CN104974161B - 作为PARP抑制剂的4H-吡唑并[1,5-α]苯并咪唑化合物的类似物 - Google Patents
作为PARP抑制剂的4H-吡唑并[1,5-α]苯并咪唑化合物的类似物 Download PDFInfo
- Publication number
- CN104974161B CN104974161B CN201410144173.0A CN201410144173A CN104974161B CN 104974161 B CN104974161 B CN 104974161B CN 201410144173 A CN201410144173 A CN 201410144173A CN 104974161 B CN104974161 B CN 104974161B
- Authority
- CN
- China
- Prior art keywords
- mmol
- fluoro
- imidazo
- benzo
- pyrazole
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- -1 benzimidazole compound Chemical class 0.000 title claims abstract description 179
- 239000012661 PARP inhibitor Substances 0.000 title abstract description 6
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 title abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 223
- 150000003839 salts Chemical class 0.000 claims abstract description 50
- 229910052757 nitrogen Inorganic materials 0.000 claims description 64
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
- 125000001424 substituent group Chemical group 0.000 claims description 42
- 229910052794 bromium Inorganic materials 0.000 claims description 36
- 229910052731 fluorine Inorganic materials 0.000 claims description 36
- 229910052740 iodine Inorganic materials 0.000 claims description 36
- 229910052801 chlorine Inorganic materials 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 238000006467 substitution reaction Methods 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 209
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 207
- 239000000203 mixture Substances 0.000 description 192
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 162
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 148
- 238000005160 1H NMR spectroscopy Methods 0.000 description 136
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 106
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 95
- 239000000243 solution Substances 0.000 description 94
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 79
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
- 239000012044 organic layer Substances 0.000 description 72
- 235000019439 ethyl acetate Nutrition 0.000 description 70
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 68
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 67
- 238000004440 column chromatography Methods 0.000 description 64
- 239000007787 solid Substances 0.000 description 61
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 60
- 239000010410 layer Substances 0.000 description 55
- 239000012267 brine Substances 0.000 description 51
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 51
- 229910052938 sodium sulfate Inorganic materials 0.000 description 48
- 235000011152 sodium sulphate Nutrition 0.000 description 48
- 238000000746 purification Methods 0.000 description 43
- 150000003254 radicals Chemical class 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- 238000001816 cooling Methods 0.000 description 37
- 238000003756 stirring Methods 0.000 description 37
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 37
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 34
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical group OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 28
- 239000000460 chlorine Substances 0.000 description 27
- 239000000706 filtrate Substances 0.000 description 27
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 24
- 125000005842 heteroatom Chemical group 0.000 description 23
- 238000000034 method Methods 0.000 description 22
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
- 238000002953 preparative HPLC Methods 0.000 description 20
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 description 19
- 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 description 18
- 239000011259 mixed solution Substances 0.000 description 17
- 229910000027 potassium carbonate Inorganic materials 0.000 description 17
- 125000004429 atom Chemical group 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 15
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 14
- 239000002585 base Substances 0.000 description 14
- 238000001914 filtration Methods 0.000 description 14
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 125000004404 heteroalkyl group Chemical group 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 125000000623 heterocyclic group Chemical group 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 229960000583 acetic acid Drugs 0.000 description 10
- 235000019270 ammonium chloride Nutrition 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- CTEDVGRUGMPBHE-UHFFFAOYSA-N tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CO)CC1 CTEDVGRUGMPBHE-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 9
