CA1199324A - Phenyl substituted pyrido¬1,4|benzodiazepines and intermediates therefor - Google Patents

Phenyl substituted pyrido¬1,4|benzodiazepines and intermediates therefor

Info

Publication number: CA1199324A
Authority: CA; Canada
Prior art keywords: pyrido; phenyl; benzodiazepine; amino; prepared
Prior art date: 1981-09-24
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA000394367A

Other languages

English (en)

French (fr)

Inventor

Chandler R. Taylor, Jr.

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Wyeth LLC

Original Assignee

AH Robins Co Inc

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

1982-01-18

Publication date

1986-01-14

1982-01-18 Application filed by AH Robins Co Inc filed Critical AH Robins Co Inc

1986-01-14 Application granted granted Critical

1986-01-14 Publication of CA1199324A publication Critical patent/CA1199324A/en

Status Expired legal-status Critical Current

Links

125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims abstract description 127
229940049706 benzodiazepine Drugs 0.000 title claims abstract description 85
239000000543 intermediate Substances 0.000 title claims abstract description 46
150000001557 benzodiazepines Chemical class 0.000 title claims abstract description 13
-1 4-pyridinyl Chemical group 0.000 claims abstract description 164
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 119
150000003839 salts Chemical class 0.000 claims abstract description 93
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 49
239000001257 hydrogen Substances 0.000 claims abstract description 47
150000002431 hydrogen Chemical group 0.000 claims abstract description 26
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 18
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 15
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims abstract description 12
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims abstract description 10
229910052736 halogen Inorganic materials 0.000 claims abstract description 10
150000002367 halogens Chemical class 0.000 claims abstract description 10
150000001412 amines Chemical class 0.000 claims abstract description 5
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 claims abstract 6
125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 2
238000000034 method Methods 0.000 claims description 246
230000008569 process Effects 0.000 claims description 204
150000001875 compounds Chemical class 0.000 claims description 128
239000000203 mixture Substances 0.000 claims description 105
239000002253 acid Substances 0.000 claims description 95
238000007792 addition Methods 0.000 claims description 83
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 59
238000002360 preparation method Methods 0.000 claims description 58
239000000047 product Substances 0.000 claims description 56
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 43
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 39
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 36
239000007795 chemical reaction product Substances 0.000 claims description 31
238000006243 chemical reaction Methods 0.000 claims description 30
239000002904 solvent Substances 0.000 claims description 29
238000010438 heat treatment Methods 0.000 claims description 24
230000001603 reducing effect Effects 0.000 claims description 22
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
125000005843 halogen group Chemical group 0.000 claims description 18
CJHKJXZMFZKGHI-UHFFFAOYSA-N 1h-pyrido[2,3-i][1,2]benzodiazepine Chemical compound N1N=CC=CC2=CC=C(N=CC=C3)C3=C12 CJHKJXZMFZKGHI-UHFFFAOYSA-N 0.000 claims description 17
229910052757 nitrogen Inorganic materials 0.000 claims description 17
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 16
MEQBJJUWDCYIAB-UHFFFAOYSA-N 2-chloropyridin-3-amine Chemical compound NC1=CC=CN=C1Cl MEQBJJUWDCYIAB-UHFFFAOYSA-N 0.000 claims description 15
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
NYYRRBOMNHUCLB-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCCl NYYRRBOMNHUCLB-UHFFFAOYSA-N 0.000 claims description 14
125000001309 chloro group Chemical group Cl* 0.000 claims description 13
230000009467 reduction Effects 0.000 claims description 12
239000007858 starting material Substances 0.000 claims description 12
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 11
238000010992 reflux Methods 0.000 claims description 11
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
125000000217 alkyl group Chemical group 0.000 claims description 9
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 8
150000002148 esters Chemical class 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 8
125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
238000007363 ring formation reaction Methods 0.000 claims description 8
239000000126 substance Substances 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
239000012280 lithium aluminium hydride Substances 0.000 claims description 7
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 claims description 6
239000003153 chemical reaction reagent Substances 0.000 claims description 6
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims description 6
101100490437 Mus musculus Acvrl1 gene Proteins 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 5
230000003301 hydrolyzing effect Effects 0.000 claims description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 5
239000012279 sodium borohydride Substances 0.000 claims description 5
229910000033 sodium borohydride Inorganic materials 0.000 claims description 5
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 claims description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 3
125000005265 dialkylamine group Chemical group 0.000 claims description 3
125000001475 halogen functional group Chemical group 0.000 claims description 3
150000003141 primary amines Chemical class 0.000 claims description 3
PELAWRHVRDOWQT-UHFFFAOYSA-N (2-amino-4-chlorophenyl)-phenylmethanone Chemical compound NC1=CC(Cl)=CC=C1C(=O)C1=CC=CC=C1 PELAWRHVRDOWQT-UHFFFAOYSA-N 0.000 claims description 2
KWZYIAJRFJVQDO-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-(2-chlorophenyl)methanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1Cl KWZYIAJRFJVQDO-UHFFFAOYSA-N 0.000 claims description 2
ZUWXHHBROGLWNH-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-phenylmethanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 ZUWXHHBROGLWNH-UHFFFAOYSA-N 0.000 claims description 2
APHLSUBLNQBFTM-UHFFFAOYSA-N (2-aminophenyl)-(4-chlorophenyl)methanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=C(Cl)C=C1 APHLSUBLNQBFTM-UHFFFAOYSA-N 0.000 claims description 2
239000000010 aprotic solvent Substances 0.000 claims description 2
125000004494 ethyl ester group Chemical group 0.000 claims description 2
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 claims 8
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 7
238000006722 reduction reaction Methods 0.000 claims 7
MNXYYAMZMWCDQR-UHFFFAOYSA-N 8-chloro-6-phenyl-11H-pyrido[2,3-b][1,4]benzodiazepine Chemical compound C12=CC(Cl)=CC=C2NC2=NC=CC=C2N=C1C1=CC=CC=C1 MNXYYAMZMWCDQR-UHFFFAOYSA-N 0.000 claims 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 5
PRSVNUAKIMADLF-UHFFFAOYSA-N 3-(6-phenylpyrido[2,3-b][1,4]benzodiazepin-11-yl)propan-1-amine Chemical compound N=1C2=CC=CN=C2N(CCCN)C2=CC=CC=C2C=1C1=CC=CC=C1 PRSVNUAKIMADLF-UHFFFAOYSA-N 0.000 claims 4
XNCXMCJPXNTROP-UHFFFAOYSA-N 2-[3-(6-phenylpyrido[2,3-b][1,4]benzodiazepin-11-yl)propyl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCCN(C1=NC=CC=C1N=1)C2=CC=CC=C2C=1C1=CC=CC=C1 XNCXMCJPXNTROP-UHFFFAOYSA-N 0.000 claims 3
WUWKXNGNBUJYDG-UHFFFAOYSA-N 6-(2-bromophenyl)-11H-pyrido[2,3-b][1,4]benzodiazepine Chemical compound BrC1=CC=CC=C1C1=NC2=CC=CN=C2NC2=CC=CC=C12 WUWKXNGNBUJYDG-UHFFFAOYSA-N 0.000 claims 3
DXRQKSAKFSJTMU-UHFFFAOYSA-N 6-(2-chlorophenyl)-11H-pyrido[2,3-b][1,4]benzodiazepine Chemical compound ClC1=CC=CC=C1C1=NC2=CC=CN=C2NC2=CC=CC=C12 DXRQKSAKFSJTMU-UHFFFAOYSA-N 0.000 claims 3
AVLLMVWZBRQLLV-UHFFFAOYSA-N 6-(2-fluorophenyl)-11H-pyrido[2,3-b][1,4]benzodiazepine Chemical compound FC1=CC=CC=C1C1=NC2=CC=CN=C2NC2=CC=CC=C12 AVLLMVWZBRQLLV-UHFFFAOYSA-N 0.000 claims 3
ONTPLJNFNFUZDH-UHFFFAOYSA-N 6-(3-chlorophenyl)-11H-pyrido[2,3-b][1,4]benzodiazepine Chemical compound ClC1=CC=CC(C=2C3=CC=CC=C3NC3=NC=CC=C3N=2)=C1 ONTPLJNFNFUZDH-UHFFFAOYSA-N 0.000 claims 3
ZKZOPKIJENNGNH-UHFFFAOYSA-N 6-(4-chlorophenyl)-11H-pyrido[2,3-b][1,4]benzodiazepine Chemical compound C1=CC(Cl)=CC=C1C1=NC2=CC=CN=C2NC2=CC=CC=C12 ZKZOPKIJENNGNH-UHFFFAOYSA-N 0.000 claims 3
WPIWBUGGJBCRMB-UHFFFAOYSA-N 6-(4-fluorophenyl)-11H-pyrido[2,3-b][1,4]benzodiazepine Chemical compound C1=CC(F)=CC=C1C1=NC2=CC=CN=C2NC2=CC=CC=C12 WPIWBUGGJBCRMB-UHFFFAOYSA-N 0.000 claims 3
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 claims 3
KUORZWTVGDBHBR-UHFFFAOYSA-N 6-(4-methylphenyl)-11H-pyrido[2,3-b][1,4]benzodiazepine Chemical compound C1=CC(C)=CC=C1C1=NC2=CC=CN=C2NC2=CC=CC=C12 KUORZWTVGDBHBR-UHFFFAOYSA-N 0.000 claims 3
SPKBRIIYTVKGPQ-UHFFFAOYSA-N 9-chloro-6-phenyl-11h-pyrido[2,3-b][1,4]benzodiazepine Chemical compound C=1C(Cl)=CC=C2C=1NC1=NC=CC=C1N=C2C1=CC=CC=C1 SPKBRIIYTVKGPQ-UHFFFAOYSA-N 0.000 claims 3
125000003545 alkoxy group Chemical group 0.000 claims 3
XPPJTTIGDJOIIU-UHFFFAOYSA-N ethyl n-[3-(6-phenylpyrido[2,3-b][1,4]benzodiazepin-11-yl)propyl]carbamate Chemical compound N=1C2=CC=CN=C2N(CCCNC(=O)OCC)C2=CC=CC=C2C=1C1=CC=CC=C1 XPPJTTIGDJOIIU-UHFFFAOYSA-N 0.000 claims 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
WRHGGQFJPWBBTG-UHFFFAOYSA-N n,n-dimethyl-3-(6-phenylpyrido[2,3-b][1,4]benzodiazepin-11-yl)propan-1-amine Chemical compound N=1C2=CC=CN=C2N(CCCN(C)C)C2=CC=CC=C2C=1C1=CC=CC=C1 WRHGGQFJPWBBTG-UHFFFAOYSA-N 0.000 claims 3
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims 3
WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylaminoethyl chloride Chemical compound CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 claims 2
BJSFITYHGLDVFE-UHFFFAOYSA-N 3-(9-chloro-6-phenylpyrido[2,3-b][1,4]benzodiazepin-11-yl)-n,n-dimethylpropan-1-amine Chemical compound N=1C2=CC=CN=C2N(CCCN(C)C)C2=CC(Cl)=CC=C2C=1C1=CC=CC=C1 BJSFITYHGLDVFE-UHFFFAOYSA-N 0.000 claims 2
UPHBWMLHRCPZGX-UHFFFAOYSA-N 3-[6-(2-bromophenyl)pyrido[2,3-b][1,4]benzodiazepin-11-yl]-n,n-dimethylpropan-1-amine Chemical compound N=1C2=CC=CN=C2N(CCCN(C)C)C2=CC=CC=C2C=1C1=CC=CC=C1Br UPHBWMLHRCPZGX-UHFFFAOYSA-N 0.000 claims 2
QHTMOFKGJVMAAW-UHFFFAOYSA-N 3-[6-(2-chlorophenyl)pyrido[2,3-b][1,4]benzodiazepin-11-yl]-n,n-dimethylpropan-1-amine Chemical compound N=1C2=CC=CN=C2N(CCCN(C)C)C2=CC=CC=C2C=1C1=CC=CC=C1Cl QHTMOFKGJVMAAW-UHFFFAOYSA-N 0.000 claims 2
SWZZIKBDURHRHD-UHFFFAOYSA-N 3-[6-(2-fluorophenyl)pyrido[2,3-b][1,4]benzodiazepin-11-yl]-n,n-dimethylpropan-1-amine Chemical compound N=1C2=CC=CN=C2N(CCCN(C)C)C2=CC=CC=C2C=1C1=CC=CC=C1F SWZZIKBDURHRHD-UHFFFAOYSA-N 0.000 claims 2
NSSGXZJCUYVURG-UHFFFAOYSA-N 6-(2-bromophenyl)-8-chloro-11-methylpyrido[2,3-b][1,4]benzodiazepine Chemical compound N=1C2=CC=CN=C2N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Br NSSGXZJCUYVURG-UHFFFAOYSA-N 0.000 claims 2
WYXAIBNXRSGGRD-UHFFFAOYSA-N 8-chloro-11-methyl-6-phenylpyrido[2,3-b][1,4]benzodiazepine Chemical compound N=1C2=CC=CN=C2N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 WYXAIBNXRSGGRD-UHFFFAOYSA-N 0.000 claims 2
JVIZVBPGVFDOTO-UHFFFAOYSA-N 8-chloro-6-(2-chlorophenyl)-11H-pyrido[2,3-b][1,4]benzodiazepine Chemical compound C12=CC(Cl)=CC=C2NC2=NC=CC=C2N=C1C1=CC=CC=C1Cl JVIZVBPGVFDOTO-UHFFFAOYSA-N 0.000 claims 2
125000003277 amino group Chemical group 0.000 claims 2
OIVGIIWPZYHINE-UHFFFAOYSA-N n,n-dimethyl-3-(6-phenyl-5,6-dihydropyrido[2,3-b][1,4]benzodiazepin-11-yl)propan-1-amine Chemical compound N1C2=CC=CN=C2N(CCCN(C)C)C2=CC=CC=C2C1C1=CC=CC=C1 OIVGIIWPZYHINE-UHFFFAOYSA-N 0.000 claims 2
HKRSAWPWRNTXRR-UHFFFAOYSA-N n,n-dimethyl-3-[6-(4-methylphenyl)pyrido[2,3-b][1,4]benzodiazepin-11-yl]propan-1-amine Chemical compound N=1C2=CC=CN=C2N(CCCN(C)C)C2=CC=CC=C2C=1C1=CC=C(C)C=C1 HKRSAWPWRNTXRR-UHFFFAOYSA-N 0.000 claims 2
QOIWUWDLTSROGY-UHFFFAOYSA-N n-methyl-3-(6-phenyl-5,6-dihydropyrido[2,3-b][1,4]benzodiazepin-11-yl)propan-1-amine Chemical compound N1C2=CC=CN=C2N(CCCNC)C2=CC=CC=C2C1C1=CC=CC=C1 QOIWUWDLTSROGY-UHFFFAOYSA-N 0.000 claims 2
125000001424 substituent group Chemical group 0.000 claims 2
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 claims 1
HDDNBUNZJIQDBQ-UHFFFAOYSA-N 1-(3-chloropropyl)piperidine Chemical compound ClCCCN1CCCCC1 HDDNBUNZJIQDBQ-UHFFFAOYSA-N 0.000 claims 1
VKJCJJYNVIYVQR-UHFFFAOYSA-N 2-(3-bromopropyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCBr)C(=O)C2=C1 VKJCJJYNVIYVQR-UHFFFAOYSA-N 0.000 claims 1
HEGDBOGOOIDODY-UHFFFAOYSA-N 2-(8-chloro-6-phenylpyrido[2,3-b][1,4]benzodiazepin-11-yl)-n,n-dimethylethanamine Chemical compound N=1C2=CC=CN=C2N(CCN(C)C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 HEGDBOGOOIDODY-UHFFFAOYSA-N 0.000 claims 1
SCCNKOAWPQHRDE-UHFFFAOYSA-N 3-(8-chloro-6-phenylpyrido[2,3-b][1,4]benzodiazepin-11-yl)-n,n-dimethylpropan-1-amine Chemical compound N=1C2=CC=CN=C2N(CCCN(C)C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 SCCNKOAWPQHRDE-UHFFFAOYSA-N 0.000 claims 1
GEASQYOWLOGKQJ-UHFFFAOYSA-N 3-[6-(3-chlorophenyl)pyrido[2,3-b][1,4]benzodiazepin-11-yl]-n,n-dimethylpropan-1-amine Chemical compound N=1C2=CC=CN=C2N(CCCN(C)C)C2=CC=CC=C2C=1C1=CC=CC(Cl)=C1 GEASQYOWLOGKQJ-UHFFFAOYSA-N 0.000 claims 1
PZCSPWKKJQHCLV-UHFFFAOYSA-N 3-[6-(4-chlorophenyl)pyrido[2,3-b][1,4]benzodiazepin-11-yl]-n,n-dimethylpropan-1-amine Chemical compound N=1C2=CC=CN=C2N(CCCN(C)C)C2=CC=CC=C2C=1C1=CC=C(Cl)C=C1 PZCSPWKKJQHCLV-UHFFFAOYSA-N 0.000 claims 1
WVUULNDRFBHTFG-UHFFFAOYSA-N 3-chloro-n,n-diethylpropan-1-amine Chemical compound CCN(CC)CCCCl WVUULNDRFBHTFG-UHFFFAOYSA-N 0.000 claims 1
LJTJCYQJCOEKDY-UHFFFAOYSA-N 4-[3-(6-phenylpyrido[2,3-b][1,4]benzodiazepin-11-yl)propyl]morpholine Chemical compound C12=CC=CC=C2C(C=2C=CC=CC=2)=NC2=CC=CN=C2N1CCCN1CCOCC1 LJTJCYQJCOEKDY-UHFFFAOYSA-N 0.000 claims 1
RZEQVNCQDMUPIH-UHFFFAOYSA-N 6-(2-bromophenyl)-8-chloro-11H-pyrido[2,3-b][1,4]benzodiazepine Chemical compound C12=CC(Cl)=CC=C2NC2=NC=CC=C2N=C1C1=CC=CC=C1Br RZEQVNCQDMUPIH-UHFFFAOYSA-N 0.000 claims 1
FFUOIFKDGRIYHR-UHFFFAOYSA-N 6-phenyl-11-(3-piperidin-1-ylpropyl)pyrido[2,3-b][1,4]benzodiazepine Chemical compound C12=CC=CC=C2C(C=2C=CC=CC=2)=NC2=CC=CN=C2N1CCCN1CCCCC1 FFUOIFKDGRIYHR-UHFFFAOYSA-N 0.000 claims 1
BZIZLNVGYWUQCE-UHFFFAOYSA-N 8-chloro-6-(2-chlorophenyl)-11-methylpyrido[2,3-b][1,4]benzodiazepine Chemical compound N=1C2=CC=CN=C2N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl BZIZLNVGYWUQCE-UHFFFAOYSA-N 0.000 claims 1
OCWGEIWZCDZNQX-UHFFFAOYSA-N 8-chloro-6-(2-chlorophenyl)-6,11-dihydro-5h-pyrido[2,3-b][1,4]benzodiazepine Chemical compound C12=CC(Cl)=CC=C2NC2=NC=CC=C2NC1C1=CC=CC=C1Cl OCWGEIWZCDZNQX-UHFFFAOYSA-N 0.000 claims 1
VILUYDOHRGAWJZ-UHFFFAOYSA-N 8-chloro-6-(2-nitrophenyl)-11H-pyrido[2,3-b][1,4]benzodiazepine Chemical compound [O-][N+](=O)C1=CC=CC=C1C1=NC2=CC=CN=C2NC2=CC=C(Cl)C=C12 VILUYDOHRGAWJZ-UHFFFAOYSA-N 0.000 claims 1
NCVDGWAAFROCBX-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]-4-chlorophenyl]-phenylmethanone Chemical compound NC1=CC=CN=C1NC1=CC(Cl)=CC=C1C(=O)C1=CC=CC=C1 NCVDGWAAFROCBX-UHFFFAOYSA-N 0.000 claims 1
NZJYWIQIHUSNGV-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-(2-chlorophenyl)methanone Chemical compound NC1=CC=CN=C1NC1=CC=CC=C1C(=O)C1=CC=CC=C1Cl NZJYWIQIHUSNGV-UHFFFAOYSA-N 0.000 claims 1
XHMMTUVPKGQQEM-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-(4-methylphenyl)methanone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=CC=C1NC1=NC=CC=C1N XHMMTUVPKGQQEM-UHFFFAOYSA-N 0.000 claims 1
125000002947 alkylene group Chemical group 0.000 claims 1
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125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
238000002560 therapeutic procedure Methods 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
229940086542 triethylamine Drugs 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000005550 wet granulation 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)

CA000394367A 1981-09-24 1982-01-18 Phenyl substituted pyrido¬1,4|benzodiazepines and intermediates therefor Expired CA1199324A (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date
US30508081A	1981-09-24	1981-09-24
US305,080		1981-09-24
US395,218		1982-07-06

Publications (1)

Publication Number	Publication Date
CA1199324A true CA1199324A (en)	1986-01-14

Family

ID=23179241

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000394367A Expired CA1199324A (en)	1981-09-24	1982-01-18	Phenyl substituted pyrido¬1,4\|benzodiazepines and intermediates therefor

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)	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)	PL143322B1 (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 HU HU843212A patent/HU189426B/hu not_active IP Right Cessation
- 1981-12-15 HU HU813777A patent/HU187393B/hu not_active IP Right Cessation
- 1981-12-15 ES ES507971A patent/ES507971A0/es active Granted
- 1981-12-21 DE DE19813150522 patent/DE3150522A1/de not_active Withdrawn
- 1981-12-23 PL PL1981253540A patent/PL143322B1/pl unknown
- 1981-12-23 PL PL1981241410A patent/PL137068B1/pl unknown
- 1981-12-23 PL PL1981234426A patent/PL138859B1/pl unknown
- 1981-12-23 PL PL1981253539A patent/PL143597B1/pl unknown
- 1981-12-23 PL PL1981241409A patent/PL139381B1/pl unknown
- 1981-12-23 PL PL1981253538A patent/PL143596B1/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/ES516051A0/es active Granted
1983
- 1983-10-19 ES ES526563A patent/ES8604531A1/es not_active Expired
- 1983-10-19 ES ES526562A patent/ES8504148A1/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
ZA817866B (en)	1982-10-27
ES8402295A1 (es)	1984-01-16
SE8600688D0 (sv)	1986-02-17
PL143597B1 (en)	1988-02-29
NO813839L (no)	1983-03-25
PH20536A (en)	1987-02-09
DK403487A (da)	1987-08-03
IN156080B (da)	1985-05-11
ES526562A0 (es)	1985-04-01
KR830009058A (ko)	1983-12-17
BE891666A (fr)	1982-04-16
ES8607726A1 (es)	1986-06-01
NL8200549A (nl)	1983-04-18
FI71935C (fi)	1987-03-09
ES8308563A1 (es)	1983-09-16
DK403387D0 (da)	1987-08-03
HUT34732A (en)	1985-04-28
ES516051A0 (es)	1983-09-16
HU189426B (en)	1986-07-28
NO157700B (no)	1988-01-25
CH651833A5 (fr)	1985-10-15
GR78473B (da)	1984-09-27
PT74286A (en)	1982-02-01
PL241409A1 (en)	1984-05-21
DE3150522A1 (de)	1983-04-07
SE448629B (sv)	1987-03-09
DK403387A (da)	1987-08-03
IL64284A (en)	1986-12-31
YU62582A (en)	1986-04-30
PL138859B1 (en)	1986-11-29
SE8106573L (sv)	1983-03-25
PL137068B1 (en)	1986-04-30
JPS5865290A (ja)	1983-04-18
IT1146728B (it)	1986-11-19
IE52493B1 (en)	1987-11-25
HU187393B (en)	1985-12-28
PL143322B1 (en)	1988-02-29
PL143596B1 (en)	1988-02-29
PL241410A1 (en)	1984-01-02
IE812769L (en)	1983-03-24
PH17847A (en)	1985-01-09
ES543328A0 (es)	1986-06-01
PT74286B (en)	1983-06-27
ES8604531A1 (es)	1986-02-01
PL139381B1 (en)	1987-01-31
DK186282A (da)	1983-03-25
IT8168605A0 (it)	1981-12-09
FR2515183B1 (fr)	1986-11-14
NO157700C (no)	1988-05-04
FI813976L (fi)	1983-03-25
FR2515183A1 (fr)	1983-04-29
ES516052A0 (es)	1984-01-16
EG15904A (en)	1987-03-30
DK403487D0 (da)	1987-08-03
SE455305B (sv)	1988-07-04
ES526563A0 (es)	1986-02-01
LU83865A1 (fr)	1983-09-02
YU46128B (sh)	1993-05-28
ES8303348A1 (es)	1983-02-01
ES8504148A1 (es)	1985-04-01
FI71935B (fi)	1986-11-28
IL64284A0 (en)	1982-02-28
KR890000764B1 (ko)	1989-04-05
NZ198999A (en)	1987-07-31
ES507971A0 (es)	1983-02-01
SE8600688L (sv)	1986-02-17
PL234426A1 (en)	1984-01-02

Publication	Publication Date	Title
CA1083149A (en)	1980-08-05	Derivatives of 10,11-dihydrobenzo 4,5 cyclohepta l,2- b -pyrazolo 4,3-e pyridine-5 (1h)ones
WO1986001510A1 (en)	1986-03-13	Tricyclic oxindole antiinflammatory agents
US4447361A (en)	1984-05-08	Aryl substituted pyrido[1,4]benzodiazepines
CA1199324A (en)	1986-01-14	Phenyl substituted pyrido¬1,4\|benzodiazepines and intermediates therefor
Hino et al.	1988	Agents Acting on the Central Nervous System.: Synthesis of 3-Phenyl-2-piperazinyl-1-benzazocines, 3-Substituted-2-piperazinyl-1-benzazepines and Related Compounds
CA2048003A1 (en)	1992-02-22	Tricyclic pyridone derivatives
US4560510A (en)	1985-12-24	Process and intermediates for the preparation of aryl substituted pyrido[1,4]benzodiazepines
US4480100A (en)	1984-10-30	[2-[(Nitropyridinyl)amino]phenyl]arymethanones
US4556667A (en)	1985-12-03	Aryl substituted pyrido[1,4]benzodiazepines and their use as antidepressives
US4495183A (en)	1985-01-22	Aryl substituted pyrido[1,4]benzodiazepines for treatment of depression
US4668675A (en)	1987-05-26	2-[(amino-pyridinyl)amine]phenyl]aryl methanones, their thioxomethyl, ketal or thioketal analogs
EP0076017B1 (en)	1990-08-16	Phenyl substituted pyrido(1,4)benzodiazepines and intermediates therefor
Kökösi et al.	1982	Nitrogen bridgehead compounds. Part 19. Synthesis of polymethylenepyrimidin‐4‐ones
US4558132A (en)	1985-12-10	Nitro, amino and aroylamino-N-phenylpyridinamines in a process for preparing pyrido[1,4]benzodiazepines
US4698430A (en)	1987-10-06	Nitro, amino and aroylamino-n-phenylpyridinamines
US4311700A (en)	1982-01-19	Pyrimidobenzodiazepinones, their use and medicaments containing them
CA1087182A (en)	1980-10-07	Substituted 1-piperazinyl-triazolo-thieno-1,4- diazepines
US4628100A (en)	1986-12-09	Intermediates for the preparation of aryl substituted pyrido[1,4]benzodiazepines
US4518603A (en)	1985-05-21	[2-[(Nitropyridinyl)amino]phenyl]arylmethanones in a process for preparing pyrido[1,4]benzodiazepines
CA1262353A (en)	1989-10-17	Aromatic ketone derivative intermediates for the preparation of antidepressant pyrido [1,4] benzodiazepines
NO872271L (no)	1983-03-25	(2-((aminopyridinyl)amino(fenyl)-arylmethanoner.
Zhao et al.	1995	A Novel Approach to the Synthesis of 1-Substituted-3, 6-diaryl-imidazo [1, 5-b] pyridazines
NO872691L (no)	1984-01-03	Nye nitro-, amino- og aroylamino-n-fenylpyridinaminer.
NO880084L (no)	1984-04-02	Utgangsmaterialer for fremstilling av pyrido(1,4)benzodiazepiner.
NO900286L (no)	1985-10-07	Fremgangsmaate for fremstilling av en pyridobenzodiazepinforbindelser.

Legal Events

Date	Code	Title	Description
2003-01-14	MKEX	Expiry