DD300434A5 - Heterozyklische derivate - Google Patents
Heterozyklische derivate Download PDFInfo
- Publication number
- DD300434A5 DD300434A5 DD344286A DD34428690A DD300434A5 DD 300434 A5 DD300434 A5 DD 300434A5 DD 344286 A DD344286 A DD 344286A DD 34428690 A DD34428690 A DD 34428690A DD 300434 A5 DD300434 A5 DD 300434A5
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- formula
- group
- methyl
- dihydro
- alkyl
- Prior art date
Links
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 47
- -1 carboxy, cyano, amino Chemical group 0.000 claims description 222
- 150000001875 compounds Chemical class 0.000 claims description 81
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 125000001424 substituent group Chemical group 0.000 claims description 44
- 150000003839 salts Chemical class 0.000 claims description 38
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 35
- 125000001153 fluoro group Chemical group F* 0.000 claims description 32
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 125000006239 protecting group Chemical group 0.000 claims description 25
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 23
- 125000003282 alkyl amino group Chemical group 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 17
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 16
- 239000005977 Ethylene Substances 0.000 claims description 16
- 230000002401 inhibitory effect Effects 0.000 claims description 16
- 125000006413 ring segment Chemical group 0.000 claims description 16
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 16
- 125000004149 thio group Chemical group *S* 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 125000001989 1,3-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([H])C([*:2])=C1[H] 0.000 claims description 11
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 11
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 claims description 9
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 9
- 150000002617 leukotrienes Chemical class 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 230000001225 therapeutic effect Effects 0.000 claims description 8
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 7
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 238000005859 coupling reaction Methods 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 230000003647 oxidation Effects 0.000 claims description 7
- 238000007254 oxidation reaction Methods 0.000 claims description 7
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 5
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 4
- 238000007796 conventional method Methods 0.000 claims description 4
- 230000008878 coupling Effects 0.000 claims description 4
- 238000010168 coupling process Methods 0.000 claims description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 4
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 4
- 230000010933 acylation Effects 0.000 claims description 3
- 238000005917 acylation reaction Methods 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 230000002152 alkylating effect Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- YYPAHTLQYHUVNX-UHFFFAOYSA-N 6-[3-(4-methoxyoxan-4-yl)phenyl]sulfanyl-1,8-dimethylquinolin-2-one Chemical compound C=1C=CC(SC=2C=C3C=CC(=O)N(C)C3=C(C)C=2)=CC=1C1(OC)CCOCC1 YYPAHTLQYHUVNX-UHFFFAOYSA-N 0.000 claims description 2
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
- 230000029936 alkylation Effects 0.000 claims description 2
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- HZMCKEWGOKWVEJ-UHFFFAOYSA-N 1-ethyl-6-[3-(4-methoxyoxan-4-yl)phenyl]sulfanylquinolin-2-one Chemical compound C1=C2C=CC(=O)N(CC)C2=CC=C1SC(C=1)=CC=CC=1C1(OC)CCOCC1 HZMCKEWGOKWVEJ-UHFFFAOYSA-N 0.000 claims 1
- QYEMNJMSULGQRD-UHFFFAOYSA-N 1-methyl-2-quinolone Chemical compound C1=CC=C2C=CC(=O)N(C)C2=C1 QYEMNJMSULGQRD-UHFFFAOYSA-N 0.000 claims 1
- BZPVOLVLAKEMHJ-UHFFFAOYSA-N 6-[3-(4-methoxyoxan-4-yl)phenyl]sulfanyl-1-methylquinolin-2-one Chemical compound C=1C=CC(SC=2C=C3C=CC(=O)N(C)C3=CC=2)=CC=1C1(OC)CCOCC1 BZPVOLVLAKEMHJ-UHFFFAOYSA-N 0.000 claims 1
