IL91246A - Thiazole [1,5] benzodiazepine compounds, their manufacture and their pharmaceutical preparations - Google Patents

Thiazole [1,5] benzodiazepine compounds, their manufacture and their pharmaceutical preparations

Info

Publication number: IL91246A
Authority: IL; Israel
Prior art keywords: alkyl; hydrogen; formula; cycloalkyl; compound
Prior art date: 1988-08-11

Application number

IL9124689A

Other languages

English (en)

Hebrew (he)

Other versions

IL91246A0 (en

Original Assignee

Lilly Industries Ltd

Priority date (The priority date 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 date listed.)

1988-08-11

Filing date

1989-08-08

Publication date

1994-01-25

1989-08-08 Application filed by Lilly Industries Ltd filed Critical Lilly Industries Ltd

1990-03-19 Publication of IL91246A0 publication Critical patent/IL91246A0/xx

1994-01-25 Publication of IL91246A publication Critical patent/IL91246A/en

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 4
238000004519 manufacturing process Methods 0.000 title description 2
WVDOASLFVLJHNK-UHFFFAOYSA-N 2h-[1,3]thiazolo[4,5-i][1,5]benzodiazepine Chemical class N1=CC=CN=C2C=CC3=NCSC3=C21 WVDOASLFVLJHNK-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 59
239000001257 hydrogen Substances 0.000 claims abstract description 37
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 37
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 21
239000002253 acid Substances 0.000 claims abstract description 19
150000003839 salts Chemical class 0.000 claims abstract description 17
125000002252 acyl group Chemical group 0.000 claims abstract description 11
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 10
150000002431 hydrogen Chemical class 0.000 claims abstract description 10
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 9
229910052736 halogen Inorganic materials 0.000 claims abstract description 9
150000002367 halogens Chemical class 0.000 claims abstract description 9
-1 phenylsulphonyl Chemical group 0.000 claims abstract description 9
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims abstract description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract 2
125000000217 alkyl group Chemical group 0.000 claims description 51
125000000753 cycloalkyl group Chemical group 0.000 claims description 13
150000001412 amines Chemical class 0.000 claims description 12
238000000034 method Methods 0.000 claims description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 7
125000001188 haloalkyl group Chemical group 0.000 claims description 7
230000029936 alkylation Effects 0.000 claims description 4
238000005804 alkylation reaction Methods 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 3
125000004438 haloalkoxy group Chemical group 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 2
229940049706 benzodiazepine Drugs 0.000 abstract description 5
230000000694 effects Effects 0.000 abstract description 5
210000003169 central nervous system Anatomy 0.000 abstract description 4
150000001557 benzodiazepines Chemical class 0.000 abstract description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 abstract 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 1
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 abstract 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
125000006656 (C2-C4) alkenyl group Chemical group 0.000 abstract 1
125000006528 (C2-C6) alkyl group Chemical group 0.000 abstract 1
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
239000000203 mixture Substances 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
239000004480 active ingredient Substances 0.000 description 13
238000006243 chemical reaction Methods 0.000 description 13
239000002904 solvent Substances 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 12
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
ZVAPWJGRRUHKGP-UHFFFAOYSA-N 1h-1,5-benzodiazepine Chemical compound N1C=CC=NC2=CC=CC=C12 ZVAPWJGRRUHKGP-UHFFFAOYSA-N 0.000 description 8
239000000543 intermediate Substances 0.000 description 8
229920002472 Starch Polymers 0.000 description 7
150000001408 amides Chemical class 0.000 description 7
235000019698 starch Nutrition 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
239000008107 starch Substances 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
229960001760 dimethyl sulfoxide Drugs 0.000 description 5
235000019359 magnesium stearate Nutrition 0.000 description 5
150000003254 radicals Chemical group 0.000 description 5
239000000243 solution Substances 0.000 description 5
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
