NO310288B1 - N-hydroksyurea-derivater som anti-inflammatoriske midler, anvendelse derav og farmasöytisk preparat - Google Patents
N-hydroksyurea-derivater som anti-inflammatoriske midler, anvendelse derav og farmasöytisk preparat Download PDFInfo
- Publication number
- NO310288B1 NO310288B1 NO19975726A NO975726A NO310288B1 NO 310288 B1 NO310288 B1 NO 310288B1 NO 19975726 A NO19975726 A NO 19975726A NO 975726 A NO975726 A NO 975726A NO 310288 B1 NO310288 B1 NO 310288B1
- Authority
- NO
- Norway
- Prior art keywords
- dihydro
- phenyloxazol
- hydroxyurea
- phenyl
- mmol
- Prior art date
Links
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical class NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 title abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 title abstract 2
- 229940121363 anti-inflammatory agent Drugs 0.000 title 1
- 239000002260 anti-inflammatory agent Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 100
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 8
- 241000124008 Mammalia Species 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- 229960001330 hydroxycarbamide Drugs 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 14
- 239000000126 substance Substances 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 230000000172 allergic effect Effects 0.000 claims description 4
- 208000010668 atopic eczema Diseases 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- IPCNNIOKNOAYBN-UHFFFAOYSA-N 1-hydroxy-1-[4-[3-(5-phenyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl]but-3-yn-2-yl]urea Chemical compound NC(=O)N(O)C(C)C#CC1=CC=CC(C=2OC(CN=2)C=2C=CC=CC=2)=C1 IPCNNIOKNOAYBN-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 229940124125 5 Lipoxygenase inhibitor Drugs 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000005551 pyridylene group Chemical group 0.000 claims description 2
- 125000001989 1,3-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([H])C([*:2])=C1[H] 0.000 claims 4
- 125000003504 2-oxazolinyl group Chemical group O1C(=NCC1)* 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 abstract description 3
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract description 3
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 2
- 206010020751 Hypersensitivity Diseases 0.000 abstract description 2
- 230000007815 allergy Effects 0.000 abstract description 2
- 208000026935 allergic disease Diseases 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 147
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 74
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 64
- 238000005160 1H NMR spectroscopy Methods 0.000 description 62
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 52
- 239000007787 solid Substances 0.000 description 40
- 239000000243 solution Substances 0.000 description 38
- 230000008018 melting Effects 0.000 description 36
- 238000002844 melting Methods 0.000 description 36
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 28
- -1 hydroperoxy fatty acids Chemical class 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 21
- 239000000543 intermediate Substances 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 17
