NO972937L - Farmasöytiske piperazinforbindelser - Google Patents
Farmasöytiske piperazinforbindelserInfo
- Publication number
- NO972937L NO972937L NO972937A NO972937A NO972937L NO 972937 L NO972937 L NO 972937L NO 972937 A NO972937 A NO 972937A NO 972937 A NO972937 A NO 972937A NO 972937 L NO972937 L NO 972937L
- Authority
- NO
- Norway
- Prior art keywords
- phenyl
- ethyl
- dimethoxy
- tetrahydro
- piperazinylidene
- Prior art date
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
- CTGLWZUKIQINSP-PPUHNOCVSA-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-[[(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=C1)=CC=C1\C=C(C(N1C)=O)/NC(=O)\C1=C\C1=CC[C@@H](C(C)=C)CC1 CTGLWZUKIQINSP-PPUHNOCVSA-N 0.000 claims description 2
- KRFVGUOETPXRIL-YZUVMVFVSA-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-pentylidenepiperazin-2-ylidene]methyl]benzamide Chemical compound N1C(=O)C(=C/CCCC)/N(C)C(=O)\C1=C\C1=CC=C(C(=O)NC=2C=CC(CCN3CC4=CC(OC)=C(OC)C=C4CC3)=CC=2)C=C1 KRFVGUOETPXRIL-YZUVMVFVSA-N 0.000 claims description 2
- HFVUKSFBQDAFSU-QMFFVPNOSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-4-[(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=C1)=CC=C1\C=C1/NC(=O)\C(=C\C(C)C)N(C)C1=O HFVUKSFBQDAFSU-QMFFVPNOSA-N 0.000 claims description 2
- JZLKDSRCXREHSD-PXDBBHOGSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-4-[(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/C3=CC=C(C=C3)C(=O)NC3=CC=C(C=C3)CCN3CCC=4C=C(C(=CC=4C3)OC)OC)=CC=C21 JZLKDSRCXREHSD-PXDBBHOGSA-N 0.000 claims description 2
- VQHLKPXPSCDSMT-RFKWEDMZSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-4-[(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/C3=CC=C(C=C3)C(=O)NC3=CC=C(C=C3)CCN3CCC=4C=C(C(=CC=4C3)OC)OC)=CN(C)C2=C1 VQHLKPXPSCDSMT-RFKWEDMZSA-N 0.000 claims description 2
- GMCRSZDLWODSOT-PCNBCNDESA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-4-[(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=C1)=CC=C1\C=C(C(N1C)=O)/NC(=O)\C1=C\C=1C=CN(C)C=1 GMCRSZDLWODSOT-PCNBCNDESA-N 0.000 claims description 2
- DUJBVWHCQLBADN-KUPSEYDISA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-4-[(z)-[(5z)-4-methyl-5-[(3-methyl-1-benzothiophen-2-yl)methylidene]-3,6-dioxopiperazin-2-ylidene]methyl]benzamide Chemical compound S1C2=CC=CC=C2C(C)=C1/C=C(N(C)C1=O)/C(=O)N\C1=C/C(C=C1)=CC=C1C(=O)NC(C=C1)=CC=C1CCN1CCC(C=C(C(=C2)OC)OC)=C2C1 DUJBVWHCQLBADN-KUPSEYDISA-N 0.000 claims description 2
- NFDHQIXYEYAGQS-RCMCUQTLSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-4-[(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=C1)=CC=C1\C=C1/NC(=O)\C(=C\CC(C)(C)C)N(C)C1=O NFDHQIXYEYAGQS-RCMCUQTLSA-N 0.000 claims description 2
- RQKXIXWCIZPXKR-HEZNUULDSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-4-[(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=C1)=CC=C1\C=C(C(N1C)=O)/NC(=O)\C1=C\C=1C=COC=1 RQKXIXWCIZPXKR-HEZNUULDSA-N 0.000 claims description 2
- KOFZHNHTMVCOKO-VANQDGIVSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-4-[(z)-[(5z)-5-[(4-methoxyphenyl)methylidene]-4-methyl-3,6-dioxopiperazin-2-ylidene]methyl]benzamide Chemical compound C1=CC(OC)=CC=C1\C=C(/N(C)C\1=O)C(=O)NC/1=C\C1=CC=C(C(=O)NC=2C=CC(CCN3CC4=CC(OC)=C(OC)C=C4CC3)=CC=2)C=C1 KOFZHNHTMVCOKO-VANQDGIVSA-N 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000004965 chloroalkyl group Chemical group 0.000 claims 1
- JROAEENSASDNBR-DBNHBIGRSA-N n-[4-[2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl]-3-[(z)-[(5z)-5-[(2-hydroxyphenyl)methylidene]-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=CC=C1O JROAEENSASDNBR-DBNHBIGRSA-N 0.000 claims 1
