IE52493B1 - Phenyl substituted pyrido(1,4)benzodiazepines - Google Patents

Phenyl substituted pyrido(1,4)benzodiazepines

Info

Publication number: IE52493B1
Authority: IE; Ireland
Prior art keywords: pyrido; benzodiazepine; compound; llh; phenyl
Prior art date: 1981-09-24

Application number

IE2769/81A

Other languages

English (en)

Other versions

IE812769L (en

Original Assignee

Robins Co Inc A H

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.)

1981-09-24

Filing date

1981-11-25

Publication date

1987-11-25

1981-11-25 Application filed by Robins Co Inc A H filed Critical Robins Co Inc A H

1981-11-25 Priority to IE1808/81A priority Critical patent/IE52494B1/en

1983-03-24 Publication of IE812769L publication Critical patent/IE812769L/xx

1987-11-25 Publication of IE52493B1 publication Critical patent/IE52493B1/en

Links

125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims description 30
OPACCTXYZFTUOQ-UHFFFAOYSA-N 1h-pyrido[2,3-i][1,4]benzodiazepine Chemical class N1C=CN=CC2=CC=C(N=CC=C3)C3=C12 OPACCTXYZFTUOQ-UHFFFAOYSA-N 0.000 title 1
150000003839 salts Chemical class 0.000 claims abstract description 18
239000000935 antidepressant agent Substances 0.000 claims abstract description 9
229940005513 antidepressants Drugs 0.000 claims abstract description 8
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 5
125000003545 alkoxy group Chemical group 0.000 claims abstract 3
150000001875 compounds Chemical class 0.000 claims description 125
229940049706 benzodiazepine Drugs 0.000 claims description 65
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 52
-1 4-pyridinyl Chemical group 0.000 claims description 48
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 46
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 33
GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical class N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 21
239000002253 acid Substances 0.000 claims description 21
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 14
150000001557 benzodiazepines Chemical class 0.000 claims description 13
229910052757 nitrogen Inorganic materials 0.000 claims description 13
239000008194 pharmaceutical composition Substances 0.000 claims description 9
125000005843 halogen group Chemical group 0.000 claims description 8
230000000694 effects Effects 0.000 claims description 7
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 6
230000001430 anti-depressive effect Effects 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 4
239000002552 dosage form Substances 0.000 claims description 4
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
UUBJKHVFGWGJKX-UHFFFAOYSA-N hydrate tetrahydrochloride Chemical compound O.Cl.Cl.Cl.Cl UUBJKHVFGWGJKX-UHFFFAOYSA-N 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
125000004494 ethyl ester group Chemical group 0.000 claims description 2
XDSFEVFCNJALNV-WLHGVMLRSA-N 1h-1,2-benzodiazepine;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.N1N=CC=CC2=CC=CC=C12 XDSFEVFCNJALNV-WLHGVMLRSA-N 0.000 claims 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
230000001419 dependent effect Effects 0.000 claims 2
241000490229 Eucephalus Species 0.000 claims 1
125000000068 chlorophenyl group Chemical group 0.000 claims 1
QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 claims 1
125000001183 hydrocarbyl group Chemical group 0.000 claims 1
125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
229910052739 hydrogen Inorganic materials 0.000 abstract description 25
MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 abstract description 4
MEQBJJUWDCYIAB-UHFFFAOYSA-N 2-chloropyridin-3-amine Chemical compound NC1=CC=CN=C1Cl MEQBJJUWDCYIAB-UHFFFAOYSA-N 0.000 abstract description 4
150000002430 hydrocarbons Chemical class 0.000 abstract description 4
125000004076 pyridyl group Chemical group 0.000 abstract description 3
239000004215 Carbon black (E152) Substances 0.000 abstract description 2
229910052736 halogen Inorganic materials 0.000 abstract description 2
150000002367 halogens Chemical class 0.000 abstract description 2
229930195733 hydrocarbon Natural products 0.000 abstract description 2
125000000217 alkyl group Chemical group 0.000 abstract 4
125000001544 thienyl group Chemical group 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 195
239000000203 mixture Substances 0.000 description 77
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 66
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 60
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 48
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
238000004458 analytical method Methods 0.000 description 37
238000000034 method Methods 0.000 description 35
239000011541 reaction mixture Substances 0.000 description 35
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
239000000243 solution Substances 0.000 description 30
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 29
239000000047 product Substances 0.000 description 28
239000000284 extract Substances 0.000 description 26
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 24
239000012312 sodium hydride Substances 0.000 description 24
229910000104 sodium hydride Inorganic materials 0.000 description 24
239000000725 suspension Substances 0.000 description 23
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 22
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
239000002904 solvent Substances 0.000 description 22
239000012458 free base Substances 0.000 description 20
WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 20
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
238000001914 filtration Methods 0.000 description 18
239000012299 nitrogen atmosphere Substances 0.000 description 18
239000007787 solid Substances 0.000 description 18
239000000706 filtrate Substances 0.000 description 16
229910052943 magnesium sulfate Inorganic materials 0.000 description 15
235000019341 magnesium sulphate Nutrition 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 14
239000004480 active ingredient Substances 0.000 description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
238000010992 reflux Methods 0.000 description 13
238000003756 stirring Methods 0.000 description 13
238000001035 drying Methods 0.000 description 12
239000002480 mineral oil Substances 0.000 description 12
235000010446 mineral oil Nutrition 0.000 description 12
239000003921 oil Substances 0.000 description 12
235000019198 oils Nutrition 0.000 description 12
235000019441 ethanol Nutrition 0.000 description 11
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
238000001816 cooling Methods 0.000 description 9
NYYRRBOMNHUCLB-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCCl NYYRRBOMNHUCLB-UHFFFAOYSA-N 0.000 description 8
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 8
238000002360 preparation method Methods 0.000 description 8
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
239000002775 capsule Substances 0.000 description 7
239000001530 fumaric acid Substances 0.000 description 7
LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 description 7
239000011734 sodium Substances 0.000 description 7
229910052708 sodium Inorganic materials 0.000 description 7
239000007858 starting material Substances 0.000 description 7
FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 7
238000004809 thin layer chromatography Methods 0.000 description 7
LJQNMDZRCXJETK-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine;hydron;chloride Chemical compound Cl.CN(C)CCCCl LJQNMDZRCXJETK-UHFFFAOYSA-N 0.000 description 6
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 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000000460 chlorine Substances 0.000 description 6
IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
239000008101 lactose Substances 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
125000001309 chloro group Chemical group Cl* 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
229910000041 hydrogen chloride Inorganic materials 0.000 description 5
229910052740 iodine Inorganic materials 0.000 description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
SAALQYKUFCIMHR-UHFFFAOYSA-N propan-2-ol;2-propan-2-yloxypropane Chemical compound CC(C)O.CC(C)OC(C)C SAALQYKUFCIMHR-UHFFFAOYSA-N 0.000 description 5
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
TXHIDIHEXDFONW-UHFFFAOYSA-N benzene;propan-2-one Chemical compound CC(C)=O.C1=CC=CC=C1 TXHIDIHEXDFONW-UHFFFAOYSA-N 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
239000013078 crystal Substances 0.000 description 4
LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 4
238000009472 formulation Methods 0.000 description 4
239000007788 liquid Substances 0.000 description 4
238000004949 mass spectrometry Methods 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
238000000638 solvent extraction Methods 0.000 description 4
239000008107 starch Substances 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
239000003826 tablet Substances 0.000 description 4
CJHKJXZMFZKGHI-UHFFFAOYSA-N 1h-pyrido[2,3-i][1,2]benzodiazepine Chemical class N1N=CC=CC2=CC=C(N=CC=C3)C3=C12 CJHKJXZMFZKGHI-UHFFFAOYSA-N 0.000 description 3
WUFWBVLAMURTLR-UHFFFAOYSA-N 6-phenyl-11H-pyrido[2,3-b][1,4]benzodiazepine Chemical compound N=1C2=CC=CN=C2NC2=CC=CC=C2C=1C1=CC=CC=C1 WUFWBVLAMURTLR-UHFFFAOYSA-N 0.000 description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
239000002585 base Substances 0.000 description 3
238000000451 chemical ionisation Methods 0.000 description 3
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 3
238000010828 elution Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
238000000605 extraction Methods 0.000 description 3
239000011521 glass Substances 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
GEVPUGOOGXGPIO-UHFFFAOYSA-N oxalic acid;dihydrate Chemical compound O.O.OC(=O)C(O)=O GEVPUGOOGXGPIO-UHFFFAOYSA-N 0.000 description 3
239000003208 petroleum Substances 0.000 description 3
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 2
MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 2
STGNLGBPLOVYMA-MAZDBSFSSA-N (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O STGNLGBPLOVYMA-MAZDBSFSSA-N 0.000 description 2
LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 2
RYCQVMPEIVZMII-UHFFFAOYSA-N 11h-pyrido[2,3-b][1,4]benzodiazepine Chemical compound C1=NC2=CC=CN=C2NC2=CC=CC=C21 RYCQVMPEIVZMII-UHFFFAOYSA-N 0.000 description 2
LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 2
GQCRQJCSOBMDBQ-UHFFFAOYSA-N 6-(4-methoxyphenyl)-11H-pyrido[2,3-b][1,4]benzodiazepine Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC=CN=C2NC2=CC=CC=C12 GQCRQJCSOBMDBQ-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
235000019739 Dicalciumphosphate Nutrition 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
101100490437 Mus musculus Acvrl1 gene Proteins 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 2
239000003929 acidic solution Substances 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
239000011260 aqueous acid Substances 0.000 description 2
239000006286 aqueous extract Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000000903 blocking effect Effects 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
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000001506 calcium phosphate Substances 0.000 description 2
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
239000008116 calcium stearate Substances 0.000 description 2
235000013539 calcium stearate Nutrition 0.000 description 2
239000000969 carrier Substances 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 2
229940038472 dicalcium phosphate Drugs 0.000 description 2
229910000390 dicalcium phosphate Inorganic materials 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
239000007789 gas Substances 0.000 description 2
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
150000003840 hydrochlorides Chemical class 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
229910000043 hydrogen iodide Inorganic materials 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
239000002198 insoluble material Substances 0.000 description 2
238000002955 isolation Methods 0.000 description 2
238000001819 mass spectrum Methods 0.000 description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
150000003891 oxalate salts Chemical class 0.000 description 2
239000008188 pellet Substances 0.000 description 2
150000003141 primary amines Chemical class 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- 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
- A61P25/24—Antidepressants
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems

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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Neurosurgery (AREA)
Life Sciences & Earth Sciences (AREA)
Neurology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Psychiatry (AREA)
Pharmacology & Pharmacy (AREA)
Biomedical Technology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pain & Pain Management (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pyridine Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

IE2769/81A 1981-09-24 1981-11-25 Phenyl substituted pyrido(1,4)benzodiazepines IE52493B1 (en)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
IE1808/81A IE52494B1 (en)	1981-09-24	1981-11-25	(2-((amino-pyridinyl)amino))phenyl derivatives

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US30508081A	1981-09-24	1981-09-24

Publications (2)

Publication Number	Publication Date
IE812769L IE812769L (en)	1983-03-24
IE52493B1 true IE52493B1 (en)	1987-11-25

Family

ID=23179241

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IE2769/81A IE52493B1 (en)	1981-09-24	1981-11-25	Phenyl substituted pyrido(1,4)benzodiazepines

Country Status (27)

Country	Link
JP (1)	JPS5865290A (da)
KR (1)	KR890000764B1 (da)
BE (1)	BE891666A (da)
CA (1)	CA1199324A (da)
CH (1)	CH651833A5 (da)
DE (1)	DE3150522A1 (da)
DK (3)	DK186282A (da)
EG (1)	EG15904A (da)
ES (6)	ES507971A0 (da)
FI (1)	FI71935C (da)
FR (1)	FR2515183B1 (da)
GR (1)	GR78473B (da)
HU (2)	HU187393B (da)
IE (1)	IE52493B1 (da)
IL (1)	IL64284A (da)
IN (1)	IN156080B (da)
IT (1)	IT1146728B (da)
LU (1)	LU83865A1 (da)
NL (1)	NL8200549A (da)
NO (1)	NO157700C (da)
NZ (1)	NZ198999A (da)
PH (2)	PH17847A (da)
PL (6)	PL139381B1 (da)
PT (1)	PT74286B (da)
SE (2)	SE448629B (da)
YU (1)	YU46128B (da)
ZA (1)	ZA817866B (da)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3825549A (en) *	1972-10-24	1974-07-23	Squibb & Sons Inc	Certain dihydropyrido(2,1-b)(1,3)benzodi-azepines and benzodiazocines
DE2424811C3 (de) *	1974-05-22	1981-08-20	Dr. Karl Thomae Gmbh, 7950 Biberach	Pyrido-benzodiazepinone, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel
SE422799B (sv) *	1975-05-28	1982-03-29	Merck & Co Inc	Analogiforfarande for framstellning av 1,3-dihydroimidazo (4,5-b)pyridin-2-oner

1981
- 1981-11-05 SE SE8106573A patent/SE448629B/sv not_active IP Right Cessation
- 1981-11-12 ZA ZA817866A patent/ZA817866B/xx unknown
- 1981-11-12 NO NO813839A patent/NO157700C/no unknown
- 1981-11-13 IN IN1261/CAL/81A patent/IN156080B/en unknown
- 1981-11-13 IL IL64284A patent/IL64284A/xx unknown
- 1981-11-17 GR GR66553A patent/GR78473B/el unknown
- 1981-11-18 PH PH26507A patent/PH17847A/en unknown
- 1981-11-25 IE IE2769/81A patent/IE52493B1/en unknown
- 1981-12-09 IT IT68605/81A patent/IT1146728B/it active
- 1981-12-10 FI FI813976A patent/FI71935C/fi not_active IP Right Cessation
- 1981-12-15 HU HU813777A patent/HU187393B/hu not_active IP Right Cessation
- 1981-12-15 HU HU843212A patent/HU189426B/hu not_active IP Right Cessation
- 1981-12-15 ES ES507971A patent/ES507971A0/es active Granted
- 1981-12-21 DE DE19813150522 patent/DE3150522A1/de not_active Withdrawn
- 1981-12-23 PL PL1981241409A patent/PL139381B1/pl unknown
- 1981-12-23 PL PL1981253539A patent/PL143597B1/pl unknown
- 1981-12-23 PL PL1981234426A patent/PL138859B1/pl unknown
- 1981-12-23 FR FR8124111A patent/FR2515183B1/fr not_active Expired
- 1981-12-23 PL PL1981253540A patent/PL143322B1/pl unknown
- 1981-12-23 PL PL1981241410A patent/PL137068B1/pl unknown
- 1981-12-23 PL PL1981253538A patent/PL143596B1/pl unknown
- 1981-12-30 BE BE0/206969A patent/BE891666A/fr not_active IP Right Cessation
1982
- 1982-01-05 LU LU83865A patent/LU83865A1/fr unknown
- 1982-01-12 EG EG11/82A patent/EG15904A/xx active
- 1982-01-14 JP JP57004813A patent/JPS5865290A/ja active Pending
- 1982-01-15 PT PT74286A patent/PT74286B/pt unknown
- 1982-01-18 CA CA000394367A patent/CA1199324A/en not_active Expired
- 1982-02-02 KR KR8200420A patent/KR890000764B1/ko not_active Expired
- 1982-02-12 NL NL8200549A patent/NL8200549A/nl not_active Application Discontinuation
- 1982-02-18 NZ NZ198999A patent/NZ198999A/en unknown
- 1982-03-23 YU YU62582A patent/YU46128B/sh unknown
- 1982-04-15 CH CH2288/82A patent/CH651833A5/fr not_active IP Right Cessation
- 1982-04-26 DK DK186282A patent/DK186282A/da not_active Application Discontinuation
- 1982-09-29 ES ES516052A patent/ES8402295A1/es not_active Expired
- 1982-09-29 ES ES516051A patent/ES8308563A1/es not_active Expired
1983
- 1983-10-19 ES ES526562A patent/ES526562A0/es active Granted
- 1983-10-19 ES ES526563A patent/ES8604531A1/es not_active Expired
1984
- 1984-08-17 PH PH31120A patent/PH20536A/en unknown
1985
- 1985-05-21 ES ES543328A patent/ES8607726A1/es not_active Expired
1986
- 1986-02-17 SE SE8600688A patent/SE455305B/sv not_active IP Right Cessation
1987
- 1987-08-03 DK DK403387A patent/DK403387A/da not_active Application Discontinuation
- 1987-08-03 DK DK403487A patent/DK403487D0/da not_active Application Discontinuation

Also Published As

Publication number	Publication date
NO813839L (no)	1983-03-25
YU46128B (sh)	1993-05-28
ES8504148A1 (es)	1985-04-01
DK403487A (da)	1987-08-03
ES8303348A1 (es)	1983-02-01
NL8200549A (nl)	1983-04-18
ES8607726A1 (es)	1986-06-01
LU83865A1 (fr)	1983-09-02
PL143596B1 (en)	1988-02-29
DK403387D0 (da)	1987-08-03
PL234426A1 (en)	1984-01-02
PT74286B (en)	1983-06-27
PL143322B1 (en)	1988-02-29
SE448629B (sv)	1987-03-09
NO157700B (no)	1988-01-25
ES526563A0 (es)	1986-02-01
PL241409A1 (en)	1984-05-21
DK186282A (da)	1983-03-25
IT8168605A0 (it)	1981-12-09
ES516052A0 (es)	1984-01-16
FR2515183A1 (fr)	1983-04-29
ES8604531A1 (es)	1986-02-01
YU62582A (en)	1986-04-30
ES543328A0 (es)	1986-06-01
CA1199324A (en)	1986-01-14
JPS5865290A (ja)	1983-04-18
KR830009058A (ko)	1983-12-17
IE812769L (en)	1983-03-24
DE3150522A1 (de)	1983-04-07
NO157700C (no)	1988-05-04
SE8600688L (sv)	1986-02-17
PL241410A1 (en)	1984-01-02
HU189426B (en)	1986-07-28
FI71935B (fi)	1986-11-28
SE8600688D0 (sv)	1986-02-17
DK403387A (da)	1987-08-03
EG15904A (en)	1987-03-30
IL64284A (en)	1986-12-31
FI813976L (fi)	1983-03-25
CH651833A5 (fr)	1985-10-15
PH20536A (en)	1987-02-09
IT1146728B (it)	1986-11-19
ES526562A0 (es)	1985-04-01
DK403487D0 (da)	1987-08-03
PT74286A (en)	1982-02-01
HU187393B (en)	1985-12-28
FI71935C (fi)	1987-03-09
SE8106573L (sv)	1983-03-25
SE455305B (sv)	1988-07-04
ZA817866B (en)	1982-10-27
PL137068B1 (en)	1986-04-30
PL139381B1 (en)	1987-01-31
IL64284A0 (en)	1982-02-28
FR2515183B1 (fr)	1986-11-14
BE891666A (fr)	1982-04-16
NZ198999A (en)	1987-07-31
PL143597B1 (en)	1988-02-29
ES507971A0 (es)	1983-02-01
ES516051A0 (es)	1983-09-16
GR78473B (da)	1984-09-27
IN156080B (da)	1985-05-11
ES8402295A1 (es)	1984-01-16
KR890000764B1 (ko)	1989-04-05
PL138859B1 (en)	1986-11-29
ES8308563A1 (es)	1983-09-16
PH17847A (en)	1985-01-09
HUT34732A (en)	1985-04-28

Publication	Publication Date	Title
US4434171A (en)	1984-02-28	Dibenzazepine derivatives, pharmaceutical compositions containing them, and pharmaceutical methods using them
FI68835C (fi)	1985-11-11	Foerfarande foer framstaellning av terapeutiskt anvaendbara 4-minoacyl-1,4,9,10-tetrahydropyrazolo(4,3-b)(1,5)bensodiaz epn-10-oner
US4447361A (en)	1984-05-08	Aryl substituted pyrido[1,4]benzodiazepines
US3849405A (en)	1974-11-19	Thieno-(2,3-e)(1,4)diazepin-2-ones
IE52493B1 (en)	1987-11-25	Phenyl substituted pyrido(1,4)benzodiazepines
US4480100A (en)	1984-10-30	[2-[(Nitropyridinyl)amino]phenyl]arymethanones
US4668675A (en)	1987-05-26	2-[(amino-pyridinyl)amine]phenyl]aryl methanones, their thioxomethyl, ketal or thioketal analogs
US4495183A (en)	1985-01-22	Aryl substituted pyrido[1,4]benzodiazepines for treatment of depression
US4556667A (en)	1985-12-03	Aryl substituted pyrido[1,4]benzodiazepines and their use as antidepressives
EP0076017B1 (en)	1990-08-16	Phenyl substituted pyrido(1,4)benzodiazepines and intermediates therefor
NZ199610A (en)	1985-05-31	Tricyclic pyrrole derivatives
US4558132A (en)	1985-12-10	Nitro, amino and aroylamino-N-phenylpyridinamines in a process for preparing pyrido[1,4]benzodiazepines
US4311700A (en)	1982-01-19	Pyrimidobenzodiazepinones, their use and medicaments containing them
FI63033C (fi)	1983-04-11	Foerfarande foer framstaellning av anxiolytiska tranquilliserande sedativa och/eller neuroleptiska substituerade 1-piperazinyl-4h-s-triazolo(3,4-c)tieno(2,3-e)-1,4-diazepiner
US3879392A (en)	1975-04-22	Pyrido(4,3-c)pyridazine compounds
US3828039A (en)	1974-08-06	2-amino-thieno(2,3-e)(1,4)diazepine compounds
JP2531678B2 (ja)	1996-09-04	トリアゾロピリダジン誘導体
US4698430A (en)	1987-10-06	Nitro, amino and aroylamino-n-phenylpyridinamines
US4518603A (en)	1985-05-21	[2-[(Nitropyridinyl)amino]phenyl]arylmethanones in a process for preparing pyrido[1,4]benzodiazepines
NO872271L (no)	1983-03-25	(2-((aminopyridinyl)amino(fenyl)-arylmethanoner.