- NIZHERJWXFHGGU-UHFFFAOYSA-N isocyanato(trimethyl)silane Chemical compound C[Si](C)(C)N=C=O NIZHERJWXFHGGU-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- 239000012267 brine Substances 0.000 description 13
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 13
- 238000001704 evaporation Methods 0.000 description 13
- 230000008020 evaporation Effects 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 12
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 12
- IJXJGQCXFSSHNL-QMMMGPOBSA-N (R)-(-)-2-Phenylglycinol Chemical compound OC[C@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-QMMMGPOBSA-N 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 9
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 102000003820 Lipoxygenases Human genes 0.000 description 6
- 108090000128 Lipoxygenases Proteins 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 229940114079 arachidonic acid Drugs 0.000 description 5
- 235000021342 arachidonic acid Nutrition 0.000 description 5
- RMVRSNDYEFQCLF-UHFFFAOYSA-N phenyl mercaptan Natural products SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- NEXUIRYGNARMPC-AWEZNQCLSA-N (4r)-2-(3-iodophenyl)-4-phenyl-4,5-dihydro-1,3-oxazole Chemical compound IC1=CC=CC(C=2OC[C@H](N=2)C=2C=CC=CC=2)=C1 NEXUIRYGNARMPC-AWEZNQCLSA-N 0.000 description 4
- PFKKANIJIXXMAC-UHFFFAOYSA-N 2-fluoro-3-iodobenzoyl chloride Chemical compound FC1=C(I)C=CC=C1C(Cl)=O PFKKANIJIXXMAC-UHFFFAOYSA-N 0.000 description 4
- OFLBLHDKAFLETC-AWEZNQCLSA-N 3-[(4r)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenol Chemical compound OC1=CC=CC(C=2OC[C@H](N=2)C=2C=CC=CC=2)=C1 OFLBLHDKAFLETC-AWEZNQCLSA-N 0.000 description 4
- OFLBLHDKAFLETC-CQSZACIVSA-N 3-[(4s)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenol Chemical compound OC1=CC=CC(C=2OC[C@@H](N=2)C=2C=CC=CC=2)=C1 OFLBLHDKAFLETC-CQSZACIVSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 150000002617 leukotrienes Chemical class 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 239000003039 volatile agent Substances 0.000 description 4
- ULSIYEODSMZIPX-QMMMGPOBSA-N (1r)-2-amino-1-phenylethanol Chemical compound NC[C@H](O)C1=CC=CC=C1 ULSIYEODSMZIPX-QMMMGPOBSA-N 0.000 description 3
- VGCOFQXDXBJVFY-AWEZNQCLSA-N (4r)-2-(3-bromophenyl)-4-phenyl-4,5-dihydro-1,3-oxazole Chemical compound BrC1=CC=CC(C=2OC[C@H](N=2)C=2C=CC=CC=2)=C1 VGCOFQXDXBJVFY-AWEZNQCLSA-N 0.000 description 3
- HLHJXRFQOPHHRY-AWEZNQCLSA-N (4r)-2-(3-iodophenyl)-4-phenyl-4,5-dihydro-1,3-thiazole Chemical compound IC1=CC=CC(C=2SC[C@H](N=2)C=2C=CC=CC=2)=C1 HLHJXRFQOPHHRY-AWEZNQCLSA-N 0.000 description 3
- ZTLMXAYPAAMVMB-INIZCTEOSA-N 2-[3-[(4r)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(C=2OC[C@H](N=2)C=2C=CC=CC=2)=C1 ZTLMXAYPAAMVMB-INIZCTEOSA-N 0.000 description 3
- OUSORHQUCAIBHP-LBPRGKRZSA-N 2-fluoro-3-[(4r)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenol Chemical compound OC1=CC=CC(C=2OC[C@H](N=2)C=2C=CC=CC=2)=C1F OUSORHQUCAIBHP-LBPRGKRZSA-N 0.000 description 3
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 3
- OCLCJJHYNXMGKB-UHFFFAOYSA-N 3-[tert-butyl(dimethyl)silyl]oxy-2-fluorobenzoic acid Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=CC(C(O)=O)=C1F OCLCJJHYNXMGKB-UHFFFAOYSA-N 0.000 description 3