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 9
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 239000013543 active substance Substances 0.000 description 8
- 229910052796 boron Inorganic materials 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 8
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- 239000007821 HATU Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 238000012856 packing Methods 0.000 description 7
- 229910000160 potassium phosphate Inorganic materials 0.000 description 7
- 235000011009 potassium phosphates Nutrition 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- MJIVRKPEXXHNJT-UHFFFAOYSA-N lutidinic acid Chemical compound OC(=O)C1=CC=NC(C(O)=O)=C1 MJIVRKPEXXHNJT-UHFFFAOYSA-N 0.000 description 6
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 125000004434 sulfur atom Chemical group 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 125000004430 oxygen atom Chemical group O* 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 239000011701 zinc Substances 0.000 description 5
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 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 description 4
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- ITYPIHCCBGIXLG-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCNCC2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCNCC2)C)C=1)C(=O)N ITYPIHCCBGIXLG-UHFFFAOYSA-N 0.000 description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- QGJOPFRUJISHPQ-UHFFFAOYSA-N carbon disulfide Substances S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 229940093915 gynecological organic acid Drugs 0.000 description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 235000005985 organic acids Nutrition 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- 238000012746 preparative thin layer chromatography Methods 0.000 description 4
- 238000010791 quenching Methods 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- BFFLLBPMZCIGRM-UHFFFAOYSA-N tert-butyl 2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1CO BFFLLBPMZCIGRM-UHFFFAOYSA-N 0.000 description 4
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- MYRABDLKFUTRHD-UHFFFAOYSA-N BrC1=C(C(=CC(=C1)F)Br)NN Chemical compound BrC1=C(C(=CC(=C1)F)Br)NN MYRABDLKFUTRHD-UHFFFAOYSA-N 0.000 description 3
- UGPMDDZOGGCMFV-UHFFFAOYSA-N C(#N)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(#N)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F UGPMDDZOGGCMFV-UHFFFAOYSA-N 0.000 description 3
- ZEZDKIABPLVDKO-UHFFFAOYSA-N C(C1=CC=CC=C1)OC=1C(=C2N(N=1)C1=C(N2)C=C(C=C1C(=O)N)F)C1(CCN(CC1)C(C)C)C Chemical compound C(C1=CC=CC=C1)OC=1C(=C2N(N=1)C1=C(N2)C=C(C=C1C(=O)N)F)C1(CCN(CC1)C(C)C)C ZEZDKIABPLVDKO-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 3
- 230000005778 DNA damage Effects 0.000 description 3
- 231100000277 DNA damage Toxicity 0.000 description 3
- XIPKFXVJONLQKW-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=C(C=3)C2CCNCC2)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=C(C=3)C2CCNCC2)C=1)C(=O)N XIPKFXVJONLQKW-UHFFFAOYSA-N 0.000 description 3
- MKTMZBIWWRJZKH-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=C(C=3C2(CCN(CC2)C(C)C)C)OC)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=C(C=3C2(CCN(CC2)C(C)C)C)OC)C=1)C(=O)N MKTMZBIWWRJZKH-UHFFFAOYSA-N 0.000 description 3
- TWVGTRDBBKNOEZ-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C(=O)N2CCN(CC2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C(=O)N2CCN(CC2)C)C=1)C(=O)N TWVGTRDBBKNOEZ-UHFFFAOYSA-N 0.000 description 3
- OVYJJMLOWBOJDB-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)C(C)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)C(C)C)C)C=1)C(=O)N OVYJJMLOWBOJDB-UHFFFAOYSA-N 0.000 description 3
- TUFJAXLIHVZUKA-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCS(C=C2)(=O)=O)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCS(C=C2)(=O)=O)C)C=1)C(=O)N TUFJAXLIHVZUKA-UHFFFAOYSA-N 0.000 description 3
- KADJYYQDTBEPQS-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2=CC=C(C=C2)C2CNCCC2)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2=CC=C(C=C2)C2CNCCC2)C=1)C(=O)N KADJYYQDTBEPQS-UHFFFAOYSA-N 0.000 description 3
- GNYABDRZRWYLCZ-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2=CC=C(C=C2)F)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2=CC=C(C=C2)F)C=1)C(=O)N GNYABDRZRWYLCZ-UHFFFAOYSA-N 0.000 description 3
- WMAWWVKHXNYCGN-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)CC(C)(C)F)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)CC(C)(C)F)C=1)C(=O)N WMAWWVKHXNYCGN-UHFFFAOYSA-N 0.000 description 3