- BMZFPKUWWKQXIG-QMHKHESXSA-N 6-[3-[(2s,4r)-4-methoxy-2-methyloxan-4-yl]phenyl]sulfonyl-1-methylquinolin-2-one Chemical compound C=1C=CC(S(=O)(=O)C=2C=C3C=CC(=O)N(C)C3=CC=2)=CC=1[C@@]1(OC)CCO[C@@H](C)C1 BMZFPKUWWKQXIG-QMHKHESXSA-N 0.000 claims 1
- YVQHLXWTJBUCQY-UHFFFAOYSA-N 6-[3-fluoro-5-(4-methoxy-2-methyloxan-2-yl)phenyl]sulfonyl-1-methylquinolin-2-one Chemical compound C1C(OC)CCOC1(C)C1=CC(F)=CC(S(=O)(=O)C=2C=C3C=CC(=O)N(C)C3=CC=2)=C1 YVQHLXWTJBUCQY-UHFFFAOYSA-N 0.000 claims 1
- BVMYEWKADOKRJT-UHFFFAOYSA-N 6-[3-fluoro-5-(4-methoxyoxan-4-yl)phenyl]sulfanyl-1-methylquinolin-2-one Chemical compound C=1C(F)=CC(SC=2C=C3C=CC(=O)N(C)C3=CC=2)=CC=1C1(OC)CCOCC1 BVMYEWKADOKRJT-UHFFFAOYSA-N 0.000 claims 1
- BZMQYDUMBXSCLR-UHFFFAOYSA-N 8-fluoro-6-[3-(4-methoxyoxan-4-yl)phenyl]sulfanyl-1-methylquinolin-2-one Chemical compound C=1C=CC(SC=2C=C3C=CC(=O)N(C)C3=C(F)C=2)=CC=1C1(OC)CCOCC1 BZMQYDUMBXSCLR-UHFFFAOYSA-N 0.000 claims 1
- 125000002619 bicyclic group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 103
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 60
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- 239000000243 solution Substances 0.000 description 38
- 238000012360 testing method Methods 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- 239000007858 starting material Substances 0.000 description 28
- 102100022364 Polyunsaturated fatty acid 5-lipoxygenase Human genes 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 101710156627 Polyunsaturated fatty acid 5-lipoxygenase Proteins 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 18
- 239000003480 eluent Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 239000003921 oil Substances 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
- 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 13
- 239000002585 base Substances 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 125000002252 acyl group Chemical group 0.000 description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 238000002844 melting Methods 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000012312 sodium hydride Substances 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 8
- 239000000443 aerosol Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000006185 dispersion Substances 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000002480 mineral oil Substances 0.000 description 7
- 235000010446 mineral oil Nutrition 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 229940114079 arachidonic acid Drugs 0.000 description 6
- 235000021342 arachidonic acid Nutrition 0.000 description 6
- 125000003435 aroyl group Chemical group 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- JPVIBGUWXITFKK-UHFFFAOYSA-N 6-iodo-1-methylquinolin-2-one Chemical compound C1=C(I)C=C2C=CC(=O)N(C)C2=C1 JPVIBGUWXITFKK-UHFFFAOYSA-N 0.000 description 5
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- LQVSZGJDXRIDDX-UHFFFAOYSA-N 3-(4-methoxyoxan-4-yl)benzenethiol Chemical compound C=1C=CC(S)=CC=1C1(OC)CCOCC1 LQVSZGJDXRIDDX-UHFFFAOYSA-N 0.000 description 4
- WLJXULCDIKXOGT-UHFFFAOYSA-N 3-fluoro-5-(4-methoxyoxan-4-yl)benzenethiol Chemical compound C=1C(F)=CC(S)=CC=1C1(OC)CCOCC1 WLJXULCDIKXOGT-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 4
- 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 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 239000012425 OXONE® Substances 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000001589 carboacyl group Chemical group 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 229960000905 indomethacin Drugs 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000003127 radioimmunoassay Methods 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 235000010265 sodium sulphite Nutrition 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- MQOPUXINXNVMKJ-YFKPBYRVSA-N (2s)-2-methyloxan-4-one Chemical compound C[C@H]1CC(=O)CCO1 MQOPUXINXNVMKJ-YFKPBYRVSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 description 3
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 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 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 239000004147 Sorbitan trioleate Substances 0.000 description 3
