ES2870203T3 - Compuesto derivado tricíclico, método para prepararlo y composición farmacéutica que comprende el mismo - Google Patents

Info

Publication number

ES2870203T3

ES2870203T3 ES16807741T ES16807741T ES2870203T3 ES 2870203 T3 ES2870203 T3 ES 2870203T3 ES 16807741 T ES16807741 T ES 16807741T ES 16807741 T ES16807741 T ES 16807741T ES 2870203 T3 ES2870203 T3 ES 2870203T3

Authority

ES

Spain

Prior art keywords

methyl

piperazin

naphthyridin

oxo

hexahydrobenzo

Prior art date

2015-06-09

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

Active

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 224
• 238000000034 method Methods 0.000 title claims description 32
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 25
• 150000003839 salts Chemical class 0.000 claims abstract description 42
• 125000005843 halogen group Chemical group 0.000 claims abstract description 25
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 24
• 230000003287 optical effect Effects 0.000 claims abstract description 24
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 18
• 125000001424 substituent group Chemical group 0.000 claims abstract description 18
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims abstract description 14
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims abstract description 14
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims abstract description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 14
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 12
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 9
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract description 8
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical group C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims abstract description 7
• FGFBEHFJSQBISW-UHFFFAOYSA-N 1h-cyclopenta[b]pyridine Chemical group C1=CNC2=CC=CC2=C1 FGFBEHFJSQBISW-UHFFFAOYSA-N 0.000 claims abstract description 7
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 claims abstract description 7
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims abstract description 7
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims abstract description 7
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims abstract description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 7
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims abstract description 7
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims abstract description 7
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims abstract description 7
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical group C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims abstract description 7
• 229930192474 thiophene Chemical group 0.000 claims abstract description 7
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims abstract description 5
• YRTCKZIKGWZNCU-UHFFFAOYSA-N furo[3,2-b]pyridine Chemical compound C1=CC=C2OC=CC2=N1 YRTCKZIKGWZNCU-UHFFFAOYSA-N 0.000 claims abstract description 5
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims abstract description 5
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract 15
• 238000006243 chemical reaction Methods 0.000 claims description 102
• -1 benisoxazolidine Chemical compound 0.000 claims description 95
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 69
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 60
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 33
• 239000000203 mixture Substances 0.000 claims description 30
• 102100037664 Poly [ADP-ribose] polymerase tankyrase-1 Human genes 0.000 claims description 27
• 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 claims description 25
• 101710129670 Poly [ADP-ribose] polymerase tankyrase-1 Proteins 0.000 claims description 25
• 230000000694 effects Effects 0.000 claims description 24
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 24
• 238000011282 treatment Methods 0.000 claims description 24
• 102100037477 Poly [ADP-ribose] polymerase tankyrase-2 Human genes 0.000 claims description 23
• 101710129674 Poly [ADP-ribose] polymerase tankyrase-2 Proteins 0.000 claims description 23
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 21
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 21
• 201000010099 disease Diseases 0.000 claims description 21
• 238000002360 preparation method Methods 0.000 claims description 17
• 125000006239 protecting group Chemical group 0.000 claims description 15
• 206010028980 Neoplasm Diseases 0.000 claims description 13
• 230000002265 prevention Effects 0.000 claims description 13
• 230000004770 neurodegeneration Effects 0.000 claims description 12
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 11
• 201000011510 cancer Diseases 0.000 claims description 11
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 10
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 10
• 229910052739 hydrogen Inorganic materials 0.000 claims description 10
• WTYLPQUOPMMOQW-UHFFFAOYSA-N 6h-1,6-naphthyridin-5-one Chemical compound C1=CC=C2C(O)=NC=CC2=N1 WTYLPQUOPMMOQW-UHFFFAOYSA-N 0.000 claims description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
• 239000003054 catalyst Substances 0.000 claims description 9
• 239000003153 chemical reaction reagent Substances 0.000 claims description 9
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 9
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 8
• 208000001132 Osteoporosis Diseases 0.000 claims description 8
• 238000007112 amidation reaction Methods 0.000 claims description 8
• 238000005576 amination reaction Methods 0.000 claims description 8
• 238000005859 coupling reaction Methods 0.000 claims description 8
• 239000003814 drug Substances 0.000 claims description 8
• 229910052751 metal Inorganic materials 0.000 claims description 7
• 239000002184 metal Substances 0.000 claims description 7
• 229910052763 palladium Inorganic materials 0.000 claims description 7
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• 208000002193 Pain Diseases 0.000 claims description 6
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 6
• 239000007864 aqueous solution Substances 0.000 claims description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• 208000029028 brain injury Diseases 0.000 claims description 6
• 238000010511 deprotection reaction Methods 0.000 claims description 6
• 208000004296 neuralgia Diseases 0.000 claims description 6
• 208000021722 neuropathic pain Diseases 0.000 claims description 6
• PVNIIMVLHYAWGP-UHFFFAOYSA-N nicotinic acid Natural products OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 6
• 125000003118 aryl group Chemical group 0.000 claims description 5
• 230000000302 ischemic effect Effects 0.000 claims description 5
• 235000001968 nicotinic acid Nutrition 0.000 claims description 5
• 239000011664 nicotinic acid Substances 0.000 claims description 5
• 229960003512 nicotinic acid Drugs 0.000 claims description 5
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
• 239000003638 chemical reducing agent Substances 0.000 claims description 4
• 230000026030 halogenation Effects 0.000 claims description 4
• 238000005658 halogenation reaction Methods 0.000 claims description 4
• 201000008482 osteoarthritis Diseases 0.000 claims description 4
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 3
• ITAWEZOLJMRDPN-UHFFFAOYSA-N 8-[[4-[4-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]-2,3,4,4a,6,6a,7,8,9,10,10a,10b-dodecahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C1CC2C(C3CCC(CC3NC2=O)CN4CCN(CC4)C5=CC=C(C=C5)C(F)(F)F)NC1 ITAWEZOLJMRDPN-UHFFFAOYSA-N 0.000 claims description 3