- ZSHFGCWAZFLDPP-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CCNCC2)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CCNCC2)C=1)C(=O)N ZSHFGCWAZFLDPP-UHFFFAOYSA-N 0.000 description 3
- PJSVOSGNYRTTPK-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CCOCC2)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CCOCC2)C=1)C(=O)N PJSVOSGNYRTTPK-UHFFFAOYSA-N 0.000 description 3
- ONWRWLYSFTTYSC-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2NCC(C2)O)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2NCC(C2)O)C=1)C(=O)N ONWRWLYSFTTYSC-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 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
- 125000004122 cyclic group Chemical group 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 3
- SNQXJPARXFUULZ-UHFFFAOYSA-N dioxolane Chemical compound C1COOC1 SNQXJPARXFUULZ-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 125000001041 indolyl group Chemical group 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 3
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 3
- 125000003373 pyrazinyl group Chemical group 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 235000010265 sodium sulphite Nutrition 0.000 description 3
- 229960004964 temozolomide Drugs 0.000 description 3
- HKIGXXRMJFUUKV-UHFFFAOYSA-N tert-butyl 3-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical group CC(C)(C)OC(=O)N1CCC(CO)C1 HKIGXXRMJFUUKV-UHFFFAOYSA-N 0.000 description 3
- YFYSPIRFZKBBAU-UHFFFAOYSA-N tert-butyl 4-(hydroxymethyl)-4-methylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C)(CO)CC1 YFYSPIRFZKBBAU-UHFFFAOYSA-N 0.000 description 3
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 125000000335 thiazolyl group Chemical group 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Substances ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 3
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 2
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 2
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- PTZNCCIULVXFIJ-UHFFFAOYSA-N 1-o-tert-butyl 4-o-methyl piperidine-1,4-dicarboxylate Chemical compound COC(=O)C1CCN(C(=O)OC(C)(C)C)CC1 PTZNCCIULVXFIJ-UHFFFAOYSA-N 0.000 description 2
- GELKGHVAFRCJNA-UHFFFAOYSA-N 2,2-Dimethyloxirane Chemical compound CC1(C)CO1 GELKGHVAFRCJNA-UHFFFAOYSA-N 0.000 description 2
- VHPLZFGCNLDYQH-UHFFFAOYSA-N 2,6-dibromo-4-fluoroaniline Chemical compound NC1=C(Br)C=C(F)C=C1Br VHPLZFGCNLDYQH-UHFFFAOYSA-N 0.000 description 2
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 2
- VQGHOUODWALEFC-UHFFFAOYSA-N 2-phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=CC=N1 VQGHOUODWALEFC-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-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
- 108091007743 BRCA1/2 Proteins 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- PLQWMLFNPGZOPC-UHFFFAOYSA-N C(#N)C1(CCN(CC1)CC1CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(#N)C1(CCN(CC1)CC1CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F PLQWMLFNPGZOPC-UHFFFAOYSA-N 0.000 description 2
- JSIRIVGRXQYFFL-UHFFFAOYSA-N C(#N)C1=C2N(N=C1)C1=C(N2)C=CC=C1C(=O)N Chemical compound C(#N)C1=C2N(N=C1)C1=C(N2)C=CC=C1C(=O)N JSIRIVGRXQYFFL-UHFFFAOYSA-N 0.000 description 2
- CCVUCMOLANHVOS-UHFFFAOYSA-N C(C)N1C2CC(CC1CC2)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1C2CC(CC1CC2)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F CCVUCMOLANHVOS-UHFFFAOYSA-N 0.000 description 2
- HQQQWHXBTUIYAN-UHFFFAOYSA-N C(C)N1CCC(CC1)C1=C2N(N=C1)C1=C(N2C)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CCC(CC1)C1=C2N(N=C1)C1=C(N2C)C=C(C=C1C(=O)N)F HQQQWHXBTUIYAN-UHFFFAOYSA-N 0.000 description 2
- YHHFHJNIDHVKNO-UHFFFAOYSA-N C(C)N1CCC(CCC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CCC(CCC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F YHHFHJNIDHVKNO-UHFFFAOYSA-N 0.000 description 2
- YUPNJZXLOODHAZ-UHFFFAOYSA-N C1(CC1)CN1CC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C1(CC1)CN1CC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F YUPNJZXLOODHAZ-UHFFFAOYSA-N 0.000 description 2
- SCOCNPKTLCOFBW-UHFFFAOYSA-N C1(CC1)CN1CCC(CC1)(C)C1=C2N(N=C1C)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C1(CC1)CN1CCC(CC1)(C)C1=C2N(N=C1C)C1=C(N2)C=C(C=C1C(=O)N)F SCOCNPKTLCOFBW-UHFFFAOYSA-N 0.000 description 2
- TUQQHCHKNBCJCM-UHFFFAOYSA-N C1(CC1)CN1CCC(CC1)(CO)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C1(CC1)CN1CCC(CC1)(CO)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F TUQQHCHKNBCJCM-UHFFFAOYSA-N 0.000 description 2