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229920000392 Zymosan Polymers 0.000 description 3
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 230000002917 arthritic effect Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000002775 capsule 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
- 229910052802 copper Inorganic materials 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 229960005168 croscarmellose Drugs 0.000 description 3
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 3
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 3
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 150000003180 prostaglandins Chemical class 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 235000019337 sorbitan trioleate Nutrition 0.000 description 3
- 229960000391 sorbitan trioleate Drugs 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 3
- 229940029284 trichlorofluoromethane Drugs 0.000 description 3
- 239000008215 water for injection Substances 0.000 description 3
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 2
- YFIIOONIABBCOF-UHFFFAOYSA-N 1-(methoxymethyl)-1,2-dimethylhydrazine Chemical compound CNN(C)COC YFIIOONIABBCOF-UHFFFAOYSA-N 0.000 description 2
- BUBAIZRPJQTWDP-UHFFFAOYSA-N 1-benzylsulfanyl-3-bromo-5-fluorobenzene Chemical compound FC1=CC(Br)=CC(SCC=2C=CC=CC=2)=C1 BUBAIZRPJQTWDP-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- HIYAVKIYRIFSCZ-CYEMHPAKSA-N 5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid Chemical compound O=C([C@@H](C)[C@H]1O[C@@]2([C@@H](C[C@H]1C)C)O[C@@H]([C@@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C1=CC=CN1 HIYAVKIYRIFSCZ-CYEMHPAKSA-N 0.000 description 2
- DXZDQONIFDRWFO-UHFFFAOYSA-N 6-iodo-1-(2,2,2-trifluoroethyl)quinolin-2-one Chemical compound C1=C(I)C=C2C=CC(=O)N(CC(F)(F)F)C2=C1 DXZDQONIFDRWFO-UHFFFAOYSA-N 0.000 description 2
- CVDKHJRRVQVFGK-UHFFFAOYSA-N 6-iodo-1-methylquinoxalin-2-one Chemical compound C1=C(I)C=C2N=CC(=O)N(C)C2=C1 CVDKHJRRVQVFGK-UHFFFAOYSA-N 0.000 description 2
- AYZCVCFJFSLWEE-UHFFFAOYSA-N 8-fluoro-1-methylquinolin-2-one Chemical compound C1=CC=C2C=CC(=O)N(C)C2=C1F AYZCVCFJFSLWEE-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 241001125671 Eretmochelys imbricata Species 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 208000019693 Lung disease Diseases 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 210000004712 air sac Anatomy 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000001387 anti-histamine Effects 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 125000005101 aryl methoxy carbonyl group Chemical group 0.000 description 2
- 125000005002 aryl methyl group Chemical group 0.000 description 2
- 239000012298 atmosphere Substances 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
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 239000002876 beta blocker Substances 0.000 description 2
- 229940097320 beta blocking agent Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- HIYAVKIYRIFSCZ-UHFFFAOYSA-N calcium ionophore A23187 Natural products N=1C2=C(C(O)=O)C(NC)=CC=C2OC=1CC(C(CC1)C)OC1(C(CC1C)C)OC1C(C)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-UHFFFAOYSA-N 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 2
- 229940117975 chromium trioxide Drugs 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 2
- 230000001120 cytoprotective effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
- 229960004279 formaldehyde Drugs 0.000 description 2
- 235000019256 formaldehyde Nutrition 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 2
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 150000003509 tertiary alcohols Chemical class 0.000 description 2
- 150000003595 thromboxanes Chemical class 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- CQTINIBMFYYWKD-GXFFZTMASA-N (2s,4r)-4-(3-bromophenyl)-4-methoxy-2-methyloxane Chemical compound C=1C=CC(Br)=CC=1[C@@]1(OC)CCO[C@@H](C)C1 CQTINIBMFYYWKD-GXFFZTMASA-N 0.000 description 1
- ZKSLQBNNKSVBAW-RNJXMRFFSA-N (2s,4r,6s)-2-ethoxy-6-methyloxan-4-ol Chemical compound CCO[C@@H]1C[C@H](O)C[C@H](C)O1 ZKSLQBNNKSVBAW-RNJXMRFFSA-N 0.000 description 1