- PUAKNYOHAPTJJK-AWEZNQCLSA-N 3-bromo-n-[(1r)-2-hydroxy-1-phenylethyl]benzamide Chemical compound N([C@@H](CO)C=1C=CC=CC=1)C(=O)C1=CC=CC(Br)=C1 PUAKNYOHAPTJJK-AWEZNQCLSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 238000006751 Mitsunobu reaction Methods 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- HVTHJHLZTRNEEH-AWEZNQCLSA-N n-[(1r)-2-hydroxy-1-phenylethyl]-3-iodobenzamide Chemical compound N([C@@H](CO)C=1C=CC=CC=1)C(=O)C1=CC=CC(I)=C1 HVTHJHLZTRNEEH-AWEZNQCLSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 150000003180 prostaglandins Chemical class 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- LRWBRTSYPZDAQL-NRFANRHFSA-N tert-butyl-dimethyl-[2-[3-[(4r)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenoxy]ethoxy]silane Chemical compound CC(C)(C)[Si](C)(C)OCCOC1=CC=CC(C=2OC[C@H](N=2)C=2C=CC=CC=2)=C1 LRWBRTSYPZDAQL-NRFANRHFSA-N 0.000 description 3
- ULSIYEODSMZIPX-MRVPVSSYSA-N (1s)-2-amino-1-phenylethanol Chemical compound NC[C@@H](O)C1=CC=CC=C1 ULSIYEODSMZIPX-MRVPVSSYSA-N 0.000 description 2
- SRQPEYLZIUEVIA-QMMMGPOBSA-N (2r)-2-amino-2-(4-fluorophenyl)ethanol Chemical compound OC[C@H](N)C1=CC=C(F)C=C1 SRQPEYLZIUEVIA-QMMMGPOBSA-N 0.000 description 2
- IJXJGQCXFSSHNL-MRVPVSSYSA-N (2s)-2-amino-2-phenylethanol Chemical compound OC[C@@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-MRVPVSSYSA-N 0.000 description 2
- MHIJAOGZCSRMRQ-ZDUSSCGKSA-N (4r)-2-(2-fluoro-3-iodophenyl)-4-phenyl-4,5-dihydro-1,3-oxazole Chemical compound FC1=C(I)C=CC=C1C1=N[C@H](C=2C=CC=CC=2)CO1 MHIJAOGZCSRMRQ-ZDUSSCGKSA-N 0.000 description 2
- WAPNOHKVXSQRPX-ZETCQYMHSA-N (S)-1-phenylethanol Chemical compound C[C@H](O)C1=CC=CC=C1 WAPNOHKVXSQRPX-ZETCQYMHSA-N 0.000 description 2
- DTMWRDOCPIVPCL-HNNXBMFYSA-N 2-[2-fluoro-3-[(5r)-5-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(C=2O[C@@H](CN=2)C=2C=CC=CC=2)=C1F DTMWRDOCPIVPCL-HNNXBMFYSA-N 0.000 description 2
- YBNHAHFRJOBQMM-SFHVURJKSA-N 2-[2-fluoro-3-[(5r)-5-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenoxy]ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCOC1=CC=CC(C=2O[C@@H](CN=2)C=2C=CC=CC=2)=C1F YBNHAHFRJOBQMM-SFHVURJKSA-N 0.000 description 2
- ZTLMXAYPAAMVMB-MRXNPFEDSA-N 2-[3-[(4s)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenoxy]ethanol Chemical compound OCCOC1=CC=CC(C=2OC[C@@H](N=2)C=2C=CC=CC=2)=C1 ZTLMXAYPAAMVMB-MRXNPFEDSA-N 0.000 description 2
- JBKINHFZTVLNEM-UHFFFAOYSA-N 2-bromoethoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCBr JBKINHFZTVLNEM-UHFFFAOYSA-N 0.000 description 2
- XGBDZGGZWCMKHK-ZDUSSCGKSA-N 2-fluoro-3-[(5r)-5-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenol Chemical compound OC1=CC=CC(C=2O[C@@H](CN=2)C=2C=CC=CC=2)=C1F XGBDZGGZWCMKHK-ZDUSSCGKSA-N 0.000 description 2
- NFSBOOGCJQDNFS-UHFFFAOYSA-N 2-fluoro-3-phenylmethoxybenzoic acid Chemical compound OC(=O)C1=CC=CC(OCC=2C=CC=CC=2)=C1F NFSBOOGCJQDNFS-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 2
- GHKYWQYWYKBOIV-INIZCTEOSA-N 3-[2-fluoro-3-[(4r)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl]prop-2-yn-1-ol Chemical compound OCC#CC1=CC=CC(C=2OC[C@H](N=2)C=2C=CC=CC=2)=C1F GHKYWQYWYKBOIV-INIZCTEOSA-N 0.000 description 2
- LASWNLPFHFTONC-UHFFFAOYSA-N 3-[tert-butyl(dimethyl)silyl]oxy-2-fluorophenol Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=CC(O)=C1F LASWNLPFHFTONC-UHFFFAOYSA-N 0.000 description 2