150000001409 amidines Chemical class 0.000 description 4
239000002585 base Substances 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
238000009472 formulation Methods 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
239000003826 tablet Substances 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
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 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
229930195725 Mannitol Natural products 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 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
239000003054 catalyst Substances 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
239000003814 drug Substances 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
125000005843 halogen group Chemical group 0.000 description 3
238000002955 isolation Methods 0.000 description 3
239000000594 mannitol Substances 0.000 description 3
235000010355 mannitol Nutrition 0.000 description 3
239000012299 nitrogen atmosphere Substances 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
238000000746 purification Methods 0.000 description 3
238000006798 ring closing metathesis reaction Methods 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
150000003573 thiols Chemical class 0.000 description 3
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 3
238000005406 washing Methods 0.000 description 3
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 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
239000002249 anxiolytic agent Substances 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
238000009833 condensation Methods 0.000 description 2
230000005494 condensation Effects 0.000 description 2
239000012043 crude product Substances 0.000 description 2
UEBLMHYADDVYBT-UHFFFAOYSA-N ethyl 2-methyl-5-(2-nitroanilino)-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(NC=2C(=CC=CC=2)[N+]([O-])=O)=C1C(=O)OCC UEBLMHYADDVYBT-UHFFFAOYSA-N 0.000 description 2
239000000284 extract Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000008187 granular material Substances 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
150000002463 imidates Chemical class 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
238000010255 intramuscular injection Methods 0.000 description 2
239000007927 intramuscular injection Substances 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
229920001021 polysulfide Polymers 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 2
229950001675 spiperone Drugs 0.000 description 2
239000001119 stannous chloride Substances 0.000 description 2
235000011150 stannous chloride Nutrition 0.000 description 2
239000012258 stirred mixture Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
238000013268 sustained release Methods 0.000 description 2
239000012730 sustained-release form Substances 0.000 description 2
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 1
RJXOVESYJFXCGI-UHFFFAOYSA-N 2,4-difluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1F RJXOVESYJFXCGI-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 1
QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
235000006491 Acacia senegal Nutrition 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
208000019901 Anxiety disease Diseases 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
108010010803 Gelatin 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
244000068988 Glycine max Species 0.000 description 1
235000010469 Glycine max Nutrition 0.000 description 1
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
229920000084 Gum arabic Polymers 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
238000005684 Liebig rearrangement reaction Methods 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
206010026749 Mania Diseases 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
HDNROQGNUSHIMT-UHFFFAOYSA-N NC1=C(N=C(S1)C)C(=O)OCC.FC=1C=CC(=C(C1)NC1=C(N=C(S1)C)C(=O)OCC)[N+](=O)[O-] Chemical compound NC1=C(N=C(S1)C)C(=O)OCC.FC=1C=CC(=C(C1)NC1=C(N=C(S1)C)C(=O)OCC)[N+](=O)[O-] HDNROQGNUSHIMT-UHFFFAOYSA-N 0.000 description 1
208000028017 Psychotic disease Diseases 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000003474 anti-emetic effect Effects 0.000 description 1
230000000949 anxiolytic effect Effects 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
230000003542 behavioural effect Effects 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
230000004071 biological effect Effects 0.000 description 1
244000309464 bull Species 0.000 description 1
125000004369 butenyl group Chemical group C(=CCC)* 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
229910052799 carbon Inorganic materials 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
