MD4793C1 - Noi compuşi de izoindolină sau izochinolină, procedeu de obţinere a lor şi compoziţii farmaceutice care le conţin - Google Patents

Info

Publication number

MD4793C1

MD4793C1 MDA20160018A MD20160018A MD4793C1 MD 4793 C1 MD4793 C1 MD 4793C1 MD A20160018 A MDA20160018 A MD A20160018A MD 20160018 A MD20160018 A MD 20160018A MD 4793 C1 MD4793 C1 MD 4793C1

Authority

MD

Moldova

Prior art keywords

methyl

carbonyl

phenyl

tetrahydroisoquinoline

carboxamide

Prior art date

2013-07-23

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• 238000000034 method Methods 0.000 title claims abstract description 569
• 230000008569 process Effects 0.000 title claims abstract description 15
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
• 238000002360 preparation method Methods 0.000 title abstract description 331
• GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 title abstract description 3
• 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title abstract 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 152
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 17
• 238000011282 treatment Methods 0.000 claims abstract description 15
• 125000001424 substituent group Chemical group 0.000 claims abstract description 9
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 5
• 230000000861 pro-apoptotic effect Effects 0.000 claims abstract description 4
• 208000026278 immune system disease Diseases 0.000 claims abstract 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 254
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 250
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 193
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 188
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 139
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 73
• 125000003118 aryl group Chemical group 0.000 claims description 65
• -1 (morpholin-4-yl)methyl group Chemical group 0.000 claims description 63
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 53
• 229910052757 nitrogen Inorganic materials 0.000 claims description 48
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 46
• 239000002253 acid Substances 0.000 claims description 41
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 41
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 37
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 35
• 125000000217 alkyl group Chemical group 0.000 claims description 33
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 30
• 125000001072 heteroaryl group Chemical group 0.000 claims description 28
• 229910052739 hydrogen Inorganic materials 0.000 claims description 22
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 21
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
• 125000004432 carbon atom Chemical group C* 0.000 claims description 19
• 150000003839 salts Chemical class 0.000 claims description 19
• 239000001257 hydrogen Substances 0.000 claims description 18
• 238000006243 chemical reaction Methods 0.000 claims description 17
• 125000002619 bicyclic group Chemical group 0.000 claims description 16
• 125000005843 halogen group Chemical group 0.000 claims description 16
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 15
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 13
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 12
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
• 201000011510 cancer Diseases 0.000 claims description 12
• 150000001768 cations Chemical class 0.000 claims description 12
• 125000005842 heteroatom Chemical group 0.000 claims description 12
• 125000002950 monocyclic group Chemical group 0.000 claims description 12
• 229910052760 oxygen Inorganic materials 0.000 claims description 12
• 239000001301 oxygen Substances 0.000 claims description 12
• 239000007858 starting material Substances 0.000 claims description 12
• 229910052717 sulfur Inorganic materials 0.000 claims description 12
• 239000011593 sulfur Chemical group 0.000 claims description 12
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
• 150000001412 amines Chemical class 0.000 claims description 10
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• 150000002367 halogens Chemical class 0.000 claims description 10
• 125000003342 alkenyl group Chemical group 0.000 claims description 9
• 125000003545 alkoxy group Chemical group 0.000 claims description 9
• 125000000304 alkynyl group Chemical group 0.000 claims description 9
• 230000015572 biosynthetic process Effects 0.000 claims description 9
• 239000012634 fragment Substances 0.000 claims description 9
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 8
• 125000002837 carbocyclic group Chemical group 0.000 claims description 8
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 8
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
• 125000004043 oxo group Chemical group O=* 0.000 claims description 8
• 238000000926 separation method Methods 0.000 claims description 8
• 125000003003 spiro group Chemical group 0.000 claims description 8
• 238000003786 synthesis reaction Methods 0.000 claims description 8
• JATHXJMZMGXQFU-MRVPVSSYSA-N (3r)-3-methyl-3,4-dihydroisoquinoline Chemical compound C1=CC=C2C=N[C@H](C)CC2=C1 JATHXJMZMGXQFU-MRVPVSSYSA-N 0.000 claims description 6
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 6
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 6
• 239000003153 chemical reaction reagent Substances 0.000 claims description 6
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 6
• 239000000543 intermediate Substances 0.000 claims description 6
• 206010041067 Small cell lung cancer Diseases 0.000 claims description 5
• 125000004429 atom Chemical group 0.000 claims description 5
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 5
• 208000000587 small cell lung carcinoma Diseases 0.000 claims description 5
• 238000005694 sulfonylation reaction Methods 0.000 claims description 5
• 125000006685 (C1-C6) polyhaloalkyl group Chemical group 0.000 claims description 4
• 206010005003 Bladder cancer Diseases 0.000 claims description 4
• 206010006187 Breast cancer Diseases 0.000 claims description 4
• 208000026310 Breast neoplasm Diseases 0.000 claims description 4
• 206010009944 Colon cancer Diseases 0.000 claims description 4
• 150000001204 N-oxides Chemical class 0.000 claims description 4
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 4
• 206010033128 Ovarian cancer Diseases 0.000 claims description 4
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
• ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 4
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
• 206010060862 Prostate cancer Diseases 0.000 claims description 4
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
• 230000009471 action Effects 0.000 claims description 4
• 230000010933 acylation Effects 0.000 claims description 4
• 238000005917 acylation reaction Methods 0.000 claims description 4
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
• 125000005110 aryl thio group Chemical group 0.000 claims description 4
• 125000004104 aryloxy group Chemical group 0.000 claims description 4
• 235000010290 biphenyl Nutrition 0.000 claims description 4
• 239000004305 biphenyl Substances 0.000 claims description 4
• 229910052799 carbon Inorganic materials 0.000 claims description 4
• 208000029742 colonic neoplasm Diseases 0.000 claims description 4
• 230000008878 coupling Effects 0.000 claims description 4
• 238000010168 coupling process Methods 0.000 claims description 4
• 238000005859 coupling reaction Methods 0.000 claims description 4
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 4
• 235000011180 diphosphates Nutrition 0.000 claims description 4
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 4
• 208000003747 lymphoid leukemia Diseases 0.000 claims description 4
• 230000003211 malignant effect Effects 0.000 claims description 4
• 201000000050 myeloid neoplasm Diseases 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 4
• 238000005897 peptide coupling reaction Methods 0.000 claims description 4
• 125000006684 polyhaloalkyl group Polymers 0.000 claims description 4
• 239000003053 toxin Substances 0.000 claims description 4
• 231100000765 toxin Toxicity 0.000 claims description 4
• 108700012359 toxins Proteins 0.000 claims description 4
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 4
• 201000005112 urinary bladder cancer Diseases 0.000 claims description 4
• GNFLFHZJXXFDRA-UHFFFAOYSA-N 1,2-dimethylpyrrole Chemical compound CC1=CC=CN1C GNFLFHZJXXFDRA-UHFFFAOYSA-N 0.000 claims description 3
• DRXOPQFEWDRGKT-UHFFFAOYSA-N 1,5-dimethylpyrrole-2-carbonitrile Chemical compound CC1=CC=C(C#N)N1C DRXOPQFEWDRGKT-UHFFFAOYSA-N 0.000 claims description 3
• SMTKZGBTAMMADH-HHHXNRCGSA-N 3-[2-[2-(2-chlorophenoxy)acetyl]-6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-dihydroisoindol-5-yl]-N-(4-hydroxyphenyl)-N-methyl-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound ClC1=C(OCC(=O)N2CC3=CC(=C(C=C3C2)C2=CC(=C3CCCCN23)C(=O)N(C)C2=CC=C(C=C2)O)C(=O)N2CC3=CC=CC=C3C[C@H]2C)C=CC=C1 SMTKZGBTAMMADH-HHHXNRCGSA-N 0.000 claims description 3
• DDXJPHQAXJXYTO-HHHXNRCGSA-N 3-[2-[2-(4-chlorophenoxy)acetyl]-6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-dihydroisoindol-5-yl]-N-(4-hydroxyphenyl)-N-methyl-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound ClC1=CC=C(OCC(=O)N2CC3=CC(=C(C=C3C2)C2=CC(=C3CCCCN23)C(=O)N(C)C2=CC=C(C=C2)O)C(=O)N2CC3=CC=CC=C3C[C@H]2C)C=C1 DDXJPHQAXJXYTO-HHHXNRCGSA-N 0.000 claims description 3
• 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
• 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 3
• LSDBELUKOABOBK-MGBGTMOVSA-N N-(4-hydroxyphenyl)-N-methyl-3-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[2-[4-(morpholin-4-ylmethyl)phenyl]acetyl]-3,4-dihydro-1H-isoquinolin-6-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C[C@@H]1Cc2ccccc2CN1C(=O)c1cc2CN(CCc2cc1-c1cc(C(=O)N(C)c2ccc(O)cc2)c2CCCCn12)C(=O)Cc1ccc(CN2CCOCC2)cc1 LSDBELUKOABOBK-MGBGTMOVSA-N 0.000 claims description 3
• MLDJYPAJCQNMQN-UUWRZZSWSA-N N-(4-hydroxyphenyl)-N-methyl-3-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[2-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]acetyl]-3,4-dihydro-1H-isoquinolin-6-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C[C@@H]1Cc2ccccc2CN1C(=O)c1cc2CN(CCc2cc1-c1cc(C(=O)N(C)c2ccc(O)cc2)c2CCCCn12)C(=O)Cc1ccc(CN2CCN(C)CC2)cc1 MLDJYPAJCQNMQN-UUWRZZSWSA-N 0.000 claims description 3
• UCZOGTLOGCSHIN-RWYGWLOXSA-N N-butyl-N-(4-hydroxyphenyl)-1,2-dimethyl-5-[7-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(2-phenylacetyl)-3,4-dihydro-1H-isoquinolin-6-yl]pyrrole-3-carboxamide Chemical compound C(CCC)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1CN1CCOCC1)C(CC1=CC=CC=C1)=O)C)C)C1=CC=C(C=C1)O UCZOGTLOGCSHIN-RWYGWLOXSA-N 0.000 claims description 3
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 3
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 3
• 208000002495 Uterine Neoplasms Diseases 0.000 claims description 3
• 150000001263 acyl chlorides Chemical class 0.000 claims description 3
• 210000004556 brain Anatomy 0.000 claims description 3
• 210000000481 breast Anatomy 0.000 claims description 3
• 239000003795 chemical substances by application Substances 0.000 claims description 3
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 3
• 210000001072 colon Anatomy 0.000 claims description 3
• 201000004101 esophageal cancer Diseases 0.000 claims description 3
• 201000007270 liver cancer Diseases 0.000 claims description 3
• 208000014018 liver neoplasm Diseases 0.000 claims description 3
• 201000001441 melanoma Diseases 0.000 claims description 3
• CHQGEIDEUQKALJ-GDLZYMKVSA-N n-(4-hydroxyphenyl)-n-methyl-3-[7-[(3r)-3-methyl-3,4-dihydro-1h-isoquinoline-2-carbonyl]-2-(2-phenylacetyl)-3,4-dihydro-1h-isoquinolin-6-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C([C@H]1C)C2=CC=CC=C2CN1C(=O)C1=CC=2CN(C(=O)CC=3C=CC=CC=3)CCC=2C=C1C(N1CCCCC1=1)=CC=1C(=O)N(C)C1=CC=C(O)C=C1 CHQGEIDEUQKALJ-GDLZYMKVSA-N 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 238000001959 radiotherapy Methods 0.000 claims description 3
• 206010046766 uterine cancer Diseases 0.000 claims description 3
• ZVOCBNCKNQJAFL-UHFFFAOYSA-N 1-methylpyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2N(C)C=CC2=C1 ZVOCBNCKNQJAFL-UHFFFAOYSA-N 0.000 claims description 2
• PPTWUVVBPFRQQG-HHHXNRCGSA-N 3-[2-[2-(3-chlorophenoxy)acetyl]-6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-dihydroisoindol-5-yl]-N-(4-hydroxyphenyl)-N-methyl-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound ClC=1C=C(OCC(=O)N2CC3=CC(=C(C=C3C2)C2=CC(=C3CCCCN23)C(=O)N(C)C2=CC=C(C=C2)O)C(=O)N2CC3=CC=CC=C3C[C@H]2C)C=CC=1 PPTWUVVBPFRQQG-HHHXNRCGSA-N 0.000 claims description 2
• QNJMXADYZKWVIJ-GDLZYMKVSA-N 3-[2-[2-(4-cyanophenyl)acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N-(4-hydroxyphenyl)-N-methyl-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C(#N)C1=CC=C(C=C1)CC(=O)N1CC2=CC(=C(C=C2CC1)C1=CC(=C2CCCCN12)C(=O)N(C)C1=CC=C(C=C1)O)C(=O)N1CC2=CC=CC=C2C[C@H]1C QNJMXADYZKWVIJ-GDLZYMKVSA-N 0.000 claims description 2
• ZAIVVAGEIPDXTO-WJOKGBTCSA-N 3-[2-[2-[4-[(dimethylamino)methyl]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N-(4-hydroxyphenyl)-N-methyl-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C[C@@H]1Cc2ccccc2CN1C(=O)c1cc2CN(CCc2cc1-c1cc(C(=O)N(C)c2ccc(O)cc2)c2CCCCn12)C(=O)Cc1ccc(CN(C)C)cc1 ZAIVVAGEIPDXTO-WJOKGBTCSA-N 0.000 claims description 2
• JZAUOSYMVYCYDR-JGCGQSQUSA-N 3-[2-[2-[4-[2-(dimethylamino)ethoxy]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N-(4-hydroxyphenyl)-N-methyl-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C[C@@H]1Cc2ccccc2CN1C(=O)c1cc2CN(CCc2cc1-c1cc(C(=O)N(C)c2ccc(O)cc2)c2CCCCn12)C(=O)Cc1ccc(OCCN(C)C)cc1 JZAUOSYMVYCYDR-JGCGQSQUSA-N 0.000 claims description 2
• PSVZJMHQMHUDDV-YPJJGMIRSA-N 3-[2-[3-(4-chlorophenyl)-2-methylpropanoyl]-6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-dihydroisoindol-5-yl]-N-(4-hydroxyphenyl)-N-methyl-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound CC(Cc1ccc(Cl)cc1)C(=O)N1Cc2cc(C(=O)N3Cc4ccccc4C[C@H]3C)c(cc2C1)-c1cc(C(=O)N(C)c2ccc(O)cc2)c2CCCCn12 PSVZJMHQMHUDDV-YPJJGMIRSA-N 0.000 claims description 2
• ZSOLCZNYJLDIQC-MGBGTMOVSA-N 3-[2-[3-[4-[2-(dimethylamino)ethylamino]phenyl]propanoyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N-(4-hydroxyphenyl)-N-methyl-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C[C@@H]1Cc2ccccc2CN1C(=O)c1cc2CN(CCc2cc1-c1cc(C(=O)N(C)c2ccc(O)cc2)c2CCCCn12)C(=O)CCc1ccc(NCCN(C)C)cc1 ZSOLCZNYJLDIQC-MGBGTMOVSA-N 0.000 claims description 2
• QYASHELNMUPRKF-UHFFFAOYSA-N 5,6,7,8-tetrahydroindolizine Chemical compound C1CCCN2C=CC=C21 QYASHELNMUPRKF-UHFFFAOYSA-N 0.000 claims description 2
• GHUWSTRHRQQXPU-GAOVHNHDSA-N 5-[2-[(E)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N-(4-hydroxyphenyl)-N,1,2-trimethylpyrrole-3-carboxamide Chemical compound CN(C(=O)c1cc(-c2cc3CCN(Cc3cc2C(=O)N2Cc3ccccc3C[C@H]2CN2CCOCC2)C(=O)\C=C\c2ccc(Cl)c(Cl)c2)n(C)c1C)c1ccc(O)cc1 GHUWSTRHRQQXPU-GAOVHNHDSA-N 0.000 claims description 2
• GJRQFCGCFGVAID-MUUNZHRXSA-N 5-[2-[2-(4-cyanophenyl)acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N,1,2-trimethyl-N-phenylpyrrole-3-carboxamide Chemical compound C(#N)C1=CC=C(C=C1)CC(=O)N1CC2=CC(=C(C=C2CC1)C1=CC(=C(N1C)C)C(=O)N(C1=CC=CC=C1)C)C(=O)N1CC2=CC=CC=C2C[C@H]1C GJRQFCGCFGVAID-MUUNZHRXSA-N 0.000 claims description 2
• WVZJJMVLDFHXJT-HHHXNRCGSA-N 5-[2-[2-(4-cyanophenyl)acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N-(4-hydroxyphenyl)-N,1,2-trimethylpyrrole-3-carboxamide Chemical compound C(#N)C1=CC=C(C=C1)CC(=O)N1CC2=CC(=C(C=C2CC1)C1=CC(=C(N1C)C)C(=O)N(C)C1=CC=C(C=C1)O)C(=O)N1CC2=CC=CC=C2C[C@H]1C WVZJJMVLDFHXJT-HHHXNRCGSA-N 0.000 claims description 2
• LYZULWSEECNBSU-FAIXQHPJSA-N 5-[2-[2-(4-cyanophenyl)acetyl]-7-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N,1,2-trimethyl-N-phenylpyrrole-3-carboxamide Chemical compound C(#N)C1=CC=C(C=C1)CC(=O)N1CC2=CC(=C(C=C2CC1)C1=CC(=C(N1C)C)C(=O)N(C1=CC=CC=C1)C)C(=O)N1CC2=CC=CC=C2C[C@H]1CN1CCOCC1 LYZULWSEECNBSU-FAIXQHPJSA-N 0.000 claims description 2
• SSYBXHJTTGQPTQ-RUZDIDTESA-N 5-[2-[2-(4-fluorophenyl)acetyl]-6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-dihydroisoindol-5-yl]-N-(4-hydroxyphenyl)-N,1,2-trimethylpyrrole-3-carboxamide Chemical compound FC1=CC=C(C=C1)CC(=O)N1CC2=CC(=C(C=C2C1)C1=CC(=C(N1C)C)C(=O)N(C)C1=CC=C(C=C1)O)C(=O)N1CC2=CC=CC=C2C[C@H]1C SSYBXHJTTGQPTQ-RUZDIDTESA-N 0.000 claims description 2
• MIGUGJQEUPWKSS-SSEXGKCCSA-N 5-[2-[2-[2-[(dimethylamino)methyl]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N,1,2-trimethyl-N-phenylpyrrole-3-carboxamide Chemical compound CN(C)CC1=C(C=CC=C1)CC(=O)N1CC2=CC(=C(C=C2CC1)C1=CC(=C(N1C)C)C(=O)N(C1=CC=CC=C1)C)C(=O)N1CC2=CC=CC=C2C[C@H]1C MIGUGJQEUPWKSS-SSEXGKCCSA-N 0.000 claims description 2
• PWVZFDRQPSWYQR-WJOKGBTCSA-N 5-[2-[2-[2-[2-(dimethylamino)ethoxy]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N,1,2-trimethyl-N-phenylpyrrole-3-carboxamide Chemical compound CN(CCOC1=C(C=CC=C1)CC(=O)N1CC2=CC(=C(C=C2CC1)C1=CC(=C(N1C)C)C(=O)N(C1=CC=CC=C1)C)C(=O)N1CC2=CC=CC=C2C[C@H]1C)C PWVZFDRQPSWYQR-WJOKGBTCSA-N 0.000 claims description 2
• LVMXIQFIWAWDAP-WJOKGBTCSA-N 5-[2-[2-[2-[2-(dimethylamino)ethyl]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N,1,2-trimethyl-N-phenylpyrrole-3-carboxamide Chemical compound CN(CCC1=C(C=CC=C1)CC(=O)N1CC2=CC(=C(C=C2CC1)C1=CC(=C(N1C)C)C(=O)N(C1=CC=CC=C1)C)C(=O)N1CC2=CC=CC=C2C[C@H]1C)C LVMXIQFIWAWDAP-WJOKGBTCSA-N 0.000 claims description 2
• YTWMWYKKOYPSDB-SSEXGKCCSA-N 5-[2-[2-[3-[(dimethylamino)methyl]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N,1,2-trimethyl-N-phenylpyrrole-3-carboxamide Chemical compound CN(C)CC=1C=C(C=CC=1)CC(=O)N1CC2=CC(=C(C=C2CC1)C1=CC(=C(N1C)C)C(=O)N(C1=CC=CC=C1)C)C(=O)N1CC2=CC=CC=C2C[C@H]1C YTWMWYKKOYPSDB-SSEXGKCCSA-N 0.000 claims description 2
• XQXBWVVFFYVNAP-WJOKGBTCSA-N 5-[2-[2-[3-[2-(dimethylamino)ethoxy]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N,1,2-trimethyl-N-phenylpyrrole-3-carboxamide Chemical compound CN(CCOC=1C=C(C=CC=1)CC(=O)N1CC2=CC(=C(C=C2CC1)C1=CC(=C(N1C)C)C(=O)N(C1=CC=CC=C1)C)C(=O)N1CC2=CC=CC=C2C[C@H]1C)C XQXBWVVFFYVNAP-WJOKGBTCSA-N 0.000 claims description 2
• VXDCKXYEMWERGG-WJOKGBTCSA-N 5-[2-[2-[3-[2-(dimethylamino)ethyl]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N,1,2-trimethyl-N-phenylpyrrole-3-carboxamide Chemical compound CN(CCC=1C=C(C=CC=1)CC(=O)N1CC2=CC(=C(C=C2CC1)C1=CC(=C(N1C)C)C(=O)N(C1=CC=CC=C1)C)C(=O)N1CC2=CC=CC=C2C[C@H]1C)C VXDCKXYEMWERGG-WJOKGBTCSA-N 0.000 claims description 2
• CPLABKXRSSWJQJ-AREMUKBSSA-N 5-[2-[3-(4-chlorophenoxy)propanoyl]-6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-dihydroisoindol-5-yl]-N-(4-hydroxyphenyl)-N,1,2-trimethylpyrrole-3-carboxamide Chemical compound ClC1=CC=C(OCCC(=O)N2CC3=CC(=C(C=C3C2)C2=CC(=C(N2C)C)C(=O)N(C)C2=CC=C(C=C2)O)C(=O)N2CC3=CC=CC=C3C[C@H]2C)C=C1 CPLABKXRSSWJQJ-AREMUKBSSA-N 0.000 claims description 2
• YZSUTIXGABYDNG-JGCGQSQUSA-N N,1,2-trimethyl-5-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[2-[2-(4-methylpiperazin-1-yl)phenyl]acetyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N-phenylpyrrole-3-carboxamide Chemical compound CN(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=C(C=CC=C1)N1CCN(CC1)C)=O)C)C)C1=CC=CC=C1 YZSUTIXGABYDNG-JGCGQSQUSA-N 0.000 claims description 2
• KBEOILANGIMPHJ-JGCGQSQUSA-N N,1,2-trimethyl-5-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[2-[3-(4-methylpiperazin-1-yl)phenyl]acetyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N-phenylpyrrole-3-carboxamide Chemical compound CN(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=CC(=CC=C1)N1CCN(CC1)C)=O)C)C)C1=CC=CC=C1 KBEOILANGIMPHJ-JGCGQSQUSA-N 0.000 claims description 2
• WNWKGHSHCIFVHB-UUWRZZSWSA-N N,N-dibutyl-1,2-dimethyl-5-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[2-[2-(4-methylpiperazin-1-yl)phenyl]acetyl]-3,4-dihydro-1H-isoquinolin-6-yl]pyrrole-3-carboxamide Chemical compound C(CCC)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=C(C=CC=C1)N1CCN(CC1)C)=O)C)C)CCCC WNWKGHSHCIFVHB-UUWRZZSWSA-N 0.000 claims description 2
• UCASCSSWCGQJDJ-UUWRZZSWSA-N N,N-dibutyl-1,2-dimethyl-5-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[2-[3-(4-methylpiperazin-1-yl)phenyl]acetyl]-3,4-dihydro-1H-isoquinolin-6-yl]pyrrole-3-carboxamide Chemical compound C(CCC)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=CC(=CC=C1)N1CCN(CC1)C)=O)C)C)CCCC UCASCSSWCGQJDJ-UUWRZZSWSA-N 0.000 claims description 2
• OCQGEZNIRVNBMR-JGCGQSQUSA-N N,N-dibutyl-5-[2-[2-[2-[(dimethylamino)methyl]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-1,2-dimethylpyrrole-3-carboxamide Chemical compound C(CCC)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=C(C=CC=C1)CN(C)C)=O)C)C)CCCC OCQGEZNIRVNBMR-JGCGQSQUSA-N 0.000 claims description 2
• XHVLPSYDBXWNAU-MGBGTMOVSA-N N,N-dibutyl-5-[2-[2-[2-[2-(dimethylamino)ethoxy]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-1,2-dimethylpyrrole-3-carboxamide Chemical compound C(CCC)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=C(C=CC=C1)OCCN(C)C)=O)C)C)CCCC XHVLPSYDBXWNAU-MGBGTMOVSA-N 0.000 claims description 2
• KTLQJWJRSZBFQK-MGBGTMOVSA-N N,N-dibutyl-5-[2-[2-[2-[2-(dimethylamino)ethyl]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-1,2-dimethylpyrrole-3-carboxamide Chemical compound C(CCC)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=C(C=CC=C1)CCN(C)C)=O)C)C)CCCC KTLQJWJRSZBFQK-MGBGTMOVSA-N 0.000 claims description 2
• MYGXQTTZYNKFJB-JGCGQSQUSA-N N,N-dibutyl-5-[2-[2-[3-[(dimethylamino)methyl]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-1,2-dimethylpyrrole-3-carboxamide Chemical compound C(CCC)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=CC(=CC=C1)CN(C)C)=O)C)C)CCCC MYGXQTTZYNKFJB-JGCGQSQUSA-N 0.000 claims description 2
• DLHMNIQQCSSFOW-MGBGTMOVSA-N N,N-dibutyl-5-[2-[2-[3-[2-(dimethylamino)ethoxy]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-1,2-dimethylpyrrole-3-carboxamide Chemical compound C(CCC)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=CC(=CC=C1)OCCN(C)C)=O)C)C)CCCC DLHMNIQQCSSFOW-MGBGTMOVSA-N 0.000 claims description 2
• SZCKZWKYTKKSHL-MGBGTMOVSA-N N,N-dibutyl-5-[2-[2-[3-[2-(dimethylamino)ethyl]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-1,2-dimethylpyrrole-3-carboxamide Chemical compound C(CCC)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=CC(=CC=C1)CCN(C)C)=O)C)C)CCCC SZCKZWKYTKKSHL-MGBGTMOVSA-N 0.000 claims description 2
• RLIHDAMWVSYBQO-MUUNZHRXSA-N N-(4-hydroxyphenyl)-3-[2-[2-(4-methoxyphenyl)acetyl]-6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-dihydroisoindol-5-yl]-N-methyl-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=CC=C(C=C1)OC)=O)C RLIHDAMWVSYBQO-MUUNZHRXSA-N 0.000 claims description 2
• MUBDETCPNUIMOM-AREMUKBSSA-N N-(4-hydroxyphenyl)-5-[2-[2-(4-methoxyphenyl)acetyl]-6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-dihydroisoindol-5-yl]-N,1,2-trimethylpyrrole-3-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C1=C(N(C(=C1)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=CC=C(C=C1)OC)=O)C)C)C MUBDETCPNUIMOM-AREMUKBSSA-N 0.000 claims description 2
• VRFUZDNKQFXBEQ-MUUNZHRXSA-N N-(4-hydroxyphenyl)-5-[2-[3-(4-methoxyphenyl)propyl]-6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-dihydroisoindol-5-yl]-N,1,2-trimethylpyrrole-3-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C1=C(N(C(=C1)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)CCCC1=CC=C(C=C1)OC)C)C)C VRFUZDNKQFXBEQ-MUUNZHRXSA-N 0.000 claims description 2
• DRJQLKWDXWKBEC-HHHXNRCGSA-N N-(4-hydroxyphenyl)-N,1,2-trimethyl-5-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(2-phenylmethoxyacetyl)-1,3-dihydroisoindol-5-yl]pyrrole-3-carboxamide Chemical compound C(C1=CC=CC=C1)OCC(=O)N1CC2=CC(=C(C=C2C1)C1=CC(=C(N1C)C)C(=O)N(C)C1=CC=C(C=C1)O)C(=O)N1CC2=CC=CC=C2C[C@H]1C DRJQLKWDXWKBEC-HHHXNRCGSA-N 0.000 claims description 2
• RCHJWQDMFLFGPZ-SSEXGKCCSA-N N-(4-hydroxyphenyl)-N-methyl-3-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[2-(4-methylphenyl)acetyl]-3,4-dihydro-1H-isoquinolin-6-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=CC=C(C=C1)C)=O)C RCHJWQDMFLFGPZ-SSEXGKCCSA-N 0.000 claims description 2
• BCEQFIZLMALFBJ-MGBGTMOVSA-N N-(4-hydroxyphenyl)-N-methyl-3-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[2-[3-(4-methylpiperazin-1-yl)phenyl]acetyl]-3,4-dihydro-1H-isoquinolin-6-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C[C@@H]1Cc2ccccc2CN1C(=O)c1cc2CN(CCc2cc1-c1cc(C(=O)N(C)c2ccc(O)cc2)c2CCCCn12)C(=O)Cc1cccc(c1)N1CCN(C)CC1 BCEQFIZLMALFBJ-MGBGTMOVSA-N 0.000 claims description 2
• VKADONZIRXQBOL-UUWRZZSWSA-N N-(4-hydroxyphenyl)-N-methyl-3-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[2-[4-(2-morpholin-4-ylethylamino)phenyl]acetyl]-3,4-dihydro-1H-isoquinolin-6-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C[C@@H]1Cc2ccccc2CN1C(=O)c1cc2CN(CCc2cc1-c1cc(C(=O)N(C)c2ccc(O)cc2)c2CCCCn12)C(=O)Cc1ccc(NCCN2CCOCC2)cc1 VKADONZIRXQBOL-UUWRZZSWSA-N 0.000 claims description 2
• 229940079156 Proteasome inhibitor Drugs 0.000 claims description 2
• 150000008064 anhydrides Chemical class 0.000 claims description 2
• 230000000340 anti-metabolite Effects 0.000 claims description 2
• 239000002256 antimetabolite Substances 0.000 claims description 2
• 229940100197 antimetabolite Drugs 0.000 claims description 2
• 239000002246 antineoplastic agent Substances 0.000 claims description 2
• 150000007942 carboxylates Chemical class 0.000 claims description 2
• 238000010511 deprotection reaction Methods 0.000 claims description 2
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
• 210000003238 esophagus Anatomy 0.000 claims description 2
• 231100000024 genotoxic Toxicity 0.000 claims description 2
• 230000001738 genotoxic effect Effects 0.000 claims description 2
• HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 claims description 2
• 125000001041 indolyl group Chemical group 0.000 claims description 2
• 229940043355 kinase inhibitor Drugs 0.000 claims description 2
• 230000000394 mitotic effect Effects 0.000 claims description 2
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
• 239000003757 phosphotransferase inhibitor Substances 0.000 claims description 2
• 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 239000003207 proteasome inhibitor Substances 0.000 claims description 2
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 2
• 239000005711 Benzoic acid Substances 0.000 claims 9
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 9
• 235000010233 benzoic acid Nutrition 0.000 claims 9
• 125000004185 ester group Chemical group 0.000 claims 3
• WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 claims 2
• AKWIAIDKXNKXDI-UHFFFAOYSA-N 1h-pyrrole-3-carboxamide Chemical compound NC(=O)C=1C=CNC=1 AKWIAIDKXNKXDI-UHFFFAOYSA-N 0.000 claims 1
• ALYDMGVZWDSMAN-HHHXNRCGSA-N 3-[2-[6-[1,5-dimethyl-4-[methyl(phenyl)carbamoyl]pyrrol-2-yl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-2-yl]-2-oxoethyl]benzoic acid Chemical compound CN1C(=CC(=C1C)C(N(C1=CC=CC=C1)C)=O)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC=1C=C(C(=O)O)C=CC=1)=O ALYDMGVZWDSMAN-HHHXNRCGSA-N 0.000 claims 1
• HPPCQEYCQSCWKN-GDLZYMKVSA-N 3-[2-[6-[4-(dibutylcarbamoyl)-1,5-dimethylpyrrol-2-yl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-2-yl]-2-oxoethyl]benzoic acid Chemical compound C(CCC)N(C(=O)C=1C=C(N(C=1C)C)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC=1C=C(C(=O)O)C=CC=1)=O)CCCC HPPCQEYCQSCWKN-GDLZYMKVSA-N 0.000 claims 1
• GPJBRIWZYUUWMF-FAIXQHPJSA-N 3-[2-[6-[4-(dibutylcarbamoyl)-1,5-dimethylpyrrol-2-yl]-7-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-2-yl]-2-oxoethyl]benzoic acid Chemical compound C(CCC)N(C(=O)C=1C=C(N(C=1C)C)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1CN1CCOCC1)C(CC=1C=C(C(=O)O)C=CC=1)=O)CCCC GPJBRIWZYUUWMF-FAIXQHPJSA-N 0.000 claims 1
• YJQGEWJBOFNQSJ-HHHXNRCGSA-N 4-[2-[6-[1,5-dimethyl-4-[methyl(phenyl)carbamoyl]pyrrol-2-yl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-2-yl]-2-oxoethyl]benzoic acid Chemical compound CN1C(=CC(=C1C)C(N(C1=CC=CC=C1)C)=O)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=CC=C(C(=O)O)C=C1)=O YJQGEWJBOFNQSJ-HHHXNRCGSA-N 0.000 claims 1
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• DUPZOFVXAWLDLZ-GDLZYMKVSA-N 4-[2-[6-[4-(dibutylcarbamoyl)-1,5-dimethylpyrrol-2-yl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-2-yl]-2-oxoethyl]benzoic acid Chemical compound C(CCC)N(C(=O)C=1C=C(N(C=1C)C)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=CC=C(C(=O)O)C=C1)=O)CCCC DUPZOFVXAWLDLZ-GDLZYMKVSA-N 0.000 claims 1
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• FVQFTTDUPKGYLN-MGBGTMOVSA-N N,N-dibutyl-5-[2-[2-[4-[2-(dimethylamino)ethyl]phenyl]acetyl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-1,2-dimethylpyrrole-3-carboxamide Chemical compound C(CCC)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=CC=C(C=C1)CCN(C)C)=O)C)C)CCCC FVQFTTDUPKGYLN-MGBGTMOVSA-N 0.000 claims 1
• MEPSHWKAVHHAPM-AYAUXRGRSA-N N-(4-hydroxyphenyl)-5-[2-[(E)-3-(3-methoxyphenyl)prop-2-enoyl]-7-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N,1,2-trimethylpyrrole-3-carboxamide Chemical compound COc1cccc(\C=C\C(=O)N2CCc3cc(-c4cc(C(=O)N(C)c5ccc(O)cc5)c(C)n4C)c(cc3C2)C(=O)N2Cc3ccccc3C[C@H]2CN2CCOCC2)c1 MEPSHWKAVHHAPM-AYAUXRGRSA-N 0.000 claims 1
• TZDRLUJQFRPRAP-NLIBRCFJSA-N N-(4-hydroxyphenyl)-N-methyl-3-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[2-methyl-3-(4-methylphenyl)propanoyl]-1,3-dihydroisoindol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound CC(Cc1ccc(C)cc1)C(=O)N1Cc2cc(C(=O)N3Cc4ccccc4C[C@H]3C)c(cc2C1)-c1cc(C(=O)N(C)c2ccc(O)cc2)c2CCCCn12 TZDRLUJQFRPRAP-NLIBRCFJSA-N 0.000 claims 1
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• KQICFEOOWYKFFN-AREMUKBSSA-N OC1=CC=C(C=C1)N(C(=O)C=1C=C(N(C=1C)C)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC=1C=C(C(=O)O)C=CC=1)=O)C Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N(C=1C)C)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC=1C=C(C(=O)O)C=CC=1)=O)C KQICFEOOWYKFFN-AREMUKBSSA-N 0.000 claims 1
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• HVJWEFLFDOAFTC-WJOKGBTCSA-N [2-(4-methylpiperazin-1-yl)phenyl] 6-[1,5-dimethyl-4-[methyl(phenyl)carbamoyl]pyrrol-2-yl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinoline-2-carboxylate Chemical compound CN1C(=CC(=C1C)C(N(C1=CC=CC=C1)C)=O)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(=O)OC1=C(C=CC=C1)N1CCN(CC1)C HVJWEFLFDOAFTC-WJOKGBTCSA-N 0.000 claims 1
• NEQOPSCISADARX-MGBGTMOVSA-N [2-(4-methylpiperazin-1-yl)phenyl] 6-[4-(dibutylcarbamoyl)-1,5-dimethylpyrrol-2-yl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinoline-2-carboxylate Chemical compound C(CCC)N(C(=O)C=1C=C(N(C=1C)C)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(=O)OC1=C(C=CC=C1)N1CCN(CC1)C)CCCC NEQOPSCISADARX-MGBGTMOVSA-N 0.000 claims 1
• GLBFIEGHRUXZOU-WJOKGBTCSA-N [3-(4-methylpiperazin-1-yl)phenyl] 6-[1,5-dimethyl-4-[methyl(phenyl)carbamoyl]pyrrol-2-yl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinoline-2-carboxylate Chemical compound CN1C(=CC(=C1C)C(N(C1=CC=CC=C1)C)=O)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(=O)OC1=CC(=CC=C1)N1CCN(CC1)C GLBFIEGHRUXZOU-WJOKGBTCSA-N 0.000 claims 1
• LXSLIPTUCQNOHZ-MGBGTMOVSA-N [3-(4-methylpiperazin-1-yl)phenyl] 6-[4-(dibutylcarbamoyl)-1,5-dimethylpyrrol-2-yl]-7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-3,4-dihydro-1H-isoquinoline-2-carboxylate Chemical compound C(CCC)N(C(=O)C=1C=C(N(C=1C)C)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(=O)OC1=CC(=CC=C1)N1CCN(CC1)C)CCCC LXSLIPTUCQNOHZ-MGBGTMOVSA-N 0.000 claims 1
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• JYEHMDDMNNLNRP-RUZDIDTESA-N N-(4-hydroxyphenyl)-N,1,2-trimethyl-5-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(2-pyrrol-1-ylacetyl)-1,3-dihydroisoindol-5-yl]pyrrole-3-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C1=C(N(C(=C1)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CN1C=CC=C1)=O)C)C)C JYEHMDDMNNLNRP-RUZDIDTESA-N 0.000 description 1
• RYCNDWXEUNHNDO-XMMPIXPASA-N N-(4-hydroxyphenyl)-N,1,2-trimethyl-5-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(2-thiophen-3-ylacetyl)-1,3-dihydroisoindol-5-yl]pyrrole-3-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C1=C(N(C(=C1)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=CSC=C1)=O)C)C)C RYCNDWXEUNHNDO-XMMPIXPASA-N 0.000 description 1
• ALIOFIVZFAWHGR-KAYWLYCHSA-N N-(4-hydroxyphenyl)-N,1,2-trimethyl-5-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[(2R)-2-phenylpropanoyl]-1,3-dihydroisoindol-5-yl]pyrrole-3-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C1=C(N(C(=C1)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C([C@H](C)C1=CC=CC=C1)=O)C)C)C ALIOFIVZFAWHGR-KAYWLYCHSA-N 0.000 description 1
• ALIOFIVZFAWHGR-SXOMAYOGSA-N N-(4-hydroxyphenyl)-N,1,2-trimethyl-5-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[(2S)-2-phenylpropanoyl]-1,3-dihydroisoindol-5-yl]pyrrole-3-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C1=C(N(C(=C1)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C([C@@H](C)C1=CC=CC=C1)=O)C)C)C ALIOFIVZFAWHGR-SXOMAYOGSA-N 0.000 description 1
• SIZAJJFBXWUFTG-BHVANESWSA-N N-(4-hydroxyphenyl)-N,1,2-trimethyl-5-[6-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1-oxo-2-(2-phenylethyl)-3H-isoindol-5-yl]pyrrole-3-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C1=C(N(C(=C1)C=1C=C2CN(C(C2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1CN1CCOCC1)=O)CCC1=CC=CC=C1)C)C)C SIZAJJFBXWUFTG-BHVANESWSA-N 0.000 description 1
• MANPQVTVPJKWGC-BHVANESWSA-N N-(4-hydroxyphenyl)-N,1,2-trimethyl-5-[6-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(2-phenoxyacetyl)-1,3-dihydroisoindol-5-yl]pyrrole-3-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C1=C(N(C(=C1)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1CN1CCOCC1)C(COC1=CC=CC=C1)=O)C)C)C MANPQVTVPJKWGC-BHVANESWSA-N 0.000 description 1
• VYIAGHTYQMKCKB-MUUNZHRXSA-N N-(4-hydroxyphenyl)-N,1,2-trimethyl-5-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(2-phenylethyl)-3,4-dihydro-1H-isoquinolin-6-yl]pyrrole-3-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)CCC1=CC=CC=C1)C)C)C VYIAGHTYQMKCKB-MUUNZHRXSA-N 0.000 description 1
• VMYWKANLKODCPD-AREMUKBSSA-N N-(4-hydroxyphenyl)-N,1,2-trimethyl-5-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(phenylsulfamoyl)-3,4-dihydro-1H-isoquinolin-6-yl]pyrrole-3-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)S(NC1=CC=CC=C1)(=O)=O)C)C)C VMYWKANLKODCPD-AREMUKBSSA-N 0.000 description 1
• SOLUWLKJVZLMFW-HHHXNRCGSA-N N-(4-hydroxyphenyl)-N,1,2-trimethyl-5-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[methyl(phenyl)sulfamoyl]-3,4-dihydro-1H-isoquinolin-6-yl]pyrrole-3-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)S(N(C1=CC=CC=C1)C)(=O)=O)C)C)C SOLUWLKJVZLMFW-HHHXNRCGSA-N 0.000 description 1
• IHGHAZNLMDAZJQ-QNGWXLTQSA-N N-(4-hydroxyphenyl)-N,1,2-trimethyl-5-[7-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1-oxo-2-(2-phenylethyl)-3,4-dihydroisoquinolin-6-yl]pyrrole-3-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(C(C2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1CN1CCOCC1)=O)CCC1=CC=CC=C1)C)C)C IHGHAZNLMDAZJQ-QNGWXLTQSA-N 0.000 description 1
• CZTABKSVCXJGAU-QNGWXLTQSA-N N-(4-hydroxyphenyl)-N,1,2-trimethyl-5-[7-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(2-phenoxyacetyl)-3,4-dihydro-1H-isoquinolin-6-yl]pyrrole-3-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C1=C(N(C(=C1)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1CN1CCOCC1)C(COC1=CC=CC=C1)=O)C)C)C CZTABKSVCXJGAU-QNGWXLTQSA-N 0.000 description 1
• WHZIERIQTFFIGO-KTPRTSPUSA-N N-(4-hydroxyphenyl)-N,1,2-trimethyl-5-[7-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[(E)-3-phenylprop-2-enoyl]-3,4-dihydro-1H-isoquinolin-6-yl]pyrrole-3-carboxamide Chemical compound CN(C(=O)c1cc(-c2cc3CCN(Cc3cc2C(=O)N2Cc3ccccc3C[C@H]2CN2CCOCC2)C(=O)\C=C\c2ccccc2)n(C)c1C)c1ccc(O)cc1 WHZIERIQTFFIGO-KTPRTSPUSA-N 0.000 description 1
• QDAULIJBICWXGG-MUUNZHRXSA-N N-(4-hydroxyphenyl)-N-methyl-3-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(2-phenylacetyl)-1,3-dihydroisoindol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC1=CC=CC=C1)=O)C QDAULIJBICWXGG-MUUNZHRXSA-N 0.000 description 1
• VGXZNYZBUGHDTN-MUUNZHRXSA-N N-(4-hydroxyphenyl)-N-methyl-3-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(2-phenylsulfanylacetyl)-1,3-dihydroisoindol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CSC1=CC=CC=C1)=O)C VGXZNYZBUGHDTN-MUUNZHRXSA-N 0.000 description 1
• RUNUGRQKIKAEAG-GDLZYMKVSA-N N-(4-hydroxyphenyl)-N-methyl-3-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(3-phenylazetidine-1-carbonyl)-1,3-dihydroisoindol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(=O)N1CC(C1)C1=CC=CC=C1)C RUNUGRQKIKAEAG-GDLZYMKVSA-N 0.000 description 1
• FQXMDHQUTCWHCZ-GDLZYMKVSA-N N-(4-hydroxyphenyl)-N-methyl-3-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(3-phenylpropanoyl)-1,3-dihydroisoindol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CCC1=CC=CC=C1)=O)C FQXMDHQUTCWHCZ-GDLZYMKVSA-N 0.000 description 1
• VAJKOLKZYHMYMH-HHHXNRCGSA-N N-(4-hydroxyphenyl)-N-methyl-3-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(pyridin-2-ylmethyl)-1,3-dihydroisoindol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)CC1=NC=CC=C1)C VAJKOLKZYHMYMH-HHHXNRCGSA-N 0.000 description 1
• MEECIINAGWYRTB-HHHXNRCGSA-N N-(4-hydroxyphenyl)-N-methyl-3-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[2-[4-(trifluoromethoxy)phenyl]acetyl]-1,3-dihydroisoindol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C[C@@H]1Cc2ccccc2CN1C(=O)c1cc2CN(Cc2cc1-c1cc(C(=O)N(C)c2ccc(O)cc2)c2CCCCn12)C(=O)Cc1ccc(OC(F)(F)F)cc1 MEECIINAGWYRTB-HHHXNRCGSA-N 0.000 description 1
• HHTLYQBSHOIQIA-HKBQPEDESA-N N-(4-hydroxyphenyl)-N-methyl-3-[6-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2,3-dihydro-1H-isoindol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CNCC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1CN1CCOCC1)C HHTLYQBSHOIQIA-HKBQPEDESA-N 0.000 description 1
• FIZRDWTUIHTOQT-QNGWXLTQSA-N N-(4-hydroxyphenyl)-N-methyl-3-[6-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(2-phenoxyacetyl)-1,3-dihydroisoindol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1CN1CCOCC1)C(COC1=CC=CC=C1)=O)C FIZRDWTUIHTOQT-QNGWXLTQSA-N 0.000 description 1
• ZXWVPDDTZQQCRH-QNGWXLTQSA-N N-(4-hydroxyphenyl)-N-methyl-3-[6-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(2-phenoxyacetyl)-1,3-dihydroisoindol-5-yl]indolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2C=CC=CC=12)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1CN1CCOCC1)C(COC1=CC=CC=C1)=O)C ZXWVPDDTZQQCRH-QNGWXLTQSA-N 0.000 description 1
• MQRVYPJRTKUDEH-XIFFEERXSA-N N-(4-hydroxyphenyl)-N-methyl-3-[6-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-propanoyl-1,3-dihydroisoindol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1CN1CCOCC1)C(CC)=O)C MQRVYPJRTKUDEH-XIFFEERXSA-N 0.000 description 1
• XSPPIOVFTSQOCI-VNNZMUOVSA-N N-(4-hydroxyphenyl)-N-methyl-3-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(2-phenylbutanoyl)-3,4-dihydro-1H-isoquinolin-6-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(C(CC)C1=CC=CC=C1)=O)C XSPPIOVFTSQOCI-VNNZMUOVSA-N 0.000 description 1
• BMVSOWWEHZODLY-SSEXGKCCSA-N N-(4-hydroxyphenyl)-N-methyl-3-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(3-phenylazetidine-1-carbonyl)-3,4-dihydro-1H-isoquinolin-6-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C[C@@H]1Cc2ccccc2CN1C(=O)c1cc2CN(CCc2cc1-c1cc(C(=O)N(C)c2ccc(O)cc2)c2CCCCn12)C(=O)N1CC(C1)c1ccccc1 BMVSOWWEHZODLY-SSEXGKCCSA-N 0.000 description 1
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• SNLPTIFNKSZUFK-LOYHVIPDSA-N N-(4-hydroxyphenyl)-N-methyl-3-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-[(2R)-2-phenylpropanoyl]-3,4-dihydro-1H-isoquinolin-6-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C([C@H](C)C1=CC=CC=C1)=O)C SNLPTIFNKSZUFK-LOYHVIPDSA-N 0.000 description 1
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• ZLODSQBADAHTJY-SSEXGKCCSA-N N-(4-hydroxyphenyl)-N-methyl-3-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-naphthalen-2-ylsulfonyl-3,4-dihydro-1H-isoquinolin-6-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)S(=O)(=O)C1=CC2=CC=CC=C2C=C1)C ZLODSQBADAHTJY-SSEXGKCCSA-N 0.000 description 1
• NVYBKMBWVFIVLC-RUZDIDTESA-N N-(4-hydroxyphenyl)-N-methyl-3-[7-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-propanoyl-3,4-dihydro-1H-isoquinolin-6-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CCN(CC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C(CC)=O)C NVYBKMBWVFIVLC-RUZDIDTESA-N 0.000 description 1
• GEPQHKOIEXNXGJ-YTTGMZPUSA-N N-(4-hydroxyphenyl)-N-methyl-3-[7-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,2,3,4-tetrahydroisoquinolin-6-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C=1C=C2CCNCC2=CC=1C(=O)N1CC2=CC=CC=C2C[C@H]1CN1CCOCC1)C GEPQHKOIEXNXGJ-YTTGMZPUSA-N 0.000 description 1
• ZPGAJRRNWBDUKW-KDXMTYKHSA-N N-(4-hydroxyphenyl)-N-methyl-3-[7-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-(2-phenylacetyl)-3,4-dihydro-1H-isoquinolin-6-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound CN(C(=O)c1cc(-c2cc3CCN(Cc3cc2C(=O)N2Cc3ccccc3C[C@H]2CN2CCOCC2)C(=O)Cc2ccccc2)n2CCCCc12)c1ccc(O)cc1 ZPGAJRRNWBDUKW-KDXMTYKHSA-N 0.000 description 1
• QVFBLUXCXXWMHX-RWYGWLOXSA-N N-(4-hydroxyphenyl)-N-methyl-3-[7-[(3S)-3-(morpholin-4-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2-naphthalen-2-ylsulfonyl-3,4-dihydro-1H-isoquinolin-6-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound CN(C(=O)c1cc(-c2cc3CCN(Cc3cc2C(=O)N2Cc3ccccc3C[C@H]2CN2CCOCC2)S(=O)(=O)c2ccc3ccccc3c2)n2CCCCc12)c1ccc(O)cc1 QVFBLUXCXXWMHX-RWYGWLOXSA-N 0.000 description 1
• FEYNFHSRETUBEM-UHFFFAOYSA-N N-[3-(1,1-difluoroethyl)phenyl]-1-(4-methoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide Chemical compound COc1ccc(cc1)N1N=C(C)C(C(=O)Nc2cccc(c2)C(C)(F)F)C1=O FEYNFHSRETUBEM-UHFFFAOYSA-N 0.000 description 1
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