- PBOOZQFGWNZNQE-UHFFFAOYSA-N 3-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(Br)=C1 PBOOZQFGWNZNQE-UHFFFAOYSA-N 0.000 description 2
- CISXCTKEQYOZAM-UHFFFAOYSA-N 3-phenylmethoxybenzoic acid Chemical compound OC(=O)C1=CC=CC(OCC=2C=CC=CC=2)=C1 CISXCTKEQYOZAM-UHFFFAOYSA-N 0.000 description 2
- HPVUGOBQRQUWMK-UHFFFAOYSA-N 3-phenylmethoxybenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(OCC=2C=CC=CC=2)=C1 HPVUGOBQRQUWMK-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- STVVMTBJNDTZBF-VIFPVBQESA-N L-phenylalaninol Chemical compound OC[C@@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-VIFPVBQESA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 229940077388 benzenesulfonate Drugs 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
- JDITTZVCPMECLZ-UHFFFAOYSA-N benzyl 2-fluoro-3-phenylmethoxybenzoate Chemical compound C1=CC=C(C(=O)OCC=2C=CC=CC=2)C(F)=C1OCC1=CC=CC=C1 JDITTZVCPMECLZ-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- RNIMPQALGZUWAE-QGZVFWFLSA-N ethyl 2-[3-[(4s)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenoxy]acetate Chemical compound CCOC(=O)COC1=CC=CC(C=2OC[C@@H](N=2)C=2C=CC=CC=2)=C1 RNIMPQALGZUWAE-QGZVFWFLSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 2
- 229940050410 gluconate Drugs 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- WTSCLFSMVAIQFC-IBYPIGCZSA-N n-[4-[3-[(4r)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl]but-3-yn-2-yl]hydroxylamine Chemical compound ONC(C)C#CC1=CC=CC(C=2OC[C@H](N=2)C=2C=CC=CC=2)=C1 WTSCLFSMVAIQFC-IBYPIGCZSA-N 0.000 description 2
- VDUIPQNXOQMTBF-UHFFFAOYSA-N n-ethylhydroxylamine Chemical compound CCNO VDUIPQNXOQMTBF-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- ULSIYEODSMZIPX-UHFFFAOYSA-N phenylethanolamine Chemical compound NCC(O)C1=CC=CC=C1 ULSIYEODSMZIPX-UHFFFAOYSA-N 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 2
- 239000001294 propane Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 150000003595 thromboxanes Chemical class 0.000 description 2
- 150000008648 triflates Chemical class 0.000 description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- PHLSHGXBEPRYMN-NRFANRHFSA-N (4r)-4-phenyl-2-(3-phenylmethoxyphenyl)-4,5-dihydro-1,3-oxazole Chemical compound C1([C@H]2N=C(OC2)C=2C=CC=C(C=2)OCC=2C=CC=CC=2)=CC=CC=C1 PHLSHGXBEPRYMN-NRFANRHFSA-N 0.000 description 1
- STVVMTBJNDTZBF-UHFFFAOYSA-N -2-Amino-3-phenyl-1-propanol Natural products OCC(N)CC1=CC=CC=C1 STVVMTBJNDTZBF-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- QFRHBDYRNHTNCV-KRWDZBQOSA-N 1-[3-[4-fluoro-3-[(4r)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl]prop-2-ynyl]-1-hydroxyurea Chemical compound NC(=O)N(O)CC#CC1=CC=C(F)C(C=2OC[C@H](N=2)C=2C=CC=CC=2)=C1 QFRHBDYRNHTNCV-KRWDZBQOSA-N 0.000 description 1
- 125000004776 1-fluoroethyl group Chemical group [H]C([H])([H])C([H])(F)* 0.000 description 1
- WUOLDGYMDSUNDS-KRWDZBQOSA-N 1-hydroxy-1-[3-[3-[(4r)-4-phenyl-4,5-dihydro-1,3-thiazol-2-yl]phenyl]prop-2-ynyl]urea Chemical compound NC(=O)N(O)CC#CC1=CC=CC(C=2SC[C@H](N=2)C=2C=CC=CC=2)=C1 WUOLDGYMDSUNDS-KRWDZBQOSA-N 0.000 description 1
