NZ198999A - Py benzodiazepine derivatives and pharmaceutical compositions - Google Patents

Py benzodiazepine derivatives and pharmaceutical compositions

Info

Publication number: NZ198999A
Authority: NZ; New Zealand
Prior art keywords: pyrido; llh; compound; benzodiazepine; phenyl
Prior art date: 1981-09-24

Application number

NZ198999A

Other languages

English (en)

Inventor

C R Taylor

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

1982-02-18

Publication date

1987-07-31

1982-02-18 Application filed by Robins Co Inc A H filed Critical Robins Co Inc A H

1982-02-18 Priority to NZ21264082A priority Critical patent/NZ212640A/en

1987-07-31 Publication of NZ198999A publication Critical patent/NZ198999A/en

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 27
229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 title 1
125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 179
-1 1-piperazinyl Chemical group 0.000 claims description 104
239000000203 mixture Substances 0.000 claims description 96
238000000034 method Methods 0.000 claims description 83
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 66
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 52
GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 50
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 50
229940049706 benzodiazepine Drugs 0.000 claims description 36
239000000243 solution Substances 0.000 claims description 33
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 30
150000003839 salts Chemical class 0.000 claims description 29
239000001257 hydrogen Substances 0.000 claims description 25
229910052739 hydrogen Inorganic materials 0.000 claims description 25
238000001914 filtration Methods 0.000 claims description 23
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 23
229910052757 nitrogen Inorganic materials 0.000 claims description 22
239000002253 acid Substances 0.000 claims description 21
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
239000004480 active ingredient Substances 0.000 claims description 13
150000003254 radicals Chemical class 0.000 claims description 13
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 10
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 10
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
UUBJKHVFGWGJKX-UHFFFAOYSA-N hydrate tetrahydrochloride Chemical compound O.Cl.Cl.Cl.Cl UUBJKHVFGWGJKX-UHFFFAOYSA-N 0.000 claims description 9
150000002431 hydrogen Chemical class 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 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 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
239000008101 lactose Substances 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
101100490437 Mus musculus Acvrl1 gene Proteins 0.000 claims description 5
150000001557 benzodiazepines Chemical class 0.000 claims description 5
125000000623 heterocyclic group Chemical group 0.000 claims description 5
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
229920002472 Starch Polymers 0.000 claims description 3
239000002552 dosage form Substances 0.000 claims description 3
125000004494 ethyl ester group Chemical group 0.000 claims description 3
125000001475 halogen functional group Chemical group 0.000 claims description 3
239000008107 starch Substances 0.000 claims description 3
235000019698 starch Nutrition 0.000 claims description 3
235000019739 Dicalciumphosphate Nutrition 0.000 claims description 2
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 2
239000001506 calcium phosphate Substances 0.000 claims description 2
125000000068 chlorophenyl group Chemical group 0.000 claims description 2
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 claims description 2
229940038472 dicalcium phosphate Drugs 0.000 claims description 2
229910000390 dicalcium phosphate Inorganic materials 0.000 claims description 2
QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 claims description 2
238000012986 modification Methods 0.000 claims description 2
230000004048 modification Effects 0.000 claims description 2
239000008174 sterile solution Substances 0.000 claims description 2
125000001183 hydrocarbyl group Chemical group 0.000 claims 3
PERYPNLSKBMHJJ-TYYBGVCCSA-N (e)-but-2-enedioic acid;propan-1-amine Chemical compound CCCN.OC(=O)\C=C\C(O)=O PERYPNLSKBMHJJ-TYYBGVCCSA-N 0.000 claims 2
229920002261 Corn starch Polymers 0.000 claims 2
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims 2
235000013539 calcium stearate Nutrition 0.000 claims 2
239000008116 calcium stearate Substances 0.000 claims 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 claims 2
239000008120 corn starch Substances 0.000 claims 2
239000008187 granular material Substances 0.000 claims 2
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims 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 1
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
241001125671 Eretmochelys imbricata Species 0.000 claims 1
125000004799 bromophenyl group Chemical group 0.000 claims 1
229960004926 chlorobutanol Drugs 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
150000002831 nitrogen free-radicals Chemical group 0.000 claims 1
QYWYGVROYHZRFV-UHFFFAOYSA-N oxalic acid;propan-1-amine Chemical compound CCCN.OC(=O)C(O)=O QYWYGVROYHZRFV-UHFFFAOYSA-N 0.000 claims 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
125000003386 piperidinyl group Chemical group 0.000 claims 1
239000003755 preservative agent Substances 0.000 claims 1
230000002335 preservative effect Effects 0.000 claims 1
PYNUOAIJIQGACY-UHFFFAOYSA-N propylazanium;chloride Chemical compound Cl.CCCN PYNUOAIJIQGACY-UHFFFAOYSA-N 0.000 claims 1
239000008215 water for injection Substances 0.000 claims 1
238000005550 wet granulation Methods 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 249
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 70
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 70
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 69
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 65
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 59
WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 49
238000004458 analytical method Methods 0.000 description 45
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
239000000543 intermediate Substances 0.000 description 38
239000000047 product Substances 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
239000007787 solid Substances 0.000 description 32
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
239000000284 extract Substances 0.000 description 31
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
239000002904 solvent Substances 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 description 27
229910000104 sodium hydride Inorganic materials 0.000 description 24
239000000725 suspension Substances 0.000 description 24
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 23
239000012312 sodium hydride Substances 0.000 description 23
239000012299 nitrogen atmosphere Substances 0.000 description 22
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
239000012458 free base Substances 0.000 description 20
229910052943 magnesium sulfate Inorganic materials 0.000 description 20
235000019341 magnesium sulphate Nutrition 0.000 description 20
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
238000003756 stirring Methods 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 16
239000000706 filtrate Substances 0.000 description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
238000002360 preparation method Methods 0.000 description 15
238000001035 drying Methods 0.000 description 14
238000010992 reflux Methods 0.000 description 13
MEQBJJUWDCYIAB-UHFFFAOYSA-N 2-chloropyridin-3-amine Chemical compound NC1=CC=CN=C1Cl MEQBJJUWDCYIAB-UHFFFAOYSA-N 0.000 description 12
LJQNMDZRCXJETK-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine;hydron;chloride Chemical compound Cl.CN(C)CCCCl LJQNMDZRCXJETK-UHFFFAOYSA-N 0.000 description 12
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 12
238000001816 cooling Methods 0.000 description 12
235000019441 ethanol Nutrition 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
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 11
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
239000000935 antidepressant agent Substances 0.000 description 9
239000002775 capsule Substances 0.000 description 9
239000001530 fumaric acid Substances 0.000 description 9
238000007363 ring formation reaction Methods 0.000 description 9
FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 9
229940005513 antidepressants Drugs 0.000 description 8
239000007858 starting material Substances 0.000 description 8
238000004809 thin layer chromatography Methods 0.000 description 8
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
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
238000001704 evaporation Methods 0.000 description 7
IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
239000011734 sodium Substances 0.000 description 7
229910052708 sodium Inorganic materials 0.000 description 7
239000012258 stirred mixture Substances 0.000 description 7
239000013078 crystal Substances 0.000 description 6
230000000694 effects Effects 0.000 description 6
125000005843 halogen group Chemical group 0.000 description 6
229910000041 hydrogen chloride Inorganic materials 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
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 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
239000002585 base Substances 0.000 description 5
TXHIDIHEXDFONW-UHFFFAOYSA-N benzene;propan-2-one Chemical compound CC(C)=O.C1=CC=CC=C1 TXHIDIHEXDFONW-UHFFFAOYSA-N 0.000 description 5
238000000451 chemical ionisation Methods 0.000 description 5
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 5
238000000638 solvent extraction Methods 0.000 description 5
MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical class NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 4
ZMLUHYJUTIZTOJ-UHFFFAOYSA-N 2-dimethylamino-2-methyl-1-chloro-ethane Natural products ClCC(C)N(C)C ZMLUHYJUTIZTOJ-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 4
230000001430 anti-depressive effect Effects 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000000605 extraction Methods 0.000 description 4
239000012065 filter cake Substances 0.000 description 4
238000009472 formulation Methods 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
150000002430 hydrocarbons Chemical group 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
239000003826 tablet Substances 0.000 description 4
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 3
LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
ALNYFJCONXXPNA-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-(4-fluorophenyl)methanone Chemical compound NC1=CC=CN=C1NC1=CC=CC=C1C(=O)C1=CC=C(F)C=C1 ALNYFJCONXXPNA-UHFFFAOYSA-N 0.000 description 3
LXQYUFJMARARJF-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-pyridin-2-ylmethanone Chemical compound NC1=CC=CN=C1NC1=CC=CC=C1C(=O)C1=CC=CC=N1 LXQYUFJMARARJF-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
239000000969 carrier Substances 0.000 description 3
239000003610 charcoal Substances 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 3
GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 3
238000010828 elution Methods 0.000 description 3
239000011521 glass Substances 0.000 description 3
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
150000004678 hydrides Chemical class 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
239000000463 material Substances 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
239000003960 organic solvent Substances 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
125000004076 pyridyl group Chemical group 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 3
GRDGBWVSVMLKBV-UHFFFAOYSA-N (2-amino-5-nitrophenyl)-(2-chlorophenyl)methanone Chemical compound NC1=CC=C([N+]([O-])=O)C=C1C(=O)C1=CC=CC=C1Cl GRDGBWVSVMLKBV-UHFFFAOYSA-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
NDYMQOUYJJXCKJ-UHFFFAOYSA-N (4-fluorophenyl)-morpholin-4-ylmethanone Chemical compound C1=CC(F)=CC=C1C(=O)N1CCOCC1 NDYMQOUYJJXCKJ-UHFFFAOYSA-N 0.000 description 2
RZJPBQGRCNJYBU-UHFFFAOYSA-N 3-chloropyridin-2-amine Chemical compound NC1=NC=CC=C1Cl RZJPBQGRCNJYBU-UHFFFAOYSA-N 0.000 description 2
KJBKPRMEMJKXDV-UHFFFAOYSA-N 3-chloropyridin-4-amine Chemical compound NC1=CC=NC=C1Cl KJBKPRMEMJKXDV-UHFFFAOYSA-N 0.000 description 2
GTLFLMZOABSJSV-UHFFFAOYSA-N 4-chloropyridin-3-amine Chemical compound NC1=CN=CC=C1Cl GTLFLMZOABSJSV-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
206010011416 Croup infectious Diseases 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical class O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
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OOLHOTFXJZEIRP-UHFFFAOYSA-N [2-[(3-amino-4-methylpyridin-2-yl)amino]phenyl]-phenylmethanone Chemical compound CC1=CC=NC(NC=2C(=CC=CC=2)C(=O)C=2C=CC=CC=2)=C1N OOLHOTFXJZEIRP-UHFFFAOYSA-N 0.000 description 1
NPWLJSUEQCDMGA-UHFFFAOYSA-N [2-[(3-amino-6-methylpyridin-2-yl)amino]phenyl]-phenylmethanone Chemical compound CC1=CC=C(N)C(NC=2C(=CC=CC=2)C(=O)C=2C=CC=CC=2)=N1 NPWLJSUEQCDMGA-UHFFFAOYSA-N 0.000 description 1
OKCUQANWJTVKIE-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]-3-methylphenyl]-phenylmethanone Chemical compound N=1C=CC=C(N)C=1NC=1C(C)=CC=CC=1C(=O)C1=CC=CC=C1 OKCUQANWJTVKIE-UHFFFAOYSA-N 0.000 description 1
ISURZRMDEHOXDI-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]-4-(trifluoromethyl)phenyl]-phenylmethanone Chemical compound NC1=CC=CN=C1NC1=CC(C(F)(F)F)=CC=C1C(=O)C1=CC=CC=C1 ISURZRMDEHOXDI-UHFFFAOYSA-N 0.000 description 1
JFNQCNAUPSGETA-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]-4-ethylphenyl]-phenylmethanone Chemical compound N=1C=CC=C(N)C=1NC1=CC(CC)=CC=C1C(=O)C1=CC=CC=C1 JFNQCNAUPSGETA-UHFFFAOYSA-N 0.000 description 1
CXSUXRCWFYTDAF-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]-4-nitrophenyl]-phenylmethanone Chemical compound NC1=CC=CN=C1NC1=CC([N+]([O-])=O)=CC=C1C(=O)C1=CC=CC=C1 CXSUXRCWFYTDAF-UHFFFAOYSA-N 0.000 description 1
DTSZGOYWJREPIZ-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]-5-chlorophenyl]-(2-chlorophenyl)methanone Chemical compound NC1=CC=CN=C1NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1Cl DTSZGOYWJREPIZ-UHFFFAOYSA-N 0.000 description 1
JILFHSGKHJIIIW-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]-6-methylphenyl]-phenylmethanone Chemical compound C=1C=CC=CC=1C(=O)C=1C(C)=CC=CC=1NC1=NC=CC=C1N JILFHSGKHJIIIW-UHFFFAOYSA-N 0.000 description 1
GIUVDXKBPBEEHB-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-(2-ethylphenyl)methanone Chemical compound CCC1=CC=CC=C1C(=O)C1=CC=CC=C1NC1=NC=CC=C1N GIUVDXKBPBEEHB-UHFFFAOYSA-N 0.000 description 1
NJZQMXHBCNCDLR-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-(2-methoxyphenyl)methanone Chemical compound COC1=CC=CC=C1C(=O)C1=CC=CC=C1NC1=NC=CC=C1N NJZQMXHBCNCDLR-UHFFFAOYSA-N 0.000 description 1
JYVVRRUYTOQNDA-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-(2-methylphenyl)methanone Chemical compound CC1=CC=CC=C1C(=O)C1=CC=CC=C1NC1=NC=CC=C1N JYVVRRUYTOQNDA-UHFFFAOYSA-N 0.000 description 1
WXFMAYCPJYZPGP-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)C=2C(=CC=CC=2)NC=2C(=CC=CN=2)N)=C1 WXFMAYCPJYZPGP-UHFFFAOYSA-N 0.000 description 1
OJNKGLCGQGJFRJ-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-(3-chlorophenyl)methanone Chemical compound NC1=CC=CN=C1NC1=CC=CC=C1C(=O)C1=CC=CC(Cl)=C1 OJNKGLCGQGJFRJ-UHFFFAOYSA-N 0.000 description 1
GUXKXUQMKMIUMK-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-(3-methoxyphenyl)methanone Chemical compound COC1=CC=CC(C(=O)C=2C(=CC=CC=2)NC=2C(=CC=CN=2)N)=C1 GUXKXUQMKMIUMK-UHFFFAOYSA-N 0.000 description 1
QQSJSJBSDAWJJS-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-(3-methylphenyl)methanone Chemical compound CC1=CC=CC(C(=O)C=2C(=CC=CC=2)NC=2C(=CC=CN=2)N)=C1 QQSJSJBSDAWJJS-UHFFFAOYSA-N 0.000 description 1
IIOYMKAYKOIEIM-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-(4-bromophenyl)methanone Chemical compound NC1=CC=CN=C1NC1=CC=CC=C1C(=O)C1=CC=C(Br)C=C1 IIOYMKAYKOIEIM-UHFFFAOYSA-N 0.000 description 1
SCGDWNNMIJKUCB-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-(4-nitrophenyl)methanone Chemical compound NC1=CC=CN=C1NC1=CC=CC=C1C(=O)C1=CC=C([N+]([O-])=O)C=C1 SCGDWNNMIJKUCB-UHFFFAOYSA-N 0.000 description 1
PQBGGLIXFGIHPA-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-pyridin-4-ylmethanone Chemical compound NC1=CC=CN=C1NC1=CC=CC=C1C(=O)C1=CC=NC=C1 PQBGGLIXFGIHPA-UHFFFAOYSA-N 0.000 description 1
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PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
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125000000217 alkyl group Chemical group 0.000 description 1
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
238000005576 amination reaction Methods 0.000 description 1
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239000003708 ampul Substances 0.000 description 1
208000003455 anaphylaxis Diseases 0.000 description 1
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230000001773 anti-convulsant effect Effects 0.000 description 1
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239000001961 anticonvulsive agent Substances 0.000 description 1
229960003965 antiepileptics Drugs 0.000 description 1
239000000739 antihistaminic agent Substances 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 1
KGYGBOORGRYDGQ-UHFFFAOYSA-N benzene;methanol Chemical compound OC.C1=CC=CC=C1 KGYGBOORGRYDGQ-UHFFFAOYSA-N 0.000 description 1
RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
239000012965 benzophenone Substances 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
239000011449 brick Substances 0.000 description 1
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239000007963 capsule composition Substances 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
231100000457 cardiotoxic Toxicity 0.000 description 1
230000001451 cardiotoxic effect Effects 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000012043 crude product Substances 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
125000002576 diazepinyl group Chemical class N1N=C(C=CC=C1)* 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
238000005538 encapsulation Methods 0.000 description 1
CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 1
210000000744 eyelid Anatomy 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
239000010931 gold Substances 0.000 description 1
229910052737 gold Inorganic materials 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
239000012943 hotmelt Substances 0.000 description 1
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical class O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
239000005457 ice water Substances 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-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
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
239000006390 lc 2 Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 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
RHMQNXNXUZLEIY-UHFFFAOYSA-N methanol;2-propan-2-yloxypropane Chemical compound OC.CC(C)OC(C)C RHMQNXNXUZLEIY-UHFFFAOYSA-N 0.000 description 1
BQFOVIOSQDLVGH-UHFFFAOYSA-N methyl n-(3-chloropropyl)-n-methylcarbamate Chemical compound COC(=O)N(C)CCCCl BQFOVIOSQDLVGH-UHFFFAOYSA-N 0.000 description 1
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 1
238000006386 neutralization reaction Methods 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229960003104 ornithine Drugs 0.000 description 1
229940053544 other antidepressants in atc Drugs 0.000 description 1
238000013021 overheating Methods 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 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
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
125000005544 phthalimido group Chemical group 0.000 description 1
239000006187 pill Substances 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
239000002243 precursor Substances 0.000 description 1
AAZYNPCMLRQUHI-UHFFFAOYSA-N propan-2-one;2-propan-2-yloxypropane Chemical compound CC(C)=O.CC(C)OC(C)C AAZYNPCMLRQUHI-UHFFFAOYSA-N 0.000 description 1
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
201000003004 ptosis Diseases 0.000 description 1
230000001528 ptotic effect Effects 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
239000011369 resultant mixture Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
238000012360 testing method Methods 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000001680 trimethoxyphenyl group Chemical group 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
238000010792 warming Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1
150000003738 xylenes Chemical class 0.000 description 1

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

Landscapes

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)

NZ198999A 1981-09-24 1982-02-18 Py benzodiazepine derivatives and pharmaceutical compositions NZ198999A (en)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
NZ21264082A NZ212640A (en)	1981-09-24	1982-02-18	(2 (ar met benzodiazepine precursors

Applications Claiming Priority (1)

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

Publications (1)

Publication Number	Publication Date
NZ198999A true NZ198999A (en)	1987-07-31

Family

ID=23179241

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NZ198999A NZ198999A (en)	1981-09-24	1982-02-18	Py benzodiazepine derivatives and pharmaceutical compositions

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)	ES8303348A1 (da)
FI (1)	FI71935C (da)
FR (1)	FR2515183B1 (da)
GR (1)	GR78473B (da)
HU (2)	HU189426B (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)	PL143597B1 (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 NO NO813839A patent/NO157700C/no unknown
- 1981-11-12 ZA ZA817866A patent/ZA817866B/xx 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 ES ES507971A patent/ES8303348A1/es not_active Expired
- 1981-12-15 HU HU843212A patent/HU189426B/hu not_active IP Right Cessation
- 1981-12-15 HU HU813777A patent/HU187393B/hu not_active IP Right Cessation
- 1981-12-21 DE DE19813150522 patent/DE3150522A1/de not_active Withdrawn
- 1981-12-23 PL PL1981253539A patent/PL143597B1/pl unknown
- 1981-12-23 PL PL1981241410A patent/PL137068B1/pl unknown
- 1981-12-23 PL PL1981253538A patent/PL143596B1/pl unknown
- 1981-12-23 PL PL1981253540A patent/PL143322B1/pl unknown
- 1981-12-23 PL PL1981234426A patent/PL138859B1/pl unknown
- 1981-12-23 PL PL1981241409A patent/PL139381B1/pl unknown
- 1981-12-23 FR FR8124111A patent/FR2515183B1/fr not_active Expired
- 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/ES516052A0/es active Granted
- 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
FI813976L (fi)	1983-03-25
SE8600688D0 (sv)	1986-02-17
ES8604531A1 (es)	1986-02-01
FR2515183B1 (fr)	1986-11-14
KR830009058A (ko)	1983-12-17
ES507971A0 (es)	1983-02-01
PL138859B1 (en)	1986-11-29
PL234426A1 (en)	1984-01-02
ES8402295A1 (es)	1984-01-16
IT8168605A0 (it)	1981-12-09
SE8106573L (sv)	1983-03-25
IL64284A0 (en)	1982-02-28
FI71935C (fi)	1987-03-09
PL241409A1 (en)	1984-05-21
IN156080B (da)	1985-05-11
SE8600688L (sv)	1986-02-17
DK403387D0 (da)	1987-08-03
IE52493B1 (en)	1987-11-25
YU62582A (en)	1986-04-30
PT74286A (en)	1982-02-01
FI71935B (fi)	1986-11-28
SE455305B (sv)	1988-07-04
ES8607726A1 (es)	1986-06-01
DK186282A (da)	1983-03-25
ES543328A0 (es)	1986-06-01
CA1199324A (en)	1986-01-14
YU46128B (sh)	1993-05-28
PL143322B1 (en)	1988-02-29
HU189426B (en)	1986-07-28
ES8504148A1 (es)	1985-04-01
SE448629B (sv)	1987-03-09
DK403487A (da)	1987-08-03
BE891666A (fr)	1982-04-16
DE3150522A1 (de)	1983-04-07
HU187393B (en)	1985-12-28
IT1146728B (it)	1986-11-19
JPS5865290A (ja)	1983-04-18
PH17847A (en)	1985-01-09
ES526562A0 (es)	1985-04-01
ES516051A0 (es)	1983-09-16
NO157700C (no)	1988-05-04
FR2515183A1 (fr)	1983-04-29
EG15904A (en)	1987-03-30
PL137068B1 (en)	1986-04-30
DK403487D0 (da)	1987-08-03
NO813839L (no)	1983-03-25
GR78473B (da)	1984-09-27
PL241410A1 (en)	1984-01-02
ES516052A0 (es)	1984-01-16
PL143596B1 (en)	1988-02-29
LU83865A1 (fr)	1983-09-02
ES526563A0 (es)	1986-02-01
IE812769L (en)	1983-03-24
PT74286B (en)	1983-06-27
PH20536A (en)	1987-02-09
PL143597B1 (en)	1988-02-29
NL8200549A (nl)	1983-04-18
NO157700B (no)	1988-01-25
CH651833A5 (fr)	1985-10-15
ES8308563A1 (es)	1983-09-16
IL64284A (en)	1986-12-31
ES8303348A1 (es)	1983-02-01
PL139381B1 (en)	1987-01-31
KR890000764B1 (ko)	1989-04-05
DK403387A (da)	1987-08-03
ZA817866B (en)	1982-10-27
HUT34732A (en)	1985-04-28

Publication	Publication Date	Title
US3763183A (en)	1973-10-02	1,2,3,10,11,11a-hexahydro-5h-pyrrolo (2,1-c)(1,4)benzodiazepines
US3953430A (en)	1976-04-27	Substituted benzodiazepin-10-ones and method of use
DE19900545A1 (de)	2000-07-13	Verwendung von Pyrimidinderivaten zur Prophylaxe und Therapie der zerebralen Ischämie
US4447361A (en)	1984-05-08	Aryl substituted pyrido[1,4]benzodiazepines
US3732212A (en)	1973-05-08	1,2,3,10,11,11a-hexahydro-5h-pyrrolo(2,1-c)(1,4)benzodiazepine-5,11-diones
PL136930B1 (en)	1986-04-30	Method of obtaining novel derivatives of benzodiazepine
NZ198999A (en)	1987-07-31	Py benzodiazepine derivatives and pharmaceutical compositions
CA1171083A (en)	1984-07-17	Tricyclic pyrroles, a process for their preparation, their use, and medicaments containing them
EP0076017B1 (en)	1990-08-16	Phenyl substituted pyrido(1,4)benzodiazepines and intermediates therefor
EP0107261B1 (en)	1988-09-21	(2-((nitropyridinyl)amino)phenyl)arylmethanones and salts, their use in medicine, pharmaceutical compositions containing them and their use in the preparation of (2-((aminopyridinyl)amino)phenyl)arylmethanones and pyrido(1,4)benzodiazepines
US4556667A (en)	1985-12-03	Aryl substituted pyrido[1,4]benzodiazepines and their use as antidepressives
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
US3828039A (en)	1974-08-06	2-amino-thieno(2,3-e)(1,4)diazepine compounds
US4180573A (en)	1979-12-25	1-Piperazino-6-phenyl-4H-s-triazolo[3,4-c]thieno[2,3-e]1,4-diazepines
US4311700A (en)	1982-01-19	Pyrimidobenzodiazepinones, their use and medicaments containing them
US3629251A (en)	1971-12-21	Derivatives of 9-aminoalkyl-1 2 8 9-tetraazaphenalenes
EP0743946A1 (en)	1996-11-27	5ht2b receptor antagonists condensed indoles
US4518603A (en)	1985-05-21	[2-[(Nitropyridinyl)amino]phenyl]arylmethanones in a process for preparing pyrido[1,4]benzodiazepines
KR810001451B1 (ko)	1981-10-22	피리도 벤조디아제피논의 제조방법
NO872271L (no)	1983-03-25	(2-((aminopyridinyl)amino(fenyl)-arylmethanoner.
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