CN109897038B - 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 - Google Patents
用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 Download PDFInfo
- Publication number
- CN109897038B CN109897038B CN201910261444.3A CN201910261444A CN109897038B CN 109897038 B CN109897038 B CN 109897038B CN 201910261444 A CN201910261444 A CN 201910261444A CN 109897038 B CN109897038 B CN 109897038B
- Authority
- CN
- China
- Prior art keywords
- nhr
- methyl
- nhc
- sulfonyl
- pyridin
- Prior art date
- 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
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 10
- 201000011510 cancer Diseases 0.000 title claims abstract description 4
- 208000023275 Autoimmune disease Diseases 0.000 title abstract description 4
- 230000006907 apoptotic process Effects 0.000 title abstract description 3
- 208000026278 immune system disease Diseases 0.000 title abstract description 3
- 230000001939 inductive effect Effects 0.000 title abstract description 3
- 239000000203 mixture Substances 0.000 claims abstract description 9
- -1 4- { [2- (4-chlorophenyl) -4, 4-dimethylcyclohex-1-en-1-yl ] methyl } piperazin-1-yl Chemical group 0.000 claims description 407
- 239000003814 drug Substances 0.000 claims description 33
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 7
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 7
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 7
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 7
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 7
- 206010005003 Bladder cancer Diseases 0.000 claims description 5
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 5
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 5
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 5
- 208000003445 Mouth Neoplasms Diseases 0.000 claims description 5
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 5
- 208000000277 Splenic Neoplasms Diseases 0.000 claims description 5
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 5
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 5
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 5
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 5
- 201000006491 bone marrow cancer Diseases 0.000 claims description 5
- 201000010881 cervical cancer Diseases 0.000 claims description 5
- 201000004101 esophageal cancer Diseases 0.000 claims description 5
- 201000003444 follicular lymphoma Diseases 0.000 claims description 5
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 5
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 claims description 5
- 230000036210 malignancy Effects 0.000 claims description 5
- 201000001441 melanoma Diseases 0.000 claims description 5
- 208000025113 myeloid leukemia Diseases 0.000 claims description 5
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 5
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 5
- 201000002471 spleen cancer Diseases 0.000 claims description 5
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 5
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 5
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 4
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 4
- 208000003747 lymphoid leukemia Diseases 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 80
- 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 abstract description 12
- 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 abstract description 12
- 230000002424 anti-apoptotic effect Effects 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 7
- 238000000034 method Methods 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
- 201000010099 disease Diseases 0.000 abstract description 4
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 abstract description 3
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 715
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 715
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 582
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 463
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 416
- 150000002390 heteroarenes Chemical class 0.000 description 194
- 150000001925 cycloalkenes Chemical class 0.000 description 192
- 150000001924 cycloalkanes Chemical class 0.000 description 184
- 239000000460 chlorine Substances 0.000 description 148
- 125000000753 cycloalkyl group Chemical group 0.000 description 147
- 229910052801 chlorine Inorganic materials 0.000 description 129
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 129
- 229910052740 iodine Inorganic materials 0.000 description 127
- 229910052794 bromium Inorganic materials 0.000 description 126
- 125000000217 alkyl group Chemical group 0.000 description 124
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 112
- 229910004013 NO 2 Inorganic materials 0.000 description 100
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 94
- 125000001072 heteroaryl group Chemical group 0.000 description 77
- 125000001424 substituent group Chemical group 0.000 description 75
- 125000000392 cycloalkenyl group Chemical group 0.000 description 74
- 229910052757 nitrogen Inorganic materials 0.000 description 74
- 125000000304 alkynyl group Chemical group 0.000 description 65
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 65
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 64
- 229910052739 hydrogen Inorganic materials 0.000 description 59
- 229910052731 fluorine Inorganic materials 0.000 description 58
- 125000003342 alkenyl group Chemical group 0.000 description 57
- 229910052799 carbon Inorganic materials 0.000 description 54
- 150000003839 salts Chemical class 0.000 description 52
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 50
- 239000002585 base Substances 0.000 description 49
- OTXBWGUYZNKPMG-UHFFFAOYSA-N isofulminic acid Chemical compound O[N+]#[C-] OTXBWGUYZNKPMG-UHFFFAOYSA-N 0.000 description 48
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 47
- 125000004429 atom Chemical group 0.000 description 44
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 38
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 36
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 33
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 27
- 125000004432 carbon atom Chemical group C* 0.000 description 27
- 125000004122 cyclic group Chemical group 0.000 description 25
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- SVSARCCKBMZNMR-UHFFFAOYSA-N [1-[2-[methyl-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethyl]amino]ethyl]pyridin-4-ylidene]methyl-oxoazanium;dichloride Chemical compound [Cl-].[Cl-].C1=CC(=C[NH+]=O)C=CN1CCN(C)CCN1C=CC(=C[NH+]=O)C=C1 SVSARCCKBMZNMR-UHFFFAOYSA-N 0.000 description 21
- 125000003386 piperidinyl group Chemical group 0.000 description 21
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 19
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 15
- 229910052717 sulfur Inorganic materials 0.000 description 15
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 14
- 125000002950 monocyclic group Chemical group 0.000 description 14
- 125000001183 hydrocarbyl group Chemical group 0.000 description 12
- 239000002207 metabolite Substances 0.000 description 12
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 12
- 125000002947 alkylene group Chemical group 0.000 description 11
- 125000004193 piperazinyl group Chemical group 0.000 description 11
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 10
- 125000005549 heteroarylene group Chemical group 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 125000004450 alkenylene group Chemical group 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 125000006588 heterocycloalkylene group Chemical group 0.000 description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 8
- OYBAZZOEJSIHOL-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[(4-methylmorpholin-2-yl)methylamino]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1N(C)CCOC1CNC1=CC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1[N+]([O-])=O OYBAZZOEJSIHOL-UHFFFAOYSA-N 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 125000005724 cycloalkenylene group Chemical group 0.000 description 7
- 125000002993 cycloalkylene group Chemical group 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- 125000002757 morpholinyl group Chemical group 0.000 description 7
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 7
- WKULGVVLSQGJTK-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-hydroxy-4-methylcyclohexyl)methylamino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCC(C)(O)CC1 WKULGVVLSQGJTK-UHFFFAOYSA-N 0.000 description 6
- RYUKEAYYUZJDNE-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[6-[(4-hydroxy-4-methylcyclohexyl)methylamino]-5-nitropyridin-3-yl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CN=C1NCC1CCC(C)(O)CC1 RYUKEAYYUZJDNE-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 6
- 125000004419 alkynylene group Chemical group 0.000 description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