- WUMBYTVRLSJLIB-UHFFFAOYSA-N C12CNCC2C1C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C12CNCC2C1C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F WUMBYTVRLSJLIB-UHFFFAOYSA-N 0.000 description 2
- PIIRUXFKGRLZDK-UHFFFAOYSA-N CCN1CCC(CC1)C1=C2C(O)C3=CC(F)=CC(C(N)=O)=C3N2N=C1 Chemical compound CCN1CCC(CC1)C1=C2C(O)C3=CC(F)=CC(C(N)=O)=C3N2N=C1 PIIRUXFKGRLZDK-UHFFFAOYSA-N 0.000 description 2
- UJJFHEWKNDQARH-UHFFFAOYSA-N CN(C1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F)C Chemical compound CN(C1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F)C UJJFHEWKNDQARH-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 2
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 2
- WEAXGVCIWNOYMI-UHFFFAOYSA-N ClC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC)C)C=1)C(=O)N Chemical compound ClC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC)C)C=1)C(=O)N WEAXGVCIWNOYMI-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 230000033616 DNA repair Effects 0.000 description 2
- MMPHWGLJTISQJS-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)C2CC(C2)F)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)C2CC(C2)F)C)C=1)C(=O)N MMPHWGLJTISQJS-UHFFFAOYSA-N 0.000 description 2
- AXMNMJMLBYAUID-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)C2CCOCC2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)C2CCOCC2)C)C=1)C(=O)N AXMNMJMLBYAUID-UHFFFAOYSA-N 0.000 description 2
- OUYFPKZRSAYIQO-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC(C)(C)O)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC(C)(C)O)C)C=1)C(=O)N OUYFPKZRSAYIQO-UHFFFAOYSA-N 0.000 description 2
- DZLTZQJWWJRDIG-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC(C)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC(C)C)C)C=1)C(=O)N DZLTZQJWWJRDIG-UHFFFAOYSA-N 0.000 description 2
- WGZXKCFLGXWMNC-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC(F)(F)F)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC(F)(F)F)C)C=1)C(=O)N WGZXKCFLGXWMNC-UHFFFAOYSA-N 0.000 description 2
- BTZWGDVFCGZCBD-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2(CC2)O)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2(CC2)O)C)C=1)C(=O)N BTZWGDVFCGZCBD-UHFFFAOYSA-N 0.000 description 2
- YCTFJBRWKQGIAI-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2(CC2)S(=O)(=O)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2(CC2)S(=O)(=O)C)C)C=1)C(=O)N YCTFJBRWKQGIAI-UHFFFAOYSA-N 0.000 description 2
- ZOMPROAOSWOOJA-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2(COC2)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2(COC2)C)C)C=1)C(=O)N ZOMPROAOSWOOJA-UHFFFAOYSA-N 0.000 description 2
- GFFSWYGAGHUXRT-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2=C(N=CS2)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2=C(N=CS2)C)C)C=1)C(=O)N GFFSWYGAGHUXRT-UHFFFAOYSA-N 0.000 description 2
- ISOMCQKZXCYOON-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2=NNC(C=C2)=O)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2=NNC(C=C2)=O)C)C=1)C(=O)N ISOMCQKZXCYOON-UHFFFAOYSA-N 0.000 description 2
- LTUOZFZDFLUXDN-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2CCOCC2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2CCOCC2)C)C=1)C(=O)N LTUOZFZDFLUXDN-UHFFFAOYSA-N 0.000 description 2
- SWKVOBKVCTWELM-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2CN(C2)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2CN(C2)C)C)C=1)C(=O)N SWKVOBKVCTWELM-UHFFFAOYSA-N 0.000 description 2
- GVXPBDBCQUSTPQ-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2COC2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC2COC2)C)C=1)C(=O)N GVXPBDBCQUSTPQ-UHFFFAOYSA-N 0.000 description 2
- QRETXGDHJVOCJZ-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC=2N(C=CN=2)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC=2N(C=CN=2)C)C)C=1)C(=O)N QRETXGDHJVOCJZ-UHFFFAOYSA-N 0.000 description 2
- MDRILFDKYBAAMB-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC=2SC=CC=2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC=2SC=CC=2)C)C=1)C(=O)N MDRILFDKYBAAMB-UHFFFAOYSA-N 0.000 description 2
- QYCJQRSFDOPVGY-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC=2SC=CN=2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CC=2SC=CN=2)C)C=1)C(=O)N QYCJQRSFDOPVGY-UHFFFAOYSA-N 0.000 description 2
- IFFAKRVQGSNUQK-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CCCOC)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CCCOC)C)C=1)C(=O)N IFFAKRVQGSNUQK-UHFFFAOYSA-N 0.000 description 2
- SHPGECHVHGLCAM-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CCOC)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CCOC)C)C=1)C(=O)N SHPGECHVHGLCAM-UHFFFAOYSA-N 0.000 description 2