• 208000024827 Alzheimer disease Diseases 0.000 claims description 3
• 208000000094 Chronic Pain Diseases 0.000 claims description 3
• 208000023105 Huntington disease Diseases 0.000 claims description 3
• 206010021143 Hypoxia Diseases 0.000 claims description 3
• 208000028389 Nerve injury Diseases 0.000 claims description 3
• 208000018737 Parkinson disease Diseases 0.000 claims description 3
• 208000006011 Stroke Diseases 0.000 claims description 3
• 208000005298 acute pain Diseases 0.000 claims description 3
• KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 3
• 230000001684 chronic effect Effects 0.000 claims description 3
• 206010015037 epilepsy Diseases 0.000 claims description 3
• 239000001257 hydrogen Substances 0.000 claims description 3
• 230000007954 hypoxia Effects 0.000 claims description 3
• 208000014674 injury Diseases 0.000 claims description 3
• 230000008764 nerve damage Effects 0.000 claims description 3
• 238000006722 reduction reaction Methods 0.000 claims description 3
• 201000000980 schizophrenia Diseases 0.000 claims description 3
• 230000008733 trauma Effects 0.000 claims description 3
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 2
• XWXPRCDFFCVMNT-UHFFFAOYSA-N 1,3-thiazole-5-carbonitrile Chemical compound N#CC1=CN=CS1 XWXPRCDFFCVMNT-UHFFFAOYSA-N 0.000 claims description 2
• XSNYVOJACDGFLR-UHFFFAOYSA-N 1-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-6,7-dihydro-5H-cyclopenta[c]pyridine-4-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=NC=C(C2=C1CCC2)C#N XSNYVOJACDGFLR-UHFFFAOYSA-N 0.000 claims description 2
• PNKMESFIJLMUPE-UHFFFAOYSA-N 10-ethoxy-8-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC=CC=C1 PNKMESFIJLMUPE-UHFFFAOYSA-N 0.000 claims description 2
• TZZRDVDRZUOVAO-UHFFFAOYSA-N 10-ethoxy-8-[(4-pyrimidin-2-ylpiperazin-1-yl)methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC=CC=N1 TZZRDVDRZUOVAO-UHFFFAOYSA-N 0.000 claims description 2
• PLWAGTSZPNUMLQ-UHFFFAOYSA-N 10-ethoxy-8-[[4-(3-fluoropyridin-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC=CC=C1F PLWAGTSZPNUMLQ-UHFFFAOYSA-N 0.000 claims description 2
• IHCRELQHDBWYSA-UHFFFAOYSA-N 10-ethoxy-8-[[4-(4-fluoro-2-methylphenyl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=C(C=C(C=C1)F)C IHCRELQHDBWYSA-UHFFFAOYSA-N 0.000 claims description 2
• FBXCTPCNOPCNCQ-UHFFFAOYSA-N 10-ethoxy-8-[[4-(5-fluoropyridin-2-yl)-2-methylpiperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1C(CN(CC1)C1=NC=C(C=C1)F)C FBXCTPCNOPCNCQ-UHFFFAOYSA-N 0.000 claims description 2
• WGHOJKMBGQOFJV-UHFFFAOYSA-N 10-ethoxy-8-[[4-(5-fluoropyridin-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC=C(C=C1)F WGHOJKMBGQOFJV-UHFFFAOYSA-N 0.000 claims description 2
• KYWGRBPHNDPXDG-UHFFFAOYSA-N 10-ethoxy-8-[[4-(5-fluoropyrimidin-2-yl)-2-methylpiperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1C(CN(CC1)C1=NC=C(C=N1)F)C KYWGRBPHNDPXDG-UHFFFAOYSA-N 0.000 claims description 2
• YMKFYWBVYMDIIA-UHFFFAOYSA-N 10-ethoxy-8-[[4-(5-fluoropyrimidin-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC=C(C=N1)F YMKFYWBVYMDIIA-UHFFFAOYSA-N 0.000 claims description 2
• VPRNMVRURRGXBM-UHFFFAOYSA-N 10-ethoxy-8-[[4-(6-fluoropyridin-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC(=CC=C1)F VPRNMVRURRGXBM-UHFFFAOYSA-N 0.000 claims description 2
• XXSHTFPXOLBIAB-UHFFFAOYSA-N 10-ethoxy-8-[[4-[6-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC(=CC=C1)C(F)(F)F XXSHTFPXOLBIAB-UHFFFAOYSA-N 0.000 claims description 2
• CTYGNSYLURCWAI-UHFFFAOYSA-N 10-fluoro-8-[(4-pyrazin-2-ylpiperazin-1-yl)methyl]-2,3,4,4a,6,6a,7,8,9,10,10a,10b-dodecahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C1CC2C(C3C(CC(CC3F)CN4CCN(CC4)C5=NC=CN=C5)NC2=O)NC1 CTYGNSYLURCWAI-UHFFFAOYSA-N 0.000 claims description 2
• ZGMGCVMYDSXGAA-UHFFFAOYSA-N 10-fluoro-8-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC=CC=C1 ZGMGCVMYDSXGAA-UHFFFAOYSA-N 0.000 claims description 2
• YUJOEMXQQWMFHW-UHFFFAOYSA-N 10-fluoro-8-[[4-(2-fluoro-4-nitrophenyl)piperazin-1-yl]methyl]-2,3,4,4a,6,6a,7,8,9,10,10a,10b-dodecahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C1CC2C(C3C(CC(CC3F)CN4CCN(CC4)C5=C(C=C(C=C5)[N+](=O)[O-])F)NC2=O)NC1 YUJOEMXQQWMFHW-UHFFFAOYSA-N 0.000 claims description 2
• XFINVNDWTKKVHT-UHFFFAOYSA-N 10-fluoro-8-[[4-(3-methylpyridin-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC=CC=C1C XFINVNDWTKKVHT-UHFFFAOYSA-N 0.000 claims description 2
• XMTDEEBBKFYDOX-UHFFFAOYSA-N 10-fluoro-8-[[4-(4-fluoro-2-methylphenyl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=C(C=C(C=C1)F)C XMTDEEBBKFYDOX-UHFFFAOYSA-N 0.000 claims description 2
• GXLCEYYXBWDRJO-UHFFFAOYSA-N 10-fluoro-8-[[4-(5-fluoropyridin-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC=C(C=C1)F GXLCEYYXBWDRJO-UHFFFAOYSA-N 0.000 claims description 2
• ZSPJQXPVYZVVOP-UHFFFAOYSA-N 10-methoxy-8-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound COC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC=CC=C1 ZSPJQXPVYZVVOP-UHFFFAOYSA-N 0.000 claims description 2
• QAPZBMSTSFDWBK-UHFFFAOYSA-N 10-methoxy-8-[[4-(3-methylpyridin-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound COC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC=CC=C1C QAPZBMSTSFDWBK-UHFFFAOYSA-N 0.000 claims description 2
• PJVQPPHJEYPUDB-UHFFFAOYSA-N 2,3-dihydrofuro[3,2-b]pyridine Chemical compound C1=CC=C2OCCC2=N1 PJVQPPHJEYPUDB-UHFFFAOYSA-N 0.000 claims description 2
• GWJWBXXEWCBTSU-UHFFFAOYSA-N 2-[4-(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridine-8-carbonyl)piperazin-1-yl]-1,3-thiazole-4-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)C(=O)N1CCN(CC1)C=1SC=C(N=1)C#N GWJWBXXEWCBTSU-UHFFFAOYSA-N 0.000 claims description 2
• TWZQEBQCXWLACN-UHFFFAOYSA-N 2-[4-(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridine-8-carbonyl)piperazin-1-yl]-1,3-thiazole-5-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)C(=O)N1CCN(CC1)C=1SC(=CN=1)C#N TWZQEBQCXWLACN-UHFFFAOYSA-N 0.000 claims description 2
• LZPDYLRFIGMNHY-UHFFFAOYSA-N 2-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-1,3-oxazole-4-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C=1OC=C(N=1)C#N LZPDYLRFIGMNHY-UHFFFAOYSA-N 0.000 claims description 2
• VOQLJAINULFPEC-UHFFFAOYSA-N 2-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-1,3-thiazole-4-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C=1SC=C(N=1)C#N VOQLJAINULFPEC-UHFFFAOYSA-N 0.000 claims description 2
• ONEIDYKHPRMDQO-UHFFFAOYSA-N 2-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-1,3-thiazole-5-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C=1SC(=CN=1)C#N ONEIDYKHPRMDQO-UHFFFAOYSA-N 0.000 claims description 2
• PITKHMJQSBHPED-UHFFFAOYSA-N 2-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-3-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=C(C#N)C=CC=N1 PITKHMJQSBHPED-UHFFFAOYSA-N 0.000 claims description 2
• CCWTWPIDXUGAKX-UHFFFAOYSA-N 2-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-4-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C=1C=C(C#N)C=CN=1 CCWTWPIDXUGAKX-UHFFFAOYSA-N 0.000 claims description 2
• IZESLSBCDWQCRJ-MRXNPFEDSA-N 2-fluoro-4-[(2R)-2-methyl-4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)N1[C@@H](CN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1)C IZESLSBCDWQCRJ-MRXNPFEDSA-N 0.000 claims description 2
• IZESLSBCDWQCRJ-INIZCTEOSA-N 2-fluoro-4-[(2S)-2-methyl-4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)N1[C@H](CN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1)C IZESLSBCDWQCRJ-INIZCTEOSA-N 0.000 claims description 2
• SOASXIFPFLUWRH-MRXNPFEDSA-N 2-fluoro-4-[(3R)-3-methyl-4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)N1C[C@H](N(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1)C SOASXIFPFLUWRH-MRXNPFEDSA-N 0.000 claims description 2