- 101150009274 nhr-1 gene Proteins 0.000 description 6
- 229930195734 saturated hydrocarbon Natural products 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 5
- 125000002541 furyl group Chemical group 0.000 description 5
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
- 125000000547 substituted alkyl group Chemical group 0.000 description 5
- LQBVNQSMGBZMKD-UHFFFAOYSA-N venetoclax Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCOCC1 LQBVNQSMGBZMKD-UHFFFAOYSA-N 0.000 description 5
- HGCQJSCVVNLDMQ-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-ethyl-4-hydroxycyclohexyl)methylamino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1CC(CC)(O)CCC1CNC1=CC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1[N+]([O-])=O HGCQJSCVVNLDMQ-UHFFFAOYSA-N 0.000 description 4
- NKITUFNNDFPWII-GTXVXJEKSA-N CC1(C)CCC(CN2CCN(CC2)c2ccc(C(=O)NS(=O)(=O)c3ccc(N[C@H]4CC[C@@H](CC4)N4CCOCC4)c(c3)[N+]([O-])=O)c(Oc3cnc4[nH]ccc4c3)c2)=C(C1)c1ccc(Cl)cc1 Chemical compound CC1(C)CCC(CN2CCN(CC2)c2ccc(C(=O)NS(=O)(=O)c3ccc(N[C@H]4CC[C@@H](CC4)N4CCOCC4)c(c3)[N+]([O-])=O)c(Oc3cnc4[nH]ccc4c3)c2)=C(C1)c1ccc(Cl)cc1 NKITUFNNDFPWII-GTXVXJEKSA-N 0.000 description 4
- 101100516561 Caenorhabditis elegans nhr-68 gene Proteins 0.000 description 4
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 229910052805 deuterium Inorganic materials 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- FGLBNVNJFBVRSE-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-3,3-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1C(C)(C)CCCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCOCC1 FGLBNVNJFBVRSE-UHFFFAOYSA-N 0.000 description 3
- JGIWGFDASVPCTP-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-[[4-(oxan-4-ylamino)cyclohexyl]amino]phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NC(CC1)CCC1NC1CCOCC1 JGIWGFDASVPCTP-UHFFFAOYSA-N 0.000 description 3
- LEHOPKMTNLSQEY-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-[[4-[4-(oxan-4-yl)piperazin-1-yl]cyclohexyl]amino]phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NC(CC1)CCC1N(CC1)CCN1C1CCOCC1 LEHOPKMTNLSQEY-UHFFFAOYSA-N 0.000 description 3
- PBWXDNYODFLHSA-ZCXBXHLPSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(1R,4R,5R,6S)-5,6-dihydroxy-2-bicyclo[2.2.1]heptanyl]methoxy]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1C(C)(C)CCC(CN2CCN(CC2)C=2C=C(OC=3C=C4C=CNC4=NC=3)C(C(=O)NS(=O)(=O)C=3C=C(C(OCC4[C@H]5C[C@H]([C@H]([C@H]5O)O)C4)=CC=3)[N+]([O-])=O)=CC=2)=C1C1=CC=C(Cl)C=C1 PBWXDNYODFLHSA-ZCXBXHLPSA-N 0.000 description 3
- PBWXDNYODFLHSA-WSVPCWEKSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(1R,4R,5S,6R)-5,6-dihydroxy-2-bicyclo[2.2.1]heptanyl]methoxy]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1C(C)(C)CCC(CN2CCN(CC2)C=2C=C(OC=3C=C4C=CNC4=NC=3)C(C(=O)NS(=O)(=O)C=3C=C(C(OCC4[C@H]5C[C@H]([C@@H]([C@@H]5O)O)C4)=CC=3)[N+]([O-])=O)=CC=2)=C1C1=CC=C(Cl)C=C1 PBWXDNYODFLHSA-WSVPCWEKSA-N 0.000 description 3
- FODFFPZUZIECRM-MLZZNZMKSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(1S,3R)-3-morpholin-4-ylcyclopentyl]methylamino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound N1([C@@H]2CC[C@@H](C2)CNC2=CC=C(C=C2[N+]([O-])=O)S(=O)(=O)NC(=O)C2=CC=C(C=C2OC=2C=C3C=CNC3=NC=2)N2CCN(CC2)CC=2CCC(CC=2C=2C=CC(Cl)=CC=2)(C)C)CCOCC1 FODFFPZUZIECRM-MLZZNZMKSA-N 0.000 description 3
- KBHSDAPEAXKGRS-DHUJRADRSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(2S)-4,4-difluoro-1-(oxetan-3-yl)pyrrolidin-2-yl]methoxy]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C([C@H]1COC2=CC=C(C=C2[N+]([O-])=O)S(=O)(=O)NC(=O)C2=CC=C(C=C2OC=2C=C3C=CNC3=NC=2)N2CCN(CC2)CC=2CCC(CC=2C=2C=CC(Cl)=CC=2)(C)C)C(F)(F)CN1C1COC1 KBHSDAPEAXKGRS-DHUJRADRSA-N 0.000 description 3
- XWCZPKOOJKYCEC-KOHORPAVSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[1-[(3R,4R)-3-fluorooxan-4-yl]piperidin-4-yl]amino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NC(CC1)CCN1[C@@H]1CCOC[C@@H]1F XWCZPKOOJKYCEC-KOHORPAVSA-N 0.000 description 3
- RMUGSEJQYOHCKD-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-cyano-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1C#N)=CC=C1NCC1CCOCC1 RMUGSEJQYOHCKD-UHFFFAOYSA-N 0.000 description 3
- IPJHSHPWOGVIPW-UUWRZZSWSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-[[(3r)-1-(oxetan-3-yl)pyrrolidin-3-yl]amino]phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C([C@H](C1)NC2=CC=C(C=C2[N+]([O-])=O)S(=O)(=O)NC(=O)C2=CC=C(C=C2OC=2C=C3C=CNC3=NC=2)N2CCN(CC2)CC=2CCC(CC=2C=2C=CC(Cl)=CC=2)(C)C)CN1C1COC1 IPJHSHPWOGVIPW-UUWRZZSWSA-N 0.000 description 3
- IPJHSHPWOGVIPW-UMSFTDKQSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-[[(3s)-1-(oxetan-3-yl)pyrrolidin-3-yl]amino]phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C([C@@H](C1)NC2=CC=C(C=C2[N+]([O-])=O)S(=O)(=O)NC(=O)C2=CC=C(C=C2OC=2C=C3C=CNC3=NC=2)N2CCN(CC2)CC=2CCC(CC=2C=2C=CC(Cl)=CC=2)(C)C)CN1C1COC1 IPJHSHPWOGVIPW-UMSFTDKQSA-N 0.000 description 3
- CPKNDGUPUXFCSU-HKBQPEDESA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-[[(3s)-1-(oxetan-3-yl)pyrrolidin-3-yl]methoxy]phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C([C@@H](C1)COC2=CC=C(C=C2[N+]([O-])=O)S(=O)(=O)NC(=O)C2=CC=C(C=C2OC=2C=C3C=CNC3=NC=2)N2CCN(CC2)CC=2CCC(CC=2C=2C=CC(Cl)=CC=2)(C)C)CN1C1COC1 CPKNDGUPUXFCSU-HKBQPEDESA-N 0.000 description 3
- MEKVNOOLCRQDHA-LHEWISCISA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-[[(3s)-2-oxopiperidin-3-yl]amino]phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1N[C@H]1CCCNC1=O MEKVNOOLCRQDHA-LHEWISCISA-N 0.000 description 3
- TZAYFMBZFWSUCQ-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-[[1-(oxan-4-yl)azetidin-3-yl]amino]phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NC(C1)CN1C1CCOCC1 TZAYFMBZFWSUCQ-UHFFFAOYSA-N 0.000 description 3
- AZIUZWNRHASVGU-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-[[1-(oxetan-3-yl)piperidin-4-yl]amino]phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NC(CC1)CCN1C1COC1 AZIUZWNRHASVGU-UHFFFAOYSA-N 0.000 description 3
- ARDFMFLYKPWMQB-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-[[1-(oxetan-3-yl)piperidin-4-yl]methoxy]phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1OCC(CC1)CCN1C1COC1 ARDFMFLYKPWMQB-UHFFFAOYSA-N 0.000 description 3
- XKEXBWKWKBRKKV-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-[[4-(oxetan-3-yl)piperazin-1-yl]amino]phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NN(CC1)CCN1C1COC1 XKEXBWKWKBRKKV-UHFFFAOYSA-N 0.000 description 3
- UMHANGCMNUIVTH-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-(1,4-dioxaspiro[4.5]decan-8-ylamino)-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NC(CC1)CCC21OCCO2 UMHANGCMNUIVTH-UHFFFAOYSA-N 0.000 description 3
- ARVNTYAWJFCNBT-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-(2-cyanoethylamino)-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C1=CC=C(NCCC#N)C([N+]([O-])=O)=C1 ARVNTYAWJFCNBT-UHFFFAOYSA-N 0.000 description 3
- HBVLATBANSZADQ-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-(4-morpholin-4-ylbut-2-ynoxy)-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1OCC#CCN1CCOCC1 HBVLATBANSZADQ-UHFFFAOYSA-N 0.000 description 3
- WWIUIQXQLHMYBL-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-(4-morpholin-4-ylpiperidin-1-yl)-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1N(CC1)CCC1N1CCOCC1 WWIUIQXQLHMYBL-UHFFFAOYSA-N 0.000 description 3
- SHPUGOCWFSTEOI-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-(morpholin-3-ylmethoxy)-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1OCC1COCCN1 SHPUGOCWFSTEOI-UHFFFAOYSA-N 0.000 description 3
- YNQNZAUOVAYQCE-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[(1-methyl-5-oxopyrrolidin-3-yl)amino]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1C(=O)N(C)CC1NC1=CC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1[N+]([O-])=O YNQNZAUOVAYQCE-UHFFFAOYSA-N 0.000 description 3
- YYCSXFRYHHWHHR-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[(1-methylpiperidin-4-yl)methoxy]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1CN(C)CCC1COC1=CC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1[N+]([O-])=O YYCSXFRYHHWHHR-UHFFFAOYSA-N 0.000 description 3
- YIWCJRDYDWHTFY-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[(1-methylpiperidin-4-yl)methylamino]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1CN(C)CCC1CNC1=CC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1[N+]([O-])=O YIWCJRDYDWHTFY-UHFFFAOYSA-N 0.000 description 3
- RSMQQIHISLSANF-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[(1-methylsulfonylpiperidin-4-yl)amino]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NC1CCN(S(C)(=O)=O)CC1 RSMQQIHISLSANF-UHFFFAOYSA-N 0.000 description 3
- VMTHNVBTTVZZPT-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[(3-hydroxy-2,2-dimethylpropyl)amino]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1=C([N+]([O-])=O)C(NCC(C)(CO)C)=CC=C1S(=O)(=O)NC(=O)C1=CC=C(N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)C=C1OC1=CN=C(NC=C2)C2=C1 VMTHNVBTTVZZPT-UHFFFAOYSA-N 0.000 description 3