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125000001309 chloro group Chemical group Cl* 0.000 description 1
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238000002425 crystallisation Methods 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
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230000003111 delayed effect Effects 0.000 description 1
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239000008121 dextrose Substances 0.000 description 1
JSYGRUBHOCKMGQ-UHFFFAOYSA-N dichloramine Chemical compound ClNCl JSYGRUBHOCKMGQ-UHFFFAOYSA-N 0.000 description 1
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239000003937 drug carrier Substances 0.000 description 1
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125000004185 ester group Chemical group 0.000 description 1
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VAHBTFRWIFXFMS-UHFFFAOYSA-N ethyl 5-(4-fluoro-2-nitroanilino)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(NC=2C(=CC(F)=CC=2)[N+]([O-])=O)=C1C(=O)OCC VAHBTFRWIFXFMS-UHFFFAOYSA-N 0.000 description 1
HNDBOQZBZYRXMF-UHFFFAOYSA-N ethyl 5-amino-2-methyl-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C=1N=C(C)SC=1N HNDBOQZBZYRXMF-UHFFFAOYSA-N 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
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239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229910052735 hafnium Inorganic materials 0.000 description 1
VBJZVLUMGGDVMO-UHFFFAOYSA-N hafnium atom Chemical compound [Hf] VBJZVLUMGGDVMO-UHFFFAOYSA-N 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
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
125000001841 imino group Chemical group [H]N=* 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000011344 liquid material Substances 0.000 description 1
HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
239000000391 magnesium silicate Substances 0.000 description 1
229910052919 magnesium silicate Inorganic materials 0.000 description 1
235000019792 magnesium silicate Nutrition 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
239000001630 malic acid Substances 0.000 description 1
239000002609 medium Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229910001510 metal chloride Inorganic materials 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical group COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
239000003176 neuroleptic agent Substances 0.000 description 1
230000000701 neuroleptic effect Effects 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
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230000003000 nontoxic effect Effects 0.000 description 1
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150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
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XVSKETOUYKZTGI-UHFFFAOYSA-N oxathiaziridine Chemical class N1OS1 XVSKETOUYKZTGI-UHFFFAOYSA-N 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000000047 product Substances 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
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201000000980 schizophrenia Diseases 0.000 description 1
239000000932 sedative agent Substances 0.000 description 1
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239000012056 semi-solid material Substances 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
CWXOAQXKPAENDI-UHFFFAOYSA-N sodium methylsulfinylmethylide Chemical compound [Na+].CS([CH2-])=O CWXOAQXKPAENDI-UHFFFAOYSA-N 0.000 description 1
239000011343 solid material Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
GLBQVJGBPFPMMV-UHFFFAOYSA-N sulfilimine Chemical class S=N GLBQVJGBPFPMMV-UHFFFAOYSA-N 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
231100001274 therapeutic index Toxicity 0.000 description 1
125000001391 thioamide group Chemical group 0.000 description 1
150000003556 thioamides Chemical class 0.000 description 1
150000003608 titanium Chemical class 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 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
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
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
238000005303 weighing Methods 0.000 description 1
229910052726 zirconium Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Neurosurgery (AREA)
General Health & Medical Sciences (AREA)
Biomedical Technology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Neurology (AREA)
Public Health (AREA)
Psychiatry (AREA)
Anesthesiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Thiazole And Isothizaole Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