- WJKISRFVKIOBCQ-UHFFFAOYSA-N 2-fluoro-4-methylphenol Chemical compound CC1=CC=C(O)C(F)=C1 WJKISRFVKIOBCQ-UHFFFAOYSA-N 0.000 description 1
- CEMYZMDITJKYDA-UHFFFAOYSA-N 2-fluoro-5-iodobenzoyl chloride Chemical compound FC1=CC=C(I)C=C1C(Cl)=O CEMYZMDITJKYDA-UHFFFAOYSA-N 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- GSLTVFIVJMCNBH-UHFFFAOYSA-N 2-isocyanatopropane Chemical compound CC(C)N=C=O GSLTVFIVJMCNBH-UHFFFAOYSA-N 0.000 description 1
- QGMROEZDWJTIDW-UHFFFAOYSA-N 3-bromopropoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCCBr QGMROEZDWJTIDW-UHFFFAOYSA-N 0.000 description 1
- HVZBXDHNZDYNAS-UHFFFAOYSA-N 3-fluoro-5-phenylmethoxybenzoic acid Chemical compound OC(=O)C1=CC(F)=CC(OCC=2C=CC=CC=2)=C1 HVZBXDHNZDYNAS-UHFFFAOYSA-N 0.000 description 1
- ZFSIGTASDSRLCO-UHFFFAOYSA-N 3-iodo-4-methoxybenzoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1I ZFSIGTASDSRLCO-UHFFFAOYSA-N 0.000 description 1
- JCOQBCLTGOENLA-UHFFFAOYSA-N 3-iodo-4-methylbenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1I JCOQBCLTGOENLA-UHFFFAOYSA-N 0.000 description 1
- ZKMUKBBWORLNLA-UHFFFAOYSA-N 4-chloro-2-fluorophenol Chemical compound OC1=CC=C(Cl)C=C1F ZKMUKBBWORLNLA-UHFFFAOYSA-N 0.000 description 1
- DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 description 1
- PCKSZTXLFMHDDO-UHFFFAOYSA-N 5-bromopyridine-3-carbonyl chloride;hydrochloride Chemical compound Cl.ClC(=O)C1=CN=CC(Br)=C1 PCKSZTXLFMHDDO-UHFFFAOYSA-N 0.000 description 1
- 101100101413 Caenorhabditis elegans ubh-4 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102100037611 Lysophospholipase Human genes 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-O Methylammonium ion Chemical compound [NH3+]C BAVYZALUXZFZLV-UHFFFAOYSA-O 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methylthiourea Natural products CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- HXBPYFMVGFDZFT-UHFFFAOYSA-N allyl isocyanate Chemical compound C=CCN=C=O HXBPYFMVGFDZFT-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 125000005002 aryl methyl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical class [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
- VEWFZHAHZPVQES-UHFFFAOYSA-N boron;n,n-diethylethanamine Chemical compound [B].CCN(CC)CC VEWFZHAHZPVQES-UHFFFAOYSA-N 0.000 description 1
- NNTOJPXOCKCMKR-UHFFFAOYSA-N boron;pyridine Chemical compound [B].C1=CC=NC=C1 NNTOJPXOCKCMKR-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-O diethylammonium Chemical compound CC[NH2+]CC HPNMFZURTQLUMO-UHFFFAOYSA-O 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 235000004626 essential fatty acids Nutrition 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 150000002366 halogen compounds Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- XGEGHDBEHXKFPX-NJFSPNSNSA-N methylurea Chemical compound [14CH3]NC(N)=O XGEGHDBEHXKFPX-NJFSPNSNSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- YPQNLUBHWQUTLQ-IBGZPJMESA-N n-[(1r)-2-[tert-butyl(dimethyl)silyl]oxy-1-phenylethyl]-3-iodobenzamide Chemical compound N([C@@H](CO[Si](C)(C)C(C)(C)C)C=1C=CC=CC=1)C(=O)C1=CC=CC(I)=C1 YPQNLUBHWQUTLQ-IBGZPJMESA-N 0.000 description 1
- PYYSRTFZKXBTGQ-NRFANRHFSA-N n-[(1r)-2-hydroxy-1-phenylethyl]-3-phenylmethoxybenzamide Chemical compound N([C@@H](CO)C=1C=CC=CC=1)C(=O)C(C=1)=CC=CC=1OCC1=CC=CC=C1 PYYSRTFZKXBTGQ-NRFANRHFSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-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