- RMQOCSXMPMQRAE-JKUQZMGJSA-N (2s,4r,6s)-6-methyloxane-2,4-diol Chemical compound C[C@H]1C[C@@H](O)C[C@@H](O)O1 RMQOCSXMPMQRAE-JKUQZMGJSA-N 0.000 description 1
- ZHPKAPJNEIKPGV-WDSKDSINSA-N (2s,4s)-2-methyloxan-4-ol Chemical compound C[C@H]1C[C@@H](O)CCO1 ZHPKAPJNEIKPGV-WDSKDSINSA-N 0.000 description 1
- IKSZUZSICAXOHV-BQBZGAKWSA-N (2s,4s)-hept-6-ene-2,4-diol Chemical compound C[C@H](O)C[C@@H](O)CC=C IKSZUZSICAXOHV-BQBZGAKWSA-N 0.000 description 1
- FMNQRUKVXAQEAZ-JNRFBPFXSA-N (5z,8s,9r,10e,12s)-9,12-dihydroxy-8-[(1s)-1-hydroxy-3-oxopropyl]heptadeca-5,10-dienoic acid Chemical compound CCCCC[C@H](O)\C=C\[C@@H](O)[C@H]([C@@H](O)CC=O)C\C=C/CCCC(O)=O FMNQRUKVXAQEAZ-JNRFBPFXSA-N 0.000 description 1
- UJPMYEOUBPIPHQ-UHFFFAOYSA-N 1,1,1-trifluoroethane Chemical compound CC(F)(F)F UJPMYEOUBPIPHQ-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- JSRLURSZEMLAFO-UHFFFAOYSA-N 1,3-dibromobenzene Chemical compound BrC1=CC=CC(Br)=C1 JSRLURSZEMLAFO-UHFFFAOYSA-N 0.000 description 1
- HETCLLKHNWYJBL-UHFFFAOYSA-N 1-(2,2,2-trifluoroethyl)quinolin-2-one Chemical compound C1=CC=C2C=CC(=O)N(CC(F)(F)F)C2=C1 HETCLLKHNWYJBL-UHFFFAOYSA-N 0.000 description 1
- LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 description 1
- UZUMQQZPGOFJBQ-UHFFFAOYSA-N 1-aminopropane-1,2-diol Chemical compound CC(O)C(N)O UZUMQQZPGOFJBQ-UHFFFAOYSA-N 0.000 description 1
- JHLKSIOJYMGSMB-UHFFFAOYSA-N 1-bromo-3,5-difluorobenzene Chemical compound FC1=CC(F)=CC(Br)=C1 JHLKSIOJYMGSMB-UHFFFAOYSA-N 0.000 description 1
- CTPUUDQIXKUAMO-UHFFFAOYSA-N 1-bromo-3-iodobenzene Chemical compound BrC1=CC=CC(I)=C1 CTPUUDQIXKUAMO-UHFFFAOYSA-N 0.000 description 1
- LJFDCNZAYVVDLI-UHFFFAOYSA-N 1-ethyl-6-iodoquinolin-2-one Chemical compound C1=C(I)C=C2C=CC(=O)N(CC)C2=C1 LJFDCNZAYVVDLI-UHFFFAOYSA-N 0.000 description 1
- JRXCUTAHLPYHAY-UHFFFAOYSA-N 1-ethylquinolin-2-one Chemical compound C1=CC=C2C=CC(=O)N(CC)C2=C1 JRXCUTAHLPYHAY-UHFFFAOYSA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- CHPVQLYVDDOWNT-UHFFFAOYSA-N 1-methylquinoxalin-2-one Chemical compound C1=CC=C2N=CC(=O)N(C)C2=C1 CHPVQLYVDDOWNT-UHFFFAOYSA-N 0.000 description 1
- OFQCQIGMURIECL-UHFFFAOYSA-N 2-[2-(diethylamino)ethyl]-2',6'-dimethylspiro[isoquinoline-4,4'-oxane]-1,3-dione;phosphoric acid Chemical compound OP(O)(O)=O.O=C1N(CCN(CC)CC)C(=O)C2=CC=CC=C2C21CC(C)OC(C)C2 OFQCQIGMURIECL-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000000872 2-diethylaminoethoxy group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- MQOPUXINXNVMKJ-UHFFFAOYSA-N 2-methyloxan-4-one Chemical compound CC1CC(=O)CCO1 MQOPUXINXNVMKJ-UHFFFAOYSA-N 0.000 description 1
- HYTIPJFUWHYQON-UHFFFAOYSA-N 3,4-dihydro-1h-quinoxalin-2-one Chemical compound C1=CC=C2NC(=O)CNC2=C1 HYTIPJFUWHYQON-UHFFFAOYSA-N 0.000 description 1
- AVJSSPXPEVGNNT-UHFFFAOYSA-N 3-(4-methoxy-2-methyloxan-2-yl)benzenethiol Chemical compound C1C(OC)CCOC1(C)C1=CC=CC(S)=C1 AVJSSPXPEVGNNT-UHFFFAOYSA-N 0.000 description 1
- LTUZDLFTZHZQRQ-GXFFZTMASA-N 3-[(2s,4r)-4-methoxy-2-methyloxan-4-yl]benzenethiol Chemical compound C=1C=CC(S)=CC=1[C@@]1(OC)CCO[C@@H](C)C1 LTUZDLFTZHZQRQ-GXFFZTMASA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- WTZGGPKYWXUDTJ-UHFFFAOYSA-N 3-fluoro-5-(4-methoxy-2-methyloxan-4-yl)benzenethiol Chemical compound C=1C(F)=CC(S)=CC=1C1(OC)CCOC(C)C1 WTZGGPKYWXUDTJ-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- TZIKYTPIRPATJZ-UHFFFAOYSA-N 4-(3-benzylsulfanyl-5-fluorophenyl)-4-methoxy-2-methyloxane Chemical compound C=1C(F)=CC(SCC=2C=CC=CC=2)=CC=1C1(OC)CCOC(C)C1 TZIKYTPIRPATJZ-UHFFFAOYSA-N 0.000 description 1
- HVVSFHGXKAGEBJ-UHFFFAOYSA-N 4-(3-benzylsulfanyl-5-fluorophenyl)oxan-4-ol Chemical compound C=1C(F)=CC(SCC=2C=CC=CC=2)=CC=1C1(O)CCOCC1 HVVSFHGXKAGEBJ-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
- DFRPVXJXSUTHFU-QMHKHESXSA-N 6-[3-[(2s,4r)-4-methoxy-2-methyloxan-4-yl]phenyl]sulfanyl-1-methylquinolin-2-one Chemical compound C=1C=CC(SC=2C=C3C=CC(=O)N(C)C3=CC=2)=CC=1[C@@]1(OC)CCO[C@@H](C)C1 DFRPVXJXSUTHFU-QMHKHESXSA-N 0.000 description 1
- LLNHXEOZQHTGPO-UHFFFAOYSA-N 8-fluoro-6-iodo-1-methylquinolin-2-one Chemical compound C1=C(I)C=C2C=CC(=O)N(C)C2=C1F LLNHXEOZQHTGPO-UHFFFAOYSA-N 0.000 description 1