- NFFTVRYSPPROOG-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CCS(=O)(=O)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CCS(=O)(=O)C)C)C=1)C(=O)N NFFTVRYSPPROOG-UHFFFAOYSA-N 0.000 description 2
- ZUFUGIGLPDVFAT-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)S(=O)(=O)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)S(=O)(=O)C)C)C=1)C(=O)N ZUFUGIGLPDVFAT-UHFFFAOYSA-N 0.000 description 2
- KZYJNLBATDRDAC-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CN(CC2)C(C)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CN(CC2)C(C)C)C)C=1)C(=O)N KZYJNLBATDRDAC-UHFFFAOYSA-N 0.000 description 2
- OVKAOGODHDKSTJ-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CN(CC2)C2COC2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CN(CC2)C2COC2)C)C=1)C(=O)N OVKAOGODHDKSTJ-UHFFFAOYSA-N 0.000 description 2
- ZGRIAFCYGNPFGU-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CN(CC2)CC(F)(F)F)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CN(CC2)CC(F)(F)F)C)C=1)C(=O)N ZGRIAFCYGNPFGU-UHFFFAOYSA-N 0.000 description 2
- XGIJZOZZMQWXBM-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CN(CC2)CCC(F)(F)F)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CN(CC2)CCC(F)(F)F)C)C=1)C(=O)N XGIJZOZZMQWXBM-UHFFFAOYSA-N 0.000 description 2
- VAYISGIKUADSCM-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CN(CC2)CCF)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CN(CC2)CCF)C)C=1)C(=O)N VAYISGIKUADSCM-UHFFFAOYSA-N 0.000 description 2
- SCEKCNTWKNPIPV-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CN(CC2)CCS(=O)(=O)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CN(CC2)CCS(=O)(=O)C)C)C=1)C(=O)N SCEKCNTWKNPIPV-UHFFFAOYSA-N 0.000 description 2
- RXDBCWCHXKSDRI-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C23CN(CC3C2)C(C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C23CN(CC3C2)C(C)C)C=1)C(=O)N RXDBCWCHXKSDRI-UHFFFAOYSA-N 0.000 description 2
- SYRCEOOSSOCESD-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C23CN(CC3C2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C23CN(CC3C2)C)C=1)C(=O)N SYRCEOOSSOCESD-UHFFFAOYSA-N 0.000 description 2
- ZNVBOXQEGKNRSY-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2=CC=C(C=C2)CNC)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2=CC=C(C=C2)CNC)C=1)C(=O)N ZNVBOXQEGKNRSY-UHFFFAOYSA-N 0.000 description 2
- ITMLWRHRFDUPKR-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2=CC=NC=C2)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2=CC=NC=C2)C=1)C(=O)N ITMLWRHRFDUPKR-UHFFFAOYSA-N 0.000 description 2
- ZROYNWDGSDPZDG-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)C(C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)C(C)C)C=1)C(=O)N ZROYNWDGSDPZDG-UHFFFAOYSA-N 0.000 description 2
- WEVNAFRPXMWJEA-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)C)C=1)C(=O)N WEVNAFRPXMWJEA-UHFFFAOYSA-N 0.000 description 2
- FBNBFHWHZYDILI-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)C2COC2)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)C2COC2)C=1)C(=O)N FBNBFHWHZYDILI-UHFFFAOYSA-N 0.000 description 2
- RRHJAPMRYCRQAZ-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)CC(C)(C)O)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)CC(C)(C)O)C=1)C(=O)N RRHJAPMRYCRQAZ-UHFFFAOYSA-N 0.000 description 2
- DWFDHIMUUYCQJT-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)CCC)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)CCC)C=1)C(=O)N DWFDHIMUUYCQJT-UHFFFAOYSA-N 0.000 description 2
- RFZUXWGKPKIJTF-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)CCF)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)CCF)C=1)C(=O)N RFZUXWGKPKIJTF-UHFFFAOYSA-N 0.000 description 2
- ZMDWEPTTYUFKBB-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)CCO)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)CCO)C=1)C(=O)N ZMDWEPTTYUFKBB-UHFFFAOYSA-N 0.000 description 2
- KSUGFMRECQBBDK-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)CCOC)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)CCOC)C=1)C(=O)N KSUGFMRECQBBDK-UHFFFAOYSA-N 0.000 description 2
- STXOGFKZGZQXLQ-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CCC2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CCC2)C)C=1)C(=O)N STXOGFKZGZQXLQ-UHFFFAOYSA-N 0.000 description 2
- GNVQEZOBAMTKIH-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CN(CC2)C(C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CN(CC2)C(C)C)C=1)C(=O)N GNVQEZOBAMTKIH-UHFFFAOYSA-N 0.000 description 2
- JSBOJHJGWIDWSE-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CN(CC2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CN(CC2)C)C=1)C(=O)N JSBOJHJGWIDWSE-UHFFFAOYSA-N 0.000 description 2
