RU2693629C2 - Новые индолизиновые соединения, способ их получения и фармацевтические композиции, содержащие их - Google Patents

Info

Publication number

RU2693629C2

RU2693629C2 RU2016105999A RU2016105999A RU2693629C2 RU 2693629 C2 RU2693629 C2 RU 2693629C2 RU 2016105999 A RU2016105999 A RU 2016105999A RU 2016105999 A RU2016105999 A RU 2016105999A RU 2693629 C2 RU2693629 C2 RU 2693629C2

Authority

RU

Russia

Prior art keywords

methyl

group

formula

compound

carbonyl

Prior art date

2013-07-23

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 165
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
• 238000004519 manufacturing process Methods 0.000 title claims description 9
• 238000000034 method Methods 0.000 claims abstract description 128
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 100
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 87
• 125000003118 aryl group Chemical group 0.000 claims abstract description 75
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 74
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 72
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 28
• 239000002253 acid Substances 0.000 claims abstract description 26
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 21
• 150000003839 salts Chemical class 0.000 claims abstract description 19
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 17
• 201000011510 cancer Diseases 0.000 claims abstract description 15
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 14
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 14
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims abstract description 12
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 12
• 150000002367 halogens Chemical class 0.000 claims abstract description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 10
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 8
• 239000001257 hydrogen Substances 0.000 claims abstract description 8
• 125000002950 monocyclic group Chemical group 0.000 claims abstract description 7
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
• 125000005843 halogen group Chemical group 0.000 claims abstract description 6
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 6
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
• 239000001301 oxygen Substances 0.000 claims abstract description 6
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 5
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
• 125000002619 bicyclic group Chemical group 0.000 claims abstract description 5
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 5
• 125000006091 1,3-dioxolane group Chemical group 0.000 claims abstract description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 4
• 150000001204 N-oxides Chemical class 0.000 claims abstract description 3
• 125000003277 amino group Chemical group 0.000 claims abstract description 3
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 3
• 150000001721 carbon Chemical group 0.000 claims abstract 2
• 230000002401 inhibitory effect Effects 0.000 claims abstract 2
• -1 2- (morpholin-4-yl) ethyl Chemical group 0.000 claims description 127
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 23
• 206010028980 Neoplasm Diseases 0.000 claims description 18
• 238000011282 treatment Methods 0.000 claims description 14
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 13
• 238000006243 chemical reaction Methods 0.000 claims description 11
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 11
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
• 150000001412 amines Chemical class 0.000 claims description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 8
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
• 206010060862 Prostate cancer Diseases 0.000 claims description 5
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 5
• 206010041067 Small cell lung cancer Diseases 0.000 claims description 5
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 5
• JBDKAABFESSFMV-UHFFFAOYSA-N pyrrolo[1,2-a]pyrimidine Chemical group N1=CC=CN2C=CC=C21 JBDKAABFESSFMV-UHFFFAOYSA-N 0.000 claims description 5
• 238000000926 separation method Methods 0.000 claims description 5
• 208000000587 small cell lung carcinoma Diseases 0.000 claims description 5
• MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 claims description 4
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
• 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 claims description 4
• 206010006187 Breast cancer Diseases 0.000 claims description 4
• 208000026310 Breast neoplasm Diseases 0.000 claims description 4
• 206010009944 Colon cancer Diseases 0.000 claims description 4
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 4
• 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 claims description 4
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 4
• 206010033128 Ovarian cancer Diseases 0.000 claims description 4
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 4
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
• 239000003054 catalyst Substances 0.000 claims description 4
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 4
• 201000010099 disease Diseases 0.000 claims description 4
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
• 230000003211 malignant effect Effects 0.000 claims description 4
• 229940126601 medicinal product Drugs 0.000 claims description 4
• 201000000050 myeloid neoplasm Diseases 0.000 claims description 4
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 4
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 4
• QYASHELNMUPRKF-UHFFFAOYSA-N 5,6,7,8-tetrahydroindolizine Chemical compound C1CCCN2C=CC=C21 QYASHELNMUPRKF-UHFFFAOYSA-N 0.000 claims description 3
• 206010005003 Bladder cancer Diseases 0.000 claims description 3
• 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
• 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 3
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 3
• 208000002495 Uterine Neoplasms Diseases 0.000 claims description 3
• 210000004556 brain Anatomy 0.000 claims description 3
• 210000000481 breast Anatomy 0.000 claims description 3
• 150000007942 carboxylates Chemical class 0.000 claims description 3
• 238000010511 deprotection reaction Methods 0.000 claims description 3
• 239000003814 drug Substances 0.000 claims description 3
• 201000004101 esophageal cancer Diseases 0.000 claims description 3
• 208000014951 hematologic disease Diseases 0.000 claims description 3
• 210000000987 immune system Anatomy 0.000 claims description 3
• 201000007270 liver cancer Diseases 0.000 claims description 3
• 208000014018 liver neoplasm Diseases 0.000 claims description 3
• 208000003747 lymphoid leukemia Diseases 0.000 claims description 3
• 201000001441 melanoma Diseases 0.000 claims description 3
• 229910052763 palladium Inorganic materials 0.000 claims description 3
• 230000000861 pro-apoptotic effect Effects 0.000 claims description 3
• 210000003932 urinary bladder Anatomy 0.000 claims description 3
• 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
• YZBDXDPBLIQCJY-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2C=CC=C21 YZBDXDPBLIQCJY-UHFFFAOYSA-N 0.000 claims description 2
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 2
• GVLRTOYGRNLSDW-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyridine Chemical compound C1=CC=C2C=NNC2=N1 GVLRTOYGRNLSDW-UHFFFAOYSA-N 0.000 claims description 2
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 2
• SRNKZYRMFBGSGE-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyrimidine Chemical compound N1=CC=CN2N=CN=C21 SRNKZYRMFBGSGE-UHFFFAOYSA-N 0.000 claims description 2
• 150000001263 acyl chlorides Chemical class 0.000 claims description 2
• 150000008064 anhydrides Chemical class 0.000 claims description 2
• 239000003795 chemical substances by application Substances 0.000 claims description 2
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims description 2
• LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 2
• LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical compound N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 claims description 2
• 238000001959 radiotherapy Methods 0.000 claims description 2
• 239000007858 starting material Substances 0.000 claims description 2
• 206010046766 uterine cancer Diseases 0.000 claims description 2
• 210000003238 esophagus Anatomy 0.000 claims 2
• 125000003172 aldehyde group Chemical group 0.000 claims 1
• 125000004185 ester group Chemical group 0.000 claims 1
• 230000000694 effects Effects 0.000 abstract description 7
• 125000000623 heterocyclic group Chemical group 0.000 abstract description 4
• 239000000126 substance Substances 0.000 abstract description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 abstract 2
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 abstract 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 abstract 1
• 208000026278 immune system disease Diseases 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 244
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 135
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
• 238000003786 synthesis reaction Methods 0.000 description 119
• 125000001931 aliphatic group Chemical group 0.000 description 117
• 230000015572 biosynthetic process Effects 0.000 description 115
• 239000000243 solution Substances 0.000 description 107
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 96
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 88
• 239000000047 product Substances 0.000 description 76
• 239000011541 reaction mixture Substances 0.000 description 69
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 67
• 238000004452 microanalysis Methods 0.000 description 67
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
• 239000012074 organic phase Substances 0.000 description 39
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 38
• 238000001308 synthesis method Methods 0.000 description 36
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 35
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 33
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
• 239000007787 solid Substances 0.000 description 31
• IXJSDKIJPVSPKF-UHFFFAOYSA-N 4-bromo-1-methylpyrazole Chemical compound CN1C=C(Br)C=N1 IXJSDKIJPVSPKF-UHFFFAOYSA-N 0.000 description 30
• 239000000741 silica gel Substances 0.000 description 28
• 229910002027 silica gel Inorganic materials 0.000 description 28
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
• ZBPHPBWGQALQCS-UHFFFAOYSA-N 1,2,3,5-tetrahydroindolizine Chemical compound C1C=CC=C2CCCN21 ZBPHPBWGQALQCS-UHFFFAOYSA-N 0.000 description 26
• 239000000203 mixture Substances 0.000 description 26
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• 239000000460 chlorine Substances 0.000 description 24
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 23
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 22
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 22
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
• 238000000746 purification Methods 0.000 description 20
• 238000003756 stirring Methods 0.000 description 20
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• 238000010898 silica gel chromatography Methods 0.000 description 18
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
• 238000004896 high resolution mass spectrometry Methods 0.000 description 17
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 16
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 238000004587 chromatography analysis Methods 0.000 description 15
• 239000000725 suspension Substances 0.000 description 15
• CSQUXTSIDQURDV-UHFFFAOYSA-N 6-bromo-1,3-benzodioxole-5-carbaldehyde Chemical compound C1=C(C=O)C(Br)=CC2=C1OCO2 CSQUXTSIDQURDV-UHFFFAOYSA-N 0.000 description 14
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
• 239000012047 saturated solution Substances 0.000 description 14
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 13
• 230000006907 apoptotic process Effects 0.000 description 12
• 238000001035 drying Methods 0.000 description 12
• 239000000843 powder Substances 0.000 description 12
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
• 210000004027 cell Anatomy 0.000 description 11
• 150000002148 esters Chemical group 0.000 description 11
• 239000012634 fragment Substances 0.000 description 11
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
• 150000001408 amides Chemical class 0.000 description 10
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
• 235000019341 magnesium sulphate Nutrition 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• AJOAHIKYBSZIEV-UHFFFAOYSA-N 2-bromo-4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C(Br)=C1 AJOAHIKYBSZIEV-UHFFFAOYSA-N 0.000 description 8
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 8
• 102000003952 Caspase 3 Human genes 0.000 description 8
• 108090000397 Caspase 3 Proteins 0.000 description 8
• 241000699670 Mus sp. Species 0.000 description 8
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 8
• 239000012043 crude product Substances 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
• 230000007935 neutral effect Effects 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 7
• 239000008346 aqueous phase Substances 0.000 description 7
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 102000004169 proteins and genes Human genes 0.000 description 7
• 108090000623 proteins and genes Proteins 0.000 description 7
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 239000002585 base Substances 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 239000003208 petroleum Substances 0.000 description 6
• 239000011780 sodium chloride Substances 0.000 description 6
• 229910000104 sodium hydride Inorganic materials 0.000 description 6
• 239000005711 Benzoic acid Substances 0.000 description 5
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
• 150000001299 aldehydes Chemical group 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• 235000010233 benzoic acid Nutrition 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• 125000000753 cycloalkyl group Chemical group 0.000 description 5
• 238000003818 flash chromatography Methods 0.000 description 5
• 230000006870 function Effects 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• 235000017557 sodium bicarbonate Nutrition 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
• VXWVFZFZYXOBTA-UHFFFAOYSA-N 5-bromo-1h-indole Chemical compound BrC1=CC=C2NC=CC2=C1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 description 4
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
• 230000004913 activation Effects 0.000 description 4
• 229910052801 chlorine Inorganic materials 0.000 description 4
• 239000013078 crystal Substances 0.000 description 4
• 238000002875 fluorescence polarization Methods 0.000 description 4
• 239000006260 foam Substances 0.000 description 4
• 235000019253 formic acid Nutrition 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 150000002500 ions Chemical class 0.000 description 4
• 229910052744 lithium Inorganic materials 0.000 description 4
• AWJZTPWDQYFQPQ-UHFFFAOYSA-N methyl 2-chloroprop-2-enoate Chemical compound COC(=O)C(Cl)=C AWJZTPWDQYFQPQ-UHFFFAOYSA-N 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
• 239000002904 solvent Substances 0.000 description 4
• 229910052717 sulfur Inorganic materials 0.000 description 4
• 239000011593 sulfur Chemical group 0.000 description 4
• 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 4
• OPZDXMCOWFPQPE-UHFFFAOYSA-N 2-bromo-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(Br)=C1 OPZDXMCOWFPQPE-UHFFFAOYSA-N 0.000 description 3
• LEHHIPIDKQVNEV-UHFFFAOYSA-N 3,3-difluoropiperidine;hydrochloride Chemical compound Cl.FC1(F)CCCNC1 LEHHIPIDKQVNEV-UHFFFAOYSA-N 0.000 description 3
• AVPAYFOQPGPSCC-UHFFFAOYSA-N 3-methoxyazetidine Chemical compound COC1CNC1 AVPAYFOQPGPSCC-UHFFFAOYSA-N 0.000 description 3
• BSDGZUDFPKIYQG-UHFFFAOYSA-N 4-bromopyridine Chemical compound BrC1=CC=NC=C1 BSDGZUDFPKIYQG-UHFFFAOYSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• 102000051485 Bcl-2 family Human genes 0.000 description 3
• 108700038897 Bcl-2 family Proteins 0.000 description 3
• 108010076667 Caspases Proteins 0.000 description 3
• 102000011727 Caspases Human genes 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• ZSKDXMLMMQFHGW-JTQLQIEISA-N [(3s)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol Chemical compound C1=CC=C2CN[C@H](CO)CC2=C1 ZSKDXMLMMQFHGW-JTQLQIEISA-N 0.000 description 3
• 239000012298 atmosphere Substances 0.000 description 3
• 239000012267 brine Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 229940125904 compound 1 Drugs 0.000 description 3
• 238000001816 cooling Methods 0.000 description 3
• DTIYPFOXKXUYLD-UHFFFAOYSA-N cyclohexa-2,4-dien-1-amine Chemical compound NC1CC=CC=C1 DTIYPFOXKXUYLD-UHFFFAOYSA-N 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 230000001506 immunosuppresive effect Effects 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 238000001819 mass spectrum Methods 0.000 description 3
• 150000004702 methyl esters Chemical class 0.000 description 3
• 125000000896 monocarboxylic acid group Chemical group 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• KWZOQFYCGQASRV-UHFFFAOYSA-N n-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-1-methylindazol-5-amine Chemical compound C=1C=C2N(C)N=CC2=CC=1NC1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1 KWZOQFYCGQASRV-UHFFFAOYSA-N 0.000 description 3
• 230000007170 pathology Effects 0.000 description 3
• 230000000144 pharmacologic effect Effects 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 150000003335 secondary amines Chemical class 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
• 125000001424 substituent group Chemical group 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 238000002054 transplantation Methods 0.000 description 3
• 210000004881 tumor cell Anatomy 0.000 description 3
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
• 125000006685 (C1-C6) polyhaloalkyl group Chemical group 0.000 description 2
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
• NDOPHXWIAZIXPR-UHFFFAOYSA-N 2-bromobenzaldehyde Chemical compound BrC1=CC=CC=C1C=O NDOPHXWIAZIXPR-UHFFFAOYSA-N 0.000 description 2
• MHNNAWXXUZQSNM-UHFFFAOYSA-N 2-methylbut-1-ene Chemical compound CCC(C)=C MHNNAWXXUZQSNM-UHFFFAOYSA-N 0.000 description 2
• BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 2
• YCYMCMYLORLIJX-UHFFFAOYSA-N 2-propyloctanoic acid Chemical compound CCCCCCC(C(O)=O)CCC YCYMCMYLORLIJX-UHFFFAOYSA-N 0.000 description 2
• NWHLLYKKRZGWOR-UHFFFAOYSA-N 3-[5-chloro-2-(3,4-dihydro-1H-isoquinoline-2-carbonyl)phenyl]-N-(4-hydroxyphenyl)-N-[1-(2-morpholin-4-ylethyl)-2,3-dihydroindol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound ClC=1C=CC(=C(C=1)C1=CC(=C2CCCCN12)C(=O)N(C=1C=C2CCN(C2=CC=1)CCN1CCOCC1)C1=CC=C(C=C1)O)C(=O)N1CC2=CC=CC=C2CC1 NWHLLYKKRZGWOR-UHFFFAOYSA-N 0.000 description 2
• QZBOKVQJJOJJFV-LJAQVGFWSA-N 3-[6-[(3s)-3-(hydroxymethyl)-3,4-dihydro-1h-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-n-(4-hydroxyphenyl)-n-phenyl-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C([C@H]1CO)C2=CC=CC=C2CN1C(=O)C1=CC=2OCOC=2C=C1C(N1CCCCC1=1)=CC=1C(=O)N(C=1C=CC(O)=CC=1)C1=CC=CC=C1 QZBOKVQJJOJJFV-LJAQVGFWSA-N 0.000 description 2
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
• JPOOXHAUVWNLJZ-UHFFFAOYSA-N 4-(3-fluoro-4-methylanilino)phenol Chemical compound C1=C(F)C(C)=CC=C1NC1=CC=C(O)C=C1 JPOOXHAUVWNLJZ-UHFFFAOYSA-N 0.000 description 2
• ASIONCPTHRYGJW-UHFFFAOYSA-N 4-(4-fluoroanilino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=C(F)C=C1 ASIONCPTHRYGJW-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• AMIAUQGXJBZXPZ-UHFFFAOYSA-N 4-[2-(5-bromoindol-1-yl)ethyl]morpholine Chemical compound C1=CC2=CC(Br)=CC=C2N1CCN1CCOCC1 AMIAUQGXJBZXPZ-UHFFFAOYSA-N 0.000 description 2
• PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 2
• BAQKUNMKVAPWGU-UHFFFAOYSA-N 4-bromopyridin-2-amine Chemical compound NC1=CC(Br)=CC=N1 BAQKUNMKVAPWGU-UHFFFAOYSA-N 0.000 description 2
• UPNCIFWZXYITRY-UHFFFAOYSA-N 4-chloro-2-[8-methoxycarbonyl-2-[(2-methylpropan-2-yl)oxycarbonyl]-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazin-6-yl]benzoic acid Chemical compound C(C)(C)(C)OC(=O)N1CC=2N(CC1)C(=CC=2C(=O)OC)C1=C(C(=O)O)C=CC(=C1)Cl UPNCIFWZXYITRY-UHFFFAOYSA-N 0.000 description 2
• LAOZSCRCYVBSJA-UHFFFAOYSA-N 5,5-dimethyl-1,3-diazinane-2,4,6-trione Chemical compound CC1(C)C(=O)NC(=O)NC1=O LAOZSCRCYVBSJA-UHFFFAOYSA-N 0.000 description 2
• JRGFWIOFVMTGGL-UHFFFAOYSA-N 6-(8-methoxycarbonylpyrrolo[1,2-a]pyrimidin-6-yl)-1,3-benzodioxole-5-carboxylic acid Chemical compound COC(=O)C=1C=C(N2C=1N=CC=C2)C=1C(=CC2=C(OCO2)C=1)C(=O)O JRGFWIOFVMTGGL-UHFFFAOYSA-N 0.000 description 2
• GRPOMPOKJNVQKD-UHFFFAOYSA-N 6-bromo-2,3-dihydro-1,4-benzodioxine-7-carbaldehyde Chemical compound O1CCOC2=C1C=C(Br)C(C=O)=C2 GRPOMPOKJNVQKD-UHFFFAOYSA-N 0.000 description 2
• BFVTWHUGYYTADQ-UHFFFAOYSA-N 7-[8-methoxycarbonyl-2-[(2-methylpropan-2-yl)oxycarbonyl]-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazin-6-yl]-2,3-dihydro-1,4-benzodioxine-6-carboxylic acid Chemical compound C(C)(C)(C)OC(=O)N1CC=2N(CC1)C(=CC=2C(=O)OC)C=1C(=CC2=C(OCCO2)C=1)C(=O)O BFVTWHUGYYTADQ-UHFFFAOYSA-N 0.000 description 2
• 102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 2
• 108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• WMKRAYAECPKEFS-UHFFFAOYSA-N BrC1=CC=C(CN2CC(CCC2)(F)F)C=C1 Chemical compound BrC1=CC=C(CN2CC(CCC2)(F)F)C=C1 WMKRAYAECPKEFS-UHFFFAOYSA-N 0.000 description 2
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
• DCVGZTSQRXSWDP-UHFFFAOYSA-N COC(=O)c1cc(-c2cc(Cl)ccc2C(O)=O)n2ccccc12 Chemical compound COC(=O)c1cc(-c2cc(Cl)ccc2C(O)=O)n2ccccc12 DCVGZTSQRXSWDP-UHFFFAOYSA-N 0.000 description 2
• NJVHOJPQAYGVQU-UHFFFAOYSA-N COC(=O)c1cc(-c2cc3OCOc3cc2C(O)=O)n2CCCCc12 Chemical compound COC(=O)c1cc(-c2cc3OCOc3cc2C(O)=O)n2CCCCc12 NJVHOJPQAYGVQU-UHFFFAOYSA-N 0.000 description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• JXBIEEFHDLIVEB-XFULWGLBSA-N Cl.C(CN1CCOCC1)[C@@H]1Cc2ccccc2CN1 Chemical compound Cl.C(CN1CCOCC1)[C@@H]1Cc2ccccc2CN1 JXBIEEFHDLIVEB-XFULWGLBSA-N 0.000 description 2
• RMMOKSHDKADJNC-DDWIOCJRSA-N Cl.C[C@@H]1Cc2ccccc2CN1 Chemical compound Cl.C[C@@H]1Cc2ccccc2CN1 RMMOKSHDKADJNC-DDWIOCJRSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 229910010082 LiAlH Inorganic materials 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
• BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
• NVQPTMARRZTENW-VQIWEWKSSA-N N-(4-hydroxyphenyl)-3-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-N-(1-methylpyridin-1-ium-4-yl)indolizine-1-carboxamide chloride Chemical compound [Cl-].C[C@@H]1CC2=C(CN1C(=O)C1=CC3=C(OCO3)C=C1C1=CC(C(=O)N(C3=CC=C(O)C=C3)C3=CC=[N+](C)C=C3)=C3C=CC=CN13)C=CC=C2 NVQPTMARRZTENW-VQIWEWKSSA-N 0.000 description 2
• YUFBDXKFITYXDQ-UHFFFAOYSA-N N-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-1-methylindol-5-amine Chemical compound Cn1ccc2cc(Nc3ccc(O[Si](C)(C)C(C)(C)C)cc3)ccc12 YUFBDXKFITYXDQ-UHFFFAOYSA-N 0.000 description 2
• KICVPQLXEOUBJV-UHFFFAOYSA-N N-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-1-methylpyrazol-4-amine Chemical compound Cn1cc(Nc2ccc(O[Si](C)(C)C(C)(C)C)cc2)cn1 KICVPQLXEOUBJV-UHFFFAOYSA-N 0.000 description 2
• AJFVZKKSAOGURR-MRXNPFEDSA-N N1(CCOCC1)CCC[C@H]1NCC2=CC=CC=C2C1 Chemical compound N1(CCOCC1)CCC[C@H]1NCC2=CC=CC=C2C1 AJFVZKKSAOGURR-MRXNPFEDSA-N 0.000 description 2
• 101150003085 Pdcl gene Proteins 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 2
• 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
• BLQSTTZAKVAGRP-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(NC2=CC=C(C=C2)CCN2CC(CCC2)(F)F)C=C1 Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(NC2=CC=C(C=C2)CCN2CC(CCC2)(F)F)C=C1 BLQSTTZAKVAGRP-UHFFFAOYSA-N 0.000 description 2
• BSXMOBWSEVWHHG-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(NC2=CC=C(C=C2)CN2CC(CCC2)(F)F)C=C1 Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(NC2=CC=C(C=C2)CN2CC(CCC2)(F)F)C=C1 BSXMOBWSEVWHHG-UHFFFAOYSA-N 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
• 235000019270 ammonium chloride Nutrition 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
• 230000003833 cell viability Effects 0.000 description 2
• 238000002512 chemotherapy Methods 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• 229940126214 compound 3 Drugs 0.000 description 2
• 230000003013 cytotoxicity Effects 0.000 description 2
• 231100000135 cytotoxicity Toxicity 0.000 description 2
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 201000003444 follicular lymphoma Diseases 0.000 description 2
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
• 150000002431 hydrogen Chemical class 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
• DHOQDVKLAJQFSP-UHFFFAOYSA-N indolizine-1-carboxamide Chemical compound C1=CC=CC2=C(C(=O)N)C=CN21 DHOQDVKLAJQFSP-UHFFFAOYSA-N 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
• 239000006166 lysate Substances 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
• QEBDFYIAVYAQRA-AREMUKBSSA-N n-(4-hydroxyphenyl)-3-[6-[(3r)-3-methyl-3,4-dihydro-1h-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-n-(1-methylindol-5-yl)-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C([C@H]1C)C2=CC=CC=C2CN1C(=O)C1=CC=2OCOC=2C=C1C(N1CCCCC1=1)=CC=1C(=O)N(C=1C=C2C=CN(C)C2=CC=1)C1=CC=C(O)C=C1 QEBDFYIAVYAQRA-AREMUKBSSA-N 0.000 description 2
• PJNPCSKARBTURZ-UHFFFAOYSA-N n-phenyl-4-phenylmethoxyaniline Chemical compound C=1C=CC=CC=1COC(C=C1)=CC=C1NC1=CC=CC=C1 PJNPCSKARBTURZ-UHFFFAOYSA-N 0.000 description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
• 230000010287 polarization Effects 0.000 description 2
• 235000011056 potassium acetate Nutrition 0.000 description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 2
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
• 238000000527 sonication Methods 0.000 description 2
• 125000003003 spiro group Chemical group 0.000 description 2
• CNAKHJPYSUZKTE-CQSZACIVSA-N tert-butyl N-[2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]carbamate Chemical compound C1N[C@@H](CC2=CC=CC=C12)CCNC(OC(C)(C)C)=O CNAKHJPYSUZKTE-CQSZACIVSA-N 0.000 description 2
• 239000003053 toxin Substances 0.000 description 2
• 231100000765 toxin Toxicity 0.000 description 2
• 108700012359 toxins Proteins 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
• ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
• STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
• OSWBUMQRTNEAKG-XFULWGLBSA-N (3S)-3-[2-(3,3-difluoropiperidin-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinoline hydrochloride Chemical compound Cl.FC1(F)CCCN(CC[C@@H]2Cc3ccccc3CN2)C1 OSWBUMQRTNEAKG-XFULWGLBSA-N 0.000 description 1
• LBWDDLDGWDFUCZ-PFEQFJNWSA-N (3S)-3-[2-(3-methoxyazetidin-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinoline hydrochloride Chemical compound Cl.COC1CN(CC[C@@H]2Cc3ccccc3CN2)C1 LBWDDLDGWDFUCZ-PFEQFJNWSA-N 0.000 description 1
• RMMOKSHDKADJNC-QRPNPIFTSA-N (3S)-3-methyl-1,2,3,4-tetrahydroisoquinoline hydrochloride Chemical compound Cl.C[C@H]1Cc2ccccc2CN1 RMMOKSHDKADJNC-QRPNPIFTSA-N 0.000 description 1
• UEKQPSAKUNXFHL-MRVPVSSYSA-N (3r)-3-methyl-1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CN[C@H](C)CC2=C1 UEKQPSAKUNXFHL-MRVPVSSYSA-N 0.000 description 1
• JATHXJMZMGXQFU-MRVPVSSYSA-N (3r)-3-methyl-3,4-dihydroisoquinoline Chemical compound C1=CC=C2C=N[C@H](C)CC2=C1 JATHXJMZMGXQFU-MRVPVSSYSA-N 0.000 description 1
• YWVQGUBCAUFBCP-INIZCTEOSA-N (3s)-2-phenylmethoxycarbonyl-3,4-dihydro-1h-isoquinoline-3-carboxylic acid Chemical compound C([C@H]1C(=O)O)C2=CC=CC=C2CN1C(=O)OCC1=CC=CC=C1 YWVQGUBCAUFBCP-INIZCTEOSA-N 0.000 description 1
• IEXRKQFZXJSHOB-UHFFFAOYSA-N (4-nitrophenyl) formate Chemical compound [O-][N+](=O)C1=CC=C(OC=O)C=C1 IEXRKQFZXJSHOB-UHFFFAOYSA-N 0.000 description 1
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• VHRBIROLSOUZQY-UHFFFAOYSA-N 1,2-dihydropyrazine-2-carboxylic acid Chemical compound OC(=O)C1NC=CN=C1 VHRBIROLSOUZQY-UHFFFAOYSA-N 0.000 description 1
• ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
• VVSASNKOFCZVES-UHFFFAOYSA-N 1,3-dimethyl-1,3-diazinane-2,4,6-trione Chemical compound CN1C(=O)CC(=O)N(C)C1=O VVSASNKOFCZVES-UHFFFAOYSA-N 0.000 description 1
• DUKUKERHBGAZKH-UHFFFAOYSA-N 1-[2-(4-bromophenyl)ethyl]-3,3-difluoropiperidine Chemical compound BrC1=CC=C(C=C1)CCN1CC(CCC1)(F)F DUKUKERHBGAZKH-UHFFFAOYSA-N 0.000 description 1
• QDFKKJYEIFBEFC-UHFFFAOYSA-N 1-bromo-3-fluorobenzene Chemical compound FC1=CC=CC(Br)=C1 QDFKKJYEIFBEFC-UHFFFAOYSA-N 0.000 description 1
• AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 1
• GQIRIWDEZSKOCN-UHFFFAOYSA-N 1-chloro-n,n,2-trimethylprop-1-en-1-amine Chemical compound CN(C)C(Cl)=C(C)C GQIRIWDEZSKOCN-UHFFFAOYSA-N 0.000 description 1
• XVGVOQXJPFQDJE-UHFFFAOYSA-N 1-formylpiperidine-2-carboxylic acid Chemical compound OC(=O)C1CCCCN1C=O XVGVOQXJPFQDJE-UHFFFAOYSA-N 0.000 description 1
• RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
• QUKAHFCVKNRRBU-MRVPVSSYSA-N 1-o-tert-butyl 3-o-methyl (3r)-piperazine-1,3-dicarboxylate Chemical compound COC(=O)[C@H]1CN(C(=O)OC(C)(C)C)CCN1 QUKAHFCVKNRRBU-MRVPVSSYSA-N 0.000 description 1
• ZAERTVXCSYRSQX-UHFFFAOYSA-N 1-o-tert-butyl 3-o-methyl 4-formylpiperazine-1,3-dicarboxylate Chemical compound COC(=O)C1CN(C(=O)OC(C)(C)C)CCN1C=O ZAERTVXCSYRSQX-UHFFFAOYSA-N 0.000 description 1
• VRUKHRNWKPWOJU-UHFFFAOYSA-N 2,2-difluoroethyl carbamate Chemical compound NC(=O)OCC(F)F VRUKHRNWKPWOJU-UHFFFAOYSA-N 0.000 description 1
• NKULBUOBGILEAR-UHFFFAOYSA-N 2,2-difluoroethyl trifluoromethanesulfonate Chemical compound FC(F)COS(=O)(=O)C(F)(F)F NKULBUOBGILEAR-UHFFFAOYSA-N 0.000 description 1
• JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
• XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 1
• KIIWIGAAPZPIKX-UHFFFAOYSA-N 2-(1-methoxycarbonylindolizin-3-yl)benzoic acid Chemical compound COC(=O)C=1C=C(N2C=CC=CC=12)C1=C(C(=O)O)C=CC=C1 KIIWIGAAPZPIKX-UHFFFAOYSA-N 0.000 description 1
• QJKULANSOVDGHS-UHFFFAOYSA-N 2-(4-bromophenyl)-1-(3,3-difluoropiperidin-1-yl)ethanone Chemical compound BrC1=CC=C(C=C1)CC(=O)N1CC(CCC1)(F)F QJKULANSOVDGHS-UHFFFAOYSA-N 0.000 description 1
• UZCADEZPIGFPJQ-UHFFFAOYSA-N 2-(4-hydroxyanilino)benzonitrile Chemical compound C1=CC(O)=CC=C1NC1=CC=CC=C1C#N UZCADEZPIGFPJQ-UHFFFAOYSA-N 0.000 description 1
• ZQBQAMXKTHNSQM-ZDUSSCGKSA-N 2-[(3s)-2-[(2-methylpropan-2-yl)oxycarbonyl]-3,4-dihydro-1h-isoquinolin-3-yl]acetic acid Chemical compound C1=CC=C2C[C@@H](CC(O)=O)N(C(=O)OC(C)(C)C)CC2=C1 ZQBQAMXKTHNSQM-ZDUSSCGKSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• BGFDUCFLQJCFCQ-UHFFFAOYSA-N 2-anilinopyrimidin-5-ol Chemical compound N1=CC(O)=CN=C1NC1=CC=CC=C1 BGFDUCFLQJCFCQ-UHFFFAOYSA-N 0.000 description 1
• ODISAUHBLBVQKC-UHFFFAOYSA-N 2-bromo-4-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(Br)=C1 ODISAUHBLBVQKC-UHFFFAOYSA-N 0.000 description 1
• MUZMDYCVUCMIDC-UHFFFAOYSA-N 2-bromo-4-methylbenzaldehyde Chemical compound CC1=CC=C(C=O)C(Br)=C1 MUZMDYCVUCMIDC-UHFFFAOYSA-N 0.000 description 1
• XNHKTMIWQCNZST-UHFFFAOYSA-N 2-bromo-5-methoxybenzaldehyde Chemical compound COC1=CC=C(Br)C(C=O)=C1 XNHKTMIWQCNZST-UHFFFAOYSA-N 0.000 description 1
• SURMYNZXHKLDFO-UHFFFAOYSA-N 2-bromopropanedial Chemical compound O=CC(Br)C=O SURMYNZXHKLDFO-UHFFFAOYSA-N 0.000 description 1
• QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
• YYVPZQADFREIFR-UHFFFAOYSA-N 3,3-difluoropyrrolidine;hydrochloride Chemical compound [Cl-].FC1(F)CC[NH2+]C1 YYVPZQADFREIFR-UHFFFAOYSA-N 0.000 description 1
• MQHMBEAEVVVLMF-UHFFFAOYSA-N 3-(4-hydroxyanilino)benzonitrile Chemical compound C1=CC(O)=CC=C1NC1=CC=CC(C#N)=C1 MQHMBEAEVVVLMF-UHFFFAOYSA-N 0.000 description 1
• GDGMYCNIDMHWMR-UHFFFAOYSA-N 3-[4-[tert-butyl(dimethyl)silyl]oxyanilino]benzonitrile Chemical compound CC(C)(C)[Si](C)(C)Oc1ccc(Nc2cccc(c2)C#N)cc1 GDGMYCNIDMHWMR-UHFFFAOYSA-N 0.000 description 1
• IDZRJIIKVSUFAI-UHFFFAOYSA-N 3-[5-chloro-2-(3,4-dihydro-1h-isoquinoline-2-carbonyl)phenyl]-n-(4-hydroxyphenyl)-n-[1-(2-morpholin-4-ylethyl)indol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C1=CC(O)=CC=C1N(C=1C=C2C=CN(CCN3CCOCC3)C2=CC=1)C(=O)C1=C2CCCCN2C(C=2C(=CC=C(Cl)C=2)C(=O)N2CC3=CC=CC=C3CC2)=C1 IDZRJIIKVSUFAI-UHFFFAOYSA-N 0.000 description 1
• DZMJYPJACIZJAO-HSZRJFAPSA-N 3-[5-chloro-2-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]phenyl]-N-(4-hydroxyphenyl)-N-(1-methylpyrazol-4-yl)-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound ClC=1C=CC(=C(C=1)C1=CC(=C2CCCCN12)C(=O)N(C=1C=NN(C=1)C)C1=CC=C(C=C1)O)C(=O)N1CC2=CC=CC=C2C[C@H]1C DZMJYPJACIZJAO-HSZRJFAPSA-N 0.000 description 1
• DWPDOGJKUMGWCJ-HSZRJFAPSA-N 3-[5-fluoro-2-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]phenyl]-N-(4-hydroxyphenyl)-N-(1-methylpyrazol-4-yl)-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound FC=1C=CC(=C(C=1)C1=CC(=C2CCCCN12)C(=O)N(C=1C=NN(C=1)C)C1=CC=C(C=C1)O)C(=O)N1CC2=CC=CC=C2C[C@H]1C DWPDOGJKUMGWCJ-HSZRJFAPSA-N 0.000 description 1
• BOQSKUNDXGQDAA-RUZDIDTESA-N 3-[5-fluoro-2-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]phenyl]-N-(4-hydroxyphenyl)-N-(1-methylpyrrolo[2,3-b]pyridin-5-yl)-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound FC=1C=CC(=C(C=1)C1=CC(=C2CCCCN12)C(=O)N(C=1C=C2C(=NC=1)N(C=C2)C)C1=CC=C(C=C1)O)C(=O)N1CC2=CC=CC=C2C[C@H]1C BOQSKUNDXGQDAA-RUZDIDTESA-N 0.000 description 1
• WBWJBVIAKPBRNZ-XMMPIXPASA-N 3-[5-fluoro-2-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]phenyl]-N-(4-hydroxyphenyl)-N-pyridin-4-yl-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound FC=1C=CC(=C(C=1)C1=CC(=C2CCCCN12)C(=O)N(C1=CC=NC=C1)C1=CC=C(C=C1)O)C(=O)N1CC2=CC=CC=C2C[C@H]1C WBWJBVIAKPBRNZ-XMMPIXPASA-N 0.000 description 1
• HBTGGEAYOIXJFG-UHFFFAOYSA-N 3-[6-(3,4-dihydro-1h-isoquinoline-2-carbonyl)-1,3-benzodioxol-5-yl]-n-(4-hydroxyphenyl)-n-methyl-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C1=C(C=2C(=CC=3OCOC=3C=2)C(=O)N2CC3=CC=CC=C3CC2)N2CCCCC2=C1C(=O)N(C)C1=CC=C(O)C=C1 HBTGGEAYOIXJFG-UHFFFAOYSA-N 0.000 description 1
• JQPHCNRUAVISCV-UHFFFAOYSA-N 3-[6-(3,4-dihydro-1h-isoquinoline-2-carbonyl)-1,3-benzodioxol-5-yl]-n-ethyl-n-(4-hydroxyphenyl)-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C1=C(C=2C(=CC=3OCOC=3C=2)C(=O)N2CC3=CC=CC=C3CC2)N2CCCCC2=C1C(=O)N(CC)C1=CC=C(O)C=C1 JQPHCNRUAVISCV-UHFFFAOYSA-N 0.000 description 1
• CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• HNNNBQRRIHKFLI-UHFFFAOYSA-N 3-bromo-5-fluoropyridine Chemical compound FC1=CN=CC(Br)=C1 HNNNBQRRIHKFLI-UHFFFAOYSA-N 0.000 description 1
• STXAVEHFKAXGOX-UHFFFAOYSA-N 3-bromobenzonitrile Chemical compound BrC1=CC=CC(C#N)=C1 STXAVEHFKAXGOX-UHFFFAOYSA-N 0.000 description 1
• NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
• QSNJQYGWTCFYOA-UHFFFAOYSA-N 4-(2,3-dihydro-1h-inden-5-ylamino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=C(CCC2)C2=C1 QSNJQYGWTCFYOA-UHFFFAOYSA-N 0.000 description 1
• KLMHMDCWVPGSQM-UHFFFAOYSA-N 4-(2,3-dihydro-1h-indol-6-ylamino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=C(CCN2)C2=C1 KLMHMDCWVPGSQM-UHFFFAOYSA-N 0.000 description 1
• FKRXJEZMMPFUFP-UHFFFAOYSA-N 4-(2,4-difluoroanilino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=C(F)C=C1F FKRXJEZMMPFUFP-UHFFFAOYSA-N 0.000 description 1
• NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 1
• WPSDZTKUCIKUSJ-UHFFFAOYSA-N 4-(2-fluoroanilino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=CC=C1F WPSDZTKUCIKUSJ-UHFFFAOYSA-N 0.000 description 1
• IXXGKMHTXUJMGE-UHFFFAOYSA-N 4-(3,4-difluoroanilino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=C(F)C(F)=C1 IXXGKMHTXUJMGE-UHFFFAOYSA-N 0.000 description 1
• LZWRXIPQGNUOOO-UHFFFAOYSA-N 4-(3,5-difluoroanilino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CC(F)=CC(F)=C1 LZWRXIPQGNUOOO-UHFFFAOYSA-N 0.000 description 1
• SMMOOIIRYHZMGV-UHFFFAOYSA-N 4-(3-chloro-4-methylanilino)phenol Chemical compound C1=C(Cl)C(C)=CC=C1NC1=CC=C(O)C=C1 SMMOOIIRYHZMGV-UHFFFAOYSA-N 0.000 description 1
• RBBFVSFXAIZOMU-UHFFFAOYSA-N 4-(3-chloroanilino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=CC(Cl)=C1 RBBFVSFXAIZOMU-UHFFFAOYSA-N 0.000 description 1
• PHKUUFHRILECEZ-UHFFFAOYSA-N 4-(3-fluoro-4-methoxyanilino)phenol Chemical compound C1=C(F)C(OC)=CC=C1NC1=CC=C(O)C=C1 PHKUUFHRILECEZ-UHFFFAOYSA-N 0.000 description 1