- 206010027654 Allergic conditions Diseases 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 1
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- 229940122204 Cyclooxygenase inhibitor Drugs 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N Glycolaldehyde Chemical compound OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 239000003810 Jones reagent Substances 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 229910021536 Zeolite Inorganic materials 0.000 description 1
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000001348 alkyl chlorides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 229950000210 beclometasone dipropionate Drugs 0.000 description 1
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- 125000006309 butyl amino group Chemical group 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000004671 cell-free system Anatomy 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- VSHWNOBYVDFOKC-UHFFFAOYSA-N dichloro(difluoro)methane;trichloro(fluoro)methane Chemical compound FC(F)(Cl)Cl.FC(Cl)(Cl)Cl VSHWNOBYVDFOKC-UHFFFAOYSA-N 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
- 125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 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
- 208000035475 disorder Diseases 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- QFWPJPIVLCBXFJ-UHFFFAOYSA-N glymidine Chemical compound N1=CC(OCCOC)=CN=C1NS(=O)(=O)C1=CC=CC=C1 QFWPJPIVLCBXFJ-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 1
- GWNVDXQDILPJIG-NXOLIXFESA-N leukotriene C4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O GWNVDXQDILPJIG-NXOLIXFESA-N 0.000 description 1
- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000008263 liquid aerosol Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 1
- 229960000582 mepyramine Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [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 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000223 polyglycerol Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 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
- FJVZDOGVDJCCCR-UHFFFAOYSA-M potassium periodate Chemical compound [K+].[O-]I(=O)(=O)=O FJVZDOGVDJCCCR-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 125000006308 propyl amino group Chemical group 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000005550 pyrazinylene group Chemical group 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005551 pyridylene group Chemical group 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000005576 pyrimidinylene group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Quinoline Compounds (AREA)
- Cephalosporin Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP89402699 | 1989-09-29 | ||
| EP90401183 | 1990-05-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD300434A5 true DD300434A5 (de) | 1992-06-11 |
Family
ID=26123295
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD344286A DD300434A5 (de) | 1989-09-29 | 1990-09-28 | Heterozyklische derivate |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US5221677A (es) |
| EP (1) | EP0420511B1 (es) |
| JP (1) | JP2996708B2 (es) |
| AT (1) | ATE110073T1 (es) |
| AU (1) | AU632356B2 (es) |
| CA (1) | CA2024258A1 (es) |
| DD (1) | DD300434A5 (es) |
| DE (1) | DE69011609T2 (es) |
| DK (1) | DK0420511T3 (es) |
| ES (1) | ES2058809T3 (es) |
| FI (1) | FI904591A0 (es) |
| GB (1) | GB9018134D0 (es) |
| HU (1) | HUT59134A (es) |
| IE (1) | IE64251B1 (es) |
| IL (1) | IL95481A (es) |
| MY (1) | MY107266A (es) |
| NO (1) | NO904249L (es) |
| NZ (1) | NZ235016A (es) |
| PT (1) | PT95455A (es) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5236919A (en) * | 1989-02-28 | 1993-08-17 | Imperial Chemical Industries Plc | Quinoxalinyl derivatives suitable for use in leukotriene mediated disease |
| US5254581A (en) * | 1990-06-21 | 1993-10-19 | Imperial Chemical Industries Plc | Pyran derivatives and their use as inhibitors of 5-lipoxygenase |
| GB9113137D0 (en) * | 1990-07-13 | 1991-08-07 | Ici Plc | Thioxo heterocycles |
| IE913655A1 (en) * | 1990-11-06 | 1992-05-22 | Zeneca Ltd | Synergistic agents |
| IE913866A1 (en) * | 1990-11-28 | 1992-06-03 | Ici Plc | Aryl derivatives |
| IE914005A1 (en) * | 1990-12-14 | 1992-06-17 | Zeneca Ltd | Novel intermediates |
| AU645159B2 (en) * | 1991-01-17 | 1994-01-06 | Ici Pharma | Sulphonamide derivatives |
| DE69206725T2 (de) * | 1991-09-10 | 1996-05-02 | Zeneca Ltd | Benzolsulfonamidderivate als 5-Lipoxygenasehemmer |
| CA2094465A1 (en) * | 1992-04-23 | 1993-10-24 | Pierre Andre Raymond Bruneau | Cycloalkane derivatives |
| CA2095006A1 (en) * | 1992-05-12 | 1993-11-13 | Philip Neil Edwards | Oxime derivatives |
| CA2095005A1 (en) * | 1992-05-12 | 1993-11-13 | Philip Neil Edwards | Hydroxylamine derivatives |
| EP0586229A1 (en) * | 1992-09-01 | 1994-03-09 | Zeneca Limited | 3-Hydroxy-3-(subst-akyl)-pyrrolidines as 5-lipoxygenase inhibitors |
| AU4444393A (en) * | 1992-09-01 | 1994-03-10 | Zeneca Limited | Pyrrolidine derivatives |
| ES2055657B1 (es) * | 1992-10-08 | 1995-02-16 | Ici Plc | Derivados de bencenosulfonamida. |
| IL109254A (en) * | 1993-04-29 | 1999-03-12 | Zeneca Ltd | History of the tetrahydropyran and tetrahydropuran site preparation and pharmaceutical preparations containing them |
| EP0702680A1 (en) * | 1993-06-07 | 1996-03-27 | Zeneca Limited | 2-oxo-1,2,3,4-tetrahydroquinoline derivatives |
| US5410054A (en) * | 1993-07-20 | 1995-04-25 | Merck Frosst Canada, Inc. | Heteroaryl quinolines as inhibitors of leukotriene biosynthesis |
| US5459271A (en) * | 1993-07-20 | 1995-10-17 | Merck Frosst Canada, Inc. | Arylbicyclooctanes as inhibitors of leukotriene biosynthesis |
| ZA945250B (en) * | 1993-07-27 | 1995-01-27 | Zeneca Ltd | Thiazole derivatives |
| IL110280A0 (en) * | 1993-07-27 | 1994-10-21 | Zeneca Ltd | Thiazole derivatives |
| EP0636624A1 (en) * | 1993-07-27 | 1995-02-01 | Zeneca Limited | Thiazole derivatives as lipoxygenase inhibitors |
| US5740861A (en) * | 1996-05-21 | 1998-04-21 | Fmc Corporation | Replaceable consumable erosion detector |
| CA2418832A1 (en) * | 2000-08-09 | 2002-02-14 | F. Hoffmann-La Roche Ag | Quinolene derivatives as anti-inflammation agents |
| US8093273B2 (en) | 2004-10-20 | 2012-01-10 | Resverlogix Corp. | Flavanoids and isoflavanoids for the prevention and treatment of cardiovascular diseases |
| KR101431279B1 (ko) | 2005-07-29 | 2014-08-20 | 리스버로직스 코퍼레이션 | 복합 질환의 예방 및 치료용 약학적 조성물 및 삽입가능한의료 장치에 의한 이의 전달 |
| MX2009008099A (es) | 2007-02-01 | 2009-12-14 | Resverlogix Corp | Compuestos para la prevencion y tratamiento de enfermedades cardiovasculares. |
| JP5602728B2 (ja) | 2008-06-26 | 2014-10-08 | レスバーロジックス コーポレイション | キナゾリノン誘導体の製造方法 |
| EP2382194B1 (en) | 2009-01-08 | 2014-03-12 | Resverlogix Corp. | Compounds for the prevention and treatment of cardiovascular disease |
| WO2010106436A2 (en) | 2009-03-18 | 2010-09-23 | Resverlogix Corp. | Novel anti-inflammatory agents |
| SI2421533T1 (sl) | 2009-04-22 | 2019-01-31 | Resverlogix Corp. | Nova protivnetna sredstva |
| CN104042617A (zh) | 2009-04-29 | 2014-09-17 | 阿马里纳药物爱尔兰有限公司 | 含有epa和心血管剂的药物组合物以及使用其的方法 |
| DK2773354T3 (da) | 2011-11-01 | 2019-08-05 | Resverlogix Corp | Oralformuleringer med øjeblikkelig frigivelse for substituerede quinazolinoner |
| WO2014080291A2 (en) | 2012-11-21 | 2014-05-30 | Rvx Therapeutics Inc. | Biaryl derivatives as bromodomain inhibitors |
| WO2014080290A2 (en) | 2012-11-21 | 2014-05-30 | Rvx Therapeutics Inc. | Cyclic amines as bromodomain inhibitors |
| CA2895905A1 (en) | 2012-12-21 | 2014-06-26 | Zenith Epigenetics Corp. | Novel heterocyclic compounds as bromodomain inhibitors |
| EP3268007B1 (en) | 2015-03-13 | 2022-11-09 | Resverlogix Corp. | Compositions and therapeutic methods for the treatment of complement-associated diseases |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1216878B (de) * | 1963-04-02 | 1966-05-18 | Cassella Farbwerke Mainkur Ag | Verfahren zur Herstellung von coronargefaesserweiternden Derivaten des 7-Hydroxy-2-oxo-1, 2-dihydrochinolins |
| US3661917A (en) * | 1970-05-21 | 1972-05-09 | Smith Kline French Lab | 3-sulfonamido-4-hydroxyphenyl-2-piperidylcarbinols |
| US3743737A (en) * | 1970-05-21 | 1973-07-03 | Smith Kline French Lab | 3-sulfonamido-4-hydroxyphenyl-2-piperindinylcarbinol compositions |
| DE2901336A1 (de) * | 1979-01-15 | 1980-07-24 | Boehringer Mannheim Gmbh | Neue arylether, verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel |
| US4794188A (en) * | 1982-12-01 | 1988-12-27 | Usv Pharmaceutical Corporation | Certain unsymmetrical quinolinyl ethers having anti-inflammatory and anti-allergic activity |
| IE56702B1 (en) * | 1982-12-01 | 1991-11-06 | Usv Pharma Corp | Antiinflammatory antiallergic compounds |
| US4567184A (en) * | 1982-12-01 | 1986-01-28 | Usv Pharmaceutical Corporation | Certain aryl or hetero-aryl derivatives of 1-hydroxy-pentane or 1-hydroxy-hexane which are useful for treating inflammation and allergies |
| NO174506B (no) * | 1984-10-30 | 1994-02-07 | Usv Pharma Corp | Analogifremgangsmaate ved fremstilling av terapeutisk aktive forbindelser |
| US4625034A (en) * | 1985-02-04 | 1986-11-25 | Usv Pharmaceutical Corp. | 1,2-Dihydro; 1,2,3,4-tetrahydro; 5,8 dihydro; and 5,6,7,8-tetrahydroquinoline derivatives |
| US4725619A (en) * | 1985-04-16 | 1988-02-16 | Usv Pharmaceutical Corporation | Aryl and heteroaryl ethers as agents for the treatment of hypersensitive ailments |
| US4631287A (en) * | 1985-04-16 | 1986-12-23 | Usv Pharmaceutical Corp. | Aryl and heteroaryl ethers as agents for the treatment of hypersensitive ailments |
| US4839369A (en) * | 1985-04-16 | 1989-06-13 | Rorer Pharmaceutical Corporation | Aryl and heteroaryl ethers as agents for the treatment of hypersensitive ailments |
| US4728668A (en) * | 1985-04-16 | 1988-03-01 | Usv Pharmaceutical Corporation | Aryl and heteroaryl ethers as agents for the treatment of hypersensitive ailments |
| US4876346A (en) * | 1985-05-02 | 1989-10-24 | American Home Products Corporation | Quinoline compounds |
| EP0271287A3 (en) * | 1986-12-11 | 1990-06-13 | Merck Frosst Canada Inc. | Quinoline dioic acids and amides |
| US4920133A (en) * | 1987-11-03 | 1990-04-24 | Rorer Pharmaceutical Corp. | Quinoline derivatives and use thereof as antagonists of leukotriene D4 |
| US4920132A (en) * | 1987-11-03 | 1990-04-24 | Rorer Pharmaceutical Corp. | Quinoline derivatives and use thereof as antagonists of leukotriene D4 |
| US4920130A (en) * | 1987-11-02 | 1990-04-24 | Rorer Pharamceutical Corp. | Quinoline derivatives and use thereof as antagonists of leukotriene D4 |
| US4920131A (en) * | 1987-11-03 | 1990-04-24 | Rorer Pharmaceutical Corp. | Quinoline derivatives and use thereof as antagonists of leukotriene D4 |
| US4918081A (en) * | 1988-06-20 | 1990-04-17 | Rorer Pharmaceutical Corp. | Quinoline derivatives and use thereof as antagonists of leukotriene d4 |
| EP0349062A1 (en) * | 1988-06-27 | 1990-01-03 | Merck Frosst Canada Inc. | Quinoline ether alkanoic acid |
| IE70521B1 (en) * | 1989-02-28 | 1996-12-11 | Zeneca Pharma Sa | Heterocycles with inhibitory activity of 5-lipoxygenase |
| IE64358B1 (en) * | 1989-07-18 | 1995-07-26 | Ici Plc | Diaryl ether heterocycles |
| GB9113137D0 (en) * | 1990-07-13 | 1991-08-07 | Ici Plc | Thioxo heterocycles |
-
1990
- 1990-08-17 GB GB909018134A patent/GB9018134D0/en active Pending
- 1990-08-21 IE IE302690A patent/IE64251B1/en not_active IP Right Cessation
- 1990-08-21 AU AU61182/90A patent/AU632356B2/en not_active Ceased
- 1990-08-22 NZ NZ235016A patent/NZ235016A/xx unknown
- 1990-08-23 IL IL9548190A patent/IL95481A/xx not_active IP Right Cessation
- 1990-08-29 CA CA002024258A patent/CA2024258A1/en not_active Abandoned
- 1990-09-18 FI FI904591A patent/FI904591A0/fi not_active Application Discontinuation
- 1990-09-21 ES ES90310332T patent/ES2058809T3/es not_active Expired - Lifetime
- 1990-09-21 US US07/585,944 patent/US5221677A/en not_active Expired - Lifetime
- 1990-09-21 EP EP90310332A patent/EP0420511B1/en not_active Expired - Lifetime
- 1990-09-21 DK DK90310332.3T patent/DK0420511T3/da active
- 1990-09-21 DE DE69011609T patent/DE69011609T2/de not_active Expired - Fee Related
- 1990-09-21 AT AT90310332T patent/ATE110073T1/de not_active IP Right Cessation
- 1990-09-27 MY MYPI90001669A patent/MY107266A/en unknown