- XSRSQZAQKMDUBK-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[(3-hydroxyphenyl)methylamino]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1=CC=CC(O)=C1 XSRSQZAQKMDUBK-UHFFFAOYSA-N 0.000 description 3
- BFSOHRWRNSMSCH-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[(3-methoxy-2,2-dimethylpropyl)amino]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1=C([N+]([O-])=O)C(NCC(C)(C)COC)=CC=C1S(=O)(=O)NC(=O)C1=CC=C(N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)C=C1OC1=CN=C(NC=C2)C2=C1 BFSOHRWRNSMSCH-UHFFFAOYSA-N 0.000 description 3
- AIKCIHDUQPPUKD-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[(4,4-difluorocyclohexyl)methylamino]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCC(F)(F)CC1 AIKCIHDUQPPUKD-UHFFFAOYSA-N 0.000 description 3
- DLRQIPOBRIJXHA-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[(4-ethylmorpholin-3-yl)methoxy]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound CCN1CCOCC1COC1=CC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1[N+]([O-])=O DLRQIPOBRIJXHA-UHFFFAOYSA-N 0.000 description 3
- BRQXNCXWHXCDPA-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[(4-hydroxy-1-adamantyl)methylamino]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1C(C)(C)CCC(CN2CCN(CC2)C=2C=C(OC=3C=C4C=CNC4=NC=3)C(C(=O)NS(=O)(=O)C=3C=C(C(NCC45CC6CC(CC(C6O)C5)C4)=CC=3)[N+]([O-])=O)=CC=2)=C1C1=CC=C(Cl)C=C1 BRQXNCXWHXCDPA-UHFFFAOYSA-N 0.000 description 3
- ZGMXABATFPPKSZ-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[(4-hydroxyphenyl)methylamino]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1=CC=C(O)C=C1 ZGMXABATFPPKSZ-UHFFFAOYSA-N 0.000 description 3
- MTYZNVLVSZYNFF-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[2-(2-methoxyethoxy)ethylsulfonyl]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1=C([N+]([O-])=O)C(S(=O)(=O)CCOCCOC)=CC=C1S(=O)(=O)NC(=O)C1=CC=C(N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)C=C1OC1=CN=C(NC=C2)C2=C1 MTYZNVLVSZYNFF-UHFFFAOYSA-N 0.000 description 3
- GKIAOZKGAIQVBO-OIDHKYIRSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[[(3r,4r)-4-(fluoromethyl)-1-(oxetan-3-yl)pyrrolidin-3-yl]methoxy]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C([C@@H]([C@H](C1)CF)COC2=CC=C(C=C2[N+]([O-])=O)S(=O)(=O)NC(=O)C2=CC=C(C=C2OC=2C=C3C=CNC3=NC=2)N2CCN(CC2)CC=2CCC(CC=2C=2C=CC(Cl)=CC=2)(C)C)N1C1COC1 GKIAOZKGAIQVBO-OIDHKYIRSA-N 0.000 description 3
- HKOUOBOWUXHPPX-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[[4-(2-morpholin-4-ylethoxy)phenyl]methylamino]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC(C=C1)=CC=C1OCCN1CCOCC1 HKOUOBOWUXHPPX-UHFFFAOYSA-N 0.000 description 3
- OBDIOCGTOVVKBJ-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[[4-fluoro-1-(oxetan-3-yl)piperidin-4-yl]methoxy]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1OCC(CC1)(F)CCN1C1COC1 OBDIOCGTOVVKBJ-UHFFFAOYSA-N 0.000 description 3
- IYJJTGJTNSOTQA-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[5-cyano-6-(oxan-4-ylmethoxy)pyridin-3-yl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1C#N)=CN=C1OCC1CCOCC1 IYJJTGJTNSOTQA-UHFFFAOYSA-N 0.000 description 3
- LPXYSNAJZKBWBC-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[5-ethynyl-6-(oxan-4-ylmethoxy)pyridin-3-yl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1C#C)=CN=C1OCC1CCOCC1 LPXYSNAJZKBWBC-UHFFFAOYSA-N 0.000 description 3
- AEVKJILLYZBTBT-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-naphthalen-2-ylsulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1C(C)(C)CCC(CN2CCN(CC2)C=2C=C(OC=3C=C4C=CNC4=NC=3)C(C(=O)NS(=O)(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=C1C1=CC=C(Cl)C=C1 AEVKJILLYZBTBT-UHFFFAOYSA-N 0.000 description 3
- RTVNBRWRPBHVKL-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1C(C)(C)CCC(C=2C=CC(Cl)=CC=2)=C1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCOCC1 RTVNBRWRPBHVKL-UHFFFAOYSA-N 0.000 description 3
- SIMDXFWGMPLGLA-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[5-cyano-6-(oxan-4-ylmethoxy)pyridin-3-yl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1C(C)(C)CCC(C=2C=CC(Cl)=CC=2)=C1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1C#N)=CN=C1OCC1CCOCC1 SIMDXFWGMPLGLA-UHFFFAOYSA-N 0.000 description 3
- LXEAMSGDMHPGRJ-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-6,6-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound CC1(C)CCCC(C=2C=CC(Cl)=CC=2)=C1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCOCC1 LXEAMSGDMHPGRJ-UHFFFAOYSA-N 0.000 description 3
- YLFDOJBSBXUPPK-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-n-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3C(=CC=CC=3)C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)=CC=C1NCC1CCOCC1 YLFDOJBSBXUPPK-UHFFFAOYSA-N 0.000 description 3
- HTGMQMQNQOJMDP-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-n-[4-(3-morpholin-4-ylpropylamino)-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3C(=CC=CC=3)C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)=CC=C1NCCCN1CCOCC1 HTGMQMQNQOJMDP-UHFFFAOYSA-N 0.000 description 3
- ITFBGCIOSFQLSO-UHFFFAOYSA-N 4-[4-[[4-(4-chlorophenyl)-6,6-dimethyl-2,5-dihydropyran-3-yl]methyl]piperazin-1-yl]-n-[4-[(4-methylpiperazin-1-yl)amino]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1CN(C)CCN1NC1=CC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3COC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1[N+]([O-])=O ITFBGCIOSFQLSO-UHFFFAOYSA-N 0.000 description 3
- JZXYEVDSJXLSPB-UHFFFAOYSA-N 4-[4-[[4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoyl]sulfamoyl]-2-nitroanilino]piperazine-1-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NN1CCN(C(O)=O)CC1 JZXYEVDSJXLSPB-UHFFFAOYSA-N 0.000 description 3
- OVDYVCQUVWIKBD-UHFFFAOYSA-N 4-[4-[[8-(4-chlorophenyl)spiro[4.5]dec-8-en-9-yl]methyl]piperazin-1-yl]-N-[4-[(4-methoxycyclohexyl)methylamino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1CC(OC)CCC1CNC1=CC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CC4(CCCC4)CCC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1[N+]([O-])=O OVDYVCQUVWIKBD-UHFFFAOYSA-N 0.000 description 3
- LIZHBRQNCSPNPN-INUXSMKFSA-N CC(=O)N[C@H]1CC[C@@H](CC1)Nc1ccc(cc1[N+]([O-])=O)S(=O)(=O)NC(=O)c1ccc(cc1Oc1cnc2[nH]ccc2c1)N1CCN(CC2=C(CC(C)(C)CC2)c2ccc(Cl)cc2)CC1 Chemical compound CC(=O)N[C@H]1CC[C@@H](CC1)Nc1ccc(cc1[N+]([O-])=O)S(=O)(=O)NC(=O)c1ccc(cc1Oc1cnc2[nH]ccc2c1)N1CCN(CC2=C(CC(C)(C)CC2)c2ccc(Cl)cc2)CC1 LIZHBRQNCSPNPN-INUXSMKFSA-N 0.000 description 3
- JNEYAGUMKHBOPX-AQIHZXJDSA-N CC1(C)CCC(CN2CCN(CC2)c2ccc(C(=O)NS(=O)(=O)c3ccc(O[C@H]4CC[C@@H](CC4)N4CCOCC4)c(c3)[N+]([O-])=O)c(Oc3cnc4[nH]ccc4c3)c2)=C(C1)c1ccc(Cl)cc1 Chemical compound CC1(C)CCC(CN2CCN(CC2)c2ccc(C(=O)NS(=O)(=O)c3ccc(O[C@H]4CC[C@@H](CC4)N4CCOCC4)c(c3)[N+]([O-])=O)c(Oc3cnc4[nH]ccc4c3)c2)=C(C1)c1ccc(Cl)cc1 JNEYAGUMKHBOPX-AQIHZXJDSA-N 0.000 description 3
- FUGPWHUMYNZEGE-MAVVKCOWSA-N CO[C@H]1CC[C@H](COc2ccc(cc2[N+]([O-])=O)S(=O)(=O)NC(=O)c2ccc(cc2Oc2cnc3[nH]ccc3c2)N2CCN(CC3=C(CC(C)(C)CC3)c3ccc(Cl)cc3)CC2)CC1 Chemical compound CO[C@H]1CC[C@H](COc2ccc(cc2[N+]([O-])=O)S(=O)(=O)NC(=O)c2ccc(cc2Oc2cnc3[nH]ccc3c2)N2CCN(CC3=C(CC(C)(C)CC3)c3ccc(Cl)cc3)CC2)CC1 FUGPWHUMYNZEGE-MAVVKCOWSA-N 0.000 description 3
- OQOFWKGPIAJVNN-UHFFFAOYSA-N ClC1=CC=C(C=C1)C1=C(CCC(C1)(C)C)CN1CCN(CC1)C1=CC(=C(CNS(=O)(=O)C2=CC(=C(C=C2)NCC2COCC2)[N+](=O)[O-])C=C1)OC=1C=C2C(=NC1)NC=C2 Chemical compound ClC1=CC=C(C=C1)C1=C(CCC(C1)(C)C)CN1CCN(CC1)C1=CC(=C(CNS(=O)(=O)C2=CC(=C(C=C2)NCC2COCC2)[N+](=O)[O-])C=C1)OC=1C=C2C(=NC1)NC=C2 OQOFWKGPIAJVNN-UHFFFAOYSA-N 0.000 description 3
- QSFWWCZYTUHVGT-UHFFFAOYSA-N ClC1=CC=C(C=C1)C1=C(CCC(C1)(C)C)CN1CCN(CC1)C1=CC(=C(CNS(=O)(=O)C2=CC(=C(C=C2)NCCOC)[N+](=O)[O-])C=C1)OC=1C=C2C(=NC1)NC=C2 Chemical compound ClC1=CC=C(C=C1)C1=C(CCC(C1)(C)C)CN1CCN(CC1)C1=CC(=C(CNS(=O)(=O)C2=CC(=C(C=C2)NCCOC)[N+](=O)[O-])C=C1)OC=1C=C2C(=NC1)NC=C2 QSFWWCZYTUHVGT-UHFFFAOYSA-N 0.000 description 3
- PHUQLEOSKXMMQY-UUWRZZSWSA-N ClC1=CC=C(C=C1)C1=C(CCC(C1)(C)C)CN1CCN(CC1)C1=CC(=C(CNS(=O)(=O)C2=CC(=C(C=C2)N[C@H]2COCC2)[N+](=O)[O-])C=C1)OC=1C=C2C(=NC1)NC=C2 Chemical compound ClC1=CC=C(C=C1)C1=C(CCC(C1)(C)C)CN1CCN(CC1)C1=CC(=C(CNS(=O)(=O)C2=CC(=C(C=C2)N[C@H]2COCC2)[N+](=O)[O-])C=C1)OC=1C=C2C(=NC1)NC=C2 PHUQLEOSKXMMQY-UUWRZZSWSA-N 0.000 description 3
- GHGQHMWYLJSPHL-UHFFFAOYSA-N N-[4-[[4-[bis(cyclopropylmethyl)amino]cyclohexyl]amino]-3-nitrophenyl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NC(CC1)CCC1N(CC1CC1)CC1CC1 GHGQHMWYLJSPHL-UHFFFAOYSA-N 0.000 description 3
- 229910006074 SO2NH2 Inorganic materials 0.000 description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 3
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 description 3
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- PVSDCKZNCMWEBM-UHFFFAOYSA-N ethyl 4-[4-[[4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzoyl]sulfamoyl]-2-nitrophenyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C1=CC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1[N+]([O-])=O PVSDCKZNCMWEBM-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- KWKXRVXKPGIIBP-UHFFFAOYSA-N n-(4-chloro-3-nitrophenyl)sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 KWKXRVXKPGIIBP-UHFFFAOYSA-N 0.000 description 3