- UBFMSLQIOOFCII-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2N(CCC2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2N(CCC2)C)C=1)C(=O)N UBFMSLQIOOFCII-UHFFFAOYSA-N 0.000 description 2
- PSONCZUDLUGDBA-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2N(CCC2)CCC)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2N(CCC2)CCC)C=1)C(=O)N PSONCZUDLUGDBA-UHFFFAOYSA-N 0.000 description 2
- KPNGVVJGCJBLTQ-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2NCCC2)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2NCCC2)C=1)C(=O)N KPNGVVJGCJBLTQ-UHFFFAOYSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-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
- 229910004373 HOAc Inorganic materials 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 229930194542 Keto Natural products 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 208000009525 Myocarditis Diseases 0.000 description 2
- DQRYHQYFZVXERW-UHFFFAOYSA-N NCC1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound NCC1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F DQRYHQYFZVXERW-UHFFFAOYSA-N 0.000 description 2
- LOKWDRYKGRCPHU-UHFFFAOYSA-N NCCN1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound NCCN1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F LOKWDRYKGRCPHU-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 description 2
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 125000006242 amine protecting group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 235000012501 ammonium carbonate Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 125000005002 aryl methyl group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001735 carboxylic acids Chemical group 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 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 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 125000005956 isoquinolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical compound C1C[C@@H](C(O)=O)[C@H](O)CN1C(C1=C(F)C=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C1CC1 IBIKHMZPHNKTHM-RDTXWAMCSA-N 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 description 2
- PCHKPVIQAHNQLW-CQSZACIVSA-N niraparib Chemical compound N1=C2C(C(=O)N)=CC=CC2=CN1C(C=C1)=CC=C1[C@@H]1CCCNC1 PCHKPVIQAHNQLW-CQSZACIVSA-N 0.000 description 2
- 229950011068 niraparib Drugs 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 125000005936 piperidyl group Chemical group 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- CMUYBJHYEACLSY-UHFFFAOYSA-N tert-butyl 4-(hydroxymethyl)azepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(CO)CC1 CMUYBJHYEACLSY-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 125000005309 thioalkoxy group Chemical group 0.000 description 2
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 2
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 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
- 235000012141 vanillin Nutrition 0.000 description 2
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 2
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
- BZMMRNKDONDVIB-UHFFFAOYSA-N (1-ethoxycyclopropyl)oxy-trimethylsilane Chemical compound CCOC1(O[Si](C)(C)C)CC1 BZMMRNKDONDVIB-UHFFFAOYSA-N 0.000 description 1
- YZJOHZHVNGHPQL-UHFFFAOYSA-N (2,6-dibromo-4-chlorophenyl)hydrazine Chemical compound BrC1=C(C(=CC(=C1)Cl)Br)NN YZJOHZHVNGHPQL-UHFFFAOYSA-N 0.000 description 1
- JINQKLMWUXOTNW-UHFFFAOYSA-N (2,6-dibromo-4-fluorophenyl)hydrazine hydrochloride Chemical compound Cl.NNc1c(Br)cc(F)cc1Br JINQKLMWUXOTNW-UHFFFAOYSA-N 0.000 description 1
- PFSHOKSZAZXWGZ-UHFFFAOYSA-N (2,6-dibromophenyl)hydrazine Chemical group NNC1=C(Br)C=CC=C1Br PFSHOKSZAZXWGZ-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- NMJRXNUMGKZPHG-UHFFFAOYSA-N (3-benzyl-3-azabicyclo[3.1.0]hexan-6-yl)methanol Chemical compound C1C2C(CO)C2CN1CC1=CC=CC=C1 NMJRXNUMGKZPHG-UHFFFAOYSA-N 0.000 description 1
- 125000000008 (C1-C10) alkyl group Chemical class 0.000 description 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
- 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 1
- 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
- 125000000196 1,4-pentadienyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])=C([H])[H] 0.000 description 1
- BRWZARWIGCMZNR-UHFFFAOYSA-N 1-(4-bromo-3-fluorophenyl)-n-methylmethanamine Chemical compound CNCC1=CC=C(Br)C(F)=C1 BRWZARWIGCMZNR-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- MKRBAPNEJMFMHU-UHFFFAOYSA-N 1-benzylpyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1CC1=CC=CC=C1 MKRBAPNEJMFMHU-UHFFFAOYSA-N 0.000 description 1
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- 125000005955 1H-indazolyl group Chemical group 0.000 description 1