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 150000003815 prostacyclins Chemical class 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- AGYFTZUMGFWUIV-QHCPKHFHSA-N tert-butyl [(2-methylpropan-2-yl)oxycarbonyl-[3-[3-[(4r)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl]prop-2-ynyl]amino] carbonate Chemical compound CC(C)(C)OC(=O)ON(C(=O)OC(C)(C)C)CC#CC1=CC=CC(C=2OC[C@H](N=2)C=2C=CC=CC=2)=C1 AGYFTZUMGFWUIV-QHCPKHFHSA-N 0.000 description 1
- AGOSGCWATIJZHQ-UHFFFAOYSA-N tert-butyl [(2-methylpropan-2-yl)oxycarbonylamino] carbonate Chemical compound CC(C)(C)OC(=O)NOC(=O)OC(C)(C)C AGOSGCWATIJZHQ-UHFFFAOYSA-N 0.000 description 1
- WQMDWUQHZUBMKP-QFIPXVFZSA-N tert-butyl [3-[2-fluoro-3-[(4r)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl]prop-2-ynyl-[(2-methylpropan-2-yl)oxycarbonyl]amino] carbonate Chemical compound CC(C)(C)OC(=O)ON(C(=O)OC(C)(C)C)CC#CC1=CC=CC(C=2OC[C@H](N=2)C=2C=CC=CC=2)=C1F WQMDWUQHZUBMKP-QFIPXVFZSA-N 0.000 description 1
- NNURAOJVJSSNAK-SFHVURJKSA-N tert-butyl-[2-fluoro-3-[(5r)-5-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenoxy]-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=CC(C=2O[C@@H](CN=2)C=2C=CC=CC=2)=C1F NNURAOJVJSSNAK-SFHVURJKSA-N 0.000 description 1
- YFORILLFFVNYHZ-GCJKJVERSA-N tert-butyl-dimethyl-[(2r)-2-[3-[(4r)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenoxy]propoxy]silane Chemical compound CC(C)(C)[Si](C)(C)OC[C@@H](C)OC1=CC=CC(C=2OC[C@H](N=2)C=2C=CC=CC=2)=C1 YFORILLFFVNYHZ-GCJKJVERSA-N 0.000 description 1
- YFORILLFFVNYHZ-AVRDEDQJSA-N tert-butyl-dimethyl-[(2s)-2-[3-[(4r)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenoxy]propoxy]silane Chemical compound CC(C)(C)[Si](C)(C)OC[C@H](C)OC1=CC=CC(C=2OC[C@H](N=2)C=2C=CC=CC=2)=C1 YFORILLFFVNYHZ-AVRDEDQJSA-N 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D263/14—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D277/10—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO19975726A NO310288B1 (no) | 1994-05-19 | 1997-12-05 | N-hydroksyurea-derivater som anti-inflammatoriske midler, anvendelse derav og farmasöytisk preparat |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12810594A JP3179286B2 (ja) | 1994-05-19 | 1994-05-19 | Ｎ−ヒドロキシ尿素系抗炎症剤 |
| CA002223023A CA2223023C (en) | 1994-05-19 | 1995-06-07 | N-hydroxyureas as antiinflammatory agents |
| PCT/JP1995/001127 WO1996040659A1 (en) | 1994-05-19 | 1995-06-07 | N-hydroxyureas as antiinflammatory agents |
| NO19975726A NO310288B1 (no) | 1994-05-19 | 1997-12-05 | N-hydroksyurea-derivater som anti-inflammatoriske midler, anvendelse derav og farmasöytisk preparat |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO975726D0 NO975726D0 (no) | 1997-12-05 |
| NO975726L NO975726L (no) | 1998-02-03 |
| NO310288B1 true NO310288B1 (no) | 2001-06-18 |
Family
ID=27170556
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19975726A NO310288B1 (no) | 1994-05-19 | 1997-12-05 | N-hydroksyurea-derivater som anti-inflammatoriske midler, anvendelse derav og farmasöytisk preparat |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US5814648A (de) |
