFFAOYSA-N 2-chloro-1,1,1-triethoxyethane Chemical compound CCOC(CCl)(OCC)OCC URFKLQSFBXBOQU-UHFFFAOYSA-N 0.000 description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- 206010007749 Cataract diabetic Diseases 0.000 description 5
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 5
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 235000011054 acetic acid Nutrition 0.000 description 5
- 201000007025 diabetic cataract Diseases 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
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- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000000600 sorbitol Substances 0.000 description 5
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 5
- 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 description 4
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 4
- 208000002177 Cataract Diseases 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 239000003288 aldose reductase inhibitor Substances 0.000 description 4
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 description 3
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- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- 208000002249 Diabetes Complications Diseases 0.000 description 3
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- 206010012689 Diabetic retinopathy Diseases 0.000 description 3
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- FBPFZTCFMRRESA-GUCUJZIJSA-N galactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-GUCUJZIJSA-N 0.000 description 3
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- 238000010561 standard procedure Methods 0.000 description 3
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- TYUWZKSJURGPRJ-UHFFFAOYSA-N (4-phenyl-1,3-thiazol-2-yl)methanol Chemical compound S1C(CO)=NC(C=2C=CC=CC=2)=C1 TYUWZKSJURGPRJ-UHFFFAOYSA-N 0.000 description 2
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 description 2
- FZWBNHMXJMCXLU-UHFFFAOYSA-N 2,3,4,5-tetrahydroxy-6-[3,4,5-trihydroxy-6-[[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxyhexanal Chemical compound OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OCC(O)C(O)C(O)C(O)C=O)O1 FZWBNHMXJMCXLU-UHFFFAOYSA-N 0.000 description 2
- ZEDQLIHBPGNGEC-UHFFFAOYSA-N 2-(4-oxo-3h-phthalazin-1-yl)acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=NNC(=O)C2=C1 ZEDQLIHBPGNGEC-UHFFFAOYSA-N 0.000 description 2
- WFLCAOGKZQTOIG-UHFFFAOYSA-N 2-(bromomethyl)-1,3-benzothiazole Chemical compound C1=CC=C2SC(CBr)=NC2=C1 WFLCAOGKZQTOIG-UHFFFAOYSA-N 0.000 description 2
- ACVAICWJHHSMGT-UHFFFAOYSA-N 2-(chloromethyl)-5-fluoro-1,3-benzothiazole Chemical compound FC1=CC=C2SC(CCl)=NC2=C1 ACVAICWJHHSMGT-UHFFFAOYSA-N 0.000 description 2
- KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 2
- LUHTVPPVLNSXLB-UHFFFAOYSA-N 2-[3-[(5-bromo-1,3-benzothiazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(Br)=CC=C2S1 LUHTVPPVLNSXLB-UHFFFAOYSA-N 0.000 description 2
- WASQBNCGNUTVNI-UHFFFAOYSA-N 2-amino-4,6-dichlorophenol Chemical compound NC1=CC(Cl)=CC(Cl)=C1O WASQBNCGNUTVNI-UHFFFAOYSA-N 0.000 description 2
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- 125000004260 quinazolin-2-yl group Chemical group [H]C1=NC(*)=NC2=C1C([H])=C([H])C([H])=C2[H] 0.000 description 1
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
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- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
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- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IRFHMTUHTBSEBK-QGZVFWFLSA-N tert-butyl n-[(2s)-2-(2,5-difluorophenyl)-3-quinolin-3-ylpropyl]carbamate Chemical compound C1([C@H](CC=2C=C3C=CC=CC3=NC=2)CNC(=O)OC(C)(C)C)=CC(F)=CC=C1F IRFHMTUHTBSEBK-QGZVFWFLSA-N 0.000 description 1