IL9124689A 1988-08-11 1989-08-08 Thiazole [1,5] benzodiazepine compounds, their manufacture and their pharmaceutical preparations IL91246A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB888819059A GB8819059D0 (en)	1988-08-11	1988-08-11	Benzodiazepine compounds & their use as pharmaceuticals

Publications (2)

Publication Number	Publication Date
IL91246A0 IL91246A0 (en)	1990-03-19
IL91246A true IL91246A (en)	1994-01-25

Family

ID=10641942

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9124689A IL91246A (en)	1988-08-11	1989-08-08	Thiazole [1,5] benzodiazepine compounds, their manufacture and their pharmaceutical preparations

Country Status (22)

Country	Link
US (2)	US4977150A (es)
EP (1)	EP0354781B1 (es)
JP (1)	JP2779219B2 (es)
KR (1)	KR0138527B1 (es)
CN (1)	CN1025857C (es)
AR (1)	AR246972A1 (es)
AT (1)	ATE113600T1 (es)
AU (1)	AU625067B2 (es)
CA (1)	CA1318669C (es)
DE (1)	DE68919154T2 (es)
DK (1)	DK393489A (es)
ES (1)	ES2062012T3 (es)
GB (1)	GB8819059D0 (es)
HU (1)	HU202239B (es)
IE (1)	IE64598B1 (es)
IL (1)	IL91246A (es)
MX (1)	MX17107A (es)
NZ (1)	NZ230251A (es)
PH (1)	PH27010A (es)
PT (1)	PT91401B (es)
RU (1)	RU2002752C1 (es)
ZA (1)	ZA896039B (es)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE1004596A4 (fr) *	1990-09-26	1992-12-22	Therabel Res S A N V	Derives de methylpiperazinoazepine, leur preparation et leur utilisation.
US5627178A (en)	1991-04-23	1997-05-06	Lilly Industries Limited	2-methyl-thieno-benzodiazepine
US5393752A (en) *	1992-05-26	1995-02-28	Therabel Research S.A./N.V.	Methylpiperazinoazepine compounds, preparation and use thereof
US6034078A (en) *	1992-05-29	2000-03-07	Eli Lilly And Company Limited	Thienobenzodiazepine compounds
US6617321B2 (en) *	1997-09-30	2003-09-09	Eli Lilly And Company	2-methyl-thieno-benzodiazepine formulation
WO2003082877A1 (en) *	2002-03-28	2003-10-09	Eli Lilly And Company	Piperazine substituted aryl benzodiazepines and their use as dopamine receptor antagonists for the treatment of psychotic disorders
DK1546134T3 (da)	2002-08-05	2007-09-10	Lilly Co Eli	Piperazinsubstituerede arylbenzodiazepiner
EP1664063A1 (en) *	2003-09-09	2006-06-07	Eli Lilly And Company	Substituted piperazines of azepines, oxazepines, and thiazepines
EP1838716B1 (en) *	2005-01-05	2011-06-01	Eli Lilly And Company	Olanzapine pamoate dihydrate

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CH468400A (de) *	1965-12-23	1969-02-15	Sandoz Ag	Verfahren zur Herstellung neuer Thieno(2,3-b)(1,5)benzothiazepin-4-on-Verbindungen
US3758479A (en) *	1967-03-22	1973-09-11	Sandoz Ag	Nitro and sulphamoyl substituted dibenzodiazepines
US3539573A (en) *	1967-03-22	1970-11-10	Jean Schmutz	11-basic substituted dibenzodiazepines and dibenzothiazepines
GB1292410A (en) *	1970-05-13	1972-10-11	Yoshitomi Pharmaceutical	Thienobenzothiazepine derivatives
CH554362A (de) *	1970-07-30	1974-09-30	Spofa Vereinigte Pharma Werke	Verfahren zur herstellung von neuen estern tricyklischer piperazinoalkanole.
US3897446A (en) *	1973-09-04	1975-07-29	Upjohn Co	6-Phenylthiazolo{8 3,2-a{9 {8 1,4{9 benzodiazepin-1-(2H)-ones, and processes
SU629879A3 (ru) *	1974-11-26	1978-10-25	Лилли Индастриз Лимитед, (Фирма)	Способ получени тиено(1,5) бензодиазепинов или их солей
US4115568A (en) *	1974-11-26	1978-09-19	Lilly Industries Limited	Thieno[3,2-b]-[1,5]benzodiazepines
US3951981A (en) *	1975-02-24	1976-04-20	American Cyanamid Company	Substituted benzodiazepines and method of use
US4404137A (en) *	1979-10-16	1983-09-13	Lilly Industries Limited	Pyrazolo [3,4-b][1,5]benzodiazepine compounds
US4431589A (en) *	1980-12-11	1984-02-14	Lilly House	Benzodiazepine compounds and their use as pharmaceuticals

1988
- 1988-08-11 GB GB888819059A patent/GB8819059D0/en active Pending
1989
- 1989-08-04 US US07/390,029 patent/US4977150A/en not_active Expired - Lifetime
- 1989-08-07 AU AU39399/89A patent/AU625067B2/en not_active Ceased
- 1989-08-07 PH PH39061A patent/PH27010A/en unknown
- 1989-08-08 MX MX1710789A patent/MX17107A/es unknown
- 1989-08-08 NZ NZ230251A patent/NZ230251A/en unknown
- 1989-08-08 IL IL9124689A patent/IL91246A/en not_active IP Right Cessation
- 1989-08-08 PT PT91401A patent/PT91401B/pt active IP Right Grant
- 1989-08-08 CA CA000607760A patent/CA1318669C/en not_active Expired - Fee Related
- 1989-08-08 ZA ZA896039A patent/ZA896039B/xx unknown
- 1989-08-09 EP EP89308099A patent/EP0354781B1/en not_active Expired - Lifetime
- 1989-08-09 ES ES89308099T patent/ES2062012T3/es not_active Expired - Lifetime
- 1989-08-09 DE DE68919154T patent/DE68919154T2/de not_active Expired - Fee Related
- 1989-08-09 AT AT89308099T patent/ATE113600T1/de not_active IP Right Cessation
- 1989-08-10 DK DK393489A patent/DK393489A/da not_active Application Discontinuation
- 1989-08-10 JP JP1207770A patent/JP2779219B2/ja not_active Expired - Lifetime
- 1989-08-10 RU SU894614830A patent/RU2002752C1/ru active
- 1989-08-10 HU HU894101A patent/HU202239B/hu not_active IP Right Cessation
- 1989-08-10 KR KR1019890011365A patent/KR0138527B1/ko not_active Expired - Fee Related
- 1989-08-10 IE IE257689A patent/IE64598B1/en not_active IP Right Cessation
- 1989-08-10 AR AR89314625A patent/AR246972A1/es active
- 1989-08-10 CN CN89105557A patent/CN1025857C/zh not_active Expired - Fee Related
1990
- 1990-08-02 US US07/562,055 patent/US5051516A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
IE892576L (en)	1990-02-11
IE64598B1 (en)	1995-08-23
ZA896039B (en)	1991-04-24
ES2062012T3 (es)	1994-12-16
HUT53109A (en)	1990-09-28
JP2779219B2 (ja)	1998-07-23
GB8819059D0 (en)	1988-09-14
DE68919154T2 (de)	1995-03-09
DE68919154D1 (de)	1994-12-08
PT91401A (pt)	1990-03-08
AU3939989A (en)	1990-02-15
RU2002752C1 (ru)	1993-11-15
MX17107A (es)	1993-08-01
PH27010A (en)	1993-02-01
EP0354781A2 (en)	1990-02-14
CN1040798A (zh)	1990-03-28
KR900003179A (ko)	1990-03-23
KR0138527B1 (ko)	1998-05-15
US5051516A (en)	1991-09-24
EP0354781A3 (en)	1991-04-03
AR246972A1 (es)	1994-10-31
CN1025857C (zh)	1994-09-07
ATE113600T1 (de)	1994-11-15
CA1318669C (en)	1993-06-01
PT91401B (pt)	1995-05-04
IL91246A0 (en)	1990-03-19
EP0354781B1 (en)	1994-11-02
DK393489D0 (da)	1989-08-10
HU202239B (en)	1991-02-28
JPH02104591A (ja)	1990-04-17
NZ230251A (en)	1992-05-26
AU625067B2 (en)	1992-07-02
DK393489A (da)	1990-02-12
US4977150A (en)	1990-12-11

Legal Events

Date	Code	Title
1999-06-20	HC	Change of name of proprietor(s)
1999-12-31	KB	Patent renewed
2004-05-12	RH1	Patent not in force

Publication	Publication Date	Title
CA2041113C (en)	1998-07-14	Thienobenzodiazepine derivatives and their use as pharmaceuticals
HUT67312A (en)	1995-03-28	Naphtalene derivatives and process for their producing
IE55156B1 (en)	1990-06-20	Pharmacologically active pyrazolo(4,3-c)pyridines
EP0027390B1 (en)	1984-07-25	Novel benzodiazepine compounds, their preparation, intermediates employed in their preparation, and pharmaceutical compositions containing them
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