JPH0555510B2 - - Google Patents
Info
- Publication number
- JPH0555510B2 JPH0555510B2 JP87289983A JP28998387A JPH0555510B2 JP H0555510 B2 JPH0555510 B2 JP H0555510B2 JP 87289983 A JP87289983 A JP 87289983A JP 28998387 A JP28998387 A JP 28998387A JP H0555510 B2 JPH0555510 B2 JP H0555510B2
- Authority
- JP
- Japan
- Prior art keywords
- chlorophenyl
- thieno
- diazepine
- ethyl
- triazolo
- 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 - Lifetime
Links
- 125000004432 carbon atom Chemical group C* 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 69
- -1 [1,4] diazepine compound Chemical class 0.000 description 59
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
- 150000001875 compounds Chemical class 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 238000003756 stirring Methods 0.000 description 48
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 36
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 32
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 28
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 238000002844 melting Methods 0.000 description 21
- 230000008018 melting Effects 0.000 description 21
- 238000010898 silica gel chromatography Methods 0.000 description 20
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 19
- 108010003541 Platelet Activating Factor Proteins 0.000 description 19
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 19
- 238000001914 filtration Methods 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- 239000000203 mixture Substances 0.000 description 16
- 235000011054 acetic acid Nutrition 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 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 13
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000012141 concentrate Substances 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical compound N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
- 241000283973 Oryctolagus cuniculus Species 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 7
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000003042 antagnostic effect Effects 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- WDCDAAMJNUHOIY-UHFFFAOYSA-N ethyl acetate;2-propan-2-yloxypropane Chemical compound CCOC(C)=O.CC(C)OC(C)C WDCDAAMJNUHOIY-UHFFFAOYSA-N 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 229940098779 methanesulfonic acid Drugs 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- WUJWIURYYPJUEM-UHFFFAOYSA-N 4-(2-chlorophenyl)-2-[2-(4-methoxyphenyl)ethyl]-9-methyl-6h-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine Chemical compound C1=CC(OC)=CC=C1CCC1=CC(C(=NCC2=NN=C(C)N22)C=3C(=CC=CC=3)Cl)=C2S1 WUJWIURYYPJUEM-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- VMZUTJCNQWMAGF-UHFFFAOYSA-N Etizolam Chemical compound S1C(CC)=CC2=C1N1C(C)=NN=C1CN=C2C1=CC=CC=C1Cl VMZUTJCNQWMAGF-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 3
- 210000003169 central nervous system Anatomy 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
- 239000008120 corn starch Substances 0.000 description 3
- 229940099112 cornstarch Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical compound [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000007280 thionation reaction Methods 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
- FGNAJWFZOBYZLR-UHFFFAOYSA-N 3h-[1,2,4]triazolo[4,3-a][1,4]diazepine Chemical compound N1=CC=CN2CN=NC2=C1 FGNAJWFZOBYZLR-UHFFFAOYSA-N 0.000 description 2
- UNRYNEUZUOGHCV-UHFFFAOYSA-N 4-(2-chlorophenyl)-2-(2-(4-isobutylphenyl)ethyl)-9-methyl-6h-thieno[3,2-f] [1,2,4]triazolo[4,3-a] [1,4]diazepine Chemical compound C1=CC(CC(C)C)=CC=C1CCC1=CC(C(=NCC2=NN=C(C)N22)C=3C(=CC=CC=3)Cl)=C2S1 UNRYNEUZUOGHCV-UHFFFAOYSA-N 0.000 description 2
- RDYBWHSOCLQMNH-UHFFFAOYSA-N 5-(2-chlorophenyl)-7-(2-phenylethyl)-1,3-dihydrothieno[2,3-e][1,4]diazepine-2-thione Chemical compound ClC1=C(C=CC=C1)C=1C2=C(NC(CN1)=S)SC(=C2)CCC2=CC=CC=C2 RDYBWHSOCLQMNH-UHFFFAOYSA-N 0.000 description 2
- 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 2
- OGAZEYYREIOAKI-UHFFFAOYSA-N 7-(2-chlorophenyl)-13-ethyl-4-[2-[4-(2-methylpropyl)phenyl]ethyl]-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaene Chemical compound S1C=2N3C(CC)=NN=C3CN=C(C=3C(=CC=CC=3)Cl)C=2C=C1CCC1=CC=C(CC(C)C)C=C1 OGAZEYYREIOAKI-UHFFFAOYSA-N 0.000 description 2
- VQKVRMMQKKRJAC-UHFFFAOYSA-N 7-(2-chlorophenyl)-13-methyl-4-(2-phenylethyl)-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaene Chemical compound S1C=2N3C(C)=NN=C3CN=C(C=3C(=CC=CC=3)Cl)C=2C=C1CCC1=CC=CC=C1 VQKVRMMQKKRJAC-UHFFFAOYSA-N 0.000 description 2
- UGSHFXMQGVBNJG-UHFFFAOYSA-N 7-(2-chlorophenyl)-13-methyl-4-[2-(4-methylphenyl)ethyl]-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaene Chemical compound S1C=2N3C(C)=NN=C3CN=C(C=3C(=CC=CC=3)Cl)C=2C=C1CCC1=CC=C(C)C=C1 UGSHFXMQGVBNJG-UHFFFAOYSA-N 0.000 description 2
- UMJHGTPDFURMHS-UHFFFAOYSA-N 7-(2-chlorophenyl)-13-methyl-4-[2-(4-phenylphenyl)ethyl]-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaene Chemical compound S1C=2N3C(C)=NN=C3CN=C(C=3C(=CC=CC=3)Cl)C=2C=C1CCC(C=C1)=CC=C1C1=CC=CC=C1 UMJHGTPDFURMHS-UHFFFAOYSA-N 0.000 description 2
- CDIYYRPFIXXTEL-UHFFFAOYSA-N 7-(2-chlorophenyl)-13-methyl-4-[4-[4-(2-methylpropyl)phenyl]butyl]-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaene Chemical compound C1=CC(CC(C)C)=CC=C1CCCCC1=CC(C(=NCC2=NN=C(C)N22)C=3C(=CC=CC=3)Cl)=C2S1 CDIYYRPFIXXTEL-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241001061127 Thione Species 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 239000003513 alkali 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
- 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
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- KYAWBGDNKNBOJF-UHFFFAOYSA-N chembl442259 Chemical compound C1=CC(CCCC)=CC=C1CCC1=CC(C(=NCC2=NN=C(C)N22)C=3C(=CC=CC=3)Cl)=C2S1 KYAWBGDNKNBOJF-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229960004404 etizolam Drugs 0.000 description 2
- 210000002683 foot Anatomy 0.000 description 2
- 210000000548 hind-foot Anatomy 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
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- RMSWMRJVUJSDGN-UHFFFAOYSA-N israpafant Chemical compound C1=CC(CC(C)C)=CC=C1CCC1=CC(C(=NC(C)C2=NN=C(C)N22)C=3C(=CC=CC=3)Cl)=C2S1 RMSWMRJVUJSDGN-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- LZTYEEBQWUSNDU-UHFFFAOYSA-N thieno[2,3-e][1,4]diazepine-2-thione Chemical compound S=C1C=NC=C2C=CSC2=N1 LZTYEEBQWUSNDU-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000002834 transmittance Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
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- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- VKKMDKZVKMTEJG-UHFFFAOYSA-N thieno[2,3-e][1,4]diazepin-2-one Chemical compound O=C1C=NC=C2C=CSC2=N1 VKKMDKZVKMTEJG-UHFFFAOYSA-N 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62289983A JPH01156982A (ja) | 1986-11-17 | 1987-11-17 | チエノトリアゾロジアゼピン誘導体 |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61-273395 | 1986-11-17 | ||
| JP27339586 | 1986-11-17 | ||
| JP62-94058 | 1987-04-15 | ||
| JP62-222721 | 1987-09-04 | ||
| JP62289983A JPH01156982A (ja) | 1986-11-17 | 1987-11-17 | チエノトリアゾロジアゼピン誘導体 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01156982A JPH01156982A (ja) | 1989-06-20 |
| JPH0555510B2 true JPH0555510B2 (ko) | 1993-08-17 |
Family
ID=26550646
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62289983A Granted JPH01156982A (ja) | 1986-11-17 | 1987-11-17 | チエノトリアゾロジアゼピン誘導体 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01156982A (ko) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998053828A1 (fr) * | 1997-05-27 | 1998-12-03 | Senju Pharmaceutical Co., Ltd. | Preparations aqueuses contenant de l'israpafant |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW219935B (ko) * | 1991-12-25 | 1994-02-01 | Mitsubishi Chemicals Co Ltd | |
| AU2939000A (en) * | 1999-03-12 | 2000-10-04 | Welfide Corporation | Preventive or therapeutic agents for inflammatory dermatoses |
-
1987
- 1987-11-17 JP JP62289983A patent/JPH01156982A/ja active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998053828A1 (fr) * | 1997-05-27 | 1998-12-03 | Senju Pharmaceutical Co., Ltd. | Preparations aqueuses contenant de l'israpafant |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH01156982A (ja) | 1989-06-20 |
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