- JZHIWRJMRVFHOR-UHFFFAOYSA-N tert-butylazanium;sulfate Chemical compound CC(C)(C)N.CC(C)(C)N.OS(O)(=O)=O JZHIWRJMRVFHOR-UHFFFAOYSA-N 0.000 description 1
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- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
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- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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- 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
- WUUHFRRPHJEEKV-UHFFFAOYSA-N tripotassium borate Chemical compound [K+].[K+].[K+].[O-]B([O-])[O-] WUUHFRRPHJEEKV-UHFFFAOYSA-N 0.000 description 1
- 229920001664 tyloxapol Polymers 0.000 description 1
- MDYZKJNTKZIUSK-UHFFFAOYSA-N tyloxapol Chemical compound O=C.C1CO1.CC(C)(C)CC(C)(C)C1=CC=C(O)C=C1 MDYZKJNTKZIUSK-UHFFFAOYSA-N 0.000 description 1
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- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US79603985A | 1985-11-07 | 1985-11-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD254001A5 true DD254001A5 (de) | 1988-02-10 |
Family
ID=25167108
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD29601286A DD254001A5 (de) | 1985-11-07 | 1986-11-06 | Verfahren zur herstellung von heterocyclischen oxophtalazinylessigsaeuren |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPS62114988A (enrdf_load_stackoverflow) |
| CA (1) | CA1299178C (enrdf_load_stackoverflow) |
| DD (1) | DD254001A5 (enrdf_load_stackoverflow) |
| PH (1) | PH26741A (enrdf_load_stackoverflow) |
| ZA (1) | ZA868450B (enrdf_load_stackoverflow) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL87709A (en) * | 1987-09-16 | 1992-11-15 | Pfizer | Process for preparing haloalkyl thiazoles and some such novel haloalkyl thiazoles |
| EP0322153A3 (en) * | 1987-12-21 | 1990-08-16 | Pfizer Inc. | Heterocyclic oxophtalazinyl acetic acids |
| US4954629A (en) * | 1989-05-11 | 1990-09-04 | Pfizer Inc. | Process and intermediates for the preparation of oxophthalazinyl acetic acids and analogs thereof |
| DK3597650T3 (da) * | 2010-07-16 | 2022-11-21 | Univ Columbia | Aldosereduktasehæmmere og anvendelser deraf |
| US8916563B2 (en) | 2010-07-16 | 2014-12-23 | The Trustees Of Columbia University In The City Of New York | Aldose reductase inhibitors and uses thereof |
| DK3352754T3 (da) | 2016-06-21 | 2020-12-07 | Univ Columbia | Aldosereduktaseinhibitorer og fremgangsmåder til anvendelse deraf |
| IL272246B1 (en) | 2017-07-28 | 2025-09-01 | Applied Therapeutics Inc | History of 2-(4-oxo/thioketone/azo-3-((substituted)benzo[d]thiazol-2-yl)methyl)- 3,4-dihydrothieno[3,4-d]pyridazin-1-yl)acetic acid for use as an aldose reductase inhibitor for the treatment of galactosemia or prevention of galactosemia-related complications |
| WO2020205846A1 (en) * | 2019-04-01 | 2020-10-08 | Applied Therapeutics Inc. | Inhibitors of aldose reductase |
| AU2020268368A1 (en) | 2019-05-07 | 2022-01-06 | Ucl Business Ltd | Treatment and detection of inherited neuropathies and associated disorders |
-
1986
- 1986-10-16 CA CA000520609A patent/CA1299178C/en not_active Expired - Lifetime
- 1986-11-06 DD DD29601286A patent/DD254001A5/de not_active IP Right Cessation
- 1986-11-06 ZA ZA868450A patent/ZA868450B/xx unknown
- 1986-11-06 PH PH34442A patent/PH26741A/en unknown
- 1986-11-07 JP JP61265436A patent/JPS62114988A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| ZA868450B (en) | 1988-06-29 |
| CA1299178C (en) | 1992-04-21 |
| PH26741A (en) | 1992-09-28 |
| JPH041747B2 (enrdf_load_stackoverflow) | 1992-01-14 |
| JPS62114988A (ja) | 1987-05-26 |
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| Date | Code | Title | Description |
|---|---|---|---|
| ENJ | Ceased due to non-payment of renewal fee |