| EP (1) | EP0832078B1 (de) |
| JP (2) | JP3179286B2 (de) |
| AT (1) | ATE185803T1 (de) |
| AU (1) | AU705505B2 (de) |
| BR (1) | BR9502072A (de) |
| CA (1) | CA2223023C (de) |
| CZ (1) | CZ286331B6 (de) |
| DE (1) | DE69512940T2 (de) |
| DK (1) | DK0832078T3 (de) |
| ES (1) | ES2138211T3 (de) |
| FI (1) | FI974444A (de) |
| GR (1) | GR3032301T3 (de) |
| HU (1) | HUT77950A (de) |
| IL (1) | IL113706A (de) |
| NO (1) | NO310288B1 (de) |
| NZ (1) | NZ287551A (de) |
| PL (1) | PL179853B1 (de) |
| WO (1) | WO1996040659A1 (de) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19548419A1 (de) * | 1995-12-22 | 1997-06-26 | Bayer Ag | Substituierte Thiazoline |
| ATE445838T1 (de) | 2001-07-25 | 2009-10-15 | Raptor Pharmaceutical Inc | Zusammensetzungen und verfahren zur modulation des transports durch die blut-hirn-schranke |
| AU2006228690A1 (en) | 2005-03-31 | 2006-10-05 | Ucb Pharma S.A. | Compounds comprising an oxazole or thiazole moiety, processes for making them, and their uses |
| EP2671508B1 (de) | 2005-04-28 | 2020-09-16 | Proteus Digital Health, Inc. | Pharma-Informatiksystem |
| CA2663377A1 (en) | 2006-09-18 | 2008-03-27 | Raptor Pharmaceutical Inc. | Treatment of liver disorders by administration of receptor-associated protein (rap)-conjugates |
| HUE059078T2 (hu) | 2009-02-20 | 2022-10-28 | Enhanx Biopharm Inc | Glutation-alapú hatóanyagszállító rendszer |
| NZ624963A (en) | 2009-04-29 | 2016-07-29 | Amarin Pharmaceuticals Ie Ltd | Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same |
| JP2012526144A (ja) | 2009-05-06 | 2012-10-25 | ラボラトリー スキン ケア インコーポレイテッド | 活性物質−リン酸カルシウム粒子複合体を含む経皮送達組成物およびその使用方法 |
| US20120077778A1 (en) | 2010-09-29 | 2012-03-29 | Andrea Bourdelais | Ladder-Frame Polyether Conjugates |
| WO2021214048A1 (en) * | 2020-04-20 | 2021-10-28 | Johann Wolfgang Goethe-Universität Frankfurt am Main | Dual inhibitors of soluble epoxide hydrolase and 5-lipoxygenase |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0819069B2 (ja) * | 1990-07-25 | 1996-02-28 | アボツト・ラボラトリーズ | リポキシゲナーゼ阻害活性を有するアセチレン誘導体 |
| JP2528741B2 (ja) * | 1991-01-09 | 1996-08-28 | ファイザー製薬株式会社 | オキサゾ―ル、チアゾ―ルおよびイミダゾ―ル化合物 |
| JPH07100687B2 (ja) * | 1991-06-13 | 1995-11-01 | ファイザー製薬株式会社 | 新規なｎ−ヒドロキシ尿素化合物および組成物 |
| US5288751A (en) * | 1992-11-06 | 1994-02-22 | Abbott Laboratories | [(Substituted) phenyalkyl]furylalkynyl-and [substituted) phenyalkyl] thienylalkynyl-N-hydroxyurea inhibitors or leukotriene biosynthesis |
| EP0693054B1 (de) * | 1993-04-07 | 1998-06-10 | Pfizer Inc. | Cycloalkylhydroxyharnstoffe und ihre verwendung als lipoxy-genase-inhibitoren |
-
1994
- 1994-05-19 JP JP12810594A patent/JP3179286B2/ja not_active Expired - Fee Related
-
1995
- 1995-05-11 IL IL11370695A patent/IL113706A/xx not_active IP Right Cessation
- 1995-05-18 BR BR9502072A patent/BR9502072A/pt not_active IP Right Cessation
- 1995-06-07 DE DE69512940T patent/DE69512940T2/de not_active Expired - Fee Related
- 1995-06-07 AU AU26294/95A patent/AU705505B2/en not_active Ceased
- 1995-06-07 WO PCT/JP1995/001127 patent/WO1996040659A1/en active IP Right Grant
- 1995-06-07 CZ CZ19973824A patent/CZ286331B6/cs not_active IP Right Cessation
- 1995-06-07 ES ES95921115T patent/ES2138211T3/es not_active Expired - Lifetime