• BDUQPTSECPBXBM-UHFFFAOYSA-N 4-(3-fluoroanilino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=CC(F)=C1 BDUQPTSECPBXBM-UHFFFAOYSA-N 0.000 description 1
• XOEXCBFCNCZHPE-UHFFFAOYSA-N 4-(3-methoxyanilino)phenol Chemical compound COC1=CC=CC(NC=2C=CC(O)=CC=2)=C1 XOEXCBFCNCZHPE-UHFFFAOYSA-N 0.000 description 1
• QYCSTVXNOIMUBN-UHFFFAOYSA-N 4-(3-methylanilino)phenol Chemical compound CC1=CC=CC(NC=2C=CC(O)=CC=2)=C1 QYCSTVXNOIMUBN-UHFFFAOYSA-N 0.000 description 1
• SIRZNJVFSXOBJH-UHFFFAOYSA-N 4-(4-chloroanilino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=C(Cl)C=C1 SIRZNJVFSXOBJH-UHFFFAOYSA-N 0.000 description 1
• JSXVEMUFCOEZPD-UHFFFAOYSA-N 4-(4-hydroxyanilino)benzonitrile Chemical compound C1=CC(O)=CC=C1NC1=CC=C(C#N)C=C1 JSXVEMUFCOEZPD-UHFFFAOYSA-N 0.000 description 1
• YRUPBAWWCPVHFT-UHFFFAOYSA-N 4-(4-hydroxyanilino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=C(O)C=C1 YRUPBAWWCPVHFT-UHFFFAOYSA-N 0.000 description 1
• PJCNSVHWHHVSMK-UHFFFAOYSA-N 4-(4-methylanilino)phenol Chemical compound C1=CC(C)=CC=C1NC1=CC=C(O)C=C1 PJCNSVHWHHVSMK-UHFFFAOYSA-N 0.000 description 1
• YUTAACGDJBMJAB-UHFFFAOYSA-N 4-(but-2-ynylamino)phenol Chemical compound CC#CCNC1=CC=C(O)C=C1 YUTAACGDJBMJAB-UHFFFAOYSA-N 0.000 description 1
• VAMBUGIXOVLJEA-UHFFFAOYSA-N 4-(butylamino)phenol Chemical compound CCCCNC1=CC=C(O)C=C1 VAMBUGIXOVLJEA-UHFFFAOYSA-N 0.000 description 1
• GJDUEJAVZRBOGB-UHFFFAOYSA-N 4-(cyclobutylmethylamino)phenol Chemical compound C1=CC(O)=CC=C1NCC1CCC1 GJDUEJAVZRBOGB-UHFFFAOYSA-N 0.000 description 1
• OYQYPHZHTCHGER-UHFFFAOYSA-N 4-(cyclopropylmethylamino)phenol Chemical compound C1=CC(O)=CC=C1NCC1CC1 OYQYPHZHTCHGER-UHFFFAOYSA-N 0.000 description 1
• UJWHLERCFNIFNJ-UHFFFAOYSA-N 4-(ethylamino)phenol Chemical compound CCNC1=CC=C(O)C=C1 UJWHLERCFNIFNJ-UHFFFAOYSA-N 0.000 description 1
• STVPBVIJXUKAMI-UHFFFAOYSA-N 4-(propan-2-ylamino)phenol Chemical compound CC(C)NC1=CC=C(O)C=C1 STVPBVIJXUKAMI-UHFFFAOYSA-N 0.000 description 1
• KDQFVEXPTHVLDV-UHFFFAOYSA-N 4-(pyrazin-2-ylamino)phenol Chemical compound Oc1ccc(Nc2cnccn2)cc1 KDQFVEXPTHVLDV-UHFFFAOYSA-N 0.000 description 1
• AMTBCBIYAXEKSP-UHFFFAOYSA-N 4-(pyridazin-3-ylamino)phenol Chemical compound Oc1ccc(Nc2cccnn2)cc1 AMTBCBIYAXEKSP-UHFFFAOYSA-N 0.000 description 1
• WGKPVKGWKUXSIQ-UHFFFAOYSA-N 4-(pyridin-2-ylamino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=CC=N1 WGKPVKGWKUXSIQ-UHFFFAOYSA-N 0.000 description 1
• WCTWFRGXNFCCBG-UHFFFAOYSA-N 4-(pyridin-3-ylamino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=CN=C1 WCTWFRGXNFCCBG-UHFFFAOYSA-N 0.000 description 1
• JHOUAJWDARLISP-UHFFFAOYSA-N 4-(pyridin-4-ylamino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=NC=C1 JHOUAJWDARLISP-UHFFFAOYSA-N 0.000 description 1
• IGPQECGFBBHHAD-UHFFFAOYSA-N 4-(pyrimidin-2-ylamino)phenol Chemical compound C1=CC(O)=CC=C1NC1=NC=CC=N1 IGPQECGFBBHHAD-UHFFFAOYSA-N 0.000 description 1
• WLDREWIRQHBESW-UHFFFAOYSA-N 4-(pyrimidin-5-ylamino)phenol Chemical compound C1=CC(O)=CC=C1NC1=CN=CN=C1 WLDREWIRQHBESW-UHFFFAOYSA-N 0.000 description 1
• QOWSWEBLNVACCL-UHFFFAOYSA-N 4-Bromophenyl acetate Chemical compound OC(=O)CC1=CC=C(Br)C=C1 QOWSWEBLNVACCL-UHFFFAOYSA-N 0.000 description 1
• NNKQJTBCFFXFRG-UHFFFAOYSA-N 4-[(1-ethyl-2,3-dihydroindol-5-yl)amino]phenol Chemical compound C=1C=C2N(CC)CCC2=CC=1NC1=CC=C(O)C=C1 NNKQJTBCFFXFRG-UHFFFAOYSA-N 0.000 description 1
• MQWTZUPCSHOKHU-UHFFFAOYSA-N 4-[(1-ethylindol-5-yl)amino]phenol Chemical compound C=1C=C2N(CC)C=CC2=CC=1NC1=CC=C(O)C=C1 MQWTZUPCSHOKHU-UHFFFAOYSA-N 0.000 description 1
• FWJMMRJAHZWBIX-UHFFFAOYSA-N 4-[(1-methyl-2,3-dihydroindol-6-yl)amino]phenol Chemical compound C1=C2N(C)CCC2=CC=C1NC1=CC=C(O)C=C1 FWJMMRJAHZWBIX-UHFFFAOYSA-N 0.000 description 1
• MZUGHCLJCOIXPQ-UHFFFAOYSA-N 4-[(1-methyl-3,4-dihydro-2h-quinolin-6-yl)amino]phenol Chemical compound C=1C=C2N(C)CCCC2=CC=1NC1=CC=C(O)C=C1 MZUGHCLJCOIXPQ-UHFFFAOYSA-N 0.000 description 1
• VIJLXAFRUUQQSE-UHFFFAOYSA-N 4-[(1-methylindazol-5-yl)amino]phenol Chemical compound C=1C=C2N(C)N=CC2=CC=1NC1=CC=C(O)C=C1 VIJLXAFRUUQQSE-UHFFFAOYSA-N 0.000 description 1
• BFMIMPGLQGNMAP-UHFFFAOYSA-N 4-[(1-methylindol-6-yl)amino]cyclohexan-1-ol Chemical compound C1=C2N(C)C=CC2=CC=C1NC1CCC(O)CC1 BFMIMPGLQGNMAP-UHFFFAOYSA-N 0.000 description 1
• PQIDIAZYFPLNEH-UHFFFAOYSA-N 4-[(1-methylindol-6-yl)amino]phenol Chemical compound C1=C2N(C)C=CC2=CC=C1NC1=CC=C(O)C=C1 PQIDIAZYFPLNEH-UHFFFAOYSA-N 0.000 description 1
• ORBYYBDLMLXWRX-UHFFFAOYSA-N 4-[(1-methylpyrazol-3-yl)methylamino]phenol Chemical compound CN1C=CC(CNC=2C=CC(O)=CC=2)=N1 ORBYYBDLMLXWRX-UHFFFAOYSA-N 0.000 description 1
• DHXKSSORRRILAW-UHFFFAOYSA-N 4-[(1-methylpyrazol-4-yl)methylamino]phenol Chemical compound C1=NN(C)C=C1CNC1=CC=C(O)C=C1 DHXKSSORRRILAW-UHFFFAOYSA-N 0.000 description 1
• NPPSTVSDTJKGMY-UHFFFAOYSA-N 4-[3-(trifluoromethyl)anilino]phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=CC(C(F)(F)F)=C1 NPPSTVSDTJKGMY-UHFFFAOYSA-N 0.000 description 1
• GROZDOHOXIUJMC-UHFFFAOYSA-N 4-[4-(diethylamino)anilino]phenol Chemical compound C1=CC(N(CC)CC)=CC=C1NC1=CC=C(O)C=C1 GROZDOHOXIUJMC-UHFFFAOYSA-N 0.000 description 1
• VWJAPTNFHDCNQL-UHFFFAOYSA-N 4-[4-(trifluoromethoxy)anilino]phenol Chemical compound C1=CC(O)=CC=C1NC1=CC=C(OC(F)(F)F)C=C1 VWJAPTNFHDCNQL-UHFFFAOYSA-N 0.000 description 1
• YDEVFKXFMJZOJU-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxy-N-(4-fluorophenyl)aniline Chemical compound CC(C)(C)[Si](C)(C)Oc1ccc(Nc2ccc(F)cc2)cc1 YDEVFKXFMJZOJU-UHFFFAOYSA-N 0.000 description 1
• CHPPNXFRCBOYOG-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxy-n-phenylaniline Chemical compound C1=CC(O[Si](C)(C)C(C)(C)C)=CC=C1NC1=CC=CC=C1 CHPPNXFRCBOYOG-UHFFFAOYSA-N 0.000 description 1
• XSVKDCVIWOKXSX-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxyaniline Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=C(N)C=C1 XSVKDCVIWOKXSX-UHFFFAOYSA-N 0.000 description 1
• YMQPKONILWWJQG-UHFFFAOYSA-N 4-bromo-1,2-difluorobenzene Chemical compound FC1=CC=C(Br)C=C1F YMQPKONILWWJQG-UHFFFAOYSA-N 0.000 description 1
• ZRXLKDCFWJECNO-UHFFFAOYSA-N 4-bromo-1-oxidopyridin-1-ium Chemical compound [O-][N+]1=CC=C(Br)C=C1 ZRXLKDCFWJECNO-UHFFFAOYSA-N 0.000 description 1
• WVGCPEDBFHEHEZ-UHFFFAOYSA-N 4-bromo-1h-pyrazole Chemical compound BrC=1C=NNC=1 WVGCPEDBFHEHEZ-UHFFFAOYSA-N 0.000 description 1
• VTRFAYHJKSKHGY-UHFFFAOYSA-N 4-bromo-2,6-dimethylpyridine Chemical compound CC1=CC(Br)=CC(C)=N1 VTRFAYHJKSKHGY-UHFFFAOYSA-N 0.000 description 1
• YZFVUQSAJMLFOZ-UHFFFAOYSA-N 4-bromo-2-fluoro-1-methylbenzene Chemical compound CC1=CC=C(Br)C=C1F YZFVUQSAJMLFOZ-UHFFFAOYSA-N 0.000 description 1
• RYVOZMPTISNBDB-UHFFFAOYSA-N 4-bromo-2-fluorophenol Chemical compound OC1=CC=C(Br)C=C1F RYVOZMPTISNBDB-UHFFFAOYSA-N 0.000 description 1
• YFTGMMXMLPTTAY-UHFFFAOYSA-N 4-bromo-2-methoxypyridine Chemical compound COC1=CC(Br)=CC=N1 YFTGMMXMLPTTAY-UHFFFAOYSA-N 0.000 description 1
• JFBMFWHEXBLFCR-UHFFFAOYSA-N 4-bromo-2-methylpyridine Chemical compound CC1=CC(Br)=CC=N1 JFBMFWHEXBLFCR-UHFFFAOYSA-N 0.000 description 1
• LUDCJEGSWQBSKR-UHFFFAOYSA-N 4-bromo-2-propan-2-ylpyridine Chemical compound CC(C)C1=CC(Br)=CC=N1 LUDCJEGSWQBSKR-UHFFFAOYSA-N 0.000 description 1
• QBLOMVIUENUOJY-UHFFFAOYSA-N 4-bromo-3-fluoropyridine Chemical compound FC1=CN=CC=C1Br QBLOMVIUENUOJY-UHFFFAOYSA-N 0.000 description 1
• ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• ZHOBFYSFEOWZJH-UHFFFAOYSA-N 4-fluoro-2-[8-methoxycarbonyl-2-[(2-methylpropan-2-yl)oxycarbonyl]-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazin-6-yl]benzoic acid Chemical compound C(C)(C)(C)OC(=O)N1CC=2N(CC1)C(=CC=2C(=O)OC)C1=C(C(=O)O)C=CC(=C1)F ZHOBFYSFEOWZJH-UHFFFAOYSA-N 0.000 description 1
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
• JTTMYKSFKOOQLP-UHFFFAOYSA-N 4-hydroxydiphenylamine Chemical compound C1=CC(O)=CC=C1NC1=CC=CC=C1 JTTMYKSFKOOQLP-UHFFFAOYSA-N 0.000 description 1
• ZFIQGRISGKSVAG-UHFFFAOYSA-N 4-methylaminophenol Chemical compound CNC1=CC=C(O)C=C1 ZFIQGRISGKSVAG-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
• PLDILAVTODSEJG-UHFFFAOYSA-N 5-(4-hydroxyanilino)-2-methoxybenzonitrile Chemical compound C1=C(C#N)C(OC)=CC=C1NC1=CC=C(O)C=C1 PLDILAVTODSEJG-UHFFFAOYSA-N 0.000 description 1
• RMCHMXPTUMFFBZ-UHFFFAOYSA-N 5-bromo-1-methylindazole Chemical compound BrC1=CC=C2N(C)N=CC2=C1 RMCHMXPTUMFFBZ-UHFFFAOYSA-N 0.000 description 1
• SBOITLSQLQGSLO-UHFFFAOYSA-N 5-bromo-1-methylindole Chemical compound BrC1=CC=C2N(C)C=CC2=C1 SBOITLSQLQGSLO-UHFFFAOYSA-N 0.000 description 1
• MZTKBGMGLWHOMN-UHFFFAOYSA-N 5-bromo-1-methylpyrazolo[3,4-b]pyridine Chemical compound BrC1=CN=C2N(C)N=CC2=C1 MZTKBGMGLWHOMN-UHFFFAOYSA-N 0.000 description 1
• FBOBGKHOQSQKRZ-UHFFFAOYSA-N 5-bromo-1-methylpyrrolo[2,3-b]pyridine Chemical compound BrC1=CN=C2N(C)C=CC2=C1 FBOBGKHOQSQKRZ-UHFFFAOYSA-N 0.000 description 1
• QEDCHCLHHGGYBT-UHFFFAOYSA-N 5-bromo-2,3-dihydro-1h-indole Chemical compound BrC1=CC=C2NCCC2=C1 QEDCHCLHHGGYBT-UHFFFAOYSA-N 0.000 description 1
• OFKWIQJLYCKDNY-UHFFFAOYSA-N 5-bromo-2-methylpyridine Chemical compound CC1=CC=C(Br)C=N1 OFKWIQJLYCKDNY-UHFFFAOYSA-N 0.000 description 1
• QSDCJUGUESYHPR-XMMPIXPASA-N 6-[5-fluoro-2-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]phenyl]-N-(3-fluoro-4-methylphenyl)-N-(4-hydroxyphenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamide Chemical compound FC=1C=CC(=C(C=1)C1=CC(=C2N1CCNC2)C(=O)N(C1=CC=C(C=C1)O)C1=CC(=C(C=C1)C)F)C(=O)N1CC2=CC=CC=C2C[C@H]1C QSDCJUGUESYHPR-XMMPIXPASA-N 0.000 description 1
• JNACYLCZRONVAW-UHFFFAOYSA-N 6-[6-(3,4-dihydro-1h-isoquinoline-2-carbonyl)-1,3-benzodioxol-5-yl]-n-(4-hydroxyphenyl)-n-methyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamide Chemical compound C1=C(C=2C(=CC=3OCOC=3C=2)C(=O)N2CC3=CC=CC=C3CC2)N2CCNCC2=C1C(=O)N(C)C1=CC=C(O)C=C1 JNACYLCZRONVAW-UHFFFAOYSA-N 0.000 description 1
• PUNQRMRIFAJJAN-UHFFFAOYSA-N 6-[6-(3,4-dihydro-1h-isoquinoline-2-carbonyl)-1,3-benzodioxol-5-yl]-n-ethyl-n-(4-hydroxyphenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamide Chemical compound C1=C(C=2C(=CC=3OCOC=3C=2)C(=O)N2CC3=CC=CC=C3CC2)N2CCNCC2=C1C(=O)N(CC)C1=CC=C(O)C=C1 PUNQRMRIFAJJAN-UHFFFAOYSA-N 0.000 description 1
• QNPALEPJRMKEEY-UHFFFAOYSA-N 6-bromo-1,3a-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound BrC=1C=NC2N(C=1)N=CN2 QNPALEPJRMKEEY-UHFFFAOYSA-N 0.000 description 1
• KNRRVDSIDHUKPT-UHFFFAOYSA-N 6-bromo-3-methylpyrazolo[1,5-a]pyrimidine Chemical compound C1=C(Br)C=NC2=C(C)C=NN21 KNRRVDSIDHUKPT-UHFFFAOYSA-N 0.000 description 1
• VDHTXLUCUNPVLO-UHFFFAOYSA-N 6-bromopyrazolo[1,5-a]pyrimidine Chemical compound C1=C(Br)C=NC2=CC=NN21 VDHTXLUCUNPVLO-UHFFFAOYSA-N 0.000 description 1
• IFIHYLCUKYCKRH-UHFFFAOYSA-N 6-bromoquinoline Chemical compound N1=CC=CC2=CC(Br)=CC=C21 IFIHYLCUKYCKRH-UHFFFAOYSA-N 0.000 description 1
• WUWNXFKNYAWAAZ-UHFFFAOYSA-N 7-bromo-2-methylimidazo[1,2-a]pyridine Chemical compound C1=CC(Br)=CC2=NC(C)=CN21 WUWNXFKNYAWAAZ-UHFFFAOYSA-N 0.000 description 1
• OASOJRLJBDCVNU-UHFFFAOYSA-N 7-bromoimidazo[1,2-a]pyridine Chemical compound C1=C(Br)C=CN2C=CN=C21 OASOJRLJBDCVNU-UHFFFAOYSA-N 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
• 102000008102 Ankyrins Human genes 0.000 description 1
• 108010049777 Ankyrins Proteins 0.000 description 1
• 102000016904 Armadillo Domain Proteins Human genes 0.000 description 1
• 108010014223 Armadillo Domain Proteins Proteins 0.000 description 1
• 208000003950 B-cell lymphoma Diseases 0.000 description 1
• 206010003908 B-cell small lymphocytic lymphoma Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• SZSLXMPFYDRHPG-UHFFFAOYSA-N C1N(CCC2=CC=CC=C12)C(=O)C=1C(=CC2=C(OCO2)C=1)C1=CC(=C2CCCCN12)C(=O)N(C1=CC=CC=C1)C1=CC=C(C=C1)O Chemical compound C1N(CCC2=CC=CC=C12)C(=O)C=1C(=CC2=C(OCO2)C=1)C1=CC(=C2CCCCN12)C(=O)N(C1=CC=CC=C1)C1=CC=C(C=C1)O SZSLXMPFYDRHPG-UHFFFAOYSA-N 0.000 description 1
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
• VVCLRJWPEQPQEF-UHFFFAOYSA-N CC(C)(C)OC(=O)CC(=O)N1CCOCC1 Chemical compound CC(C)(C)OC(=O)CC(=O)N1CCOCC1 VVCLRJWPEQPQEF-UHFFFAOYSA-N 0.000 description 1
• HDFBWYYUQWMWEZ-UHFFFAOYSA-N CC(C)N1CCc2cc(Nc3ccc(O)cc3)ccc12 Chemical compound CC(C)N1CCc2cc(Nc3ccc(O)cc3)ccc12 HDFBWYYUQWMWEZ-UHFFFAOYSA-N 0.000 description 1
• KRQZLLVZQCMVRL-OAQYLSRUSA-N CC1=CC=C(C=C1)S(=O)(=O)N1CC2=CC=CC=C2C[C@H]1CCC(=O)N1CCOCC1 Chemical compound CC1=CC=C(C=C1)S(=O)(=O)N1CC2=CC=CC=C2C[C@H]1CCC(=O)N1CCOCC1 KRQZLLVZQCMVRL-OAQYLSRUSA-N 0.000 description 1
• GJXSRLSAYDJHMV-JOCHJYFZSA-N CC1=CC=C(C=C1)S(=O)(=O)N1CC2=CC=CC=C2C[C@H]1CCCN1CCOCC1 Chemical compound CC1=CC=C(C=C1)S(=O)(=O)N1CC2=CC=CC=C2C[C@H]1CCCN1CCOCC1 GJXSRLSAYDJHMV-JOCHJYFZSA-N 0.000 description 1
• ZCLAXNYKTVJJHU-UHFFFAOYSA-N CN1CC(C)(C)c2cc(Nc3ccc(O)cc3)ccc12 Chemical compound CN1CC(C)(C)c2cc(Nc3ccc(O)cc3)ccc12 ZCLAXNYKTVJJHU-UHFFFAOYSA-N 0.000 description 1
• QAQKMWDMLNMMNQ-UHFFFAOYSA-N CN1CC2(CC2)c2cc(Nc3ccc(O)cc3)ccc12 Chemical compound CN1CC2(CC2)c2cc(Nc3ccc(O)cc3)ccc12 QAQKMWDMLNMMNQ-UHFFFAOYSA-N 0.000 description 1
• HEYJRPSZBLNWGH-UHFFFAOYSA-N CN1CCOc2cc(Nc3ccc(O)cc3)ccc12 Chemical compound CN1CCOc2cc(Nc3ccc(O)cc3)ccc12 HEYJRPSZBLNWGH-UHFFFAOYSA-N 0.000 description 1
• NVBYFIPGQUXHPV-UHFFFAOYSA-N COC(=O)c1cc(-c2cc(F)ccc2C(O)=O)n2ccccc12 Chemical compound COC(=O)c1cc(-c2cc(F)ccc2C(O)=O)n2ccccc12 NVBYFIPGQUXHPV-UHFFFAOYSA-N 0.000 description 1
• WKIZQVQIPCPNQF-UHFFFAOYSA-N COC(=O)c1cc(-c2cc3OCCOc3cc2C(O)=O)n2CCCCc12 Chemical compound COC(=O)c1cc(-c2cc3OCCOc3cc2C(O)=O)n2CCCCc12 WKIZQVQIPCPNQF-UHFFFAOYSA-N 0.000 description 1
• ULACHKZJGGOHNR-UHFFFAOYSA-N COC(=O)c1cc(-c2cc3OCOc3cc2C(O)=O)n2CCN(Cc12)C(=O)OC(C)(C)C Chemical compound COC(=O)c1cc(-c2cc3OCOc3cc2C(O)=O)n2CCN(Cc12)C(=O)OC(C)(C)C ULACHKZJGGOHNR-UHFFFAOYSA-N 0.000 description 1
• HEBHAVUMROXQBP-UHFFFAOYSA-N COC(=O)c1cc(-c2cc3OCOc3cc2C(O)=O)n2ccccc12 Chemical compound COC(=O)c1cc(-c2cc3OCOc3cc2C(O)=O)n2ccccc12 HEBHAVUMROXQBP-UHFFFAOYSA-N 0.000 description 1
• GQJTXZJMPWGXSJ-UHFFFAOYSA-N COC(=O)c1cc(-c2ccccc2C(O)=O)n2CCCCc12 Chemical compound COC(=O)c1cc(-c2ccccc2C(O)=O)n2CCCCc12 GQJTXZJMPWGXSJ-UHFFFAOYSA-N 0.000 description 1
• XBMJGYXLOWXRIO-UHFFFAOYSA-N COc1c(F)cc(Nc2ccc(O)cc2)cc1F Chemical compound COc1c(F)cc(Nc2ccc(O)cc2)cc1F XBMJGYXLOWXRIO-UHFFFAOYSA-N 0.000 description 1
• DKHNSBHNEHXYJS-UHFFFAOYSA-N COc1ccc(Nc2ccc(O)cc2)cc1C(F)(F)F Chemical compound COc1ccc(Nc2ccc(O)cc2)cc1C(F)(F)F DKHNSBHNEHXYJS-UHFFFAOYSA-N 0.000 description 1
• YBCAYYGWFJXLSQ-CQSZACIVSA-N C[C@H]1N(CC2=CC=CC=C2C1)S(=O)(=O)C1=CC=C(C=C1)C Chemical compound C[C@H]1N(CC2=CC=CC=C2C1)S(=O)(=O)C1=CC=C(C=C1)C YBCAYYGWFJXLSQ-CQSZACIVSA-N 0.000 description 1
• NARNFVMKHMHIIE-UHFFFAOYSA-N C[SiH2]C.C(C)(C)(C)Cl Chemical compound C[SiH2]C.C(C)(C)(C)Cl NARNFVMKHMHIIE-UHFFFAOYSA-N 0.000 description 1
• LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• 208000005623 Carcinogenesis Diseases 0.000 description 1
• NMSNGBOLOTXERK-AIBWNMTMSA-N Cc1ccc(cc1)S(=O)(=O)N1Cc2ccccc2C[C@H]1CC(C(O)=O)C(=O)N1CCOCC1 Chemical compound Cc1ccc(cc1)S(=O)(=O)N1Cc2ccccc2C[C@H]1CC(C(O)=O)C(=O)N1CCOCC1 NMSNGBOLOTXERK-AIBWNMTMSA-N 0.000 description 1
• NQEVEVIXYNLCHV-UQKRIMTDSA-N Cl.O=C(C[C@@H]1Cc2ccccc2CN1)N1CCOCC1 Chemical compound Cl.O=C(C[C@@H]1Cc2ccccc2CN1)N1CCOCC1 NQEVEVIXYNLCHV-UQKRIMTDSA-N 0.000 description 1
• XHOWGSWHRGXODC-UHFFFAOYSA-N Cn1ccc2cc(NCCCCO)ccc12 Chemical compound Cn1ccc2cc(NCCCCO)ccc12 XHOWGSWHRGXODC-UHFFFAOYSA-N 0.000 description 1
• GQSPUBFCGUWXFU-UHFFFAOYSA-N Cn1ccc2cc(Nc3ccc(O)c(F)c3)ccc12 Chemical compound Cn1ccc2cc(Nc3ccc(O)c(F)c3)ccc12 GQSPUBFCGUWXFU-UHFFFAOYSA-N 0.000 description 1
• XOQJRASGSQSIHU-UHFFFAOYSA-N Cn1ccc2cc(Nc3ccc(O)cc3)cnc12 Chemical compound Cn1ccc2cc(Nc3ccc(O)cc3)cnc12 XOQJRASGSQSIHU-UHFFFAOYSA-N 0.000 description 1
• GEIVBOAQUYFSMS-UHFFFAOYSA-N Cn1ccc2ccc(Nc3ccc(CO)cc3)cc12 Chemical compound Cn1ccc2ccc(Nc3ccc(CO)cc3)cc12 GEIVBOAQUYFSMS-UHFFFAOYSA-N 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 108010086821 DEVDase Proteins 0.000 description 1
• 241000289632 Dasypodidae Species 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 238000002965 ELISA Methods 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 102100037362 Fibronectin Human genes 0.000 description 1
• 102000002090 Fibronectin type III Human genes 0.000 description 1
• 108050009401 Fibronectin type III Proteins 0.000 description 1
• 108010067306 Fibronectins Proteins 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• 108060003951 Immunoglobulin Proteins 0.000 description 1
• HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 108010006444 Leucine-Rich Repeat Proteins Proteins 0.000 description 1
• 102000019298 Lipocalin Human genes 0.000 description 1
• 108050006654 Lipocalin Proteins 0.000 description 1
• 235000019759 Maize starch Nutrition 0.000 description 1
• 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 1
• 241000237852 Mollusca Species 0.000 description 1
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
• SFUAMSBCVQMGOX-VQIWEWKSSA-N N-(4-hydroxyphenyl)-3-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-N-(1-methylpyridin-1-ium-4-yl)indolizine-1-carboxamide iodide Chemical compound [I-].OC1=CC=C(C=C1)N(C1=CC=[N+](C=C1)C)C(=O)C=1C=C(N2C=CC=CC=12)C1=CC2=C(OCO2)C=C1C(=O)N1CC2=CC=CC=C2C[C@H]1C SFUAMSBCVQMGOX-VQIWEWKSSA-N 0.000 description 1
• GWXXTPSFXFAOTD-MGBGTMOVSA-N N-(4-hydroxyphenyl)-3-[6-[(3S)-3-[2-(3-methoxyazetidin-1-yl)ethyl]-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-N-phenyl-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C1=CC2=C(OCO2)C=C1C(=O)N1CC2=CC=CC=C2C[C@H]1CCN1CC(C1)OC)C1=CC=CC=C1 GWXXTPSFXFAOTD-MGBGTMOVSA-N 0.000 description 1
• RICFRVGBHLTGOV-UHFFFAOYSA-N N-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-1-methylpyrrolo[2,3-b]pyridin-5-amine Chemical compound Cn1ccc2cc(Nc3ccc(O[Si](C)(C)C(C)(C)C)cc3)cnc12 RICFRVGBHLTGOV-UHFFFAOYSA-N 0.000 description 1
• ZMWRJRBPGBNYRE-UHFFFAOYSA-N N-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-3,4-difluoroaniline Chemical compound CC(C)(C)[Si](C)(C)Oc1ccc(Nc2ccc(F)c(F)c2)cc1 ZMWRJRBPGBNYRE-UHFFFAOYSA-N 0.000 description 1
• IUKFMDVTQWYBAF-UHFFFAOYSA-N N-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-3-fluoro-4-methylaniline Chemical compound Cc1ccc(Nc2ccc(O[Si](C)(C)C(C)(C)C)cc2)cc1F IUKFMDVTQWYBAF-UHFFFAOYSA-N 0.000 description 1
• DZGLEGLKARUBHS-UHFFFAOYSA-N N-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]pyrazolo[1,5-a]pyrimidin-6-amine Chemical compound C(C)(C)(C)[Si](OC1=CC=C(C=C1)NC=1C=NC=2N(C1)N=CC2)(C)C DZGLEGLKARUBHS-UHFFFAOYSA-N 0.000 description 1