- 239000008024 pharmaceutical diluent Substances 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 27
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 14
- GOUHYARYYWKXHS-UHFFFAOYSA-N 4-formylbenzoic acid Chemical compound OC(=O)C1=CC=C(C=O)C=C1 GOUHYARYYWKXHS-UHFFFAOYSA-N 0.000 description 13
- 239000000460 chlorine Substances 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 12
- 101001017818 Homo sapiens ATP-dependent translocase ABCB1 Proteins 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- 206010028980 Neoplasm Diseases 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 229940127089 cytotoxic agent Drugs 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 238000001953 recrystallisation Methods 0.000 description 9
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- 239000002246 antineoplastic agent Substances 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 229960004679 doxorubicin Drugs 0.000 description 8
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- UHDNUPHSDMOGCR-UHFFFAOYSA-N 3-Formylbenzoic acid Chemical compound OC(=O)C1=CC=CC(C=O)=C1 UHDNUPHSDMOGCR-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 239000002254 cytotoxic agent Substances 0.000 description 6
- 231100000599 cytotoxic agent Toxicity 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 244000052769 pathogen Species 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 238000009825 accumulation Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 229960000975 daunorubicin Drugs 0.000 description 4
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 150000004820 halides Chemical group 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 3
- CBBKKVPJPRZOCM-UHFFFAOYSA-N 1,4-diacetylpiperazine-2,5-dione Chemical compound CC(=O)N1CC(=O)N(C(C)=O)CC1=O CBBKKVPJPRZOCM-UHFFFAOYSA-N 0.000 description 3
- FYDIVWLLJXNXCE-UHFFFAOYSA-N 4-formylbenzoyl chloride Chemical compound ClC(=O)C1=CC=C(C=O)C=C1 FYDIVWLLJXNXCE-UHFFFAOYSA-N 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 3
- 206010001513 AIDS related complex Diseases 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010001986 Amoebic dysentery Diseases 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 208000004554 Leishmaniasis Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 150000008064 anhydrides Chemical group 0.000 description 3
- 230000008499 blood brain barrier function Effects 0.000 description 3
- 210000001218 blood-brain barrier Anatomy 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 230000000973 chemotherapeutic effect Effects 0.000 description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 201000004792 malaria Diseases 0.000 description 3
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- JTHRRMFZHSDGNJ-UHFFFAOYSA-N piperazine-2,3-dione Chemical class O=C1NCCNC1=O JTHRRMFZHSDGNJ-UHFFFAOYSA-N 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 229940032147 starch Drugs 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 201000008827 tuberculosis Diseases 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- MJCOATFQVUUHFN-XFFZJAGNSA-N (3z)-1-acetyl-3-benzylidenepiperazine-2,5-dione Chemical compound O=C1N(C(=O)C)CC(=O)N\C1=C/C1=CC=CC=C1 MJCOATFQVUUHFN-XFFZJAGNSA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 2
- ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 description 2
- LGLVQYWIIFXBTD-UHFFFAOYSA-N 6-benzyl-1-methylpiperazine-2,5-dione Chemical compound O=C1NCC(=O)N(C)C1CC1=CC=CC=C1 LGLVQYWIIFXBTD-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 2
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 2
- OJGMBLNIHDZDGS-UHFFFAOYSA-N N-Ethylaniline Chemical compound CCNC1=CC=CC=C1 OJGMBLNIHDZDGS-UHFFFAOYSA-N 0.000 description 2
- 206010034133 Pathogen resistance Diseases 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000223960 Plasmodium falciparum Species 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229940122803 Vinca alkaloid Drugs 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 229940034982 antineoplastic agent Drugs 0.000 description 2
- 239000012911 assay medium Substances 0.000 description 2
- 150000003935 benzaldehydes Chemical class 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- CZFNISFYDPIDNM-UHFFFAOYSA-N n,n-dimethylformamide;oxolane Chemical compound CN(C)C=O.C1CCOC1 CZFNISFYDPIDNM-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 229960001722 verapamil Drugs 0.000 description 2
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 1
- MGFREDWKELGWML-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinolin-2-ium;chloride Chemical compound [Cl-].C1=CC=C2C[NH2+]CCC2=C1 MGFREDWKELGWML-UHFFFAOYSA-N 0.000 description 1
- QEUDTZHHQGKLNV-UHFFFAOYSA-N 1-acetyl-3-benzylidene-4-ethylpiperazine-2,5-dione Chemical compound CCN1C(=O)CN(C(C)=O)C(=O)C1=CC1=CC=CC=C1 QEUDTZHHQGKLNV-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- UPXASELIVPAVIA-GPEZSHSTSA-N 3-[(z)-[(5z)-5-benzylidene-4-[2-(dimethylamino)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 C1C=2C=C(OC)C(OC)=CC=2CCN1CCC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1\C=C(C(N1CCN(C)C)=O)/NC(=O)\C1=C\C1=CC=CC=C1 UPXASELIVPAVIA-GPEZSHSTSA-N 0.000 description 1
- LNRRJKXBZVUZHJ-UHFFFAOYSA-N 3-formylbenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(C=O)=C1 LNRRJKXBZVUZHJ-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- NMHDEMMOFNSQES-UHFFFAOYSA-N 4-(3-bromopropyl)benzoic acid Chemical compound OC(=O)C1=CC=C(CCCBr)C=C1 NMHDEMMOFNSQES-UHFFFAOYSA-N 0.000 description 1
- CQQSQBRPAJSTFB-UHFFFAOYSA-N 4-(bromomethyl)benzoic acid Chemical compound OC(=O)C1=CC=C(CBr)C=C1 CQQSQBRPAJSTFB-UHFFFAOYSA-N 0.000 description 1
- QWBAWIVAZGDFRA-LPIHMFRFSA-N 4-[(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 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=C1Cl QWBAWIVAZGDFRA-LPIHMFRFSA-N 0.000 description 1
- NIRCAUPPZAUKDX-UHFFFAOYSA-N 5-benzyl-2-[[4-(3-chlorophenyl)piperazin-1-yl]methyl]-6-methylpyridazin-3-one Chemical compound O=C1C=C(CC=2C=CC=CC=2)C(C)=NN1CN(CC1)CCN1C1=CC=CC(Cl)=C1 NIRCAUPPZAUKDX-UHFFFAOYSA-N 0.000 description 1
- SHOWAGCIRTUYNA-UHFFFAOYSA-N 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline;hydron;chloride Chemical compound [Cl-].C1C[NH2+]CC2=C1C=C(OC)C(OC)=C2 SHOWAGCIRTUYNA-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- MNQZXJOMYWMBOU-VKHMYHEASA-N D-glyceraldehyde Chemical compound OC[C@@H](O)C=O MNQZXJOMYWMBOU-VKHMYHEASA-N 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 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 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229910020889 NaBH3 Inorganic materials 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 229910006124 SOCl2 Inorganic materials 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 239000003817 anthracycline antibiotic agent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000001555 benzenes Chemical group 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical class CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000013505 freshwater Substances 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
- 230000014509 gene expression Effects 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 229960004393 lidocaine hydrochloride Drugs 0.000 description 1
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002790 naphthalenes Chemical group 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 229940085033 nolvadex Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 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)
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 (cs) |
| JP (1) | JPH10511384A (cs) |
| CN (1) | CN1175253A (cs) |
| AU (1) | AU698828B2 (cs) |
| BG (1) | BG101602A (cs) |
| BR (1) | BR9510410A (cs) |
| CA (1) | CA2207500A1 (cs) |
| CZ (1) | CZ190097A3 (cs) |
| FI (1) | FI972660A7 (cs) |
| GB (1) | GB9426224D0 (cs) |
| HU (1) | HUT77943A (cs) |
| IL (1) | IL116525A0 (cs) |
| NO (1) | NO972937L (cs) |
| NZ (1) | NZ297847A (cs) |
| PL (1) | PL320916A1 (cs) |
| SK (1) | SK83697A3 (cs) |
| TW (1) | TW358094B (cs) |
| WO (1) | WO1996020190A1 (cs) |
| ZA (1) | ZA9510909B (cs) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9717576D0 (en) * | 1997-08-19 | 1997-10-22 | Xenova Ltd | Pharmaceutical compounds |
| ZA979329B (en) * | 1996-10-18 | 1999-04-19 | Xenova Ltd | Pharmaceutical compounds |
| GB9708805D0 (en) | 1997-05-01 | 1997-06-25 | Smithkline Beecham Plc | Compounds |
| GB9810876D0 (en) | 1998-05-20 | 1998-07-22 | Smithkline Beecham Plc | Compounds |
| AP2001002114A0 (en) | 1998-10-08 | 2001-06-30 | Smithkline Beecham Plc | Tetrahydrobenzazepine derivatives useful as modulators of dopamine D3 receptors (antipsychotic agents). |
| BRPI0017067B8 (pt) * | 2000-01-18 | 2021-05-25 | Beyondspring Pharmaceuticals Inc | inibidor de divisão de célula, desidrogenase, método para a produção de um inibidor de divisão de célula e composto |
| CA2453050A1 (en) | 2000-09-06 | 2002-03-14 | A.P. 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 |
| ES2295695T3 (es) | 2002-08-02 | 2008-04-16 | Nereus Pharmaceuticals, Inc. | Deshidrofenilahistinas y sus analogos y la sintesis de deshidrofenilahistinas y sus analogos. |
| 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 |
| CA2978679A1 (en) | 2015-03-06 | 2016-09-15 | Beyondspring Pharmaceuticals, Inc. | Method of treating a brain tumor |
| SG11201707127VA (en) | 2015-03-06 | 2017-09-28 | Beyondspring Pharmaceuticals Inc | Method of treating cancer associated with a ras mutation |
| SG10202108194XA (en) | 2015-07-13 | 2021-09-29 | Beyondspring Pharmaceuticals Inc | Plinabulin compositions |
| RU2753543C1 (ru) | 2016-02-08 | 2021-08-17 | Бейондспринг Фармасьютикалс, Инк. | Композиции, содержащие тукаресол или его аналоги |
| CN118304304A (zh) | 2016-06-06 | 2024-07-09 | 大连万春布林医药有限公司 | 用于减少中性粒细胞减少症的组合物和方法 |
| EP3565812B1 (en) | 2017-01-06 | 2023-12-27 | Beyondspring Pharmaceuticals, Inc. | Tubulin binding compounds and therapeutic use thereof |
| CN110381938A (zh) | 2017-02-01 | 2019-10-25 | 大连万春布林医药有限公司 | 减少中性粒细胞缺乏症的方法 |
| US11786523B2 (en) | 2018-01-24 | 2023-10-17 | Beyondspring Pharmaceuticals, Inc. | Composition and method for reducing thrombocytopenia |
| US20240197723A1 (en) | 2021-04-09 | 2024-06-20 | Beyondspring Pharmaceuticals, Inc. | Therapeutic compositions and methods for treating tumors |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0649410B1 (en) * | 1992-07-10 | 1997-05-02 | Laboratoires Glaxo Sa | Anilide derivatives |
| 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 HU HU9800398A patent/HUT77943A/hu unknown
- 1995-12-22 CA CA002207500A patent/CA2207500A1/en not_active Abandoned
- 1995-12-22 CN CN95197672A patent/CN1175253A/zh active Pending
- 1995-12-22 WO PCT/GB1995/003027 patent/WO1996020190A1/en not_active Application Discontinuation
- 1995-12-22 NZ NZ297847A patent/NZ297847A/en unknown
- 1995-12-22 BR BR9510410-0A patent/BR9510410A/pt not_active Application Discontinuation
- 1995-12-22 IL IL11652595A patent/IL116525A0/xx unknown
- 1995-12-22 CZ CZ971900A patent/CZ190097A3/cs unknown
- 1995-12-22 SK SK836-97A patent/SK83697A3/sk unknown
- 1995-12-22 PL PL95320916A patent/PL320916A1/xx unknown
- 1995-12-22 FI FI972660A patent/FI972660A7/fi unknown
- 1995-12-22 AU AU43100/96A patent/AU698828B2/en not_active Ceased
- 1995-12-22 JP JP8520301A patent/JPH10511384A/ja active Pending
- 1995-12-22 EP EP95941797A patent/EP0799222A1/en not_active Withdrawn
- 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 |
|---|---|
| NZ297847A (en) | 1999-04-29 |
| BG101602A (en) | 1998-02-27 |
| CA2207500A1 (en) | 1996-07-04 |
| NO972937D0 (no) | 1997-06-23 |
| CZ190097A3 (cs) | 1998-01-14 |
| EP0799222A1 (en) | 1997-10-08 |
| ZA9510909B (en) | 1996-08-30 |
| HUT77943A (hu) | 1998-12-28 |
| BR9510410A (pt) | 1999-09-08 |
| WO1996020190A1 (en) | 1996-07-04 |
| FI972660A0 (fi) | 1997-06-19 |
| JPH10511384A (ja) | 1998-11-04 |
| FI972660L (fi) | 1997-08-22 |
| TW358094B (en) | 1999-05-11 |
| CN1175253A (zh) | 1998-03-04 |
| PL320916A1 (en) | 1997-11-10 |
| AU698828B2 (en) | 1998-11-05 |
| GB9426224D0 (en) | 1995-02-22 |
| IL116525A0 (en) | 1996-03-31 |
| FI972660A7 (fi) | 1997-08-22 |
| AU4310096A (en) | 1996-07-19 |
| SK83697A3 (en) | 1998-05-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO972937L (no) | Farmasöytiske piperazinforbindelser | |
| WO2023280182A1 (zh) | 作为kat6抑制剂的化合物 | |
| JP2010514689A (ja) | 癌、炎症およびウイルス感染症の処置のためのｃｄｋ阻害剤としてのヘテロアリール−ヘテロアリール化合物 | |
| JP6731917B2 (ja) | Ｄｐｐ−４阻害剤としてのベンゼン縮合６員環誘導体およびその使用 | |
| CA3059255A1 (en) | Inhibitors of short-chain dehydrogenase activity for treating coronary disorders | |
| CN102875560A (zh) | 5-取代粉防己碱类化合物及其在制备抗癌药增敏剂中的用途 | |
| US11834432B2 (en) | Substituted amino six-membered nitric heterocyclic ring compound and preparation and use thereof | |
| WO2004060871A1 (de) | Indol-phenylsulfonamid-derivate als ppar-delta aktivierende verbindungen | |
| EP0799210B1 (en) | Piperazine-2,5-dione derivatives as modulators of multidrug resistance | |
| CN114436975B (zh) | 2-三氟甲基-4-氨基喹唑啉类化合物及其应用 | |
| CN110023310B (zh) | 用于调节激酶级联的联芳组合物和方法 | |
| CN112243437B (zh) | 含丙烯酰基的核转运调节剂及其用途 | |
| WO2011111675A1 (ja) | 新規インドール誘導体 | |
| WO2004069834A1 (ja) | 三環性化合物、その製造方法および用途 | |
| KR20220158228A (ko) | Nr2f6 조절을 위한 헤테로시클릭 화합물 | |
| WO2007004733A1 (ja) | ペルオキシソーム増殖剤活性化受容体δの活性化剤 | |
| JP2022552231A (ja) | Ａｔｆ６モジュレーターおよびその使用 | |
| Srinivas et al. | Design and synthesis of quinoxaline-piperazine-pyrazolo conjugates as VEGFR-2 targeting agents and ADMET studies | |
| CN112010789A (zh) | 乙烯基磺酰胺或乙烯基酰胺类化合物及其制备方法和用途 | |
| CN104016942B (zh) | 噻唑啉酮类衍生物及其药物组合物与应用 | |
| CN102516066B (zh) | Ostopanic acid类似物及制备方法及用途 | |
| CN115260194B (zh) | 新型egfr降解剂 | |
| JPH0543544A (ja) | インドール誘導体およびそれらを有効成分とする抗癌剤耐性克服物質 | |
| US12297193B2 (en) | PTPN2/PTP1B degrader and therapeutic method thereof | |
| CN112480100B (zh) | 吡咯烷酮衍生物 |