• SOASXIFPFLUWRH-INIZCTEOSA-N 2-fluoro-4-[(3S)-3-methyl-4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)N1C[C@@H](N(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1)C SOASXIFPFLUWRH-INIZCTEOSA-N 0.000 claims description 2
• SOASXIFPFLUWRH-UHFFFAOYSA-N 2-fluoro-4-[3-methyl-4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)N1CC(N(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1)C SOASXIFPFLUWRH-UHFFFAOYSA-N 0.000 claims description 2
• BJXGUSFDTYIQIN-UHFFFAOYSA-N 2-fluoro-4-[4-[(10-methoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)OC BJXGUSFDTYIQIN-UHFFFAOYSA-N 0.000 claims description 2
• FJOFREJOLJFMNF-UHFFFAOYSA-N 2-fluoro-4-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 FJOFREJOLJFMNF-UHFFFAOYSA-N 0.000 claims description 2
• OXULFDKDMPHAFP-UHFFFAOYSA-N 2-fluoro-4-[8-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)N1CC2CCC(C1)N2CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 OXULFDKDMPHAFP-UHFFFAOYSA-N 0.000 claims description 2
• FBIGNDFZRCUSDQ-UHFFFAOYSA-N 2-methyl-4-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound CC1=C(C#N)C=CC(=C1)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 FBIGNDFZRCUSDQ-UHFFFAOYSA-N 0.000 claims description 2
• BNWLAJWZQLNPJG-UHFFFAOYSA-N 3,5-difluoro-4-[4-[(10-methoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=C(C=1N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)OC)F BNWLAJWZQLNPJG-UHFFFAOYSA-N 0.000 claims description 2
• MCCBTXRJCXUYOY-UHFFFAOYSA-N 3,5-difluoro-4-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=C(C=1N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1)F MCCBTXRJCXUYOY-UHFFFAOYSA-N 0.000 claims description 2
• CINNRILLZCDNOZ-UHFFFAOYSA-N 3-acetyl-4-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound C(C)(=O)C=1C=C(C#N)C=CC=1N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 CINNRILLZCDNOZ-UHFFFAOYSA-N 0.000 claims description 2
• HPNPGKDJVPSETA-UHFFFAOYSA-N 3-bromo-4-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound BrC=1C=C(C#N)C=CC=1N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 HPNPGKDJVPSETA-UHFFFAOYSA-N 0.000 claims description 2
• NPOFZKXRQDDDDY-MRXNPFEDSA-N 3-fluoro-4-[(2R)-2-methyl-4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=CC=1N1[C@@H](CN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1)C NPOFZKXRQDDDDY-MRXNPFEDSA-N 0.000 claims description 2
• MWLJLVHPVHBVDL-MRXNPFEDSA-N 3-fluoro-4-[(3R)-3-methyl-4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=CC=1N1C[C@H](N(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1)C MWLJLVHPVHBVDL-MRXNPFEDSA-N 0.000 claims description 2
• MWLJLVHPVHBVDL-INIZCTEOSA-N 3-fluoro-4-[(3S)-3-methyl-4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=CC=1N1C[C@@H](N(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1)C MWLJLVHPVHBVDL-INIZCTEOSA-N 0.000 claims description 2
• MWLJLVHPVHBVDL-UHFFFAOYSA-N 3-fluoro-4-[3-methyl-4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=CC=1N1CC(N(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1)C MWLJLVHPVHBVDL-UHFFFAOYSA-N 0.000 claims description 2
• ZMRSDMLCFJDLKR-UHFFFAOYSA-N 3-fluoro-4-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=CC=1N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 ZMRSDMLCFJDLKR-UHFFFAOYSA-N 0.000 claims description 2
• WEFPHDYTHUNVAM-UHFFFAOYSA-N 3-methoxy-4-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound COC=1C=C(C#N)C=CC=1N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 WEFPHDYTHUNVAM-UHFFFAOYSA-N 0.000 claims description 2
• GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims description 2
• ZEDFNDQAVSBMDX-UHFFFAOYSA-N 4-[4-[(10-ethoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-2-fluoro-N-methylbenzamide Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=CC(=C(C(=O)NC)C=C1)F ZEDFNDQAVSBMDX-UHFFFAOYSA-N 0.000 claims description 2
• SUAJRPKGKHBFPC-UHFFFAOYSA-N 4-[4-[(10-ethoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-2-fluorobenzonitrile Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=CC(=C(C#N)C=C1)F SUAJRPKGKHBFPC-UHFFFAOYSA-N 0.000 claims description 2
• MXMQYIKWXHYYDX-UHFFFAOYSA-N 4-[4-[(10-ethoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-3,5-difluorobenzonitrile Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=C(C=C(C#N)C=C1F)F MXMQYIKWXHYYDX-UHFFFAOYSA-N 0.000 claims description 2
• SHXKQDRLYRXAJU-UHFFFAOYSA-N 4-[4-[(10-ethoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-3-fluorobenzonitrile Chemical compound FC=1C=C(C#N)C=CC=1N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)OCC SHXKQDRLYRXAJU-UHFFFAOYSA-N 0.000 claims description 2
• WSBQUUZVCMHNBF-UHFFFAOYSA-N 4-[4-[(10-ethoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-3-methylbenzonitrile Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=C(C=C(C#N)C=C1)C WSBQUUZVCMHNBF-UHFFFAOYSA-N 0.000 claims description 2
• PJGALROURWRGFT-UHFFFAOYSA-N 4-[4-[(10-ethoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-N,3-dimethylbenzamide Chemical compound CCOC1=C2C(NC(=O)C3=C2NCCC3)=CC(CN2CCN(CC2)C2=C(C)C=C(C=C2)C(=O)NC)=C1 PJGALROURWRGFT-UHFFFAOYSA-N 0.000 claims description 2
• PBVHQDGIPPPUPV-UHFFFAOYSA-N 4-[4-[(10-ethoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-N-ethyl-2-fluorobenzamide Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=CC(=C(C(=O)NCC)C=C1)F PBVHQDGIPPPUPV-UHFFFAOYSA-N 0.000 claims description 2
• MLGRFFDUAPKRQW-UHFFFAOYSA-N 4-[4-[(10-ethoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-N-ethyl-3-methylbenzamide Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=C(C=C(C(=O)NCC)C=C1)C MLGRFFDUAPKRQW-UHFFFAOYSA-N 0.000 claims description 2
• GUAVHSNDCRTVMZ-UHFFFAOYSA-N 4-[4-[(10-ethoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-N-ethylbenzamide Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=CC=C(C(=O)NCC)C=C1 GUAVHSNDCRTVMZ-UHFFFAOYSA-N 0.000 claims description 2
• WEKCQPVMVKJTQD-UHFFFAOYSA-N 4-[4-[(10-fluoro-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-3-methoxybenzonitrile Chemical compound FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=C(C=C(C#N)C=C1)OC WEKCQPVMVKJTQD-UHFFFAOYSA-N 0.000 claims description 2
• MBRBCDCMWKTZBM-UHFFFAOYSA-N 4-[4-[(10-methoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-3-methylbenzonitrile Chemical compound COC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=C(C=C(C#N)C=C1)C MBRBCDCMWKTZBM-UHFFFAOYSA-N 0.000 claims description 2
• VQHKTDOVOZYHCZ-UHFFFAOYSA-N 4-[4-[(10-methoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound COC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=CC=C(C#N)C=C1 VQHKTDOVOZYHCZ-UHFFFAOYSA-N 0.000 claims description 2
• AXAVOVXYAFPCSL-UHFFFAOYSA-N 4-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-2-(trifluoromethyl)benzonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=CC(=C(C#N)C=C1)C(F)(F)F AXAVOVXYAFPCSL-UHFFFAOYSA-N 0.000 claims description 2
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
• IWIRGSJMTCVGQQ-UHFFFAOYSA-N 4-fluoro-2-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC1=CC(=C(C#N)C=C1)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 IWIRGSJMTCVGQQ-UHFFFAOYSA-N 0.000 claims description 2
• RSZFCUWJGDNCGK-UHFFFAOYSA-N 4-methoxy-6-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-3-carbonitrile Chemical compound COC1=CC(=NC=C1C#N)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 RSZFCUWJGDNCGK-UHFFFAOYSA-N 0.000 claims description 2
• OOWRFWSYHOPDLB-UHFFFAOYSA-N 5-[4-(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridine-8-carbonyl)piperazin-1-yl]thiophene-2-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)C(=O)N1CCN(CC1)C1=CC=C(S1)C#N OOWRFWSYHOPDLB-UHFFFAOYSA-N 0.000 claims description 2
• RAPGQTWOPCNSEJ-UHFFFAOYSA-N 5-[4-[(10-fluoro-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-2-carbonitrile Chemical compound FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C=1C=CC(=NC=1)C#N RAPGQTWOPCNSEJ-UHFFFAOYSA-N 0.000 claims description 2
• BRHAGWRGTMVKQA-UHFFFAOYSA-N 5-[4-[(10-fluoro-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]thiophene-2-carbonitrile Chemical compound FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=CC=C(S1)C#N BRHAGWRGTMVKQA-UHFFFAOYSA-N 0.000 claims description 2
• CBRIZHZYFLCPAP-UHFFFAOYSA-N 5-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-1,2,4-thiadiazole-3-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=NC(=NS1)C#N CBRIZHZYFLCPAP-UHFFFAOYSA-N 0.000 claims description 2
• QFIPDHPQCAZUOH-UHFFFAOYSA-N 5-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-1,3,4-oxadiazole-2-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=NN=C(O1)C#N QFIPDHPQCAZUOH-UHFFFAOYSA-N 0.000 claims description 2
• LZKGLICEGUTSDW-UHFFFAOYSA-N 5-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-1,3,4-thiadiazole-2-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=NN=C(S1)C#N LZKGLICEGUTSDW-UHFFFAOYSA-N 0.000 claims description 2
• DBLBOZLZPCJKAH-UHFFFAOYSA-N 5-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyrazine-2-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C=1N=CC(=NC=1)C#N DBLBOZLZPCJKAH-UHFFFAOYSA-N 0.000 claims description 2
• QBLCDAXXROYNNC-UHFFFAOYSA-N 5-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]thiophene-2-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=CC=C(S1)C#N QBLCDAXXROYNNC-UHFFFAOYSA-N 0.000 claims description 2
• ZUXIOPFYSMZLKD-UHFFFAOYSA-N 6-[3-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]-3,8-diazabicyclo[3.2.1]octan-8-yl]pyridine-3-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CC2CCC(C1)N2C1=NC=C(C#N)C=C1 ZUXIOPFYSMZLKD-UHFFFAOYSA-N 0.000 claims description 2
• PSFLDSBRRNQGMG-UHFFFAOYSA-N 6-[4-[(10-ethoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-3-carbonitrile Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC=C(C#N)C=C1 PSFLDSBRRNQGMG-UHFFFAOYSA-N 0.000 claims description 2
• JQJGYBASPJXNIJ-UHFFFAOYSA-N 6-[4-[(10-fluoro-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridazine-3-carbonitrile Chemical compound FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=CC=C(N=N1)C#N JQJGYBASPJXNIJ-UHFFFAOYSA-N 0.000 claims description 2
• XUFWBGKENCGHSD-UHFFFAOYSA-N 6-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridazine-3-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=CC=C(N=N1)C#N XUFWBGKENCGHSD-UHFFFAOYSA-N 0.000 claims description 2
• SLFOPCGYYAWVOV-UHFFFAOYSA-N 6-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-2-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=CC=CC(=N1)C#N SLFOPCGYYAWVOV-UHFFFAOYSA-N 0.000 claims description 2
• GRPXLKXGJAGYSD-UHFFFAOYSA-N 6-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-3-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=NC=C(C#N)C=C1 GRPXLKXGJAGYSD-UHFFFAOYSA-N 0.000 claims description 2
• GXXRJPKTTBCLNF-UHFFFAOYSA-N 6-[8-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridine-3-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1C2CN(CC1CC2)C1=NC=C(C#N)C=C1 GXXRJPKTTBCLNF-UHFFFAOYSA-N 0.000 claims description 2
• FSFKDNPHPFINJD-UHFFFAOYSA-N 8-[(3-pyrazin-2-yl-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound N1=C(C=NC=C1)N1CC2CCC(C1)N2CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 FSFKDNPHPFINJD-UHFFFAOYSA-N 0.000 claims description 2
• ICWAHMDHBIKSJI-UHFFFAOYSA-N 8-[(4-pyrazin-2-ylpiperazin-1-yl)methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound N1=C(C=NC=C1)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 ICWAHMDHBIKSJI-UHFFFAOYSA-N 0.000 claims description 2
• XAYYEWSLLDWCNN-UHFFFAOYSA-N 8-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound N1=C(C=CC=C1)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 XAYYEWSLLDWCNN-UHFFFAOYSA-N 0.000 claims description 2
• DNVWMTSPHCCJCK-KBPBESRZSA-N 8-[[(1S,4S)-5-(6-chloropyridazin-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl]-10-fluoro-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound ClC1=CC=C(N=N1)N1[C@@H]2CN([C@H](C1)C2)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)F DNVWMTSPHCCJCK-KBPBESRZSA-N 0.000 claims description 2
• MEUPGVYNDJKQDV-UHFFFAOYSA-N 8-[[4-(1,2-benzoxazol-5-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound O1N=CC2=C1C=CC(=C2)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 MEUPGVYNDJKQDV-UHFFFAOYSA-N 0.000 claims description 2
• RMXRKPRIWWJAPC-UHFFFAOYSA-N 8-[[4-(2,3-dihydrofuro[2,3-b]pyridin-6-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound O1CCC=2C1=NC(=CC=2)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 RMXRKPRIWWJAPC-UHFFFAOYSA-N 0.000 claims description 2
• REYKGSARKODXFQ-UHFFFAOYSA-N 8-[[4-(2-methyl-1,3-benzoxazol-6-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound CC=1OC2=C(N=1)C=CC(=C2)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 REYKGSARKODXFQ-UHFFFAOYSA-N 0.000 claims description 2
• ORSBXGBOZDSEJT-UHFFFAOYSA-N 8-[[4-(3-methyl-1,2-benzoxazol-5-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound CC1=NOC2=C1C=C(C=C2)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 ORSBXGBOZDSEJT-UHFFFAOYSA-N 0.000 claims description 2
• HMJITMWZHWTWNK-UHFFFAOYSA-N 8-[[4-(4-methoxyphenyl)piperazin-1-yl]methyl]-3,4,4a,6-tetrahydro-2H-benzo[h][1,6]naphthyridin-5-one Chemical compound COC1=CC=C(C=C1)N2CCN(CC2)CC3=CC4=C(C=C3)C5=NCCCC5C(=O)N4 HMJITMWZHWTWNK-UHFFFAOYSA-N 0.000 claims description 2
• WQHHVXNIRJJQKQ-UHFFFAOYSA-N 8-[[4-(5-bromopyridin-2-yl)piperazin-1-yl]methyl]-10-ethoxy-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound BrC=1C=CC(=NC=1)N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)OCC WQHHVXNIRJJQKQ-UHFFFAOYSA-N 0.000 claims description 2
• OBBWKFAMLXSUHC-UHFFFAOYSA-N 8-[[4-(5-chloro-3-fluoropyridin-2-yl)piperazin-1-yl]methyl]-10-ethoxy-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound ClC=1C=C(C(=NC=1)N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)OCC)F OBBWKFAMLXSUHC-UHFFFAOYSA-N 0.000 claims description 2
• LSSDLFDFMUHJML-UHFFFAOYSA-N 8-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]methyl]-10-ethoxy-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound ClC=1C=CC(=NC=1)N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)OCC LSSDLFDFMUHJML-UHFFFAOYSA-N 0.000 claims description 2
• SJYGJUQORXZRIJ-UHFFFAOYSA-N 8-[[4-(5-fluoro-3-methylpyridin-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound FC=1C=C(C(=NC=1)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1)C SJYGJUQORXZRIJ-UHFFFAOYSA-N 0.000 claims description 2
• JFAYZWSBJJISMX-UHFFFAOYSA-N 8-[[4-(5-fluoropyridin-2-yl)piperazin-1-yl]methyl]-10-methoxy-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound FC=1C=CC(=NC=1)N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)OC JFAYZWSBJJISMX-UHFFFAOYSA-N 0.000 claims description 2
• NRDDMPIVXPOIMZ-UHFFFAOYSA-N 8-[[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl]-10-fluoro-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound ClC1=CC=C(N=N1)N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)F NRDDMPIVXPOIMZ-UHFFFAOYSA-N 0.000 claims description 2
• FEJSZHYTJZOZCI-UHFFFAOYSA-N 8-[[4-([1,3]oxazolo[4,5-b]pyridin-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound O1C(=NC2=NC=CC=C21)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 FEJSZHYTJZOZCI-UHFFFAOYSA-N 0.000 claims description 2
• KCKQGUXPHXIAKY-UHFFFAOYSA-N 8-[[4-([1,3]oxazolo[5,4-b]pyridin-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound N1=C(OC2=NC=CC=C21)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 KCKQGUXPHXIAKY-UHFFFAOYSA-N 0.000 claims description 2
• BXKYDIPNRSEYHO-UHFFFAOYSA-N 8-[[4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]methyl]-10-ethoxy-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound CCOc1cc(CN2CCN(CC2)c2ncc(cc2Cl)C(F)(F)F)cc2[nH]c(=O)c3CCCNc3c12 BXKYDIPNRSEYHO-UHFFFAOYSA-N 0.000 claims description 2
• GBEWXEQDDXPZJQ-UHFFFAOYSA-N 8-[[4-[5-(methoxymethyl)pyridin-2-yl]piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound COCC=1C=CC(=NC=1)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 GBEWXEQDDXPZJQ-UHFFFAOYSA-N 0.000 claims description 2
• 206010002383 Angina Pectoris Diseases 0.000 claims description 2
• 201000001320 Atherosclerosis Diseases 0.000 claims description 2
• ZZBBBZFQCDNCQW-HOTGVXAUSA-N FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1[C@@H]2CN([C@H](C1)C2)N1NC=CC=C1 Chemical compound FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1[C@@H]2CN([C@H](C1)C2)N1NC=CC=C1 ZZBBBZFQCDNCQW-HOTGVXAUSA-N 0.000 claims description 2
• 208000031226 Hyperlipidaemia Diseases 0.000 claims description 2
• JGIHYUWTUFLIMS-UHFFFAOYSA-N N-[3-fluoro-4-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]phenyl]propanamide Chemical compound FC=1C=C(C=CC=1N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1)NC(CC)=O JGIHYUWTUFLIMS-UHFFFAOYSA-N 0.000 claims description 2
• BFPLMTPHDFFMTG-UHFFFAOYSA-N [1,3]oxazolo[5,4-b]pyridine Chemical compound C1=CN=C2OC=NC2=C1 BFPLMTPHDFFMTG-UHFFFAOYSA-N 0.000 claims description 2
• 230000000747 cardiac effect Effects 0.000 claims description 2
• 208000029078 coronary artery disease Diseases 0.000 claims description 2
• 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
• 208000010125 myocardial infarction Diseases 0.000 claims description 2
• 230000035939 shock Effects 0.000 claims description 2
• 230000000451 tissue damage Effects 0.000 claims description 2
• 231100000827 tissue damage Toxicity 0.000 claims description 2
• 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 claims 2
• DQVCQZTZEXRNSY-UHFFFAOYSA-N 10-ethoxy-8-[[4-(3-methylpyridin-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC=CC=C1C DQVCQZTZEXRNSY-UHFFFAOYSA-N 0.000 claims 1
• JXQBRNYBIADQDA-UHFFFAOYSA-N 3-chloro-4-[4-[(10-ethoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-N-ethylbenzamide Chemical compound ClC=1C=C(C(=O)NCC)C=CC=1N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)OCC JXQBRNYBIADQDA-UHFFFAOYSA-N 0.000 claims 1
• NILIKCUPTSFMAY-UHFFFAOYSA-N 3-chloro-4-[4-[(10-ethoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-N-methylbenzamide Chemical compound ClC=1C=C(C(=O)NC)C=CC=1N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)OCC NILIKCUPTSFMAY-UHFFFAOYSA-N 0.000 claims 1
• XDCAKBHBFAMHOV-UHFFFAOYSA-N 3-chloro-4-[4-[(10-ethoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound ClC=1C=C(C#N)C=CC=1N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)OCC XDCAKBHBFAMHOV-UHFFFAOYSA-N 0.000 claims 1
• AMWNTQXPBJQZET-ROUUACIJSA-N 3-fluoro-4-[(1S,4S)-5-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=CC=1N1[C@@H]2CN([C@H](C1)C2)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 AMWNTQXPBJQZET-ROUUACIJSA-N 0.000 claims 1
• PZYRHYWULWFGBG-UHFFFAOYSA-N 4-chloro-6-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-3-carbonitrile Chemical compound ClC1=CC(=NC=C1C#N)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 PZYRHYWULWFGBG-UHFFFAOYSA-N 0.000 claims 1
• ZQOOYSDYFDOSOW-UHFFFAOYSA-N 5-chloro-2-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-4-carbonitrile Chemical compound ClC1=CN=C(C=C1C#N)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 ZQOOYSDYFDOSOW-UHFFFAOYSA-N 0.000 claims 1
• DBTLGWQFPVIXTJ-UHFFFAOYSA-N 5-chloro-6-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-3-carbonitrile Chemical compound ClC=1C(=NC=C(C#N)C=1)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 DBTLGWQFPVIXTJ-UHFFFAOYSA-N 0.000 claims 1
• AURCLDMUVVKGCY-IRXDYDNUSA-N 6-[(1S,4S)-5-[(10-fluoro-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyridine-3-carbonitrile Chemical compound FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1[C@@H]2CN([C@H](C1)C2)C1=NC=C(C#N)C=C1 AURCLDMUVVKGCY-IRXDYDNUSA-N 0.000 claims 1
• LBBSYTSQXIKGBX-OALUTQOASA-N 6-[(1S,4S)-5-[(2-oxo-3,4,5,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyridine-3-carbonitrile Chemical compound O=C1NC=2C3=C(NCC=2CC1)C=C(C=C3)CN1[C@@H]2CN([C@H](C1)C2)C1=NC=C(C#N)C=C1 LBBSYTSQXIKGBX-OALUTQOASA-N 0.000 claims 1
• HGJVONCBQFKWRI-UHFFFAOYSA-N 6-[8-[(10-fluoro-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridine-3-carbonitrile Chemical compound FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1C2CN(CC1CC2)C1=NC=C(C#N)C=C1 HGJVONCBQFKWRI-UHFFFAOYSA-N 0.000 claims 1
• UWIOUEAALWYOMW-UHFFFAOYSA-N 6-chloro-4-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-3-carbonitrile Chemical compound ClC1=NC=C(C#N)C(=C1)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 UWIOUEAALWYOMW-UHFFFAOYSA-N 0.000 claims 1
• WPSFTNDXYZENJA-UHFFFAOYSA-N 8-[[3-(6-chloropyridazin-3-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound ClC1=CC=C(N=N1)N1CC2CCC(C1)N2CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 WPSFTNDXYZENJA-UHFFFAOYSA-N 0.000 claims 1
• XKGXGUQJXNJWSC-UHFFFAOYSA-N 8-[[4-(3-chloropyridin-2-yl)piperazin-1-yl]methyl]-10-ethoxy-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound ClC=1C(=NC=CC=1)N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)OCC XKGXGUQJXNJWSC-UHFFFAOYSA-N 0.000 claims 1
• FKWXKKZUUCOCBQ-UHFFFAOYSA-N 8-[[4-(5-bromo-4-methoxypyridin-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound BrC=1C(=CC(=NC=1)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1)OC FKWXKKZUUCOCBQ-UHFFFAOYSA-N 0.000 claims 1
• SKNWKWMXEYWOSA-UHFFFAOYSA-N 8-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]methyl]-10-fluoro-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound ClC=1C=CC(=NC=1)N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)F SKNWKWMXEYWOSA-UHFFFAOYSA-N 0.000 claims 1
• YNEGLOCHVHRKSY-UHFFFAOYSA-N 8-[[4-(6-chloropyridin-2-yl)piperazin-1-yl]methyl]-10-ethoxy-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound ClC1=CC=CC(=N1)N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)OCC YNEGLOCHVHRKSY-UHFFFAOYSA-N 0.000 claims 1
• 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 102
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
• 239000007787 solid Substances 0.000 description 41
• 239000000243 solution Substances 0.000 description 39
• 238000003786 synthesis reaction Methods 0.000 description 37
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
• 230000015572 biosynthetic process Effects 0.000 description 34
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
• 238000005160 1H NMR spectroscopy Methods 0.000 description 29
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 21
• 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 21
• 239000002904 solvent Substances 0.000 description 21
• 102100034905 Protein mono-ADP-ribosyltransferase TIPARP Human genes 0.000 description 20
• 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 18
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 125000000217 alkyl group Chemical group 0.000 description 15
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
• 238000003756 stirring Methods 0.000 description 13
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 12
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
• 230000002411 adverse Effects 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
• 239000002585 base Substances 0.000 description 11
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 210000004027 cell Anatomy 0.000 description 9
• 238000004440 column chromatography Methods 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 239000003960 organic solvent Substances 0.000 description 9
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 8
• 239000012661 PARP inhibitor Substances 0.000 description 8
• 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 8
• UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 8
• 230000002401 inhibitory effect Effects 0.000 description 8
• 239000010410 layer Substances 0.000 description 8
• 229910052799 carbon Inorganic materials 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• 239000012280 lithium aluminium hydride Substances 0.000 description 7
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
• 239000003085 diluting agent Substances 0.000 description 6
• 230000005764 inhibitory process Effects 0.000 description 6
• ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 6
• 229910000027 potassium carbonate Inorganic materials 0.000 description 6
• 230000033616 DNA repair Effects 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• 125000003545 alkoxy group Chemical group 0.000 description 5
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 5
• 125000004093 cyano group Chemical group *C#N 0.000 description 5
• 239000000546 pharmaceutical excipient Substances 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• 108020004414 DNA Proteins 0.000 description 4
• 108010033040 Histones Proteins 0.000 description 4
• JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 4
• MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 4
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• 238000007796 conventional method Methods 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 238000010790 dilution Methods 0.000 description 4
• 239000012895 dilution Substances 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 208000027866 inflammatory disease Diseases 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• 229920006395 saturated elastomer Polymers 0.000 description 4
• 239000011780 sodium chloride Substances 0.000 description 4
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
• 230000000699 topical effect Effects 0.000 description 4
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 230000005778 DNA damage Effects 0.000 description 3
• 231100000277 DNA damage Toxicity 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 206010029719 Nonspecific reaction Diseases 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
• 239000006180 TBST buffer Substances 0.000 description 3
• 108010017601 Tankyrases Proteins 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
• 238000011534 incubation Methods 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 239000002480 mineral oil Substances 0.000 description 3
• 235000010446 mineral oil Nutrition 0.000 description 3
• 239000001301 oxygen Substances 0.000 description 3
• 229910052760 oxygen Inorganic materials 0.000 description 3
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 3
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
• 229910052700 potassium Inorganic materials 0.000 description 3
• 239000011591 potassium Substances 0.000 description 3
• 235000018102 proteins Nutrition 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 239000011541 reaction mixture Substances 0.000 description 3
• 238000010992 reflux Methods 0.000 description 3
• 239000012279 sodium borohydride Substances 0.000 description 3
• 229910000033 sodium borohydride Inorganic materials 0.000 description 3
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 102000055501 telomere Human genes 0.000 description 3
• 108091035539 telomere Proteins 0.000 description 3
• 210000003411 telomere Anatomy 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
• LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
• AVJKDKWRVSSJPK-UHFFFAOYSA-N 1-(4-fluorophenyl)piperazine Chemical compound C1=CC(F)=CC=C1N1CCNCC1 AVJKDKWRVSSJPK-UHFFFAOYSA-N 0.000 description 2
• IBRSSZOHCGUTHI-UHFFFAOYSA-N 2-chloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1Cl IBRSSZOHCGUTHI-UHFFFAOYSA-N 0.000 description 2
• SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 2
• 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 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• 102000053602 DNA Human genes 0.000 description 2
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 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 2
• 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 2
• 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 229930195725 Mannitol Natural products 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 2
• 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 description 2
• YHHUFFJGFSAMHN-UHFFFAOYSA-N O=C1Nc(cc(CN(CC2)CCN2c2ccc(C(F)(F)F)cc2)cc2)c2C2=C1CCCN2 Chemical compound O=C1Nc(cc(CN(CC2)CCN2c2ccc(C(F)(F)F)cc2)cc2)c2C2=C1CCCN2 YHHUFFJGFSAMHN-UHFFFAOYSA-N 0.000 description 2
• 102000003992 Peroxidases Human genes 0.000 description 2
• 102100023652 Poly [ADP-ribose] polymerase 2 Human genes 0.000 description 2
• 101710144590 Poly [ADP-ribose] polymerase 2 Proteins 0.000 description 2
• 229920001213 Polysorbate 20 Polymers 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• 108010090804 Streptavidin Proteins 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 229910052783 alkali metal Inorganic materials 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• 239000002246 antineoplastic agent Substances 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• 210000004204 blood vessel Anatomy 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 230000002490 cerebral effect Effects 0.000 description 2
• 206010008118 cerebral infarction Diseases 0.000 description 2
• 208000026106 cerebrovascular disease Diseases 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 230000002950 deficient Effects 0.000 description 2
• 206010012601 diabetes mellitus Diseases 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
• 229910000397 disodium phosphate Inorganic materials 0.000 description 2
• 235000019800 disodium phosphate Nutrition 0.000 description 2
• 239000002270 dispersing agent Substances 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 239000012091 fetal bovine serum Substances 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 229910052736 halogen Inorganic materials 0.000 description 2
• 150000002367 halogens Chemical class 0.000 description 2
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
• 239000007972 injectable composition Substances 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 239000000594 mannitol Substances 0.000 description 2
• 235000010355 mannitol Nutrition 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 235000019799 monosodium phosphate Nutrition 0.000 description 2
• 238000006386 neutralization reaction Methods 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• 238000011275 oncology therapy Methods 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 239000012044 organic layer Substances 0.000 description 2
• MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 2
• 108040007629 peroxidase activity proteins Proteins 0.000 description 2
• IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 2
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 238000007363 ring formation reaction Methods 0.000 description 2
• 230000019491 signal transduction Effects 0.000 description 2
• SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
• 230000003007 single stranded DNA break Effects 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 235000017557 sodium bicarbonate Nutrition 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 2
• 229910000162 sodium phosphate Inorganic materials 0.000 description 2
• GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 230000002195 synergetic effect Effects 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• 239000000080 wetting agent Substances 0.000 description 2
• 229910052727 yttrium Inorganic materials 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• WGOBPPNNYVSJTE-UHFFFAOYSA-N 1-diphenylphosphanylpropan-2-yl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)CP(C=1C=CC=CC=1)C1=CC=CC=C1 WGOBPPNNYVSJTE-UHFFFAOYSA-N 0.000 description 1
• RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
• RXTRRIFWCJEMEL-UHFFFAOYSA-N 2-chloropyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1Cl RXTRRIFWCJEMEL-UHFFFAOYSA-N 0.000 description 1
• LRLQQERNMXHASR-UHFFFAOYSA-N 2-diphenylphosphanylpropan-2-yl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)(C)P(C=1C=CC=CC=1)C1=CC=CC=C1 LRLQQERNMXHASR-UHFFFAOYSA-N 0.000 description 1
• NJQTWWNECKEAQJ-OALUTQOASA-N 2-fluoro-4-[(1S,4S)-5-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)N1[C@@H]2CN([C@H](C1)C2)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 NJQTWWNECKEAQJ-OALUTQOASA-N 0.000 description 1
• LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
• NXHQOGQCVYTDHU-UHFFFAOYSA-N 3,4,4a,5-tetrahydro-2h-phenanthridin-1-one Chemical class C1=CC=CC2=C3C(=O)CCCC3NC=C21 NXHQOGQCVYTDHU-UHFFFAOYSA-N 0.000 description 1
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
• ZKWZQSHOSWBPRG-UHFFFAOYSA-N 3-fluoro-4-[4-[(10-methoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound FC=1C=C(C#N)C=CC=1N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)OC ZKWZQSHOSWBPRG-UHFFFAOYSA-N 0.000 description 1
• SVYQAPDHJLXDGC-UHFFFAOYSA-N 3-methyl-4-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound CC=1C=C(C#N)C=CC=1N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 SVYQAPDHJLXDGC-UHFFFAOYSA-N 0.000 description 1
• FFSBZRRDJJMRCB-UHFFFAOYSA-N 4-[4-[(10-ethoxy-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound C(C)OC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=CC=C(C#N)C=C1 FFSBZRRDJJMRCB-UHFFFAOYSA-N 0.000 description 1
• XGFMLKJENFANEN-UHFFFAOYSA-N 6-[4-(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridine-8-carbonyl)piperazin-1-yl]pyridine-3-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)C(=O)N1CCN(CC1)C1=NC=C(C#N)C=C1 XGFMLKJENFANEN-UHFFFAOYSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• AFWLAWBSENRTOI-UHFFFAOYSA-N 8-[[4-(1,3-thiazol-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound S1C(=NC=C1)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 AFWLAWBSENRTOI-UHFFFAOYSA-N 0.000 description 1
• GDNMTVWYLXJWMC-UHFFFAOYSA-N 8-[[4-(4-fluoro-2-methylphenyl)piperazin-1-yl]methyl]-10-methoxy-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound FC1=CC(=C(C=C1)N1CCN(CC1)CC=1C=C(C2=C(NC(C=3CCCNC2=3)=O)C=1)OC)C GDNMTVWYLXJWMC-UHFFFAOYSA-N 0.000 description 1
• KOMGSVVWXUEBNT-UHFFFAOYSA-N 8-[[4-(4-fluorophenyl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound FC1=CC=C(C=C1)N1CCN(CC1)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 KOMGSVVWXUEBNT-UHFFFAOYSA-N 0.000 description 1
• KJLFPHLLVUYURJ-UHFFFAOYSA-N 8-[[4-(5-chloro-1,3-benzoxazol-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound ClC=1C=CC2=C(N=C(O2)N2CCN(CC2)CC=2C=CC3=C(NC(C=4CCCNC3=4)=O)C=2)C=1 KJLFPHLLVUYURJ-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 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
• 239000005711 Benzoic acid Substances 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• ZPLPMPHMFXXSIE-UHFFFAOYSA-N CCOC(c(cc1N2COC)ccc1C(NCCC1)=C1C2=O)=O Chemical compound CCOC(c(cc1N2COC)ccc1C(NCCC1)=C1C2=O)=O ZPLPMPHMFXXSIE-UHFFFAOYSA-N 0.000 description 1
• JNUNUGJENRLJQQ-UHFFFAOYSA-N CCOC(c1cccc(N(COC)C(c(cccn2)c2Cl)=O)c1)=O Chemical compound CCOC(c1cccc(N(COC)C(c(cccn2)c2Cl)=O)c1)=O JNUNUGJENRLJQQ-UHFFFAOYSA-N 0.000 description 1
• AMCACAXNHBPZEO-UHFFFAOYSA-N CCOC(c1cccc(NC(c2cccnc2Cl)=O)c1)=O Chemical compound CCOC(c1cccc(NC(c2cccnc2Cl)=O)c1)=O AMCACAXNHBPZEO-UHFFFAOYSA-N 0.000 description 1
• RZZPDXZPRHQOCG-OJAKKHQRSA-O CDP-choline(1+) Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-OJAKKHQRSA-O 0.000 description 1
• IOIZIRYETJETGE-UHFFFAOYSA-N COCN(c1cc(CO)ccc1C1=C2CCCN1)C2=O Chemical compound COCN(c1cc(CO)ccc1C1=C2CCCN1)C2=O IOIZIRYETJETGE-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
• 0 Cc(cc1N2)cc(CC*)c1*(NCCC1)=C1C2=O Chemical compound Cc(cc1N2)cc(CC*)c1*(NCCC1)=C1C2=O 0.000 description 1
• PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• INIPMYXWTDPDTO-UHFFFAOYSA-N Cl.N1(CCNCC1)C1=CC=C(S1)C#N Chemical compound Cl.N1(CCNCC1)C1=CC=C(S1)C#N INIPMYXWTDPDTO-UHFFFAOYSA-N 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• 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 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• 230000005971 DNA damage repair Effects 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• 239000004386 Erythritol Substances 0.000 description 1
• UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
• 206010073306 Exposure to radiation Diseases 0.000 description 1
• 239000004606 Fillers/Extenders Substances 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 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 1
• 102000018899 Glutamate Receptors Human genes 0.000 description 1
• 108010027915 Glutamate Receptors Proteins 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 101000735473 Homo sapiens Protein mono-ADP-ribosyltransferase TIPARP Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• 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 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• 206010028851 Necrosis Diseases 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
• NAZKLLYRVKKHAN-UHFFFAOYSA-N O=C1Nc(cc(CCl)cc2)c2C2=C1CCCN2 Chemical compound O=C1Nc(cc(CCl)cc2)c2C2=C1CCCN2 NAZKLLYRVKKHAN-UHFFFAOYSA-N 0.000 description 1
• GVXPOEVDJWMNTQ-UHFFFAOYSA-N OCc(cc1)cc(N2)c1C(NCCC1)=C1C2=O Chemical compound OCc(cc1)cc(N2)c1C(NCCC1)=C1C2=O GVXPOEVDJWMNTQ-UHFFFAOYSA-N 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 102000008212 P-Selectin Human genes 0.000 description 1
• 108010035766 P-Selectin Proteins 0.000 description 1
• 239000004264 Petrolatum Substances 0.000 description 1
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 229920001214 Polysorbate 60 Polymers 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 101710176890 Protein ADP-ribosyltransferase PARP3 Proteins 0.000 description 1
• 102100040847 Protein mono-ADP-ribosyltransferase PARP10 Human genes 0.000 description 1
• 101710127122 Protein mono-ADP-ribosyltransferase PARP10 Proteins 0.000 description 1
• 102100040850 Protein mono-ADP-ribosyltransferase PARP11 Human genes 0.000 description 1
• 101710127120 Protein mono-ADP-ribosyltransferase PARP11 Proteins 0.000 description 1
• 102100034935 Protein mono-ADP-ribosyltransferase PARP3 Human genes 0.000 description 1
• 101710204718 Protein mono-ADP-ribosyltransferase PARP3 Proteins 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 239000012979 RPMI medium Substances 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 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 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 108010017842 Telomerase Proteins 0.000 description 1
• BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
• 239000004164 Wax ester Substances 0.000 description 1
• TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 229940124532 absorption promoter Drugs 0.000 description 1
• 159000000021 acetate salts Chemical class 0.000 description 1
• 239000003929 acidic solution Substances 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
• IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
• 125000004849 alkoxymethyl group Chemical group 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 230000009435 amidation Effects 0.000 description 1
• 125000003277 amino group Chemical class 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 230000001093 anti-cancer Effects 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 229940041181 antineoplastic drug Drugs 0.000 description 1
• 229940045985 antineoplastic platinum compound Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 229960005261 aspartic acid Drugs 0.000 description 1
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 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
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 210000004958 brain cell Anatomy 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 239000000378 calcium silicate Substances 0.000 description 1
• 229910052918 calcium silicate Inorganic materials 0.000 description 1
• 235000012241 calcium silicate Nutrition 0.000 description 1
• OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
• 239000003560 cancer drug Substances 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• 229960004562 carboplatin Drugs 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 230000022131 cell cycle Effects 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 229940081733 cetearyl alcohol Drugs 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
• 229960004316 cisplatin Drugs 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 238000012258 culturing Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
• HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical group C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000008387 emulsifying waxe Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940095399 enema Drugs 0.000 description 1
• UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
• 235000019414 erythritol Nutrition 0.000 description 1
• 229940009714 erythritol Drugs 0.000 description 1
• 238000010931 ester hydrolysis Methods 0.000 description 1
• PANOWIMQYAXFEV-UHFFFAOYSA-N ethyl 3-[(2-chloropyridine-3-carbonyl)-(methoxymethyl)amino]-5-fluorobenzoate Chemical compound ClC1=C(C(=O)N(COC)C=2C=C(C(=O)OCC)C=C(C=2)F)C=CC=N1 PANOWIMQYAXFEV-UHFFFAOYSA-N 0.000 description 1
• LJGOXBGOXOYPOP-UHFFFAOYSA-N ethyl 3-amino-2,4-dichloro-5-fluorobenzoate Chemical compound CCOC(=O)C1=CC(F)=C(Cl)C(N)=C1Cl LJGOXBGOXOYPOP-UHFFFAOYSA-N 0.000 description 1
• WWQHGHVXYIMKGU-UHFFFAOYSA-N ethyl 3-amino-5-fluorobenzoate Chemical compound CCOC(=O)C1=CC(N)=CC(F)=C1 WWQHGHVXYIMKGU-UHFFFAOYSA-N 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 229940097043 glucuronic acid Drugs 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 229940071870 hydroiodic acid Drugs 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000007919 intrasynovial administration Methods 0.000 description 1
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
• 229960004768 irinotecan Drugs 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 150000003893 lactate salts Chemical class 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000000845 maltitol Substances 0.000 description 1
• 235000010449 maltitol Nutrition 0.000 description 1
• VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
• 229940035436 maltitol Drugs 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical class [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
• FBBDOOHMGLLEGJ-UHFFFAOYSA-N methane;hydrochloride Chemical compound C.Cl FBBDOOHMGLLEGJ-UHFFFAOYSA-N 0.000 description 1
• GXHMMDRXHUIUMN-UHFFFAOYSA-N methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O GXHMMDRXHUIUMN-UHFFFAOYSA-N 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 229940042472 mineral oil Drugs 0.000 description 1
• 230000011278 mitosis Effects 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• LQZPJQKYAOYUJS-UHFFFAOYSA-N n,n-diethyl-2-phenothiazin-10-ylethanamine;hydron;chloride Chemical compound Cl.C1=CC=C2N(CCN(CC)CC)C3=CC=CC=C3SC2=C1 LQZPJQKYAOYUJS-UHFFFAOYSA-N 0.000 description 1
• 229940097496 nasal spray Drugs 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 230000017074 necrotic cell death Effects 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• 210000000440 neutrophil Anatomy 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
• 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• MRDGZSKYFPGAKP-UHFFFAOYSA-N para-methoxyphenylpiperazine Chemical compound C1=CC(OC)=CC=C1N1CCNCC1 MRDGZSKYFPGAKP-UHFFFAOYSA-N 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• 229940066842 petrolatum Drugs 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229960005235 piperonyl butoxide Drugs 0.000 description 1
• 150000003058 platinum compounds Chemical class 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
• 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
• 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 229940113124 polysorbate 60 Drugs 0.000 description 1
• 229920000053 polysorbate 80 Polymers 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
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• 230000001376 precipitating effect Effects 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• YQUVCSBJEUQKSH-UHFFFAOYSA-N protochatechuic acid Natural products OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 1
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 229940100618 rectal suppository Drugs 0.000 description 1
• 239000006215 rectal suppository Substances 0.000 description 1
• 230000008439 repair process Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
• 229910001958 silver carbonate Inorganic materials 0.000 description 1
• 229910001961 silver nitrate Inorganic materials 0.000 description 1
• 235000020183 skimmed milk Nutrition 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• 235000009518 sodium iodide Nutrition 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 239000001587 sorbitan monostearate Substances 0.000 description 1
• 235000011076 sorbitan monostearate Nutrition 0.000 description 1
• 229940035048 sorbitan monostearate Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 150000003890 succinate salts Chemical class 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 150000003892 tartrate salts Chemical class 0.000 description 1
• 229960004964 temozolomide Drugs 0.000 description 1
• JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
• 238000011287 therapeutic dose Methods 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
• 229960000303 topotecan Drugs 0.000 description 1
• 230000005945 translocation Effects 0.000 description 1
• ZMCBYSBVJIMENC-UHFFFAOYSA-N tricaine Chemical compound CCOC(=O)C1=CC=CC(N)=C1 ZMCBYSBVJIMENC-UHFFFAOYSA-N 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• JUDXOKKZTISQDJ-UHFFFAOYSA-N triphenylphosphane;hydrochloride Chemical compound Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 JUDXOKKZTISQDJ-UHFFFAOYSA-N 0.000 description 1
• WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 description 1
• TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 description 1
• 235000019386 wax ester Nutrition 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• 239000000811 xylitol Substances 0.000 description 1
• 235000010447 xylitol Nutrition 0.000 description 1
• HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
• 229960002675 xylitol Drugs 0.000 description 1