• ISFWMAYGOXNDGY-UHFFFAOYSA-N N-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]pyridin-3-amine Chemical compound CC(C)(C)[Si](C)(C)Oc1ccc(Nc2cccnc2)cc1 ISFWMAYGOXNDGY-UHFFFAOYSA-N 0.000 description 1
• JFTFITBWDFMDIO-UHFFFAOYSA-N N-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]pyridin-4-amine Chemical compound CC(C)(C)[Si](C)(C)Oc1ccc(Nc2ccncc2)cc1 JFTFITBWDFMDIO-UHFFFAOYSA-N 0.000 description 1
• 102000006538 Nitric Oxide Synthase Type I Human genes 0.000 description 1
• 108010008858 Nitric Oxide Synthase Type I Proteins 0.000 description 1
• HJROSMXXPMZWIF-RUZDIDTESA-N OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C1=CC2=C(OCO2)C=C1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C1=CC=CC=C1 Chemical compound OC1=CC=C(C=C1)N(C(=O)C=1C=C(N2CCCCC=12)C1=CC2=C(OCO2)C=C1C(=O)N1CC2=CC=CC=C2C[C@H]1C)C1=CC=CC=C1 HJROSMXXPMZWIF-RUZDIDTESA-N 0.000 description 1
• KCJWFRFFVOKUDB-GOSISDBHSA-N OCC[C@H]1N(CC2=CC=CC=C2C1)C(=O)OCC1=CC=CC=C1 Chemical compound OCC[C@H]1N(CC2=CC=CC=C2C1)C(=O)OCC1=CC=CC=C1 KCJWFRFFVOKUDB-GOSISDBHSA-N 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 108090000526 Papain Proteins 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 102000057297 Pepsin A Human genes 0.000 description 1
• 108090000284 Pepsin A Proteins 0.000 description 1
• ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 229940079156 Proteasome inhibitor Drugs 0.000 description 1
• 241000239226 Scorpiones Species 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• 108010088160 Staphylococcal Protein A Proteins 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 102000002933 Thioredoxin Human genes 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• ZSKDXMLMMQFHGW-SNVBAGLBSA-N [(3r)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol Chemical compound C1=CC=C2CN[C@@H](CO)CC2=C1 ZSKDXMLMMQFHGW-SNVBAGLBSA-N 0.000 description 1
• FTXXGEULDXJPKO-UHFFFAOYSA-N [Br-].OC(=O)C[NH+]1CC=CC=C1 Chemical compound [Br-].OC(=O)C[NH+]1CC=CC=C1 FTXXGEULDXJPKO-UHFFFAOYSA-N 0.000 description 1
• ZMSPDIFUEUTQHM-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=C(C=NC=C1)F Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=C(C=NC=C1)F ZMSPDIFUEUTQHM-UHFFFAOYSA-N 0.000 description 1
• ZZJVGYQVEUJJKX-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC(=C(C=C1)OCCN1CCOCC1)F Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC(=C(C=C1)OCCN1CCOCC1)F ZZJVGYQVEUJJKX-UHFFFAOYSA-N 0.000 description 1
• IEVKWFUEJYFIHE-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC(=NC(=C1)C)C Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC(=NC(=C1)C)C IEVKWFUEJYFIHE-UHFFFAOYSA-N 0.000 description 1
• KWDBPIRHWOQRHE-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC(=NC=C1)C Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC(=NC=C1)C KWDBPIRHWOQRHE-UHFFFAOYSA-N 0.000 description 1
• IAFXMEBODLDGTR-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC(=NC=C1)C(C)C Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC(=NC=C1)C(C)C IAFXMEBODLDGTR-UHFFFAOYSA-N 0.000 description 1
• VDUFTJWOFFOENP-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC(=NC=C1)OC Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC(=NC=C1)OC VDUFTJWOFFOENP-UHFFFAOYSA-N 0.000 description 1
• WSGSVTBWFQKIBE-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC=2N(C=C1)C=C(N=2)C Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC=2N(C=C1)C=C(N=2)C WSGSVTBWFQKIBE-UHFFFAOYSA-N 0.000 description 1
• VNDKIGHXJKUSQC-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC=2N(C=C1)C=CN=2 Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC=2N(C=C1)C=CN=2 VNDKIGHXJKUSQC-UHFFFAOYSA-N 0.000 description 1
• GSBOPFRPZIJMPV-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC=[N+](C=C1)[O-] Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC1=CC=[N+](C=C1)[O-] GSBOPFRPZIJMPV-UHFFFAOYSA-N 0.000 description 1
• CDSHDELHDFLZIW-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=C2C=CC=NC2=CC=1 Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=C2C=CC=NC2=CC=1 CDSHDELHDFLZIW-UHFFFAOYSA-N 0.000 description 1
• BJPQIZBMAVINKV-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=C2C=CN(C2=CC=1)CCN1CCOCC1 Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=C2C=CN(C2=CC=1)CCN1CCOCC1 BJPQIZBMAVINKV-UHFFFAOYSA-N 0.000 description 1
• IYNHBFSVNUGQLE-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=C2CCN(C2=CC=1)CCN1CCOCC1 Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=C2CCN(C2=CC=1)CCN1CCOCC1 IYNHBFSVNUGQLE-UHFFFAOYSA-N 0.000 description 1
• LFNUOOQCGSNXCT-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=NC(=CC=1)C Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=NC(=CC=1)C LFNUOOQCGSNXCT-UHFFFAOYSA-N 0.000 description 1
• SIYHSCIFFQCNKL-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=NC2N(C=1)N=CN2 Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=NC2N(C=1)N=CN2 SIYHSCIFFQCNKL-UHFFFAOYSA-N 0.000 description 1
• FPHYFSNBJHCBBX-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=NC=2N(C=1)N=CC=2C Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=NC=2N(C=1)N=CC=2C FPHYFSNBJHCBBX-UHFFFAOYSA-N 0.000 description 1
• SXCAFVRWILEDTM-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=NC=C(C=1)F Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=NC=C(C=1)F SXCAFVRWILEDTM-UHFFFAOYSA-N 0.000 description 1
• NPTIJDFJGFEEDD-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=NN(C=1)CCN1CCOCC1 Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(C=C1)NC=1C=NN(C=1)CCN1CCOCC1 NPTIJDFJGFEEDD-UHFFFAOYSA-N 0.000 description 1
• NSXTXFPCTUWOCJ-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC=C(NC2=CC=C(C=C2)CCN2CC(CC2)(F)F)C=C1 Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC=C(NC2=CC=C(C=C2)CCN2CC(CC2)(F)F)C=C1 NSXTXFPCTUWOCJ-UHFFFAOYSA-N 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
• WFKAJVHLWXSISD-UHFFFAOYSA-N anhydrous dimethyl-acetamide Natural products CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 230000002424 anti-apoptotic effect Effects 0.000 description 1
• 229940124650 anti-cancer therapies Drugs 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 230000000259 anti-tumor effect Effects 0.000 description 1
• 238000011319 anticancer therapy Methods 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 238000003782 apoptosis assay Methods 0.000 description 1
• 239000012300 argon atmosphere Substances 0.000 description 1
• 125000005110 aryl thio group Chemical group 0.000 description 1
• 125000004104 aryloxy group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 208000037979 autoimmune inflammatory disease Diseases 0.000 description 1
• ZXVOCOLRQJZVBW-UHFFFAOYSA-N azane;ethanol Chemical compound N.CCO ZXVOCOLRQJZVBW-UHFFFAOYSA-N 0.000 description 1
• DJBDCMBUPNOCMN-GOSISDBHSA-N benzyl (3S)-3-(2-aminoethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylate Chemical compound NCC[C@H]1N(CC2=CC=CC=C2C1)C(=O)OCC1=CC=CC=C1 DJBDCMBUPNOCMN-GOSISDBHSA-N 0.000 description 1
• UZEVIJLCWYQKJV-LJQANCHMSA-N benzyl (3S)-3-(2-methylsulfonyloxyethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylate Chemical compound CS(=O)(=O)OCC[C@H]1N(CC2=CC=CC=C2C1)C(=O)OCC1=CC=CC=C1 UZEVIJLCWYQKJV-LJQANCHMSA-N 0.000 description 1
• ALYHRGLJXYXRKL-GOSISDBHSA-N benzyl (3S)-3-(cyanomethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylate Chemical compound C(#N)C[C@H]1N(CC2=CC=CC=C2C1)C(=O)OCC1=CC=CC=C1 ALYHRGLJXYXRKL-GOSISDBHSA-N 0.000 description 1
• KHDAZFUMAQFRPY-OAQYLSRUSA-N benzyl (3S)-3-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]-3,4-dihydro-1H-isoquinoline-2-carboxylate Chemical compound C(C)(C)(C)OC(=O)NCC[C@H]1N(CC2=CC=CC=C2C1)C(=O)OCC1=CC=CC=C1 KHDAZFUMAQFRPY-OAQYLSRUSA-N 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
• 230000036952 cancer formation Effects 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 150000003857 carboxamides Chemical class 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 239000003610 charcoal Substances 0.000 description 1
• KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 238000004737 colorimetric analysis Methods 0.000 description 1
• 229940125878 compound 36 Drugs 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 230000003831 deregulation Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 238000002050 diffraction method Methods 0.000 description 1
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• SACNIGZYDTUHKB-UHFFFAOYSA-N ditert-butyl-[2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C(C)(C)C)C(C)(C)C SACNIGZYDTUHKB-UHFFFAOYSA-N 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 230000035622 drinking Effects 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 230000013020 embryo development Effects 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 229940088598 enzyme Drugs 0.000 description 1
• WBQWTKGUVJOZPV-XMMPIXPASA-N ethyl 3-[6-[(3S)-3-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)NCC[C@H]1N(CC2=CC=CC=C2C1)C(=O)C=1C(=CC2=C(OCO2)C=1)C1=CC(=C2CCCCN12)C(=O)OCC WBQWTKGUVJOZPV-XMMPIXPASA-N 0.000 description 1
• WECBRKGOCVGBTE-RUZDIDTESA-N ethyl 3-[6-[(3S)-3-[2-[2,2-difluoroethyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N(CC[C@H]1N(CC2=CC=CC=C2C1)C(=O)C=1C(=CC2=C(OCO2)C=1)C1=CC(=C2CCCCN12)C(=O)OCC)CC(F)F WECBRKGOCVGBTE-RUZDIDTESA-N 0.000 description 1
• WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 238000013467 fragmentation Methods 0.000 description 1
• 238000006062 fragmentation reaction Methods 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 230000014509 gene expression Effects 0.000 description 1
• 230000008570 general process Effects 0.000 description 1
• 231100000024 genotoxic Toxicity 0.000 description 1
• 230000001738 genotoxic effect Effects 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 102000018358 immunoglobulin Human genes 0.000 description 1
• 229940072221 immunoglobulins Drugs 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 230000005917 in vivo anti-tumor Effects 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 230000031146 intracellular signal transduction Effects 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000004816 latex Substances 0.000 description 1
• 229920000126 latex Polymers 0.000 description 1
• 210000004901 leucine-rich repeat Anatomy 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• HGVQJZLJIRTTIK-UHFFFAOYSA-N methyl 1,4-dioxa-8-azaspiro[4.5]decane-7-carboxylate Chemical compound C1CNC(C(=O)OC)CC21OCCO2 HGVQJZLJIRTTIK-UHFFFAOYSA-N 0.000 description 1
• ZDUBLLCAMMIGFH-UHFFFAOYSA-N methyl 2-pyrimidin-2-ylacetate Chemical compound COC(=O)CC1=NC=CC=N1 ZDUBLLCAMMIGFH-UHFFFAOYSA-N 0.000 description 1
• BULNGUMJKIKAJI-QGZVFWFLSA-N methyl 3-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxylate Chemical compound C[C@H]1N(CC2=CC=CC=C2C1)C(=O)C=1C(=CC2=C(OCO2)C=1)C1=CC(=C2CCCCN12)C(=O)OC BULNGUMJKIKAJI-QGZVFWFLSA-N 0.000 description 1
• AYIUVCLRRDJVEU-MRXNPFEDSA-N methyl 3-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-7-oxo-6,8-dihydro-5H-indolizine-1-carboxylate Chemical compound C[C@H]1N(CC2=CC=CC=C2C1)C(=O)C=1C(=CC2=C(OCO2)C=1)C1=CC(=C2CC(CCN12)=O)C(=O)OC AYIUVCLRRDJVEU-MRXNPFEDSA-N 0.000 description 1
• FBDLHFFPPKPNRF-IBGZPJMESA-N methyl 3-[6-[(3S)-3-(hydroxymethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxylate Chemical compound OC[C@H]1N(CC2=CC=CC=C2C1)C(=O)C=1C(=CC2=C(OCO2)C=1)C1=CC(=C2CCCCN12)C(=O)OC FBDLHFFPPKPNRF-IBGZPJMESA-N 0.000 description 1
• IGKUEKJRDGZKOJ-QFIPXVFZSA-N methyl 3-[6-[(3S)-3-(prop-2-enoxymethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxylate Chemical compound C(C=C)OC[C@H]1N(CC2=CC=CC=C2C1)C(=O)C=1C(=CC2=C(OCO2)C=1)C1=CC(=C2CCCCN12)C(=O)OC IGKUEKJRDGZKOJ-QFIPXVFZSA-N 0.000 description 1
• TYKHGHUSNORTKP-HSZRJFAPSA-N methyl 3-[6-[(3S)-3-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)NCC[C@H]1N(CC2=CC=CC=C2C1)C(=O)C=1C(=CC2=C(OCO2)C=1)C1=CC(=C2CCCCN12)C(=O)OC TYKHGHUSNORTKP-HSZRJFAPSA-N 0.000 description 1
• KWZCGWINZLJUEJ-UHFFFAOYSA-N methyl 6-(6-formyl-1,3-benzodioxol-5-yl)pyrrolo[1,2-a]pyrimidine-8-carboxylate Chemical compound C(=O)C=1C(=CC2=C(OCO2)C=1)C1=CC(=C2N1C=CC=N2)C(=O)OC KWZCGWINZLJUEJ-UHFFFAOYSA-N 0.000 description 1
• GFQVKQYYERJWIR-VTBWFHPJSA-N methyl 7-hydroxy-3-[6-[(3R)-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxylate Chemical compound OC1CCN2C(=CC(=C2C1)C(=O)OC)C1=CC2=C(OCO2)C=C1C(=O)N1CC2=CC=CC=C2C[C@H]1C GFQVKQYYERJWIR-VTBWFHPJSA-N 0.000 description 1
• RPWTVOCDYOZRDR-UHFFFAOYSA-N methyl pyrrolo[1,2-a]pyrimidine-8-carboxylate Chemical compound N=1C=2N(C=CC=1)C=CC=2C(=O)OC RPWTVOCDYOZRDR-UHFFFAOYSA-N 0.000 description 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
• 230000000394 mitotic effect Effects 0.000 description 1
• 230000004660 morphological change Effects 0.000 description 1
• LGVIBLHCPQVSMT-HSZRJFAPSA-N n,n-dibutyl-6-[6-[(3r)-3-methyl-3,4-dihydro-1h-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamide Chemical compound N12CCNCC2=C(C(=O)N(CCCC)CCCC)C=C1C(C(=C1)C(=O)N2[C@@H](CC3=CC=CC=C3C2)C)=CC2=C1OCO2 LGVIBLHCPQVSMT-HSZRJFAPSA-N 0.000 description 1
• GGKWAKQAJLAXDM-JOCHJYFZSA-N n-(4-hydroxyphenyl)-6-[6-[(3r)-3-methyl-3,4-dihydro-1h-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-n-propan-2-yl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamide Chemical compound C1=C(C=2C(=CC=3OCOC=3C=2)C(=O)N2[C@@H](CC3=CC=CC=C3C2)C)N2CCNCC2=C1C(=O)N(C(C)C)C1=CC=C(O)C=C1 GGKWAKQAJLAXDM-JOCHJYFZSA-N 0.000 description 1
• YJZUCBNHWFEQRZ-OAQYLSRUSA-N n-(4-hydroxyphenyl)-n-methyl-3-[6-[(3r)-3-methyl-3,4-dihydro-1h-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C([C@H]1C)C2=CC=CC=C2CN1C(=O)C1=CC=2OCOC=2C=C1C(N1CCCCC1=1)=CC=1C(=O)N(C)C1=CC=C(O)C=C1 YJZUCBNHWFEQRZ-OAQYLSRUSA-N 0.000 description 1
• YJZUCBNHWFEQRZ-NRFANRHFSA-N n-(4-hydroxyphenyl)-n-methyl-3-[6-[(3s)-3-methyl-3,4-dihydro-1h-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C([C@@H]1C)C2=CC=CC=C2CN1C(=O)C1=CC=2OCOC=2C=C1C(N1CCCCC1=1)=CC=1C(=O)N(C)C1=CC=C(O)C=C1 YJZUCBNHWFEQRZ-NRFANRHFSA-N 0.000 description 1
• UKAOYPXNWBXQTJ-HXUWFJFHSA-N n-(4-hydroxyphenyl)-n-methyl-6-[6-[(3r)-3-methyl-3,4-dihydro-1h-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamide Chemical compound C([C@H]1C)C2=CC=CC=C2CN1C(=O)C1=CC=2OCOC=2C=C1C(N1CCNCC1=1)=CC=1C(=O)N(C)C1=CC=C(O)C=C1 UKAOYPXNWBXQTJ-HXUWFJFHSA-N 0.000 description 1
• OELAFDUKIVVJJS-UHFFFAOYSA-N n-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-3-fluoroaniline Chemical compound C1=CC(O[Si](C)(C)C(C)(C)C)=CC=C1NC1=CC=CC(F)=C1 OELAFDUKIVVJJS-UHFFFAOYSA-N 0.000 description 1
• WGCXBCCWWQCQKW-UHFFFAOYSA-N n-butyl-3-[6-(3,4-dihydro-1h-isoquinoline-2-carbonyl)-1,3-benzodioxol-5-yl]-n-(4-hydroxyphenyl)-5,6,7,8-tetrahydroindolizine-1-carboxamide Chemical compound C1=C(C=2C(=CC=3OCOC=3C=2)C(=O)N2CC3=CC=CC=C3CC2)N2CCCCC2=C1C(=O)N(CCCC)C1=CC=C(O)C=C1 WGCXBCCWWQCQKW-UHFFFAOYSA-N 0.000 description 1
• KLCHBGRPQDPGJF-HSZRJFAPSA-N n-butyl-n-(4-hydroxyphenyl)-6-[6-[(3r)-3-methyl-3,4-dihydro-1h-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamide Chemical compound C1=C(C=2C(=CC=3OCOC=3C=2)C(=O)N2[C@@H](CC3=CC=CC=C3C2)C)N2CCNCC2=C1C(=O)N(CCCC)C1=CC=C(O)C=C1 KLCHBGRPQDPGJF-HSZRJFAPSA-N 0.000 description 1
• ZPJPOUHAGWLZGL-OAQYLSRUSA-N n-ethyl-n-(4-hydroxyphenyl)-6-[6-[(3r)-3-methyl-3,4-dihydro-1h-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamide Chemical compound C1=C(C=2C(=CC=3OCOC=3C=2)C(=O)N2[C@@H](CC3=CC=CC=C3C2)C)N2CCNCC2=C1C(=O)N(CC)C1=CC=C(O)C=C1 ZPJPOUHAGWLZGL-OAQYLSRUSA-N 0.000 description 1
• ZPJPOUHAGWLZGL-NRFANRHFSA-N n-ethyl-n-(4-hydroxyphenyl)-6-[6-[(3s)-3-methyl-3,4-dihydro-1h-isoquinoline-2-carbonyl]-1,3-benzodioxol-5-yl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamide Chemical compound C1=C(C=2C(=CC=3OCOC=3C=2)C(=O)N2[C@H](CC3=CC=CC=C3C2)C)N2CCNCC2=C1C(=O)N(CC)C1=CC=C(O)C=C1 ZPJPOUHAGWLZGL-NRFANRHFSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 229940055729 papain Drugs 0.000 description 1
• 235000019834 papain Nutrition 0.000 description 1
• IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 1
• 229940111202 pepsin Drugs 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 108010025221 plasma protein Z Proteins 0.000 description 1
• 231100000614 poison Toxicity 0.000 description 1
• 239000002574 poison Substances 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 238000002360 preparation method Methods 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 238000004393 prognosis Methods 0.000 description 1
• 230000005522 programmed cell death Effects 0.000 description 1
• 239000003207 proteasome inhibitor Substances 0.000 description 1
• 229940121649 protein inhibitor Drugs 0.000 description 1
• 239000012268 protein inhibitor Substances 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 230000006798 recombination Effects 0.000 description 1
• 238000006722 reduction reaction Methods 0.000 description 1
• 230000003252 repetitive effect Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• 125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
• 229910001958 silver carbonate Inorganic materials 0.000 description 1
• LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
• 239000006190 sub-lingual tablet Substances 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• NINYRRRZJPYSLY-KRWDZBQOSA-N tert-butyl (3S)-3-(2-morpholin-4-yl-2-oxoethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylate Chemical compound CC(C)(C)OC(=O)N1Cc2ccccc2C[C@H]1CC(=O)N1CCOCC1 NINYRRRZJPYSLY-KRWDZBQOSA-N 0.000 description 1
• JVXDVBOJSOXNSA-LFQPHHBNSA-N tert-butyl 2-[[(3R)-2-(4-methylphenyl)sulfonyl-3,4-dihydro-1H-isoquinolin-3-yl]methyl]-3-morpholin-4-yl-3-oxopropanoate Chemical compound Cc1ccc(cc1)S(=O)(=O)N1Cc2ccccc2C[C@H]1CC(C(=O)OC(C)(C)C)C(=O)N1CCOCC1 JVXDVBOJSOXNSA-LFQPHHBNSA-N 0.000 description 1
• YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 108060008226 thioredoxin Proteins 0.000 description 1
• 229940094937 thioredoxin Drugs 0.000 description 1
• 230000030968 tissue homeostasis Effects 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 238000000825 ultraviolet detection Methods 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 229940100445 wheat starch Drugs 0.000 description 1