ES2595240T3 - Derivados de tetrahidroquinazolinona como inhibidores de PARP - Google Patents

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Publication number

ES2595240T3

ES2595240T3 ES13742752.2T ES13742752T ES2595240T3 ES 2595240 T3 ES2595240 T3 ES 2595240T3 ES 13742752 T ES13742752 T ES 13742752T ES 2595240 T3 ES2595240 T3 ES 2595240T3

Authority

ES

Spain

Prior art keywords

compound

spiro

alkyl

dihydro

piperazin

Prior art date

2012-07-09

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.)

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• 239000012661 PARP inhibitor Substances 0.000 title description 12
• 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 title description 12
• TYNNEEKKMHSZMO-UHFFFAOYSA-N 3,4,4a,5-tetrahydro-1h-quinazolin-2-one Chemical class C1C=CC=C2NC(=O)NCC21 TYNNEEKKMHSZMO-UHFFFAOYSA-N 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 502
• -1 cyano, hydroxy Chemical group 0.000 claims abstract description 277
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 267
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 60
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 50
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 48
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 47
• 150000002367 halogens Chemical class 0.000 claims abstract description 47
• 239000001257 hydrogen Substances 0.000 claims abstract description 47
• 150000003839 salts Chemical class 0.000 claims abstract description 41
• 125000003118 aryl group Chemical group 0.000 claims abstract description 40
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 40
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 40
• 125000003342 alkenyl group Chemical group 0.000 claims abstract description 31
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 28
• 125000001424 substituent group Chemical group 0.000 claims abstract description 28
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 27
• 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 25
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 23
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 20
• 125000004429 atom Chemical group 0.000 claims abstract description 18
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 9
• 229910006074 SO2NH2 Inorganic materials 0.000 claims abstract description 8
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 8
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 5
• 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 59
• KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 34
• 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 claims description 25
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 22
• 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims description 22
• 101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 claims description 21
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
• MNLVCBKWEVXHGE-UHFFFAOYSA-N [CH]1[CH]CC[CH]1 Chemical group [CH]1[CH]CC[CH]1 MNLVCBKWEVXHGE-UHFFFAOYSA-N 0.000 claims description 20
• 238000011282 treatment Methods 0.000 claims description 20
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
• 206010028980 Neoplasm Diseases 0.000 claims description 15
• 201000011510 cancer Diseases 0.000 claims description 14
• 230000005764 inhibitory process Effects 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
• 208000035475 disorder Diseases 0.000 claims description 12
• 239000002246 antineoplastic agent Substances 0.000 claims description 11
• 230000002265 prevention Effects 0.000 claims description 11
• 230000000694 effects Effects 0.000 claims description 10
• 229960003966 nicotinamide Drugs 0.000 claims description 10
• 235000005152 nicotinamide Nutrition 0.000 claims description 10
• 239000011570 nicotinamide Substances 0.000 claims description 10
• NCMKSUPPUIAWGL-UHFFFAOYSA-N 2-[3-[3-(4-fluorophenyl)-3,8-diazabicyclo[3.2.1]octan-8-yl]propyl]spiro[1,5,7,8-tetrahydroquinazoline-6,1'-cyclopropane]-4-one Chemical compound C1=CC(F)=CC=C1N1CC(N2CCCC=3NC=4CCC5(CC5)CC=4C(=O)N=3)CCC2C1 NCMKSUPPUIAWGL-UHFFFAOYSA-N 0.000 claims description 9
• TXJIZRWOMFSPJT-UHFFFAOYSA-N 2-[3-[4-(4-chlorophenyl)piperazin-1-yl]propyl]spiro[1,5,7,8-tetrahydroquinazoline-6,1'-cyclopropane]-4-one Chemical compound C1=CC(Cl)=CC=C1N1CCN(CCCC=2NC=3CCC4(CC4)CC=3C(=O)N=2)CC1 TXJIZRWOMFSPJT-UHFFFAOYSA-N 0.000 claims description 9
• 201000009030 Carcinoma Diseases 0.000 claims description 9
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 8
• MWEJVEMCWSJRMO-UHFFFAOYSA-N 2-[3-[8-(4-fluorophenyl)-3,8-diazabicyclo[3.2.1]octan-3-yl]propyl]spiro[1,5,7,8-tetrahydroquinazoline-6,1'-cyclopropane]-4-one Chemical compound C1=CC(F)=CC=C1N1C2CCC1CN(CCCC=1NC=3CCC4(CC4)CC=3C(=O)N=1)C2 MWEJVEMCWSJRMO-UHFFFAOYSA-N 0.000 claims description 7
• 229940127089 cytotoxic agent Drugs 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
• 201000001441 melanoma Diseases 0.000 claims description 7
• BQFSTYUCVIIVBW-UHFFFAOYSA-N 2-[3-[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]propyl]spiro[1,5,7,8-tetrahydroquinazoline-6,1'-cyclopropane]-4-one Chemical compound C1=CC(F)=CC=C1C(CC1)=CCN1CCCC(N1)=NC(=O)C2=C1CCC1(CC1)C2 BQFSTYUCVIIVBW-UHFFFAOYSA-N 0.000 claims description 6
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 6
• 239000003795 chemical substances by application Substances 0.000 claims description 6
• BGGALFIXXQOTPY-NRFANRHFSA-N C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC Chemical compound C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC BGGALFIXXQOTPY-NRFANRHFSA-N 0.000 claims description 5
• QBYJBZPUGVGKQQ-SJJAEHHWSA-N aldrin Chemical compound C1[C@H]2C=C[C@@H]1[C@H]1[C@@](C3(Cl)Cl)(Cl)C(Cl)=C(Cl)[C@@]3(Cl)[C@H]12 QBYJBZPUGVGKQQ-SJJAEHHWSA-N 0.000 claims description 5
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
• 229940125782 compound 2 Drugs 0.000 claims description 5
• 230000003211 malignant effect Effects 0.000 claims description 5
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 125000000335 thiazolyl group Chemical group 0.000 claims description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
• IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 claims description 4
• LIMFPAAAIVQRRD-BCGVJQADSA-N N-[2-[(3S,4R)-3-fluoro-4-methoxypiperidin-1-yl]pyrimidin-4-yl]-8-[(2R,3S)-2-methyl-3-(methylsulfonylmethyl)azetidin-1-yl]-5-propan-2-ylisoquinolin-3-amine Chemical compound F[C@H]1CN(CC[C@H]1OC)C1=NC=CC(=N1)NC=1N=CC2=C(C=CC(=C2C=1)C(C)C)N1[C@@H]([C@H](C1)CS(=O)(=O)C)C LIMFPAAAIVQRRD-BCGVJQADSA-N 0.000 claims description 4
• 206010029260 Neuroblastoma Diseases 0.000 claims description 4
• BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 4
• 230000000973 chemotherapeutic effect Effects 0.000 claims description 4
• 229940125898 compound 5 Drugs 0.000 claims description 4
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 4
• 229960004679 doxorubicin Drugs 0.000 claims description 4
• 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 claims description 4
• 229960004768 irinotecan Drugs 0.000 claims description 4
• VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 claims description 4
• 208000032839 leukemia Diseases 0.000 claims description 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
• 229960004964 temozolomide Drugs 0.000 claims description 4
• 125000001544 thienyl group Chemical group 0.000 claims description 4
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 claims description 3
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 claims description 3
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 claims description 3
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 claims description 3
• WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 claims description 3
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims description 3
• IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims description 3
• UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 claims description 3
• OIIOPWHTJZYKIL-PMACEKPBSA-N (5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one Chemical compound C1(=C(N=C(C2=C(C(C3=CC=CC(=C3Cl)C3=NC(OC)=C(N=C3)CNC[C@H]3NC(=O)CC3)=CC=C2)Cl)C=N1)OC)CNC[C@H]1NC(=O)CC1 OIIOPWHTJZYKIL-PMACEKPBSA-N 0.000 claims description 3
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 claims description 3
• UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 claims description 3
• MXTLQAPYJLCOIA-PXNSSMCTSA-N 2-[(1S,3S)-3-[4-(3-fluorophenyl)piperazin-1-yl]cyclopentyl]spiro[3,5,7,8-tetrahydroquinazoline-6,1'-cyclopropane]-4-one Chemical compound Fc1cccc(c1)N1CCN(CC1)[C@H]1CC[C@@H](C1)c1nc2CCC3(CC3)Cc2c(=O)[nH]1 MXTLQAPYJLCOIA-PXNSSMCTSA-N 0.000 claims description 3
• BVBBTMVFSYCQAX-UHFFFAOYSA-N 2-[3-[2-(4-fluorophenyl)-2,5-diazabicyclo[2.2.1]heptan-5-yl]propyl]spiro[1,5,7,8-tetrahydroquinazoline-6,1'-cyclopropane]-4-one Chemical compound C1=CC(F)=CC=C1N1C(CN2CCCC=3NC=4CCC5(CC5)CC=4C(=O)N=3)CC2C1 BVBBTMVFSYCQAX-UHFFFAOYSA-N 0.000 claims description 3
• KZWDJBSJFGPKST-UHFFFAOYSA-N 2-[3-[4-(3,4-dichlorophenyl)piperazin-1-yl]propyl]spiro[1,5,7,8-tetrahydroquinazoline-6,1'-cyclopropane]-4-one Chemical compound C1=C(Cl)C(Cl)=CC=C1N1CCN(CCCC=2NC=3CCC4(CC4)CC=3C(=O)N=2)CC1 KZWDJBSJFGPKST-UHFFFAOYSA-N 0.000 claims description 3
• PYAAMQHOVWZXLA-UHFFFAOYSA-N 2-[3-[4-(4-chlorophenyl)piperazin-1-yl]propyl]spiro[1,5,6,7-tetrahydroquinazoline-8,1'-cyclopropane]-4-one Chemical compound C1=CC(Cl)=CC=C1N1CCN(CCCC=2NC=3C4(CC4)CCCC=3C(=O)N=2)CC1 PYAAMQHOVWZXLA-UHFFFAOYSA-N 0.000 claims description 3
• QNVYRIZIUSMUAD-UHFFFAOYSA-N 2-[3-[4-(4-fluorophenyl)piperazin-1-yl]propyl]spiro[1,5,6,7-tetrahydroquinazoline-8,1'-cyclopropane]-4-one Chemical compound C1=CC(F)=CC=C1N1CCN(CCCC=2NC=3C4(CC4)CCCC=3C(=O)N=2)CC1 QNVYRIZIUSMUAD-UHFFFAOYSA-N 0.000 claims description 3
• ODFSAHAVAVSIJD-UHFFFAOYSA-N 2-[3-[4-(4-fluorophenyl)piperazin-1-yl]propyl]spiro[1,5,7,8-tetrahydroquinazoline-6,1'-cyclopropane]-4-one Chemical compound C1=CC(F)=CC=C1N1CCN(CCCC=2NC=3CCC4(CC4)CC=3C(=O)N=2)CC1 ODFSAHAVAVSIJD-UHFFFAOYSA-N 0.000 claims description 3
• PAYROHWFGZADBR-UHFFFAOYSA-N 2-[[4-amino-5-(5-iodo-4-methoxy-2-propan-2-ylphenoxy)pyrimidin-2-yl]amino]propane-1,3-diol Chemical compound C1=C(I)C(OC)=CC(C(C)C)=C1OC1=CN=C(NC(CO)CO)N=C1N PAYROHWFGZADBR-UHFFFAOYSA-N 0.000 claims description 3
• WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 claims description 3
• MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 claims description 3
• GSDQYSSLIKJJOG-UHFFFAOYSA-N 4-chloro-2-(3-chloroanilino)benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1NC1=CC=CC(Cl)=C1 GSDQYSSLIKJJOG-UHFFFAOYSA-N 0.000 claims description 3
• NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 claims description 3
• IJRKLHTZAIFUTB-UHFFFAOYSA-N 5-nitro-2-(2-phenylethylamino)benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NCCC1=CC=CC=C1 IJRKLHTZAIFUTB-UHFFFAOYSA-N 0.000 claims description 3
• IRBAWVGZNJIROV-SFHVURJKSA-N 9-(2-cyclopropylethynyl)-2-[[(2s)-1,4-dioxan-2-yl]methoxy]-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=C2C3=CC=C(C#CC4CC4)C=C3CCN2C(=O)N=C1OC[C@@H]1COCCO1 IRBAWVGZNJIROV-SFHVURJKSA-N 0.000 claims description 3
• IYHHRZBKXXKDDY-UHFFFAOYSA-N BI-605906 Chemical compound N=1C=2SC(C(N)=O)=C(N)C=2C(C(F)(F)CC)=CC=1N1CCC(S(C)(=O)=O)CC1 IYHHRZBKXXKDDY-UHFFFAOYSA-N 0.000 claims description 3
• 108010006654 Bleomycin Proteins 0.000 claims description 3
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