- 1990-09-28 HU HU906252A patent/HUT59134A/hu unknown
- 1990-09-28 JP JP2260280A patent/JP2996708B2/ja not_active Expired - Fee Related
- 1990-09-28 PT PT95455A patent/PT95455A/pt not_active Application Discontinuation
- 1990-09-28 NO NO90904249A patent/NO904249L/no unknown
- 1990-09-28 DD DD344286A patent/DD300434A5/de unknown
-
1993
- 1993-02-08 US US08/014,673 patent/US5302594A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| PT95455A (pt) | 1991-05-22 |
| JP2996708B2 (ja) | 2000-01-11 |
| IL95481A0 (en) | 1991-06-30 |
| NO904249D0 (no) | 1990-09-28 |
| US5302594A (en) | 1994-04-12 |
| HUT59134A (en) | 1992-04-28 |
| EP0420511B1 (en) | 1994-08-17 |
| DK0420511T3 (da) | 1994-09-12 |
| NO904249L (no) | 1991-04-02 |
| IL95481A (en) | 1994-11-28 |
| EP0420511A3 (en) | 1991-08-28 |
| AU632356B2 (en) | 1992-12-24 |
| IE64251B1 (en) | 1995-07-26 |
| JPH03130281A (ja) | 1991-06-04 |
| IE903026A1 (en) | 1991-04-10 |
| MY107266A (en) | 1995-10-31 |
| NZ235016A (en) | 1993-04-28 |
| ATE110073T1 (de) | 1994-09-15 |
| FI904591A0 (fi) | 1990-09-18 |
| DE69011609D1 (de) | 1994-09-22 |
| DE69011609T2 (de) | 1994-11-24 |
| US5221677A (en) | 1993-06-22 |
| EP0420511A2 (en) | 1991-04-03 |
| GB9018134D0 (en) | 1990-10-03 |
| HU906252D0 (en) | 1991-03-28 |
| AU6118290A (en) | 1991-04-11 |
| ES2058809T3 (es) | 1994-11-01 |
| CA2024258A1 (en) | 1991-03-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DD300434A5 (de) | Heterozyklische derivate | |
| DE69113148T2 (de) | Thioxo-Heterocyclen und ihre pharmazeutische Verwendung. | |
| DE69024076T2 (de) | Heterozyklische Verbindungen mit hemmender Wirkung auf 5-Lipoxygenase | |
| EP0134400B1 (de) | Anti-sekretorische, Fluoralkoxy-substituierte Pyridylmethylthio-(oder sulfinyl-)benzimidazole | |
| DE3784478T2 (de) | Benzopyran-verbindungen, verfahren zu ihrer herstellung und ihre pharmazeutische verwendung. | |
| EP0013894B1 (de) | Neue Arylether, Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende Arzneimittel | |
| DE3788982T2 (de) | Trans-6-[2-(N-heteroaryl)-3,5-disubstituiertes)pyrazol-4-yl)-ethyl] oder -ethenyl]tetrahydro-4-hydroxypyran-2-on-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung. | |
| DE69023940T2 (de) | Heterozyklische Zykloalkane mit hemmender Wirkung auf 5-Lipoxygenase. | |
| CH655110A5 (de) | Carbostyrilderivate, verfahren zu deren herstellung und arzneimittel, welche diese enthalten. | |
| DE60307875T2 (de) | Imidazopyrin-derivate, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische zusamensetzungen | |
| US5250547A (en) | Benzopyran derivatives | |
| DE2940833A1 (de) | 2-methyl-dihydropyridin-verbindung, verfahren zu ihrer herstellung und sie enthaltendes pharmazeutisches mittel | |
| DE68917556T2 (de) | Quinolyloxazol-2-one, nützlich als Proteinkinase-C-Inhibitoren. | |
| DE69206725T2 (de) | Benzolsulfonamidderivate als 5-Lipoxygenasehemmer | |
| DE60020885T2 (de) | Tetrahydropyridine, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische zubereitungen | |
| EP0546389B1 (de) | Piperidylmethyl substituierte Chromanderivate als Wirkstoffe zur Behandlung von Erkrankungen des Zentralnervensystems | |
| DE69209099T2 (de) | Sulfonamidderivate | |
| EP0064255B1 (de) | Benzopyranylether, Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende Arzneimittel und Zwischenprodukte | |
| DE69615019T2 (de) | Benzopyrane und diese enthaltende pharmazeutische zusammenstellungen | |
| US6518282B1 (en) | 4-Arylpiperidine derivatives for the treatment of pruritus | |
| EP0489327A1 (de) | Chromanderivate | |
| EP1944024A1 (en) | O-substituted aniline derivative and antioxidant drug | |
| DD281385A5 (de) | Verfahren zur herstellung von einem 1,3-dioxynalkansaeurederivat | |
| DE69002340T2 (de) | Pyrimidin-Derivate, 2-[4-(Alpha-heteroaryl-alpha-aryl-(alpha-alkyl)-methoxy)-butyl)-1-piperazinyl] mit serotoninergischer Wirkung. | |
| DE69128845T2 (de) | 4-[3-(4-Oxothiazoldinyl)]butynylamine, Verfahren zu deren Herstellung und ihre Verwendung als Medikament |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| IF04 | In force in the year 2004 |
Expiry date: 20100929 |