- 1995-06-07 HU HU9801930A patent/HUT77950A/hu unknown
- 1995-06-07 AT AT95921115T patent/ATE185803T1/de not_active IP Right Cessation
- 1995-06-07 PL PL95324012A patent/PL179853B1/pl not_active IP Right Cessation
- 1995-06-07 DK DK95921115T patent/DK0832078T3/da active
- 1995-06-07 EP EP95921115A patent/EP0832078B1/de not_active Expired - Lifetime
- 1995-06-07 CA CA002223023A patent/CA2223023C/en not_active Expired - Fee Related
- 1995-06-07 US US08/945,671 patent/US5814648A/en not_active Expired - Fee Related
- 1995-06-07 JP JP9500299A patent/JPH10506649A/ja active Pending
- 1995-06-07 NZ NZ287551A patent/NZ287551A/xx unknown
-
1997
- 1997-12-05 FI FI974444A patent/FI974444A/fi not_active IP Right Cessation
- 1997-12-05 NO NO19975726A patent/NO310288B1/no not_active IP Right Cessation
-
2000
- 2000-01-04 GR GR20000400001T patent/GR3032301T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07309849A (ja) | 1995-11-28 |
| NO975726D0 (no) | 1997-12-05 |
| DE69512940T2 (de) | 2000-02-17 |
| MX9709986A (es) | 1998-03-29 |
| EP0832078A1 (de) | 1998-04-01 |
| JPH10506649A (ja) | 1998-06-30 |
| NZ287551A (en) | 1999-02-25 |
| AU2629495A (en) | 1996-12-30 |
| IL113706A (en) | 1999-08-17 |
| PL179853B1 (pl) | 2000-11-30 |
| PL324012A1 (en) | 1998-04-27 |
| ATE185803T1 (de) | 1999-11-15 |
| HUT77950A (hu) | 1998-12-28 |
| NO975726L (no) | 1998-02-03 |
| CZ286331B6 (cs) | 2000-03-15 |
| EP0832078B1 (de) | 1999-10-20 |
| IL113706A0 (en) | 1995-08-31 |
| DE69512940D1 (de) | 1999-11-25 |
| FI974444A (fi) | 1998-02-04 |
| BR9502072A (pt) | 1996-04-09 |
| ES2138211T3 (es) | 2000-01-01 |
| DK0832078T3 (da) | 2000-04-25 |
| CA2223023C (en) | 2001-07-17 |
| FI974444A0 (fi) | 1997-12-05 |
| GR3032301T3 (en) | 2000-04-27 |
| WO1996040659A1 (en) | 1996-12-19 |
| US5814648A (en) | 1998-09-29 |
| CA2223023A1 (en) | 1996-12-19 |
| AU705505B2 (en) | 1999-05-27 |
| CZ382497A3 (cs) | 1999-03-17 |
| JP3179286B2 (ja) | 2001-06-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6610696B2 (en) | Modulators of peroxisome proliferator activated receptors | |
| EP0544696B1 (de) | Hypoglykämische hydroxyharnstoffderivate | |
| HUT65603A (en) | Process for preparing 3-aryl- or heteroaryl-propionic or propenoic acid derivatives and pharmaceutical compositions containing them | |
| KR20000068151A (ko) | 프로피온산 유도체 및 그의 용도 | |
| EP0207454A2 (de) | Isoxazol- und Furanderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als antivirale Mittel | |
| EP0832078B1 (de) | N-hydroxy-harnstoff-derivate als entzündunghemmende mittel | |
| US4968707A (en) | Oxazolidin-2-one derivatives as hypoglycemic agents | |
| KR20030027054A (ko) | 옥사졸릴-아릴프로피온산 유도체 및 ｐｐａｒ효능제로서의 그의 용도 | |
| EP1313717B1 (de) | Oxazolylarylpropionsäure derivate und ihre verwendung als ppar agonisten | |
| RU2152935C2 (ru) | N-гидроксилмочевины в качестве противовоспалительных средств | |
| WO2004063184A1 (en) | Thiophene derivative ppar modulators | |
| KR100296157B1 (ko) | 엔-하이드록시우레아소염제 | |
| EP0736006A1 (de) | Phenylthiophenyl cycloalkenylhydroxyharnstoffe als lipoxygenasehemmer | |
| MXPA97009986A (en) | N-hydroxyurees, their use and anti-inflammatory composition that contains them |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |