NO972937L - Farmasöytiske piperazinforbindelser - Google Patents

Farmasöytiske piperazinforbindelser

Info

Publication number: NO972937L
Authority: NO; Norway
Prior art keywords: phenyl; ethyl; dimethoxy; tetrahydro; piperazinylidene
Prior art date: 1994-12-23

Application number

NO972937A

Other languages

English (en)

Norwegian (no)

Other versions

NO972937D0 (no

Inventor

Philip Anthony Ashworth

Sukhjit Hunjan

Ian Andrew Pretswell

Hamish Ryder

Stephen James Brocchini

Original Assignee

Xenova Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1994-12-23

Filing date

1997-06-23

Publication date

1997-06-23

1997-06-23 Application filed by Xenova Ltd filed Critical Xenova Ltd

1997-06-23 Publication of NO972937D0 publication Critical patent/NO972937D0/no

1997-06-23 Publication of NO972937L publication Critical patent/NO972937L/no

Links

150000004885 piperazines Chemical class 0.000 title claims description 3
150000001875 compounds Chemical class 0.000 claims description 132
238000000034 method Methods 0.000 claims description 34
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 29
229910052739 hydrogen Inorganic materials 0.000 claims description 29
230000036457 multidrug resistance Effects 0.000 claims description 29
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
239000001257 hydrogen Substances 0.000 claims description 27
XXUNIGZDNWWYED-UHFFFAOYSA-N 2-methylbenzamide Chemical compound CC1=CC=CC=C1C(N)=O XXUNIGZDNWWYED-UHFFFAOYSA-N 0.000 claims description 20
229910052736 halogen Inorganic materials 0.000 claims description 18
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
150000002367 halogens Chemical class 0.000 claims description 17
150000003839 salts Chemical class 0.000 claims description 17
-1 methylenedioxy group Chemical group 0.000 claims description 15
239000000203 mixture Substances 0.000 claims description 15
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 13
239000003814 drug Substances 0.000 claims description 12
229940079593 drug Drugs 0.000 claims description 11
239000003960 organic solvent Substances 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 10
150000002431 hydrogen Chemical class 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 7
125000000217 alkyl group Chemical group 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
125000002541 furyl group Chemical group 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
125000004076 pyridyl group Chemical group 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
125000001544 thienyl group Chemical group 0.000 claims description 4
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
GAEOJCDYFMABJF-LPIHMFRFSA-N 2-[(2z,5z)-2-benzylidene-5-[[3-[[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]carbamoyl]phenyl]methylidene]-3,6-dioxopiperazin-1-yl]acetic acid Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C(C(N1CC(O)=O)=O)/NC(=O)\C1=C\C1=CC=CC=C1 GAEOJCDYFMABJF-LPIHMFRFSA-N 0.000 claims description 2
VZHRVVBUCDKXIJ-LPIHMFRFSA-N 3-[(Z)-[(5Z)-5-[(2-chlorophenyl)methylidene]-4-methyl-3,6-dioxopiperazin-2-ylidene]methyl]-N-[4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]phenyl]benzamide Chemical compound COC1=CC2=C(CN(CCC3=CC=C(NC(=O)C4=CC(\C=C5/NC(=O)\C(=C\C6=C(Cl)C=CC=C6)N(C)C5=O)=CC=C4)C=C3)CC2)C=C1OC VZHRVVBUCDKXIJ-LPIHMFRFSA-N 0.000 claims description 2
VSWPXILDBNFXIB-YWQXDYITSA-N 3-[(z)-[(5z)-5-(cyclohexylmethylidene)-4-methyl-3,6-dioxopiperazin-2-ylidene]methyl]-n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C(C(N1C)=O)/NC(=O)\C1=C\C1CCCCC1 VSWPXILDBNFXIB-YWQXDYITSA-N 0.000 claims description 2
AFSLGMUGRASLRI-LPIHMFRFSA-N 3-[(z)-[(5z)-5-[(3-chlorophenyl)methylidene]-4-methyl-3,6-dioxopiperazin-2-ylidene]methyl]-n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C(C(N1C)=O)/NC(=O)\C1=C\C1=CC=CC(Cl)=C1 AFSLGMUGRASLRI-LPIHMFRFSA-N 0.000 claims description 2
LULGGPSIFKBXMT-CKPXSJKLSA-N 3-[(z)-[(5z)-5-benzylidene-4-(cyclopropylmethyl)-3,6-dioxopiperazin-2-ylidene]methyl]-n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C(C(N1CC2CC2)=O)/NC(=O)\C1=C\C1=CC=CC=C1 LULGGPSIFKBXMT-CKPXSJKLSA-N 0.000 claims description 2
LNDHBVSESSZAIU-HSZPEWSQSA-N 3-[(z)-[(5z)-5-benzylidene-4-ethyl-3,6-dioxopiperazin-2-ylidene]methyl]-n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]benzamide Chemical compound CCN1C(=O)\C(=C\C=2C=C(C=CC=2)C(=O)NC=2C=CC(CCN3CC4=CC(OC)=C(OC)C=C4CC3)=CC=2)NC(=O)\C1=C\C1=CC=CC=C1 LNDHBVSESSZAIU-HSZPEWSQSA-N 0.000 claims description 2
JWMWQAUZAUFNIN-QASZCPKBSA-N 4-[(z)-[(5z)-4-benzyl-5-benzylidene-3,6-dioxopiperazin-2-ylidene]methyl]-n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1\C=C(C(N1CC=2C=CC=CC=2)=O)/NC(=O)\C1=C\C1=CC=CC=C1 JWMWQAUZAUFNIN-QASZCPKBSA-N 0.000 claims description 2
AZDVUUMYSDAHFB-YWQXDYITSA-N 4-[(z)-[(5z)-5-(cyclohexylmethylidene)-4-methyl-3,6-dioxopiperazin-2-ylidene]methyl]-n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1\C=C(C(N1C)=O)/NC(=O)\C1=C\C1CCCCC1 AZDVUUMYSDAHFB-YWQXDYITSA-N 0.000 claims description 2
HHGLBCGKPGBNMG-LPIHMFRFSA-N 4-[(z)-[(5z)-5-[(3-chlorophenyl)methylidene]-4-methyl-3,6-dioxopiperazin-2-ylidene]methyl]-n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1\C=C(C(N1C)=O)/NC(=O)\C1=C\C1=CC=CC(Cl)=C1 HHGLBCGKPGBNMG-LPIHMFRFSA-N 0.000 claims description 2
IBVIZIOPXPHKOB-LPIHMFRFSA-N 4-[(z)-[(5z)-5-[(4-chlorophenyl)methylidene]-4-methyl-3,6-dioxopiperazin-2-ylidene]methyl]-n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1\C=C(C(N1C)=O)/NC(=O)\C1=C\C1=CC=C(Cl)C=C1 IBVIZIOPXPHKOB-LPIHMFRFSA-N 0.000 claims description 2
IMNHZHFEHWIUPQ-HSZPEWSQSA-N 4-[(z)-[(5z)-5-benzylidene-4-ethyl-3,6-dioxopiperazin-2-ylidene]methyl]-n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]benzamide Chemical compound CCN1C(=O)\C(=C\C=2C=CC(=CC=2)C(=O)NC=2C=CC(CCN3CC4=CC(OC)=C(OC)C=C4CC3)=CC=2)NC(=O)\C1=C\C1=CC=CC=C1 IMNHZHFEHWIUPQ-HSZPEWSQSA-N 0.000 claims description 2
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
GJPZEJYOLLPGKQ-PXDBBHOGSA-N N-[4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]phenyl]-3-[(Z)-[(5Z)-4-methyl-5-(naphthalen-1-ylmethylidene)-3,6-dioxopiperazin-2-ylidene]methyl]benzamide Chemical compound c1c(OC)c(OC)cc(C2)c1CCN2CCc1ccc(NC(=O)c2cccc(c2)\C=c/2c(=O)n(C)c(/c([nH]\2)=O)=C\c2cccc3c2cccc3)cc1 GJPZEJYOLLPGKQ-PXDBBHOGSA-N 0.000 claims description 2
YNVWWCFEGXMQMQ-VANQDGIVSA-N [2-[(z)-[(5z)-5-[[3-[[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]carbamoyl]phenyl]methylidene]-1-methyl-3,6-dioxopiperazin-2-ylidene]methyl]phenyl] acetate Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C(C(N1C)=O)/NC(=O)\C1=C\C1=CC=CC=C1OC(C)=O YNVWWCFEGXMQMQ-VANQDGIVSA-N 0.000 claims description 2
NEMWFLYOMMLWMD-XEMPJQOTSA-N [3-[(z)-[(5z)-5-[[3-[[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]carbamoyl]phenyl]methylidene]-1-methyl-3,6-dioxopiperazin-2-ylidene]methyl]phenyl] acetate Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C(C(N1C)=O)/NC(=O)\C1=C\C1=CC=CC(OC(C)=O)=C1 NEMWFLYOMMLWMD-XEMPJQOTSA-N 0.000 claims description 2
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
UTHDNQZLEUCHCA-JTTISPGVSA-N ethyl 2-[(2z,5z)-2-benzylidene-5-[[3-[[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]carbamoyl]phenyl]methylidene]-3,6-dioxopiperazin-1-yl]acetate Chemical compound CCOC(=O)CN1C(=O)\C(=C\C=2C=C(C=CC=2)C(=O)NC=2C=CC(CCN3CC4=CC(OC)=C(OC)C=C4CC3)=CC=2)NC(=O)\C1=C\C1=CC=CC=C1 UTHDNQZLEUCHCA-JTTISPGVSA-N 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
WZXXNTKUPAIPGW-VANQDGIVSA-N methyl 2-[(2z,5z)-2-benzylidene-5-[[3-[[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]carbamoyl]phenyl]methylidene]-3,6-dioxopiperazin-1-yl]acetate Chemical compound COC(=O)CN1C(=O)\C(=C\C=2C=C(C=CC=2)C(=O)NC=2C=CC(CCN3CC4=CC(OC)=C(OC)C=C4CC3)=CC=2)NC(=O)\C1=C\C1=CC=CC=C1 WZXXNTKUPAIPGW-VANQDGIVSA-N 0.000 claims description 2
WLFJHNWIUYKMRL-VFHXEFSMSA-N n-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]-3-[(z)-[(5z)-4-methyl-3,6-dioxo-5-(3-phenylpropylidene)piperazin-2-ylidene]methyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCNC(=O)C(C=1)=CC=CC=1\C=C(C(N1C)=O)/NC(=O)\C1=C\CCC1=CC=CC=C1 WLFJHNWIUYKMRL-VFHXEFSMSA-N 0.000 claims description 2
NIHYIHSLXCXAFX-KRFZJYALSA-N n-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]-4-[(z)-[(5z)-4-methyl-3,6-dioxo-5-(3-phenylpropylidene)piperazin-2-ylidene]methyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCNC(=O)C(C=C1)=CC=C1\C=C(C(N1C)=O)/NC(=O)\C1=C\CCC1=CC=CC=C1 NIHYIHSLXCXAFX-KRFZJYALSA-N 0.000 claims description 2
VLGMBRZXBCWLPY-BEORVMNHSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-3-[(z)-[(5z)-4-methyl-3,6-dioxo-5-(thiophen-2-ylmethylidene)piperazin-2-ylidene]methyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C(C(N1C)=O)/NC(=O)\C1=C\C1=CC=CS1 VLGMBRZXBCWLPY-BEORVMNHSA-N 0.000 claims description 2
JVLZNBZOCPFCJN-HEZNUULDSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-3-[(z)-[(5z)-4-methyl-3,6-dioxo-5-(thiophen-3-ylmethylidene)piperazin-2-ylidene]methyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C(C(N1C)=O)/NC(=O)\C1=C\C=1C=CSC=1 JVLZNBZOCPFCJN-HEZNUULDSA-N 0.000 claims description 2
DHHYWFVEXOEYQF-PPUHNOCVSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-3-[(z)-[(5z)-4-methyl-3,6-dioxo-5-[[(4s)-4-prop-1-en-2-ylcyclohexen-1-yl]methylidene]piperazin-2-ylidene]methyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C(C(N1C)=O)/NC(=O)\C1=C\C1=CC[C@@H](C(C)=C)CC1 DHHYWFVEXOEYQF-PPUHNOCVSA-N 0.000 claims description 2
LLHJNNKUEFHGMG-GCEMHJBXSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-3-[(z)-[(5z)-4-methyl-3,6-dioxo-5-pentylidenepiperazin-2-ylidene]methyl]benzamide Chemical compound N1C(=O)C(=C/CCCC)/N(C)C(=O)\C1=C\C1=CC=CC(C(=O)NC=2C=CC(CCN3CC4=CC(OC)=C(OC)C=C4CC3)=CC=2)=C1 LLHJNNKUEFHGMG-GCEMHJBXSA-N 0.000 claims description 2
QEGNZHVGNUUXJD-UXNCMSBCSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-3-[(z)-[(5z)-4-methyl-5-(2-methylpropylidene)-3,6-dioxopiperazin-2-ylidene]methyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C1/NC(=O)\C(=C\C(C)C)N(C)C1=O QEGNZHVGNUUXJD-UXNCMSBCSA-N 0.000 claims description 2
UMVDXPFNYQMLDY-PXDBBHOGSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-3-[(z)-[(5z)-4-methyl-5-(naphthalen-2-ylmethylidene)-3,6-dioxopiperazin-2-ylidene]methyl]benzamide Chemical compound C1=CC=CC2=CC(/C=C3/C(=O)N\C(C(N3C)=O)=C/C=3C=CC=C(C=3)C(=O)NC3=CC=C(C=C3)CCN3CCC=4C=C(C(=CC=4C3)OC)OC)=CC=C21 UMVDXPFNYQMLDY-PXDBBHOGSA-N 0.000 claims description 2
VQVILPCHXGJQTD-RFKWEDMZSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-3-[(z)-[(5z)-4-methyl-5-[(1-methylindol-3-yl)methylidene]-3,6-dioxopiperazin-2-ylidene]methyl]benzamide Chemical compound C1=CC=C2C(/C=C3/C(=O)N\C(C(N3C)=O)=C/C=3C=CC=C(C=3)C(=O)NC3=CC=C(C=C3)CCN3CCC=4C=C(C(=CC=4C3)OC)OC)=CN(C)C2=C1 VQVILPCHXGJQTD-RFKWEDMZSA-N 0.000 claims description 2
FXAUBFKBIZUBOO-PCNBCNDESA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-3-[(z)-[(5z)-4-methyl-5-[(1-methylpyrrol-3-yl)methylidene]-3,6-dioxopiperazin-2-ylidene]methyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C(C(N1C)=O)/NC(=O)\C1=C\C=1C=CN(C)C=1 FXAUBFKBIZUBOO-PCNBCNDESA-N 0.000 claims description 2
LWCNHERLJGRQMD-XREVHHEISA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-3-[(z)-[(5z)-5-(3,3-dimethylbutylidene)-4-methyl-3,6-dioxopiperazin-2-ylidene]methyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C1/NC(=O)\C(=C\CC(C)(C)C)N(C)C1=O LWCNHERLJGRQMD-XREVHHEISA-N 0.000 claims description 2
DJNAGHXXJTWJHR-BEORVMNHSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-3-[(z)-[(5z)-5-(furan-2-ylmethylidene)-4-methyl-3,6-dioxopiperazin-2-ylidene]methyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C(C(N1C)=O)/NC(=O)\C1=C\C1=CC=CO1 DJNAGHXXJTWJHR-BEORVMNHSA-N 0.000 claims description 2
IIEKSEMMAMJSLP-HEZNUULDSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-3-[(z)-[(5z)-5-(furan-3-ylmethylidene)-4-methyl-3,6-dioxopiperazin-2-ylidene]methyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C(C(N1C)=O)/NC(=O)\C1=C\C=1C=COC=1 IIEKSEMMAMJSLP-HEZNUULDSA-N 0.000 claims description 2
PBIASUOLHHQIHG-VANQDGIVSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-3-[(z)-[(5z)-5-[(3-methoxyphenyl)methylidene]-4-methyl-3,6-dioxopiperazin-2-ylidene]methyl]benzamide Chemical compound COC1=CC=CC(\C=C/2C(NC(=C\C=3C=C(C=CC=3)C(=O)NC=3C=CC(CCN4CC5=CC(OC)=C(OC)C=C5CC4)=CC=3)/C(=O)N\2C)=O)=C1 PBIASUOLHHQIHG-VANQDGIVSA-N 0.000 claims description 2
QQDGGFKWPHSTIN-PCNBCNDESA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-4-[(z)-[(5z)-4-methyl-3,6-dioxo-5-(pyridin-3-ylmethylidene)piperazin-2-ylidene]methyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1\C=C(C(N1C)=O)/NC(=O)\C1=C\C1=CC=CN=C1 QQDGGFKWPHSTIN-PCNBCNDESA-N 0.000 claims description 2
HPEWOOFNLLPKBJ-HEZNUULDSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-4-[(z)-[(5z)-4-methyl-3,6-dioxo-5-(thiophen-3-ylmethylidene)piperazin-2-ylidene]methyl]benzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1\C=C(C(N1C)=O)/NC(=O)\C1=C\C=1C=CSC=1 HPEWOOFNLLPKBJ-HEZNUULDSA-N 0.000 claims description 2
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229960003171 plicamycin Drugs 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229940068965 polysorbates Drugs 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
235000019422 polyvinyl alcohol Nutrition 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229910052814 silicon oxide Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
235000015424 sodium Nutrition 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000000243 solution Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
239000007940 sugar coated tablet Substances 0.000 description 1
238000009495 sugar coating Methods 0.000 description 1
231100000338 sulforhodamine B assay Toxicity 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229960001603 tamoxifen Drugs 0.000 description 1
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000012360 testing method Methods 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000004448 titration Methods 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
108700012359 toxins Proteins 0.000 description 1
238000001890 transfection Methods 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
229960004528 vincristine Drugs 0.000 description 1
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

NO972937A 1994-12-23 1997-06-23 Farmasöytiske piperazinforbindelser NO972937L (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9426224.3A GB9426224D0 (en)	1994-12-23	1994-12-23	Pharmaceutical compounds
PCT/GB1995/003027 WO1996020190A1 (en)	1994-12-23	1995-12-22	Piperazine 2,5 dione derivatives as modulators of multi-drug resistance

Publications (2)

Publication Number	Publication Date
NO972937D0 NO972937D0 (no)	1997-06-23
NO972937L true NO972937L (no)	1997-06-23

Family

ID=10766589

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO972937A NO972937L (no)	1994-12-23	1997-06-23	Farmasöytiske piperazinforbindelser

Country Status (19)

Country	Link
EP (1)	EP0799222A1 (ja)
JP (1)	JPH10511384A (ja)
CN (1)	CN1175253A (ja)
AU (1)	AU698828B2 (ja)
BG (1)	BG101602A (ja)
BR (1)	BR9510410A (ja)
CA (1)	CA2207500A1 (ja)
CZ (1)	CZ190097A3 (ja)
FI (1)	FI972660L (ja)
GB (1)	GB9426224D0 (ja)
HU (1)	HUT77943A (ja)
IL (1)	IL116525A0 (ja)
NO (1)	NO972937L (ja)
NZ (1)	NZ297847A (ja)
PL (1)	PL320916A1 (ja)
SK (1)	SK83697A3 (ja)
TW (1)	TW358094B (ja)
WO (1)	WO1996020190A1 (ja)
ZA (1)	ZA9510909B (ja)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9717576D0 (en) *	1997-08-19	1997-10-22	Xenova Ltd	Pharmaceutical compounds
HUP0001531A3 (en) *	1996-10-18	2000-09-28	Xenova Ltd Slough	Anthranilic acid derivatives as multi drug resistance modulators
GB9708805D0 (en)	1997-05-01	1997-06-25	Smithkline Beecham Plc	Compounds
GB9810876D0 (en)	1998-05-20	1998-07-22	Smithkline Beecham Plc	Compounds
CA2346689A1 (en)	1998-10-08	2000-04-20	Gregor James Macdonald	Tetrahydrobenzazepine derivatives useful as modulators of dopamine d3 receptors (antipsychotic agents)
EP1264831A4 (en) *	2000-01-18	2005-11-23	Nereus Pharmaceuticals Inc	Cell division inhibitors and a method for fixing the same
WO2002020663A2 (en)	2000-09-06	2002-03-14	Ap Pharma, Inc.	Degradable polyacetal polymers
US6693099B2 (en)	2000-10-17	2004-02-17	The Procter & Gamble Company	Substituted piperazine compounds optionally containing a quinolyl moiety for treating multidrug resistance
US7935704B2 (en)	2003-08-01	2011-05-03	Nereus Pharmaceuticals, Inc.	Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof
AU2003302721B2 (en)	2002-08-02	2009-10-08	Beyondspring Pharmaceuticals, Inc.	Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof
US7919497B2 (en)	2002-08-02	2011-04-05	Nereus Pharmaceuticals, Inc.	Analogs of dehydrophenylahistins and their therapeutic use
US8129527B2 (en)	2006-11-03	2012-03-06	Nereus Pharmacuticals, Inc.	Analogs of dehydrophenylahistins and their therapeutic use
CN103396372B (zh) *	2013-08-09	2015-05-20	中国科学院南海海洋研究所	一类2,5-二酮哌嗪衍生物及其制备方法和在制备抗海洋污损生物防除剂中的应用
HK1249052A1 (zh)	2015-03-06	2018-10-26	BeyondSpring Pharmaceuticals Inc.	治疗与ras突变相关的癌症的方法
WO2016144636A1 (en)	2015-03-06	2016-09-15	Beyondspring Pharmaceuticals, Inc.	Method of treating a brain tumor
EP3334726B1 (en)	2015-07-13	2022-03-16	Beyondspring Pharmaceuticals, Inc.	Plinabulin compositions
US10912748B2 (en)	2016-02-08	2021-02-09	Beyondspring Pharmaceuticals, Inc.	Compositions containing tucaresol or its analogs
CN109475524A (zh)	2016-06-06	2019-03-15	万春药业公司	用于减少中性粒细胞减少症的组合物和方法
WO2018129381A1 (en)	2017-01-06	2018-07-12	Beyondspring Pharmaceuticals, Inc.	Tubulin binding compounds and therapeutic use thereof
KR20190109479A (ko)	2017-02-01	2019-09-25	비욘드스프링 파마수티컬스, 인코포레이티드.	호중구감소증의 감소 방법
WO2019147615A1 (en)	2018-01-24	2019-08-01	Beyondspring Pharmaceuticals, Inc.	Composition and method for reducing thrombocytopenia via the administration of plinabulin
EP4319751A4 (en)	2021-04-09	2025-02-26	Beyondspring Pharmaceuticals, Inc.	THERAPEUTIC COMPOSITIONS AND METHODS FOR THE TREATING OF TUMORS

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5663179A (en) *	1992-07-10	1997-09-02	Laboratoires Glaxo Sa	Certain isoquinoline derivatives having anti-tumor properties
GB9217331D0 (en) *	1992-08-14	1992-09-30	Xenova Ltd	Pharmaceutical compounds

1994
- 1994-12-23 GB GBGB9426224.3A patent/GB9426224D0/en active Pending
1995
- 1995-12-21 ZA ZA9510909A patent/ZA9510909B/xx unknown
- 1995-12-22 WO PCT/GB1995/003027 patent/WO1996020190A1/en not_active Ceased
- 1995-12-22 CN CN95197672A patent/CN1175253A/zh active Pending
- 1995-12-22 NZ NZ297847A patent/NZ297847A/en unknown
- 1995-12-22 CA CA002207500A patent/CA2207500A1/en not_active Abandoned
- 1995-12-22 BR BR9510410-0A patent/BR9510410A/pt not_active Application Discontinuation
- 1995-12-22 EP EP95941797A patent/EP0799222A1/en not_active Withdrawn
- 1995-12-22 HU HU9800398A patent/HUT77943A/hu unknown
- 1995-12-22 PL PL95320916A patent/PL320916A1/xx unknown
- 1995-12-22 SK SK836-97A patent/SK83697A3/sk unknown
- 1995-12-22 CZ CZ971900A patent/CZ190097A3/cs unknown
- 1995-12-22 IL IL11652595A patent/IL116525A0/xx unknown
- 1995-12-22 FI FI972660A patent/FI972660L/fi unknown
- 1995-12-22 JP JP8520301A patent/JPH10511384A/ja active Pending
- 1995-12-22 AU AU43100/96A patent/AU698828B2/en not_active Ceased
- 1995-12-23 TW TW084113836A patent/TW358094B/zh active
1997
- 1997-06-11 BG BG101602A patent/BG101602A/xx unknown
- 1997-06-23 NO NO972937A patent/NO972937L/no unknown

Also Published As

Publication number	Publication date
FI972660A0 (fi)	1997-06-19
TW358094B (en)	1999-05-11
IL116525A0 (en)	1996-03-31
AU698828B2 (en)	1998-11-05
EP0799222A1 (en)	1997-10-08
CZ190097A3 (cs)	1998-01-14
CN1175253A (zh)	1998-03-04
JPH10511384A (ja)	1998-11-04
FI972660A7 (fi)	1997-08-22
NZ297847A (en)	1999-04-29
BG101602A (en)	1998-02-27
CA2207500A1 (en)	1996-07-04
NO972937D0 (no)	1997-06-23
ZA9510909B (en)	1996-08-30
PL320916A1 (en)	1997-11-10
AU4310096A (en)	1996-07-19
WO1996020190A1 (en)	1996-07-04
GB9426224D0 (en)	1995-02-22
FI972660L (fi)	1997-08-22
HUT77943A (hu)	1998-12-28
BR9510410A (pt)	1999-09-08
SK83697A3 (en)	1998-05-06

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