- OUOACBSTPFLIPY-UHFFFAOYSA-N n-[4-[(1-acetylpiperidin-3-yl)methylamino]-3-nitrophenyl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1N(C(=O)C)CCCC1CNC1=CC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1[N+]([O-])=O OUOACBSTPFLIPY-UHFFFAOYSA-N 0.000 description 3
- LIUHPDJIEFPSBJ-UHFFFAOYSA-N n-[4-[(1-acetylpyrrolidin-3-yl)methylamino]-3-nitrophenyl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1N(C(=O)C)CCC1CNC1=CC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1[N+]([O-])=O LIUHPDJIEFPSBJ-UHFFFAOYSA-N 0.000 description 3
- AWQBEZQZXIAGFK-UHFFFAOYSA-N n-[4-[(4-acetylmorpholin-2-yl)methylamino]-3-nitrophenyl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1N(C(=O)C)CCOC1CNC1=CC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1[N+]([O-])=O AWQBEZQZXIAGFK-UHFFFAOYSA-N 0.000 description 3
- KWHHZWYNCFXJQW-UUWRZZSWSA-N n-[4-[[(3r)-1-acetylpyrrolidin-3-yl]amino]-3-nitrophenyl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1N(C(=O)C)CC[C@H]1NC1=CC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1[N+]([O-])=O KWHHZWYNCFXJQW-UUWRZZSWSA-N 0.000 description 3
- UPMGBEHMGMQOBT-UHFFFAOYSA-N n-[5-bromo-6-[(1-methylpiperidin-4-yl)methoxy]pyridin-3-yl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1CN(C)CCC1COC1=NC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1Br UPMGBEHMGMQOBT-UHFFFAOYSA-N 0.000 description 3
- SUXRJZQNKLFVRB-UHFFFAOYSA-N n-[5-bromo-6-[(4-ethylmorpholin-3-yl)methoxy]pyridin-3-yl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound CCN1CCOCC1COC1=NC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C1Br SUXRJZQNKLFVRB-UHFFFAOYSA-N 0.000 description 3
- CPETXTUMYSFBBH-UHFFFAOYSA-N n-[5-chloro-6-(oxan-4-ylmethoxy)pyridin-3-yl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1Cl)=CN=C1OCC1CCOCC1 CPETXTUMYSFBBH-UHFFFAOYSA-N 0.000 description 3
- 235000005152 nicotinamide Nutrition 0.000 description 3
- 239000011570 nicotinamide Substances 0.000 description 3
- 229960003966 nicotinamide Drugs 0.000 description 3
- 125000003566 oxetanyl group Chemical group 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 125000006033 1,1-dimethyl-2-propenyl group Chemical group 0.000 description 2
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 description 2
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 2
- 125000006032 3-methyl-3-butenyl group Chemical group 0.000 description 2
- KNVQPTSRJUELFP-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[4-[2-cyanoethyl(cyclopropyl)amino]cyclohexyl]amino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NC(CC1)CCC1N(CCC#N)C1CC1 KNVQPTSRJUELFP-UHFFFAOYSA-N 0.000 description 2
- OVDFETFTUQPQFG-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-(2-oxaspiro[3.5]nonan-7-ylmethoxy)phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1OCC(CC1)CCC21COC2 OVDFETFTUQPQFG-UHFFFAOYSA-N 0.000 description 2
- KZFSLJUCIKSUAM-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-(2-oxaspiro[3.5]nonan-7-ylmethylamino)phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC(CC1)CCC21COC2 KZFSLJUCIKSUAM-UHFFFAOYSA-N 0.000 description 2
- DHEHLTGGZQAKJX-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-[[1-(oxetan-3-yl)azetidin-3-yl]amino]phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NC(C1)CN1C1COC1 DHEHLTGGZQAKJX-UHFFFAOYSA-N 0.000 description 2
- UDFKZHVUMFTJKD-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-(furan-3-ylmethoxy)-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1OCC=1C=COC=1 UDFKZHVUMFTJKD-UHFFFAOYSA-N 0.000 description 2
- LGHVXUGTPXYGCJ-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-(morpholin-2-ylmethylamino)-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CNCCO1 LGHVXUGTPXYGCJ-UHFFFAOYSA-N 0.000 description 2
- LCOMZWJSJOFOEF-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[(4-cyclopropylmorpholin-2-yl)methoxy]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1OCC(OCC1)CN1C1CC1 LCOMZWJSJOFOEF-UHFFFAOYSA-N 0.000 description 2
- JWICLIKRPNQLLC-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[3-(cyclopropylamino)propylamino]-3-nitrophenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCCCNC1CC1 JWICLIKRPNQLLC-UHFFFAOYSA-N 0.000 description 2
- LFYSIPPFXXVTSA-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[5-cyano-6-[2-(oxan-4-yl)ethoxy]pyridin-3-yl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1C#N)=CN=C1OCCC1CCOCC1 LFYSIPPFXXVTSA-UHFFFAOYSA-N 0.000 description 2
- VPCQNTSGSDBEGN-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[5-fluoro-6-(oxan-4-ylmethoxy)pyridin-3-yl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1F)=CN=C1OCC1CCOCC1 VPCQNTSGSDBEGN-UHFFFAOYSA-N 0.000 description 2
- PDFGQOUGJMWTIA-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[6-[(4-fluorooxan-4-yl)methoxy]pyridin-3-yl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=N1)=CC=C1OCC1(F)CCOCC1 PDFGQOUGJMWTIA-UHFFFAOYSA-N 0.000 description 2
- YXSRAWIUHWKKHX-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperidin-1-yl]-n-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CC(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCOCC1 YXSRAWIUHWKKHX-UHFFFAOYSA-N 0.000 description 2
- ORQVWASBAMIFHZ-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-5,5-difluorocyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CC(F)(F)CCC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)=CC=C1NCC1CCOCC1 ORQVWASBAMIFHZ-UHFFFAOYSA-N 0.000 description 2
- OUUANQIXKOTMKG-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-5-methoxy-5-methylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-hydroxy-4-methylcyclohexyl)methylamino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1C(OC)(C)CCC(C=2C=CC(Cl)=CC=2)=C1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCC(C)(O)CC1 OUUANQIXKOTMKG-UHFFFAOYSA-N 0.000 description 2
- JTUKXKJWRQZHBJ-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)phenyl]methyl]-4-fluoropiperidin-1-yl]-n-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCC(F)(CC=3C(=CC=CC=3)C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)=CC=C1NCC1CCOCC1 JTUKXKJWRQZHBJ-UHFFFAOYSA-N 0.000 description 2
- RPMQNDHUVHPJEJ-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)phenyl]methyl]-4-methoxypiperidin-1-yl]-n-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C1CN(C=2C=C(OC=3C=C4C=CNC4=NC=3)C(C(=O)NS(=O)(=O)C=3C=C(C(NCC4CCOCC4)=CC=3)[N+]([O-])=O)=CC=2)CCC1(OC)CC1=CC=CC=C1C1=CC=C(Cl)C=C1 RPMQNDHUVHPJEJ-UHFFFAOYSA-N 0.000 description 2
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- CKEDDJRMVZKPDQ-UEOVJWFCSA-N C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NC[C@H]1CC[C@H](C#N)CC1 Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NC[C@H]1CC[C@H](C#N)CC1 CKEDDJRMVZKPDQ-UEOVJWFCSA-N 0.000 description 2
- JHPHSPYSBGEZFM-UHFFFAOYSA-N N-[5-chloro-6-[(4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1Cl)=CN=C1OCC1CCC(C)(O)CC1 JHPHSPYSBGEZFM-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical group C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 2
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000005411 dithiolanyl group Chemical group S1SC(CC1)* 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 2
- 230000000155 isotopic effect Effects 0.000 description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 2
- QFRVJWHHCKIPLD-UHFFFAOYSA-N n-[3-chloro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1Cl)=CC=C1NCC1CCOCC1 QFRVJWHHCKIPLD-UHFFFAOYSA-N 0.000 description 2
- SIQONKZGLLDYCT-UHFFFAOYSA-N n-[3-chloro-4-(oxolan-3-ylmethoxy)phenyl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1Cl)=CC=C1OCC1CCOC1 SIQONKZGLLDYCT-UHFFFAOYSA-N 0.000 description 2
- MONFKNTWTDORSO-UHFFFAOYSA-N n-[3-chloro-4-[[1-(oxetan-3-yl)piperidin-4-yl]methoxy]phenyl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1Cl)=CC=C1OCC(CC1)CCN1C1COC1 MONFKNTWTDORSO-UHFFFAOYSA-N 0.000 description 2
- RAZGFHDBOJFDAQ-UHFFFAOYSA-N n-[4-[[4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzoyl]sulfamoyl]-2-nitrophenyl]morpholine-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NC(=O)N1CCOCC1 RAZGFHDBOJFDAQ-UHFFFAOYSA-N 0.000 description 2
- KRNRKSAICMJQAD-UHFFFAOYSA-N n-[5-chloro-6-[(4-fluorooxan-4-yl)methoxy]pyridin-3-yl]sulfonyl-4-[4-[[2-(4-chlorophenyl)phenyl]methyl]-4-fluoropiperidin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide Chemical compound N=1C=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCC(F)(CC=3C(=CC=CC=3)C=3C=CC(Cl)=CC=3)CC2)OC=2C=C3C=CNC3=NC=2)C=C(Cl)C=1OCC1(F)CCOCC1 KRNRKSAICMJQAD-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 2
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 2
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 2
- 125000005943 1,2,3,6-tetrahydropyridyl group Chemical group 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- 125000003562 2,2-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- 125000003660 2,3-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- WFEGLEDZKOWLCH-UHFFFAOYSA-N 2-(9h-carbazol-4-yloxy)-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[3-nitro-4-(3-pyrrolidin-1-ylpropylamino)phenyl]sulfonylbenzamide Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=3C4=CC=CC=C4NC=3C=CC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCCCN1CCCC1 WFEGLEDZKOWLCH-UHFFFAOYSA-N 0.000 description 1
- ZJYOFGZSKAWHHC-UHFFFAOYSA-N 2-(9h-carbazol-4-yloxy)-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-n-[4-[(1-methylpiperidin-4-yl)amino]-3-nitrophenyl]sulfonylbenzamide Chemical compound C1CN(C)CCC1NC1=CC=C(S(=O)(=O)NC(=O)C=2C(=CC(=CC=2)N2CCN(CC=3CCC(C)(C)CC=3C=3C=CC(Cl)=CC=3)CC2)OC=2C=3C4=CC=CC=C4NC=3C=CC=2)C=C1[N+]([O-])=O ZJYOFGZSKAWHHC-UHFFFAOYSA-N 0.000 description 1
- 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 1
- 125000003469 3-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- JRBAQAMOIBHJRP-UHFFFAOYSA-N 4,5,6,7-tetrahydro-3ah-indene Chemical compound C1CCCC2=CC=CC21 JRBAQAMOIBHJRP-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000006043 5-hexenyl group Chemical group 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 239000012664 BCL-2-inhibitor Substances 0.000 description 1
- 229940123711 Bcl2 inhibitor Drugs 0.000 description 1
- 206010048396 Bone marrow transplant rejection Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 102220492229 Replication stress response regulator SDE2_R37A_mutation Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- QAOWNCQODCNURD-ZSJDYOACSA-N Sulfuric acid-d2 Chemical compound [2H]OS(=O)(=O)O[2H] QAOWNCQODCNURD-ZSJDYOACSA-N 0.000 description 1
- 241000009298 Trigla lyra Species 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000001980 alanyl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000003725 azepanyl group Chemical group 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 125000003943 azolyl group Chemical group 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- GPRLTFBKWDERLU-UHFFFAOYSA-N bicyclo[2.2.2]octane Chemical compound C1CC2CCC1CC2 GPRLTFBKWDERLU-UHFFFAOYSA-N 0.000 description 1
- SHOMMGQAMRXRRK-UHFFFAOYSA-N bicyclo[3.1.1]heptane Chemical compound C1C2CC1CCC2 SHOMMGQAMRXRRK-UHFFFAOYSA-N 0.000 description 1
- GNTFBMAGLFYMMZ-UHFFFAOYSA-N bicyclo[3.2.2]nonane Chemical compound C1CC2CCC1CCC2 GNTFBMAGLFYMMZ-UHFFFAOYSA-N 0.000 description 1
- WNTGVOIBBXFMLR-UHFFFAOYSA-N bicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1C2 WNTGVOIBBXFMLR-UHFFFAOYSA-N 0.000 description 1
- KVLCIHRZDOKRLK-UHFFFAOYSA-N bicyclo[4.2.1]nonane Chemical compound C1C2CCC1CCCC2 KVLCIHRZDOKRLK-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- PWLNAUNEAKQYLH-UHFFFAOYSA-N butyric acid octyl ester Natural products CCCCCCCCOC(=O)CCC PWLNAUNEAKQYLH-UHFFFAOYSA-N 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000004956 cyclohexylene group Chemical group 0.000 description 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004980 dosimetry Methods 0.000 description 1
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000019000 fluorine Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000001965 increasing effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000005969 isothiazolinyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 238000001948 isotopic labelling Methods 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- UUIQMZJEGPQKFD-UHFFFAOYSA-N n-butyric acid methyl ester Natural products CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004957 naphthylene group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ZCYXXKJEDCHMGH-UHFFFAOYSA-N nonane Chemical compound CCCC[CH]CCCC ZCYXXKJEDCHMGH-UHFFFAOYSA-N 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000005882 oxadiazolinyl group Chemical group 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000005968 oxazolinyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000005304 thiadiazolidinyl group Chemical group 0.000 description 1
- 125000005305 thiadiazolinyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- PCFIPYFVXDCWBW-UHFFFAOYSA-N tricyclo[3.3.1.03,7]nonane Chemical compound C1C(C2)C3CC2CC1C3 PCFIPYFVXDCWBW-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Transplantation (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Indole Compounds (AREA)
- Peptides Or Proteins (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18120309P | 2009-05-26 | 2009-05-26 | |
| US61/181203 | 2009-05-26 | ||
| PCT/US2010/036198 WO2010138588A2 (en) | 2009-05-26 | 2010-05-26 | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| CN201080023068.1A CN102448959B (zh) | 2009-05-26 | 2010-05-26 | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201080023068.1A Division CN102448959B (zh) | 2009-05-26 | 2010-05-26 | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109897038A CN109897038A (zh) | 2019-06-18 |
| CN109897038B true CN109897038B (zh) | 2022-04-05 |
Family
ID=42677657
Family Applications (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910261444.3A Active CN109897038B (zh) | 2009-05-26 | 2010-05-26 | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 |
| CN201510165051.4A Active CN104876927B (zh) | 2009-05-26 | 2010-05-26 | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 |
| CN201910270919.5A Pending CN109966294A (zh) | 2009-05-26 | 2010-05-26 | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 |
| CN201510215766.6A Pending CN104906100A (zh) | 2009-05-26 | 2010-05-26 | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 |
| CN201080023068.1A Active CN102448959B (zh) | 2009-05-26 | 2010-05-26 | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 |
Family Applications After (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510165051.4A Active CN104876927B (zh) | 2009-05-26 | 2010-05-26 | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 |
| CN201910270919.5A Pending CN109966294A (zh) | 2009-05-26 | 2010-05-26 | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 |
| CN201510215766.6A Pending CN104906100A (zh) | 2009-05-26 | 2010-05-26 | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 |
| CN201080023068.1A Active CN102448959B (zh) | 2009-05-26 | 2010-05-26 | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 |
Country Status (43)
Families Citing this family (114)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8557983B2 (en) | 2008-12-04 | 2013-10-15 | Abbvie Inc. | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| US20100160322A1 (en) | 2008-12-04 | 2010-06-24 | Abbott Laboratories | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| EP2376480B1 (en) * | 2008-12-05 | 2016-06-01 | AbbVie Inc. | Sulfonamide derivatives as bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases |
| US8586754B2 (en) | 2008-12-05 | 2013-11-19 | Abbvie Inc. | BCL-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases |
| US8563735B2 (en) | 2008-12-05 | 2013-10-22 | Abbvie Inc. | Bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases |
| ES2536090T3 (es) * | 2009-01-19 | 2015-05-20 | Abbvie Inc. | Agentes inductores de la apoptosis para el tratamiento del cáncer y enfermedades inmunitarias y autoinmunitarias |
| US8546399B2 (en) * | 2009-05-26 | 2013-10-01 | Abbvie Inc. | Apoptosis inducing agents for the treatment of cancer and immune and autoimmune diseases |
| BR122019016429B1 (pt) * | 2009-05-26 | 2020-03-24 | Abbvie Ireland Unlimited Company | Compostos inibidores da atividade de proteínas bcl-2 antiapoptótica e composição farmacêutica compreendendo ditos compostos |
| US9034875B2 (en) | 2009-05-26 | 2015-05-19 | Abbvie Inc. | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| US20220315555A1 (en) | 2009-05-26 | 2022-10-06 | Abbvie Inc. | Apoptosis inducing agents for the treatment of cancer and immune and autoimmune diseases |
| TWI520960B (zh) | 2010-05-26 | 2016-02-11 | 艾伯維有限公司 | 用於治療癌症及免疫及自體免疫疾病之細胞凋亡誘導劑 |
| EA201890869A3 (ru) | 2010-06-03 | 2019-03-29 | Фармасайкликс, Инк. | Применение ингибиторов тирозинкиназы брутона (btk) |
| TWI535712B (zh) | 2010-08-06 | 2016-06-01 | 阿斯特捷利康公司 | 化合物 |
| ES2699205T3 (es) * | 2010-10-29 | 2019-02-07 | Abbvie Inc | Dispersiones sólidas que contienen un agente que induce la apoptosis |
| UA113500C2 (xx) * | 2010-10-29 | 2017-02-10 | Одержані екструзією розплаву тверді дисперсії, що містять індукуючий апоптоз засіб | |
| AU2011332043C1 (en) | 2010-11-23 | 2016-11-10 | Abbvie Inc. | Salts and crystalline forms of an apoptosis-inducing agent |
| NZ708508A (en) | 2010-11-23 | 2016-06-24 | Abbvie Bahamas Ltd | Methods of treatment using selective bcl-2 inhibitors |
| CN104557646B (zh) | 2011-02-15 | 2017-08-29 | 宇部兴产株式会社 | 生产芳基硫五氟化物的工业方法 |
| CN102241649A (zh) * | 2011-07-08 | 2011-11-16 | 陈飞 | 3-四氢呋喃甲醇的制备方法 |
| CN103958508B (zh) | 2011-10-14 | 2019-02-12 | 艾伯维公司 | 用于治疗癌症以及免疫与自身免疫性疾病的细胞凋亡诱导剂 |
| WO2013185202A1 (en) * | 2012-06-14 | 2013-12-19 | Beta Pharma Canada Inc | Apoptosis inducers |
| WO2014018567A1 (en) | 2012-07-24 | 2014-01-30 | Pharmacyclics, Inc. | Mutations associated with resistance to inhibitors of bruton's tyrosine kinase (btk) |
| JP6225187B2 (ja) * | 2012-08-13 | 2017-11-01 | アッヴィ・インコーポレイテッド | アポトーシス誘発剤 |
| CN111481552A (zh) | 2012-09-07 | 2020-08-04 | 吉宁特有限公司 | II型抗CD20抗体与选择性Bcl-2抑制剂的组合治疗 |
| LT6064B (lt) | 2012-10-15 | 2014-08-25 | Vilniaus Universitetas | Fluorinti benzensulfonamidai kaip karboanhidrazės inhibitoriai |
| LT2914296T (lt) | 2012-11-01 | 2018-09-25 | Infinity Pharmaceuticals, Inc. | Vėžio gydymas, panaudojant p13 kinazės izoformos moduliatorius |
| US20150283142A1 (en) * | 2013-03-15 | 2015-10-08 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| AR095265A1 (es) | 2013-03-13 | 2015-09-30 | Abbvie Inc | Procesos para la preparación de un agente inductor de la apoptosis |
| US20140275082A1 (en) | 2013-03-14 | 2014-09-18 | Abbvie Inc. | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| BR112015025711A8 (pt) * | 2013-04-08 | 2019-12-17 | Janssen Pharmaceutica Nv | uso de ibrutinibe e coposição farmacêutica compreendendo ibrutinibe e um agente anticâncer |
| TWI594975B (zh) | 2013-04-24 | 2017-08-11 | 第一三共股份有限公司 | 二羧酸化合物 |
| US9238652B2 (en) | 2014-03-04 | 2016-01-19 | Abbvie Inc. | Processes for the preparation of an apoptosis-inducing agent |
| EP3708170A1 (en) | 2014-05-05 | 2020-09-16 | BioVentures, LLC | Compositions and methods for inhibiting antiapoptotic bcl-2 proteins as anti-aging agents |
| EP3177144A4 (en) | 2014-07-22 | 2018-01-24 | Bioventures, LLC. | Compositions and methods for selectively depleting senescent cells |
| CN104163798A (zh) * | 2014-07-29 | 2014-11-26 | 苏州康润医药有限公司 | 3-氨基-8-三氟甲基喹啉的合成方法 |
| LT3179991T (lt) | 2014-08-11 | 2021-11-10 | Acerta Pharma B.V. | Terapiniai btk inhibitoriaus ir bcl-2 inhibitoriaus deriniai |
| IL313498A (en) | 2014-10-06 | 2024-08-01 | Vertex Pharma | Modulators of the cystic fibrosis transmembrane conductance regulator |
| US10195213B2 (en) | 2015-03-13 | 2019-02-05 | Unity Biotechnology, Inc. | Chemical entities that kill senescent cells for use in treating age-related disease |
| LT3319995T (lt) | 2015-07-07 | 2019-07-10 | F. Hoffmann-La Roche Ag | Sudėtinis gydymas anti-her-2 antikūno-vaisto konjugatu ir bcl-2 inhibitoriumi |
| WO2017063572A1 (zh) * | 2015-10-13 | 2017-04-20 | 苏州晶云药物科技有限公司 | 细胞凋亡诱导剂的新晶型及其制备方法 |
| CN108367006B (zh) | 2015-12-04 | 2021-12-31 | 博尔托拉制药公司 | 用于治疗血液癌症的赛度替尼 |
| US11001582B2 (en) | 2016-03-10 | 2021-05-11 | Assia Chemical Industries Ltd. | Solid state forms of Venetoclax and processes for preparation of Venetoclax |
| EP3442584B1 (en) | 2016-03-15 | 2021-07-28 | Seagen Inc. | Combinations of pbd-based antibody drug conjugates with bcl-2 inhibitors |
| CN120661674A (zh) | 2016-03-15 | 2025-09-19 | 奥莱松基因组股份有限公司 | 用于治疗实体瘤的lsd1抑制剂的组合 |
| US11013698B2 (en) | 2016-03-15 | 2021-05-25 | Oryzon Genomics S.A. | Combinations of LSD1 inhibitors for the treatment of hematological malignancies |
| EP3436446B1 (en) | 2016-03-31 | 2023-06-07 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| EP3445452A4 (en) | 2016-04-21 | 2019-10-30 | BioVentures, LLC | COMPOUNDS FOR INDUCING THE DEGRADATION OF ANTIAPOPTOTIC PROTEINS OF THE BCL-2 FAMILY AND USES THEREOF |
| KR102429704B1 (ko) * | 2016-08-05 | 2022-08-04 | 더 리젠츠 오브 더 유니버시티 오브 미시건 | Bcl-2 억제제로서의 n-(페닐설포닐)벤즈아미드 및 관련 화합물 |
| CN109641897B (zh) * | 2016-09-01 | 2021-12-07 | 北京赛林泰医药技术有限公司 | Bcl-2选择性抑制剂及其制备和用途 |
| HRP20211683T1 (hr) | 2016-09-30 | 2022-03-04 | Vertex Pharmaceuticals Incorporated | Modulator transmembranskog regulatora provodljivosti cistične fibroze, farmaceutski pripravci, postupci liječenja, i postupak za pripravu modulatora |
| CN106749233B (zh) * | 2016-11-24 | 2020-04-21 | 中山大学 | 一类磺酰胺衍生物及其应用 |
| RS64976B1 (sr) | 2016-12-01 | 2024-01-31 | Arvinas Operations Inc | Derivati tetrahidronaftalena i tetrahidroizohinolina kao degradatori estrogenih receptora |
| MX2021013639A (es) | 2016-12-09 | 2022-09-30 | Vertex Pharma | Forma cristalina del compuesto 1, un modulador del regulador de conductancia transmembrana de fibrosis quística, procesos para su preparación, composiciones farmacéuticas del compuesto 1, y su uso en el tratamiento de fibrosis quística. |
| WO2018127130A1 (en) * | 2017-01-07 | 2018-07-12 | Shanghai Fochon Pharmaceutical Co., Ltd. | Compounds as bcl-2-selective apoptosis-inducing agents |
| JOP20190191A1 (ar) | 2017-02-22 | 2019-08-08 | Astrazeneca Ab | وحدات شجرية علاجية |
| WO2018167652A1 (en) * | 2017-03-13 | 2018-09-20 | Laurus Labs Limited | Process for preparation of amorphous form of venetoclax |
| CN110546151B (zh) * | 2017-04-18 | 2023-04-28 | 重庆复创医药研究有限公司 | 凋亡诱导剂 |
| CN107089981A (zh) * | 2017-04-24 | 2017-08-25 | 杭州科耀医药科技有限公司 | 一种BCL‑2抑制剂Venetoclax的合成方法 |
| AU2018279646B2 (en) | 2017-06-08 | 2023-04-06 | Vertex Pharmaceuticals Incorporated | Methods of treatment for cystic fibrosis |
| ES3028360T3 (en) * | 2017-06-26 | 2025-06-19 | Shenzhen Targetrx Inc | Deuterated n-benzenesulfonylbenzamide compound for inhibiting bcl-2 protein and composition and use thereof |
| AU2018304168B2 (en) | 2017-07-17 | 2023-05-04 | Vertex Pharmaceuticals Incorporated | Methods of treatment for cystic fibrosis |
| JP2020528061A (ja) | 2017-07-26 | 2020-09-17 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | ＢＥＴ阻害剤、Ｂｃｌ−２阻害剤及び抗ＣＤ２０抗体を用いた併用療法 |
| EP3658188A1 (en) | 2017-07-26 | 2020-06-03 | H. Hoffnabb-La Roche Ag | Combination therapy with a bet inhibitor and a bcl-2 inhibitor |
| TWI799435B (zh) | 2017-08-02 | 2023-04-21 | 美商維泰克斯製藥公司 | 製備化合物之製程 |
| EP3672975B1 (en) | 2017-08-23 | 2023-04-12 | Guangzhou Lupeng Pharmaceutical Company Ltd. | Condensed heterocyclic derivatives as bcl-2 inhibitors for the treatment of neoplastic diseases |
| WO2019079760A1 (en) | 2017-10-19 | 2019-04-25 | Vertex Pharmaceuticals Incorporated | CRYSTALLINE FORMS AND COMPOSITIONS OF CFTR MODULATORS |
| CN108037196B (zh) * | 2017-11-23 | 2020-06-23 | 中山奕安泰医药科技有限公司 | 一种3-硝基-4-[[(四氢-2h-吡喃-4-基)甲基]氨基]苯磺酰胺的检测方法 |
| US11465985B2 (en) | 2017-12-08 | 2022-10-11 | Vertex Pharmaceuticals Incorporated | Processes for making modulators of cystic fibrosis transmembrane conductance regulator |
| SG11202005985PA (en) | 2018-01-10 | 2020-07-29 | Recurium Ip Holdings Llc | Benzamide compounds |
| CN112105360B (zh) | 2018-01-22 | 2024-01-30 | 生物风险投资有限责任公司 | 用于癌症治疗的bcl-2蛋白降解剂 |
| TWI810243B (zh) | 2018-02-05 | 2023-08-01 | 美商維泰克斯製藥公司 | 用於治療囊腫纖化症之醫藥組合物 |
| CA3090177A1 (en) | 2018-02-16 | 2019-08-22 | Abbvie Inc. | Selective bcl-2 inhibitors in combination with an anti-pd-1 or an anti-pd-l1 antibody for the treatment of cancers |
| TW202002952A (zh) | 2018-03-15 | 2020-01-16 | 美商艾伯維有限公司 | 用於治療胰臟癌之abbv-621與抗癌劑之組合 |
| CN114369094B (zh) * | 2018-03-30 | 2023-09-29 | 正大天晴药业集团股份有限公司 | 三氟甲基取代的磺酰胺类选择性bcl-2抑制剂 |
| WO2019200246A1 (en) | 2018-04-13 | 2019-10-17 | Alexander Russell Abela | Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator |
| FI3788042T3 (fi) * | 2018-04-29 | 2025-04-07 | Beigene Switzerland Gmbh | Bcl-2-inhibiittoreita |
| JP7324778B2 (ja) | 2018-05-04 | 2023-08-10 | ポートラ ファーマシューティカルズ， エルエルシー | セルデュラチニブ（ｃｅｒｄｕｌａｔｉｎｉｂ）の固体形態 |
| WO2019221755A1 (en) | 2018-05-18 | 2019-11-21 | Bioventures, Llc | Piperlongumine analogues and uses thereof |
| WO2020023435A1 (en) | 2018-07-24 | 2020-01-30 | Albany Molecular Research, Inc. | Venetoclax basic salts and processes for the purification of venetoclax |
| TW202023568A (zh) | 2018-07-30 | 2020-07-01 | 瑞典商阿斯特捷利康公司 | 用於治療癌症之組合療法 |
| US11554127B2 (en) | 2018-07-31 | 2023-01-17 | Ascentage Pharma (Suzhou) Co., Ltd. | Synergistic antitumor effect of Bcl-2 inhibitor combined with rituximab and/or bendamustine or Bcl-2 inhibitor combined with CHOP |
| CN110772521A (zh) | 2018-07-31 | 2020-02-11 | 苏州亚盛药业有限公司 | Bcl-2抑制剂或Bcl-2/Bcl-xL抑制剂与BTK抑制剂的组合产品及其用途 |
| CA3095699A1 (en) | 2018-07-31 | 2020-02-06 | Ascentage Pharma (Suzhou) Co., Ltd. | Combination product of bcl-2 inhibitor and chemotherapeutic agent and use thereof in the prevention and/or treatment of diseases |
| EP3672594B1 (en) | 2018-07-31 | 2021-09-29 | Ascentage Pharma (Suzhou) Co., Ltd. | Combination product of bcl-2 inhibitor and mdm2 inhibitor and use thereof in the prevention and/or treatment of diseases |
| WO2020041406A1 (en) | 2018-08-22 | 2020-02-27 | Newave Pharmaceutical Inc. | Bcl-2 inhibitors |
| CA3117849A1 (en) * | 2018-10-29 | 2020-05-07 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Trifluoromethyl-substituted sulfonamide as bcl-2-selective inhibitor |
| CN109438441A (zh) * | 2018-11-30 | 2019-03-08 | 重庆三圣实业股份有限公司 | 一种维奈妥拉的制备方法及其产品 |
| CN109320516A (zh) * | 2018-11-30 | 2019-02-12 | 重庆三圣实业股份有限公司 | 一种维奈妥拉中间体的制备方法及其产品 |
| WO2020232214A1 (en) | 2019-05-14 | 2020-11-19 | Abbvie Inc. | Treating acute myeloid leukemia (aml) with mivebresib, a bromodomain inhibitor |
| WO2020234445A1 (en) | 2019-05-23 | 2020-11-26 | F. Hoffmann-La Roche Ag | Combination therapy with a bet inhibitor and a bcl-2 inhibitor |
| EP3978494A4 (en) * | 2019-05-24 | 2023-04-19 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | METHYL AND TRFLUOROMETHYL CONTAINING DISUBSTITUTED SULFONAMIDE SELECTIVE BCL-2 INHIBITORS |
| KR20220054347A (ko) | 2019-08-26 | 2022-05-02 | 아비나스 오퍼레이션스, 인코포레이티드 | 에스트로겐 수용체 분해제로서의 테트라히드로나프탈렌 유도체로 유방암을 치료하는 방법 |
| WO2021037933A1 (en) | 2019-08-28 | 2021-03-04 | Astrazeneca Ab | Combination of azd2811 nanoparticles, 5-azacitidine and venetoclax for use in the treatment of cancer |
| CN112661751B (zh) * | 2019-10-16 | 2024-06-14 | 南京天印健华医药科技有限公司 | 作为bcl-2抑制剂的杂环化合物 |
| EP4051676A4 (en) * | 2019-10-28 | 2023-11-22 | BeiGene, Ltd. | BCL-2 INHIBITORS |
| WO2021110102A1 (en) * | 2019-12-02 | 2021-06-10 | Beigene, Ltd. | Methods of cancer treatment using bcl-2 inhibitor |
| TW202200574A (zh) | 2020-04-15 | 2022-01-01 | 英屬開曼群島商百濟神州有限公司 | Bcl-2抑制劑 |
| TWI896655B (zh) * | 2020-04-29 | 2025-09-11 | 大陸商正大天晴藥業集團股份有限公司 | 三氟甲基和氯雙取代的磺醯胺類選擇性bcl-2抑制劑的晶體 |
| CN111848607B (zh) * | 2020-07-22 | 2023-03-17 | 长沙创新药物工业技术研究院有限公司 | 一种新型bcl-2/bcl-xl抑制剂、药物组合物及用途 |
| CN114057728A (zh) * | 2020-08-06 | 2022-02-18 | 北京诺诚健华医药科技有限公司 | 作为bcl-2抑制剂的杂环化合物 |
| US20230398110A1 (en) * | 2020-08-21 | 2023-12-14 | Ascentage Pharma (Suzhou) Co., Ltd. | Compositions and methods for treating non-alcoholic steatohepatitis |
| CN114478520B (zh) * | 2020-10-28 | 2025-01-10 | 杭州和正医药有限公司 | Bcl-2蛋白凋亡诱导剂及应用 |
| CN114736203A (zh) * | 2021-01-07 | 2022-07-12 | 南京天印健华医药科技有限公司 | 作为bcl-2抑制剂的杂环化合物 |
| CA3211639A1 (en) | 2021-03-19 | 2022-09-22 | Volodymyr KYSIL | Compounds having ((3-nitrophenyl)sulfonyl)acetamide as bcl-2 inhibitors |
| WO2022218311A1 (en) * | 2021-04-13 | 2022-10-20 | Appicine Therapeutics (Hk) Limited | Modulators of bcl-2 or bcl-2/bcl-xl and uses thereof |
| EP4353722A4 (en) | 2021-06-04 | 2025-06-18 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Phosphate of trifluoromethyl-substituted sulfonamide compound |
| MX2024002465A (es) * | 2021-08-31 | 2024-04-29 | Beigene Ltd | Formas solidas de inhibidores de bcl-2, metodo de preparacion y sus usos. |
| IT202100025976A1 (it) | 2021-10-06 | 2023-04-06 | Univ Degli Studi Di Perugia | Combinazione di principi attivi per il trattamento della leucemia acuta mieloide (LAM) con mutazione della nucleofosmina (NPM1) |
| US20250154141A1 (en) | 2021-12-09 | 2025-05-15 | University Of Florida Research Foundation, Incorporated | Bcl-xl/bcl-2 dual degraders for treatment of cancers |
| WO2024012557A1 (en) * | 2022-07-15 | 2024-01-18 | Berrybio (Hong Kong) Limited | Anti-apoptotic bcl-2 family protein degraders, pharmaceutical compositions, and therapeutic applications |
| KR20250079128A (ko) * | 2022-07-21 | 2025-06-04 | 베이진 스위찰랜드 게엠베하 | Bcl-2 저해제를 사용한 다발성 골수종의 치료 방법 |
| CN115260191B (zh) * | 2022-09-29 | 2022-12-27 | 上海睿跃生物科技有限公司 | 哌啶类化合物及其制备方法和应用 |
| KR102598137B1 (ko) | 2022-11-24 | 2023-11-06 | 율촌화학 주식회사 | 고차단성 생분해 필름 및 이의 제조방법 |
| EP4421075A1 (en) | 2023-02-27 | 2024-08-28 | KRKA, d.d., Novo mesto | Process for the preparation of venetoclax and intermediates used therein |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1665802A (zh) * | 2002-07-05 | 2005-09-07 | 西克拉塞尔有限公司 | 双芳基磺酰胺化合物及其在癌症治疗中的用途 |
| CN1906183A (zh) * | 2003-11-13 | 2007-01-31 | 艾博特公司 | N－酰基磺酰胺细胞程序死亡促进剂 |
| US20070072860A1 (en) * | 2003-11-13 | 2007-03-29 | Milan Bruncko | Apoptosis promoters |
| CN101175738A (zh) * | 2005-05-12 | 2008-05-07 | 艾博特公司 | 细胞凋亡促进剂 |
Family Cites Families (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2579596B1 (fr) * | 1985-03-26 | 1987-11-20 | Inst Nat Sante Rech Med | (imidazolyl-4) piperidines, leur preparation et leur application en therapeutique |
| CA1338238C (en) * | 1988-01-07 | 1996-04-09 | David John Carini | Angiotensin ii receptor blocking imidazoles and combinations thereof with diuretics and nsaids |
| CA2016710A1 (en) * | 1989-05-15 | 1990-11-15 | Prasun K. Chakravarty | Substituted benzimidazoles as angiotensin ii antagonists |
| GB9110625D0 (en) * | 1991-05-16 | 1991-07-03 | Glaxo Group Ltd | Chemical compounds |
| ATE234270T1 (de) * | 1992-12-02 | 2003-03-15 | Pfizer | Cathecoldiether als selektive pde iv hemmungsmittel |
| MY115155A (en) | 1993-09-09 | 2003-04-30 | Upjohn Co | Substituted oxazine and thiazine oxazolidinone antimicrobials. |
| PT1019385E (pt) | 1995-09-15 | 2004-06-30 | Upjohn Co | N-oxidos de aminoaril-oxazolidinona |
| WO1999018099A1 (en) * | 1997-10-03 | 1999-04-15 | Merck Frosst Canada & Co. | Aryl thiophene derivatives as pde iv inhibitors |
| US20030220234A1 (en) | 1998-11-02 | 2003-11-27 | Selvaraj Naicker | Deuterated cyclosporine analogs and their use as immunodulating agents |
| CN1149196C (zh) * | 1998-07-06 | 2004-05-12 | 布里斯托尔-迈尔斯斯奎布公司 | 作为血管紧张肽和内皮肽受体双重拮抗剂的联苯基磺酰胺 |
| DE19830430A1 (de) * | 1998-07-08 | 2000-01-13 | Hoechst Marion Roussel De Gmbh | Schwefelsubstituierte Sulfonylamino-carbonsäure-N-arylamide, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| GB9918037D0 (en) | 1999-07-30 | 1999-09-29 | Biochemie Gmbh | Organic compounds |
| KR100641802B1 (ko) * | 1999-12-28 | 2006-11-02 | 에자이 가부시키가이샤 | 술폰아미드 함유 복소환 화합물 |
| GB2361003A (en) * | 2000-04-07 | 2001-10-10 | Astrazeneca Ab | Novel compounds |
| US20020055631A1 (en) * | 2000-09-20 | 2002-05-09 | Augeri David J. | N-acylsulfonamide apoptosis promoters |
| UY26942A1 (es) * | 2000-09-20 | 2002-04-26 | Abbott Lab | N-acilsulfonamidas promotoras de la apoptosis |
| US6720338B2 (en) * | 2000-09-20 | 2004-04-13 | Abbott Laboratories | N-acylsulfonamide apoptosis promoters |
| US6995162B2 (en) | 2001-01-12 | 2006-02-07 | Amgen Inc. | Substituted alkylamine derivatives and methods of use |
| WO2002098848A1 (en) | 2001-06-06 | 2002-12-12 | Eli Lilly And Company | Benzoylsulfonamides and sulfonylbenzamidines for use as antitumour agents |
| US20030059489A1 (en) | 2001-09-24 | 2003-03-27 | Canolio Inc. | Genital lubricating compositions and uses thereof |
| US20030134853A1 (en) * | 2001-09-26 | 2003-07-17 | Priestley Eldon Scott | Compounds useful for treating hepatitis C virus |
| FR2836914B1 (fr) * | 2002-03-11 | 2008-03-14 | Aventis Pharma Sa | Indazoles substitues, compositions les contenant, procede de fabrication et utilisation |
| US6995787B2 (en) | 2002-08-21 | 2006-02-07 | Adams Steven L | Sports projectile and camera apparatus |
| JP4336678B2 (ja) | 2003-09-04 | 2009-09-30 | 株式会社日立超エル・エス・アイ・システムズ | 半導体装置 |
| US7767684B2 (en) * | 2003-11-13 | 2010-08-03 | Abbott Laboratories | Apoptosis promoters |
| US8614318B2 (en) * | 2003-11-13 | 2013-12-24 | Abbvie Inc. | Apoptosis promoters |
| US7642260B2 (en) * | 2003-11-13 | 2010-01-05 | Abbott Laboratories, Inc. | Apoptosis promoters |
| DE602004009344T2 (de) | 2004-04-19 | 2008-07-10 | Symed Labs Ltd., Hyderabad | Neues verfahren zur herstellung von linezolid und verwandten verbindungen |
| PL1768966T3 (pl) * | 2004-06-17 | 2012-08-31 | Infinity Discovery Inc | Związki i sposoby hamowania oddziaływania białek BCL z partnerami wiążącymi |
| DE602004020812D1 (de) | 2004-07-20 | 2009-06-04 | Symed Labs Ltd | Neue zwischenprodukte für linezolid und verwandte verbindungen |
| US7361764B2 (en) * | 2004-07-27 | 2008-04-22 | Sgx Pharmaceuticals, Inc. | Pyrrolo-pyridine kinase modulators |
| US7511013B2 (en) | 2004-09-29 | 2009-03-31 | Amr Technology, Inc. | Cyclosporin analogues and their pharmaceutical uses |
| US8624027B2 (en) * | 2005-05-12 | 2014-01-07 | Abbvie Inc. | Combination therapy for treating cancer and diagnostic assays for use therein |
| CN101218241B (zh) * | 2005-05-16 | 2011-02-16 | Irm责任有限公司 | 用作蛋白激酶抑制剂的吡咯并吡啶衍生物 |
| TW200716636A (en) | 2005-05-31 | 2007-05-01 | Speedel Experimenta Ag | Heterocyclic spiro-compounds |
| UA95244C2 (ru) | 2005-06-22 | 2011-07-25 | Плексикон, Инк. | Соединения и способ модулирования активности киназ, и показания для их применения |
| US7514068B2 (en) | 2005-09-14 | 2009-04-07 | Concert Pharmaceuticals Inc. | Biphenyl-pyrazolecarboxamide compounds |
| US20070115787A1 (en) * | 2005-11-23 | 2007-05-24 | Seagate Technology Llc | Planar optical device for generating optical nanojets |
| JP5277168B2 (ja) * | 2006-09-05 | 2013-08-28 | アボット・ラボラトリーズ | 血小板過剰を治療するｂｃｌインヒビター |
| US8796267B2 (en) | 2006-10-23 | 2014-08-05 | Concert Pharmaceuticals, Inc. | Oxazolidinone derivatives and methods of use |
| US20080182845A1 (en) * | 2006-11-16 | 2008-07-31 | Abbott Laboratories | Method of preventing or treating organ, hematopoietic stem cell or bone marrow transplant rejection |
| EP2121641B1 (en) | 2007-02-15 | 2014-09-24 | F. Hoffmann-La Roche AG | 2-aminooxazolines as taar1 ligands |
| US8536157B2 (en) | 2007-04-13 | 2013-09-17 | The University Of Melbourne | Non-steroidal compounds |
| US7528131B2 (en) | 2007-04-19 | 2009-05-05 | Concert Pharmaceuticals Inc. | Substituted morpholinyl compounds |
| US7531685B2 (en) | 2007-06-01 | 2009-05-12 | Protia, Llc | Deuterium-enriched oxybutynin |
| US20090131485A1 (en) | 2007-09-10 | 2009-05-21 | Concert Pharmaceuticals, Inc. | Deuterated pirfenidone |
| US20090118238A1 (en) | 2007-09-17 | 2009-05-07 | Protia, Llc | Deuterium-enriched alendronate |
| US20090088416A1 (en) | 2007-09-26 | 2009-04-02 | Protia, Llc | Deuterium-enriched lapaquistat |
| US20090082471A1 (en) | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched fingolimod |
| EP2209774A1 (en) | 2007-10-02 | 2010-07-28 | Concert Pharmaceuticals Inc. | Pyrimidinedione derivatives |
| US20090098118A1 (en) * | 2007-10-15 | 2009-04-16 | Thomas Friess | Combination therapy of a type ii anti-cd20 antibody with an anti-bcl-2 active agent |
| EP2212298B1 (en) | 2007-10-18 | 2013-03-27 | Concert Pharmaceuticals Inc. | Deuterated etravirine |
| US20090105338A1 (en) | 2007-10-18 | 2009-04-23 | Protia, Llc | Deuterium-enriched gabexate mesylate |
| US20090131363A1 (en) | 2007-10-26 | 2009-05-21 | Harbeson Scott L | Deuterated darunavir |
| US8168784B2 (en) * | 2008-06-20 | 2012-05-01 | Abbott Laboratories | Processes to make apoptosis promoters |
| US20100160322A1 (en) * | 2008-12-04 | 2010-06-24 | Abbott Laboratories | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| UA108193C2 (uk) | 2008-12-04 | 2015-04-10 | Апоптозіндукуючий засіб для лікування раку і імунних і аутоімунних захворювань | |
| US8557983B2 (en) * | 2008-12-04 | 2013-10-15 | Abbvie Inc. | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| US8586754B2 (en) * | 2008-12-05 | 2013-11-19 | Abbvie Inc. | BCL-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases |
| EP2376480B1 (en) | 2008-12-05 | 2016-06-01 | AbbVie Inc. | Sulfonamide derivatives as bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases |
| US8563735B2 (en) * | 2008-12-05 | 2013-10-22 | Abbvie Inc. | Bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases |
| US20110245156A1 (en) | 2008-12-09 | 2011-10-06 | Cytokine Pharmasciences, Inc. | Novel antiviral compounds, compositions, and methods of use |
| US20120094963A1 (en) | 2008-12-23 | 2012-04-19 | of Queen Elizabeth near Dublin | Targeting prodrugs and compositions for the treatment of gastrointestinal diseases |
| CN104945311A (zh) * | 2009-01-19 | 2015-09-30 | Abbvie公司 | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 |
| ES2536090T3 (es) * | 2009-01-19 | 2015-05-20 | Abbvie Inc. | Agentes inductores de la apoptosis para el tratamiento del cáncer y enfermedades inmunitarias y autoinmunitarias |
| US8546399B2 (en) * | 2009-05-26 | 2013-10-01 | Abbvie Inc. | Apoptosis inducing agents for the treatment of cancer and immune and autoimmune diseases |
| BR122019016429B1 (pt) * | 2009-05-26 | 2020-03-24 | Abbvie Ireland Unlimited Company | Compostos inibidores da atividade de proteínas bcl-2 antiapoptótica e composição farmacêutica compreendendo ditos compostos |
| TWI520960B (zh) * | 2010-05-26 | 2016-02-11 | 艾伯維有限公司 | 用於治療癌症及免疫及自體免疫疾病之細胞凋亡誘導劑 |
-
2010
- 2010-05-26 BR BR122019016429-0A patent/BR122019016429B1/pt active IP Right Grant
- 2010-05-26 CA CA3052016A patent/CA3052016A1/en not_active Abandoned
- 2010-05-26 BR BRPI1014359-9A patent/BRPI1014359B1/pt active IP Right Grant
- 2010-05-26 IL IL299019A patent/IL299019A/en unknown
- 2010-05-26 CN CN201910261444.3A patent/CN109897038B/zh active Active
- 2010-05-26 CR CR20170019A patent/CR20170019A/es unknown
- 2010-05-26 KR KR1020237028352A patent/KR20230128571A/ko active Pending
- 2010-05-26 MX MX2011012257A patent/MX339469B/es active IP Right Grant
- 2010-05-26 KR KR1020177008201A patent/KR20170037683A/ko not_active Abandoned
- 2010-05-26 DK DK10721246.6T patent/DK2435432T6/da active
- 2010-05-26 ME MEP-2015-124A patent/ME02205B/me unknown
- 2010-05-26 RS RS20150592A patent/RS54234B2/sr unknown
- 2010-05-26 CA CA3206963A patent/CA3206963A1/en active Pending
- 2010-05-26 PT PT107212466T patent/PT2435432E/pt unknown
- 2010-05-26 RU RU2011152973A patent/RU2535347C3/ru active Protection Beyond IP Right Term
- 2010-05-26 AR ARP100101806A patent/AR076705A1/es active IP Right Grant
- 2010-05-26 EP EP24195253.0A patent/EP4474383A3/en active Pending
- 2010-05-26 EP EP15167892.7A patent/EP2944638A1/en not_active Withdrawn
- 2010-05-26 PH PH1/2015/500297A patent/PH12015500297B1/en unknown
- 2010-05-26 JP JP2012513209A patent/JP5747025B2/ja active Active
- 2010-05-26 PE PE2011002025A patent/PE20120345A1/es active IP Right Grant
- 2010-05-26 ES ES10721246T patent/ES2546294T7/es active Active
- 2010-05-26 KR KR1020157014221A patent/KR101723378B1/ko active Active
- 2010-05-26 IL IL319747A patent/IL319747A/en unknown
- 2010-05-26 CA CA2929347A patent/CA2929347A1/en not_active Abandoned
- 2010-05-26 UY UY0001032668A patent/UY32668A/es active IP Right Grant
- 2010-05-26 KR KR1020197020313A patent/KR20190086591A/ko not_active Abandoned
- 2010-05-26 EP EP10721246.6A patent/EP2435432B3/en active Active
- 2010-05-26 CN CN201510165051.4A patent/CN104876927B/zh active Active
- 2010-05-26 PL PL10721246.6T patent/PL2435432T6/pl unknown
- 2010-05-26 SI SI201031011T patent/SI2435432T2/sl unknown
- 2010-05-26 KR KR1020117030916A patent/KR101659583B1/ko active Active
- 2010-05-26 NZ NZ595708A patent/NZ595708A/en unknown
- 2010-05-26 HR HRP20151001TT patent/HRP20151001T4/hr unknown
- 2010-05-26 KR KR1020187032920A patent/KR102001418B1/ko active Active
- 2010-05-26 KR KR1020197033737A patent/KR20190130676A/ko active Pending
- 2010-05-26 TW TW103138402A patent/TWI537269B/zh active
- 2010-05-26 MY MYPI2011005633A patent/MY155645A/en unknown
- 2010-05-26 CA CA2759182A patent/CA2759182C/en active Active
- 2010-05-26 CN CN201910270919.5A patent/CN109966294A/zh active Pending
- 2010-05-26 UA UAA201115309A patent/UA106079C2/uk unknown
- 2010-05-26 KR KR1020187011857A patent/KR101920202B1/ko active Active
- 2010-05-26 EP EP19195104.5A patent/EP3656771A1/en not_active Withdrawn
- 2010-05-26 SG SG10201704742YA patent/SG10201704742YA/en unknown
- 2010-05-26 AU AU2010254160A patent/AU2010254160C1/en active Active
- 2010-05-26 TW TW099116922A patent/TWI476195B/zh active
- 2010-05-26 RU RU2014132884/04A patent/RU2573832C2/ru active
- 2010-05-26 TW TW104138114A patent/TWI561523B/zh active
- 2010-05-26 CN CN201510215766.6A patent/CN104906100A/zh active Pending
- 2010-05-26 CN CN201080023068.1A patent/CN102448959B/zh active Active
- 2010-05-26 HU HUE10721246A patent/HUE027698T2/en unknown
- 2010-05-26 SG SG2011075843A patent/SG175253A1/en unknown
- 2010-05-26 WO PCT/US2010/036198 patent/WO2010138588A2/en not_active Ceased
- 2010-11-22 US US12/951,344 patent/US8580794B2/en active Active
- 2010-11-23 UY UY0001033047A patent/UY33047A/es not_active Application Discontinuation
-
2011
- 2011-10-09 IL IL215644A patent/IL215644A/en active IP Right Grant
- 2011-11-17 MX MX2019012154A patent/MX2019012154A/es unknown
- 2011-11-22 CL CL2011002949A patent/CL2011002949A1/es unknown
- 2011-11-23 ZA ZA2011/08616A patent/ZA201108616B/en unknown
- 2011-11-25 CR CR20110632A patent/CR20110632A/es unknown
- 2011-11-25 DO DO2011000367A patent/DOP2011000367A/es unknown
- 2011-12-26 CO CO11178424A patent/CO6480950A2/es not_active Application Discontinuation
- 2011-12-26 EC EC2011011554A patent/ECSP11011554A/es unknown
-
2015
- 2015-01-09 JP JP2015003098A patent/JP6038195B2/ja active Active
- 2015-09-23 CY CY20151100832T patent/CY1117423T1/el unknown
- 2015-09-24 SM SM201500225T patent/SMT201500225B/xx unknown
- 2015-12-18 RU RU2015154494A patent/RU2628885C2/ru active
-
2016
- 2016-03-25 HK HK16103532.1A patent/HK1215576A1/en unknown
- 2016-10-31 JP JP2016212548A patent/JP6353506B2/ja active Active
-
2017
- 2017-05-16 NL NL300873C patent/NL300873I2/nl unknown
- 2017-05-16 HU HUS1700021C patent/HUS1700021I1/hu unknown
- 2017-05-18 LT LTPA2017015C patent/LTC2435432I2/lt unknown
- 2017-05-25 CY CY2017019C patent/CY2017019I1/el unknown
- 2017-05-29 NO NO2017023C patent/NO2017023I1/no unknown
- 2017-05-29 FI FIEP10721246.6T patent/FI2435432T6/fi active
- 2017-08-07 IL IL253891A patent/IL253891A0/en unknown
- 2017-10-18 AR ARP170102895A patent/AR109974A2/es active IP Right Grant
-
2018
- 2018-04-18 JP JP2018079598A patent/JP2018138577A/ja not_active Ceased
- 2018-07-31 UY UY0001037825A patent/UY37825A/es active IP Right Grant
-
2019
- 2019-09-03 IL IL26909219A patent/IL269092A/en unknown
- 2019-10-17 JP JP2019189974A patent/JP2020023545A/ja not_active Ceased
-
2021
- 2021-09-01 IL IL286036A patent/IL286036A/en unknown
- 2021-12-09 JP JP2021199837A patent/JP2022033939A/ja not_active Ceased
-
2023
- 2023-01-10 JP JP2023001499A patent/JP2023040165A/ja active Pending
-
2025
- 2025-02-10 JP JP2025019817A patent/JP2025072583A/ja active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1665802A (zh) * | 2002-07-05 | 2005-09-07 | 西克拉塞尔有限公司 | 双芳基磺酰胺化合物及其在癌症治疗中的用途 |
| CN1906183A (zh) * | 2003-11-13 | 2007-01-31 | 艾博特公司 | N－酰基磺酰胺细胞程序死亡促进剂 |
| US20070072860A1 (en) * | 2003-11-13 | 2007-03-29 | Milan Bruncko | Apoptosis promoters |
| CN101175738A (zh) * | 2005-05-12 | 2008-05-07 | 艾博特公司 | 细胞凋亡促进剂 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109897038B (zh) | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 | |
| CN103153993B (zh) | 治疗癌症和免疫与自身免疫疾病的细胞程序死亡诱导药剂 | |
| US11897864B2 (en) | Apoptosis inducing agents for the treatment of cancer and immune and autoimmune diseases | |
| AU2015202183B2 (en) | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases | |
| HK40009800A (en) | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |