JPS6355508B2 - - Google Patents
Info
- Publication number
- JPS6355508B2 JPS6355508B2 JP59200297A JP20029784A JPS6355508B2 JP S6355508 B2 JPS6355508 B2 JP S6355508B2 JP 59200297 A JP59200297 A JP 59200297A JP 20029784 A JP20029784 A JP 20029784A JP S6355508 B2 JPS6355508 B2 JP S6355508B2
- Authority
- JP
- Japan
- Prior art keywords
- mmol
- solution
- added
- reduced pressure
- under reduced
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- -1 3,5-dimethoxy-4-toluoyloxy group Chemical group 0.000 claims description 51
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 claims description 28
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 claims description 28
- 150000001408 amides Chemical class 0.000 claims description 25
- 239000003112 inhibitor Substances 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 239000000243 solution Substances 0.000 description 252
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 183
- 238000006243 chemical reaction Methods 0.000 description 93
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 78
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 74
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 74
- 239000000203 mixture Substances 0.000 description 67
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 59
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 58
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- 238000010898 silica gel chromatography Methods 0.000 description 57
- 239000012300 argon atmosphere Substances 0.000 description 49
- 239000012044 organic layer Substances 0.000 description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
- 238000010992 reflux Methods 0.000 description 43
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 41
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- 238000004611 spectroscopical analysis Methods 0.000 description 38
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 37
- 238000010828 elution Methods 0.000 description 29
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 28
- 238000000605 extraction Methods 0.000 description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 26
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 25
- 238000005160 1H NMR spectroscopy Methods 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 25
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- 229920006395 saturated elastomer Polymers 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 20
- 235000017557 sodium bicarbonate Nutrition 0.000 description 20
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 14
- 229910000029 sodium carbonate Inorganic materials 0.000 description 14
- 229960000278 theophylline Drugs 0.000 description 14
- 238000004440 column chromatography Methods 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 230000002401 inhibitory effect Effects 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- WGJCBBASTRWVJL-UHFFFAOYSA-N 1,3-thiazolidine-2-thione Chemical compound SC1=NCCS1 WGJCBBASTRWVJL-UHFFFAOYSA-N 0.000 description 8
- 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 8
- 239000011541 reaction mixture Substances 0.000 description 8
- MBFDHHKTIBKZNR-UHFFFAOYSA-N 1-(2-benzhydryloxyethyl)piperazine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)OCCN1CCNCC1 MBFDHHKTIBKZNR-UHFFFAOYSA-N 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 229920005654 Sephadex Polymers 0.000 description 6
- 239000012507 Sephadex™ Substances 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- QZPPWEOXIVWVIC-UHFFFAOYSA-N 1-(3-benzhydryloxypropyl)piperazine Chemical compound C1CNCCN1CCCOC(C=1C=CC=CC=1)C1=CC=CC=C1 QZPPWEOXIVWVIC-UHFFFAOYSA-N 0.000 description 5
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 150000002617 leukotrienes Chemical class 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 5
- 206010020751 Hypersensitivity Diseases 0.000 description 4
- 241001061127 Thione Species 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 230000007815 allergy Effects 0.000 description 4
- 229940114079 arachidonic acid Drugs 0.000 description 4
- 235000021342 arachidonic acid Nutrition 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- KTCLLKYOZHQLKJ-UHFFFAOYSA-N 5-[3-methoxy-4-(2-methoxyethoxymethoxy)phenyl]-1-(2-sulfanylidene-1,3-thiazolidin-3-yl)penta-2,4-dien-1-one Chemical compound C1=C(OC)C(OCOCCOC)=CC=C1C=CC=CC(=O)N1C(=S)SCC1 KTCLLKYOZHQLKJ-UHFFFAOYSA-N 0.000 description 3
- YPXQSGWOGQPLQO-UHFFFAOYSA-N 5-nitro-1,3-dihydrobenzimidazole-2-thione Chemical compound [O-][N+](=O)C1=CC=C2N=C(S)NC2=C1 YPXQSGWOGQPLQO-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 3
- 150000004885 piperazines Chemical class 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- HPZCLQIOEWWRPK-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-1-(2-sulfanylidene-1,3-thiazolidin-3-yl)prop-2-en-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C=CC(=O)N1C(=S)SCC1 HPZCLQIOEWWRPK-UHFFFAOYSA-N 0.000 description 2
- QYIWGYGJBOSBCJ-UHFFFAOYSA-N 3-[3,5-dimethoxy-4-(2-methoxyethoxymethoxy)phenyl]-1-(2-sulfanylidene-1,3-thiazolidin-3-yl)prop-2-en-1-one Chemical compound C1=C(OC)C(OCOCCOC)=C(OC)C=C1C=CC(=O)N1C(=S)SCC1 QYIWGYGJBOSBCJ-UHFFFAOYSA-N 0.000 description 2
- ZUNZWUVAFHLTNE-UHFFFAOYSA-N 3-[3-methoxy-4-(2-methoxyethoxymethoxy)phenyl]-1-(2-sulfanylidene-1,3-thiazolidin-3-yl)prop-2-en-1-one Chemical compound C1=C(OC)C(OCOCCOC)=CC=C1C=CC(=O)N1C(=S)SCC1 ZUNZWUVAFHLTNE-UHFFFAOYSA-N 0.000 description 2
- BKZTVCXWSKWPID-UHFFFAOYSA-N 5-(3,4-dimethoxyphenyl)-1-(2-sulfanylidene-1,3-thiazolidin-3-yl)penta-2,4-dien-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C=CC=CC(=O)N1C(=S)SCC1 BKZTVCXWSKWPID-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- ZNVASENTCOLNJT-UHFFFAOYSA-N [2-chloroethoxy(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(OCCCl)C1=CC=CC=C1 ZNVASENTCOLNJT-UHFFFAOYSA-N 0.000 description 2
- FDUFCAQXASQRLX-UHFFFAOYSA-N [3-chloropropoxy(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(OCCCCl)C1=CC=CC=C1 FDUFCAQXASQRLX-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 201000009961 allergic asthma Diseases 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- 239000000043 antiallergic agent Substances 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- QILSFLSDHQAZET-UHFFFAOYSA-N diphenylmethanol Chemical compound C=1C=CC=CC=1C(O)C1=CC=CC=C1 QILSFLSDHQAZET-UHFFFAOYSA-N 0.000 description 2
- NWVNXDKZIQLBNM-UHFFFAOYSA-N diphenylmethylpiperazine Chemical compound C1CNCCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 NWVNXDKZIQLBNM-UHFFFAOYSA-N 0.000 description 2
- LNOQURRKNJKKBU-UHFFFAOYSA-N ethyl piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCNCC1 LNOQURRKNJKKBU-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000010410 layer Substances 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
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- KGIJOOYOSFUGPC-LJQANCHMSA-N (5s)-5-hydroxyicosa-6,8,11,14-tetraenoic acid Chemical compound CCCCCC=CCC=CCC=CC=C[C@@H](O)CCCC(O)=O KGIJOOYOSFUGPC-LJQANCHMSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- IHXQTFNKTLUVOE-UHFFFAOYSA-N 1-(2-sulfanylidene-1,3-thiazolidin-3-yl)-5-(3,4,5-trimethoxyphenyl)penta-2,4-dien-1-one Chemical compound COC1=C(OC)C(OC)=CC(C=CC=CC(=O)N2C(SCC2)=S)=C1 IHXQTFNKTLUVOE-UHFFFAOYSA-N 0.000 description 1
- UZKBSZSTDQSMDR-UHFFFAOYSA-N 1-[(4-chlorophenyl)-phenylmethyl]piperazine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)N1CCNCC1 UZKBSZSTDQSMDR-UHFFFAOYSA-N 0.000 description 1
- SFLJFQHSMPXYMR-UHFFFAOYSA-N 1-[4-(2-benzhydryloxyethyl)piperazin-1-yl]-3-(3,4-dihydroxyphenyl)prop-2-en-1-one Chemical compound C1=C(O)C(O)=CC=C1C=CC(=O)N1CCN(CCOC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 SFLJFQHSMPXYMR-UHFFFAOYSA-N 0.000 description 1
- ZHCDXWWOGNYZFO-UHFFFAOYSA-N 1-[4-(2-benzhydryloxyethyl)piperazin-1-yl]-5-(4-hydroxy-3-methoxyphenyl)penta-2,4-dien-1-one Chemical compound C1=C(O)C(OC)=CC(C=CC=CC(=O)N2CCN(CCOC(C=3C=CC=CC=3)C=3C=CC=CC=3)CC2)=C1 ZHCDXWWOGNYZFO-UHFFFAOYSA-N 0.000 description 1
- RSJZJQKOMGWHQC-UHFFFAOYSA-N 1-[4-(2-benzhydryloxyethyl)piperazin-1-yl]-5-[3,5-dimethoxy-4-(2-methoxyethoxymethoxy)phenyl]penta-2,4-dien-1-one Chemical compound C1=C(OC)C(OCOCCOC)=C(OC)C=C1C=CC=CC(=O)N1CCN(CCOC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RSJZJQKOMGWHQC-UHFFFAOYSA-N 0.000 description 1
- NXGHAWPEUGBRGC-UHFFFAOYSA-N 1-[4-(3-benzhydryloxypropyl)piperazin-1-yl]-3-(4-hydroxy-3,5-dimethoxyphenyl)prop-2-en-1-one Chemical compound COC1=C(O)C(OC)=CC(C=CC(=O)N2CCN(CCCOC(C=3C=CC=CC=3)C=3C=CC=CC=3)CC2)=C1 NXGHAWPEUGBRGC-UHFFFAOYSA-N 0.000 description 1
- GUAUKXXLVZMQON-UHFFFAOYSA-N 1-[4-(3-benzhydryloxypropyl)piperazin-1-yl]-5-[3-methoxy-4-(2-methoxyethoxymethoxy)phenyl]penta-2,4-dien-1-one Chemical compound C1=C(OC)C(OCOCCOC)=CC=C1C=CC=CC(=O)N1CCN(CCCOC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUAUKXXLVZMQON-UHFFFAOYSA-N 0.000 description 1
- UXFWTIGUWHJKDD-UHFFFAOYSA-N 2-(4-bromobutyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCCBr)C(=O)C2=C1 UXFWTIGUWHJKDD-UHFFFAOYSA-N 0.000 description 1
- NFJFUDGBWGXTHS-UHFFFAOYSA-N 2-benzhydryloxyethanamine Chemical compound C=1C=CC=CC=1C(OCCN)C1=CC=CC=C1 NFJFUDGBWGXTHS-UHFFFAOYSA-N 0.000 description 1
- SZIFAVKTNFCBPC-UHFFFAOYSA-N 2-chloroethanol Chemical compound OCCCl SZIFAVKTNFCBPC-UHFFFAOYSA-N 0.000 description 1
- PKUXVZMMVVBXCL-UHFFFAOYSA-N 3-[3,4-bis(2-methoxyethoxymethoxy)phenyl]-1-(2-sulfanylidene-1,3-thiazolidin-3-yl)prop-2-en-1-one Chemical compound C1=C(OCOCCOC)C(OCOCCOC)=CC=C1C=CC(=O)N1C(=S)SCC1 PKUXVZMMVVBXCL-UHFFFAOYSA-N 0.000 description 1
- LAMUXTNQCICZQX-UHFFFAOYSA-N 3-chloropropan-1-ol Chemical compound OCCCCl LAMUXTNQCICZQX-UHFFFAOYSA-N 0.000 description 1
- HOCPDSKONPQIQM-UHFFFAOYSA-N 4-(2-bromoethyl)isoindole-1,3-dione Chemical compound BrCCC1=CC=CC2=C1C(=O)NC2=O HOCPDSKONPQIQM-UHFFFAOYSA-N 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- KGIJOOYOSFUGPC-CABOLEKPSA-N 5-HETE Natural products CCCCC\C=C/C\C=C/C\C=C/C=C/[C@H](O)CCCC(O)=O KGIJOOYOSFUGPC-CABOLEKPSA-N 0.000 description 1
- GSLPKZMLUHNVHB-UHFFFAOYSA-N 5-[3,5-dimethoxy-4-(2-methoxyethoxymethoxy)phenyl]-1-(2-sulfanylidene-1,3-thiazolidin-3-yl)penta-2,4-dien-1-one Chemical compound C1=C(OC)C(OCOCCOC)=C(OC)C=C1C=CC=CC(=O)N1C(=S)SCC1 GSLPKZMLUHNVHB-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 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 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- PVQATPQSBYNMGE-UHFFFAOYSA-N [benzhydryloxy(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)OC(C=1C=CC=CC=1)C1=CC=CC=C1 PVQATPQSBYNMGE-UHFFFAOYSA-N 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 102000011759 adducin Human genes 0.000 description 1
- 108010076723 adducin Proteins 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000007640 basal medium Substances 0.000 description 1
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229940126086 compound 21 Drugs 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 229940126540 compound 41 Drugs 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- PNWGDUVBYMXASW-UHFFFAOYSA-N ethyl 4-(2-benzhydryloxyethyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CCOC(C=1C=CC=CC=1)C1=CC=CC=C1 PNWGDUVBYMXASW-UHFFFAOYSA-N 0.000 description 1
- PQBJWJBVWLZJSI-UHFFFAOYSA-N ethyl 4-(3-benzhydryloxypropyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CCCOC(C=1C=CC=CC=1)C1=CC=CC=C1 PQBJWJBVWLZJSI-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000008101 lactose Substances 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
- 239000012669 liquid formulation Substances 0.000 description 1
- RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 201000006512 mast cell neoplasm Diseases 0.000 description 1
- 208000006971 mastocytoma Diseases 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- CWEYKGCJLUDHHU-UHFFFAOYSA-N n-(3-benzhydryloxypropyl)-3-[3-methoxy-4-(2-methoxyethoxymethoxy)phenyl]prop-2-enamide Chemical compound C1=C(OC)C(OCOCCOC)=CC=C1C=CC(=O)NCCCOC(C=1C=CC=CC=1)C1=CC=CC=C1 CWEYKGCJLUDHHU-UHFFFAOYSA-N 0.000 description 1
- YPYBPCJXABGCDF-UHFFFAOYSA-N n-[4-(4-benzhydrylpiperazin-1-yl)butyl]-5-(4-hydroxy-3-methoxyphenyl)penta-2,4-dienamide Chemical compound C1=C(O)C(OC)=CC(C=CC=CC(=O)NCCCCN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 YPYBPCJXABGCDF-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- 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)
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59200297A JPS6178756A (ja) | 1984-09-25 | 1984-09-25 | アミド誘導体およびこれを含有する５−リポキシゲナ−ゼ作用阻害剤 |
| US06/719,131 US4673684A (en) | 1984-04-04 | 1985-04-02 | Amide derivatives and 5-lipoxygenase inhibitors containing the same as an active ingredient |
| EP90112056A EP0399569B1 (en) | 1984-04-04 | 1985-04-03 | Amide derivatives and 5-lipoxygenase inhibitors containing the same as an active ingredient |
| EP85104034A EP0157420B1 (en) | 1984-04-04 | 1985-04-03 | Amide derivatives and 5-lipoxygenase inhibitors containing the same as an active ingredient |
| DE8585104034T DE3584846D1 (de) | 1984-04-04 | 1985-04-03 | Amid-derivate und 5-lipoxygenase-inhibitoren die diese als wirksame substanz enthalten. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59200297A JPS6178756A (ja) | 1984-09-25 | 1984-09-25 | アミド誘導体およびこれを含有する５−リポキシゲナ−ゼ作用阻害剤 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6178756A JPS6178756A (ja) | 1986-04-22 |
| JPS6355508B2 true JPS6355508B2 (zh) | 1988-11-02 |
Family
ID=16421970
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59200297A Granted JPS6178756A (ja) | 1984-04-04 | 1984-09-25 | アミド誘導体およびこれを含有する５−リポキシゲナ−ゼ作用阻害剤 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6178756A (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0926138A4 (en) * | 1996-08-23 | 2006-04-12 | Kowa Co | DIAMIDE COMPOUNDS AND MEDICAMENTS CONTAINING THEM |
-
1984
- 1984-09-25 JP JP59200297A patent/JPS6178756A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6178756A (ja) | 1986-04-22 |
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