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
- OEICGMPRFOJHKO-UHFFFAOYSA-N 2-(ethoxymethylidene)propanedinitrile Chemical compound CCOC=C(C#N)C#N OEICGMPRFOJHKO-UHFFFAOYSA-N 0.000 description 1
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- LHNFGFSSFSLREC-UHFFFAOYSA-N 2-cyano-2-[4-methyl-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]acetic acid Chemical compound C(C)(C)(C)OC(=O)N1CCC(CC1)(C)C(C(=O)O)C#N LHNFGFSSFSLREC-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- QXCAHEXKUMUTRF-UHFFFAOYSA-N 3,6-dihydro-2h-pyran-4-yl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CCOCC1 QXCAHEXKUMUTRF-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- OOPOXPCVFCABPQ-UHFFFAOYSA-N 4-[tert-butyl(diphenyl)silyl]oxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C(C)(C)(C)OC(=O)N1C(CC(C1)O[Si](C1=CC=CC=C1)(C1=CC=CC=C1)C(C)(C)C)C(=O)O OOPOXPCVFCABPQ-UHFFFAOYSA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
- SWHUROFMIMHWKS-UHFFFAOYSA-N 4-bromo-3-fluorobenzaldehyde Chemical compound FC1=CC(C=O)=CC=C1Br SWHUROFMIMHWKS-UHFFFAOYSA-N 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- 125000005986 4-piperidonyl group Chemical group 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- 125000001826 4H-pyranyl group Chemical group O1C(=CCC=C1)* 0.000 description 1
- 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
- TUWARWGEOHQXCO-UHFFFAOYSA-N 5-methoxyindole-3-carbaldehyde Chemical compound COC1=CC=C2NC=C(C=O)C2=C1 TUWARWGEOHQXCO-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- HKXICUDOIXLKLJ-UHFFFAOYSA-N 8-[(2-methylpropan-2-yl)oxycarbonyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid Chemical compound C1C(C(O)=O)CC2CCC1N2C(=O)OC(C)(C)C HKXICUDOIXLKLJ-UHFFFAOYSA-N 0.000 description 1
- 230000005730 ADP ribosylation Effects 0.000 description 1
- SRNWOUGRCWSEMX-KEOHHSTQSA-N ADP-beta-D-ribose Chemical group C([C@H]1O[C@H]([C@@H]([C@@H]1O)O)N1C=2N=CN=C(C=2N=C1)N)OP(O)(=O)OP(O)(=O)OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O SRNWOUGRCWSEMX-KEOHHSTQSA-N 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 108700020463 BRCA1 Proteins 0.000 description 1
- 102000036365 BRCA1 Human genes 0.000 description 1
- 101150072950 BRCA1 gene Proteins 0.000 description 1
- 108700020462 BRCA2 Proteins 0.000 description 1
- 102000052609 BRCA2 Human genes 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- IQUUNIBISXZNBV-UHFFFAOYSA-N BrC1=C(C(=CC(=C1)F)Br)N1N=CC=C1C(=O)N(C)OC Chemical compound BrC1=C(C(=CC(=C1)F)Br)N1N=CC=C1C(=O)N(C)OC IQUUNIBISXZNBV-UHFFFAOYSA-N 0.000 description 1
- SIWYRSHNPHCJQP-UHFFFAOYSA-N BrC1=C(C(=CC(=C1)F)Br)N1N=CC=C1C(=O)O Chemical compound BrC1=C(C(=CC(=C1)F)Br)N1N=CC=C1C(=O)O SIWYRSHNPHCJQP-UHFFFAOYSA-N 0.000 description 1
- JKWQSLNETUWGLA-UHFFFAOYSA-N BrC1=C(C(=CC(=C1)F)Br)N1N=CC=C1C(=O)OCC Chemical compound BrC1=C(C(=CC(=C1)F)Br)N1N=CC=C1C(=O)OCC JKWQSLNETUWGLA-UHFFFAOYSA-N 0.000 description 1
- XFWOMGYJCATOFA-UHFFFAOYSA-N BrC1=C2N(N=C1)C1=C(N2COCC[Si](C)(C)C)C=C(C=C1C(=O)N)F Chemical compound BrC1=C2N(N=C1)C1=C(N2COCC[Si](C)(C)C)C=C(C=C1C(=O)N)F XFWOMGYJCATOFA-UHFFFAOYSA-N 0.000 description 1
- UJBYFXGUBZHTEE-UHFFFAOYSA-N BrC1=C2N(N=C1)C1=C(N2COCC[Si](C)(C)C)C=C(C=C1C(=O)O)F Chemical compound BrC1=C2N(N=C1)C1=C(N2COCC[Si](C)(C)C)C=C(C=C1C(=O)O)F UJBYFXGUBZHTEE-UHFFFAOYSA-N 0.000 description 1
- FPQQCXSXPRZRFZ-UHFFFAOYSA-N BrC1=C2N(N=C1)C1=C(N2COCC[Si](C)(C)C)C=C(C=C1C(=O)OC)F Chemical compound BrC1=C2N(N=C1)C1=C(N2COCC[Si](C)(C)C)C=C(C=C1C(=O)OC)F FPQQCXSXPRZRFZ-UHFFFAOYSA-N 0.000 description 1
- CCZIUFFMEYFUIA-UHFFFAOYSA-N BrC1=CC(=CC=2N(C=3N(N=CC=3)C=21)COCC[Si](C)(C)C)F Chemical compound BrC1=CC(=CC=2N(C=3N(N=CC=3)C=21)COCC[Si](C)(C)C)F CCZIUFFMEYFUIA-UHFFFAOYSA-N 0.000 description 1
- YIBQPVKSNIWIOT-UHFFFAOYSA-N BrC1=CC(=CC=2N(C=3N(N=CC=3C(=O)N3CCN(CC3)C(=O)OC(C)(C)C)C=21)COCC[Si](C)(C)C)F Chemical compound BrC1=CC(=CC=2N(C=3N(N=CC=3C(=O)N3CCN(CC3)C(=O)OC(C)(C)C)C=21)COCC[Si](C)(C)C)F YIBQPVKSNIWIOT-UHFFFAOYSA-N 0.000 description 1
- VDRPJDQAYFOQHB-UHFFFAOYSA-N BrC1=CC(=CC=2N(C=3N(N=CC=3C(=O)O)C=21)COCC[Si](C)(C)C)F Chemical compound BrC1=CC(=CC=2N(C=3N(N=CC=3C(=O)O)C=21)COCC[Si](C)(C)C)F VDRPJDQAYFOQHB-UHFFFAOYSA-N 0.000 description 1
- KMGIFPXKIIREQG-UHFFFAOYSA-N BrC1=CC(=CC=2N(C=3N(N=CC=3C(=O)OCC)C=21)COCC[Si](C)(C)C)F Chemical compound BrC1=CC(=CC=2N(C=3N(N=CC=3C(=O)OCC)C=21)COCC[Si](C)(C)C)F KMGIFPXKIIREQG-UHFFFAOYSA-N 0.000 description 1
- NQMSBAMXCWOLNV-UHFFFAOYSA-N BrC1=CC(=CC=2NC=3N(N=C(C=3)C3CCN(CC3)C(=O)OC(C)(C)C)C=21)F Chemical compound BrC1=CC(=CC=2NC=3N(N=C(C=3)C3CCN(CC3)C(=O)OC(C)(C)C)C=21)F NQMSBAMXCWOLNV-UHFFFAOYSA-N 0.000 description 1
- KYMCXQZOIHGJAV-UHFFFAOYSA-N BrC1=CC(=CC=2NC=3N(N=C(C=3C3(CCN(CC3)C(=O)OC(C)(C)C)C)C)C=21)F Chemical compound BrC1=CC(=CC=2NC=3N(N=C(C=3C3(CCN(CC3)C(=O)OC(C)(C)C)C)C)C=21)F KYMCXQZOIHGJAV-UHFFFAOYSA-N 0.000 description 1
- JTADCHOJVJCRJA-UHFFFAOYSA-N BrC1=CC(=CC=2NC=3N(N=C(C=3C3(CCN(CC3)C(=O)OC(C)(C)C)C)OC)C=21)F Chemical compound BrC1=CC(=CC=2NC=3N(N=C(C=3C3(CCN(CC3)C(=O)OC(C)(C)C)C)OC)C=21)F JTADCHOJVJCRJA-UHFFFAOYSA-N 0.000 description 1
- ABLDVFAFJQSZTN-UHFFFAOYSA-N BrC1=CC(=CC=2NC=3N(N=CC=3)C=21)F Chemical compound BrC1=CC(=CC=2NC=3N(N=CC=3)C=21)F ABLDVFAFJQSZTN-UHFFFAOYSA-N 0.000 description 1
- RMSONPHDUIEMKB-UHFFFAOYSA-N BrC1=CC(=CC=2NC=3N(N=CC=3C#N)C=21)F Chemical compound BrC1=CC(=CC=2NC=3N(N=CC=3C#N)C=21)F RMSONPHDUIEMKB-UHFFFAOYSA-N 0.000 description 1
- SKTJACSHFLFXKM-UHFFFAOYSA-N BrC1=CC(=CC=2NC=3N(N=CC=3C(=O)O)C=21)F Chemical compound BrC1=CC(=CC=2NC=3N(N=CC=3C(=O)O)C=21)F SKTJACSHFLFXKM-UHFFFAOYSA-N 0.000 description 1
- ZBBWQNHSUULJSP-UHFFFAOYSA-N BrC1=CC(=CC=2NC=3N(N=CC=3C(=O)OCC)C=21)F Chemical compound BrC1=CC(=CC=2NC=3N(N=CC=3C(=O)OCC)C=21)F ZBBWQNHSUULJSP-UHFFFAOYSA-N 0.000 description 1
- WQORXBHCJWIETE-UHFFFAOYSA-N BrC1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)C(=O)OC(C)(C)C)C#N)C=21)F Chemical compound BrC1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)C(=O)OC(C)(C)C)C#N)C=21)F WQORXBHCJWIETE-UHFFFAOYSA-N 0.000 description 1
- SKUQOLZIBRNDTR-UHFFFAOYSA-N BrC1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)C(=O)OC(C)(C)C)C(=O)O)C=21)F Chemical compound BrC1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)C(=O)OC(C)(C)C)C(=O)O)C=21)F SKUQOLZIBRNDTR-UHFFFAOYSA-N 0.000 description 1
- QCBXQXUVGRPONM-UHFFFAOYSA-N BrC1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)C(=O)OC(C)(C)C)C)C=21)F Chemical compound BrC1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)C(=O)OC(C)(C)C)C)C=21)F QCBXQXUVGRPONM-UHFFFAOYSA-N 0.000 description 1
- DVHODDHMDZZNKH-UHFFFAOYSA-N BrC1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)C(=O)OC(C)(C)C)CO)C=21)F Chemical compound BrC1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)C(=O)OC(C)(C)C)CO)C=21)F DVHODDHMDZZNKH-UHFFFAOYSA-N 0.000 description 1
- AANWTJBZKBDMHM-UHFFFAOYSA-N BrC1=CC(=CC=2NC=3N(N=CC=3C3(CCSCC3)C)C=21)F Chemical compound BrC1=CC(=CC=2NC=3N(N=CC=3C3(CCSCC3)C)C=21)F AANWTJBZKBDMHM-UHFFFAOYSA-N 0.000 description 1
- DSWBYAIDIYZCHH-UHFFFAOYSA-N BrC1=CC(=CC=2NC=3N(N=CC=3C3CCN(CC3)C(=O)OC(C)(C)C)C=21)F Chemical compound BrC1=CC(=CC=2NC=3N(N=CC=3C3CCN(CC3)C(=O)OC(C)(C)C)C=21)F DSWBYAIDIYZCHH-UHFFFAOYSA-N 0.000 description 1
- 101150008921 Brca2 gene Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- AZWMODHPERDSGD-UHFFFAOYSA-N C(#N)C(C(=O)NNC1=C(C=C(C=C1Br)F)Br)C1(CCN(CC1)C(=O)OC(C)(C)C)C Chemical compound C(#N)C(C(=O)NNC1=C(C=C(C=C1Br)F)Br)C1(CCN(CC1)C(=O)OC(C)(C)C)C AZWMODHPERDSGD-UHFFFAOYSA-N 0.000 description 1
- UAONGNNCILHFPC-UHFFFAOYSA-N C(#N)C(C(C)=O)C1(CCN(CC1)C(=O)OC(C)(C)C)C Chemical compound C(#N)C(C(C)=O)C1(CCN(CC1)C(=O)OC(C)(C)C)C UAONGNNCILHFPC-UHFFFAOYSA-N 0.000 description 1
- MBPVXAOMKXOUKB-UHFFFAOYSA-N C(#N)C(C=NNC1=C(C=C(C=C1Br)F)Br)C1CCN(CC1)C(=O)OC(C)(C)C Chemical compound C(#N)C(C=NNC1=C(C=C(C=C1Br)F)Br)C1CCN(CC1)C(=O)OC(C)(C)C MBPVXAOMKXOUKB-UHFFFAOYSA-N 0.000 description 1
- FCKGVOUBWQMIBD-UHFFFAOYSA-N C(#N)C(C=O)C1(CCN(CC1)C(=O)OC(C)(C)C)C Chemical compound C(#N)C(C=O)C1(CCN(CC1)C(=O)OC(C)(C)C)C FCKGVOUBWQMIBD-UHFFFAOYSA-N 0.000 description 1
- WWGWKOTVWXOYMU-UHFFFAOYSA-N C(#N)C1(CC1)CN1CC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(#N)C1(CC1)CN1CC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F WWGWKOTVWXOYMU-UHFFFAOYSA-N 0.000 description 1
- IBYSFHPBQSZCCL-UHFFFAOYSA-N C(#N)C1(CC1)CN1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(#N)C1(CC1)CN1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F IBYSFHPBQSZCCL-UHFFFAOYSA-N 0.000 description 1
- MRPNCUBKQAQYJK-UHFFFAOYSA-N C(#N)C1(CCC1)CN1CC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(#N)C1(CCC1)CN1CC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F MRPNCUBKQAQYJK-UHFFFAOYSA-N 0.000 description 1
- DYSNVPMCJXETSZ-UHFFFAOYSA-N C(#N)C1(CCC1)CN1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(#N)C1(CCC1)CN1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F DYSNVPMCJXETSZ-UHFFFAOYSA-N 0.000 description 1
- CXRJOIAXOUTPHW-UHFFFAOYSA-N C(#N)C1(CCN(CC1)C(=O)OC(C)(C)C)CC#N Chemical compound C(#N)C1(CCN(CC1)C(=O)OC(C)(C)C)CC#N CXRJOIAXOUTPHW-UHFFFAOYSA-N 0.000 description 1
- KDIVUVMUPAOTME-UHFFFAOYSA-N C(#N)C1(CCNCC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(#N)C1(CCNCC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F KDIVUVMUPAOTME-UHFFFAOYSA-N 0.000 description 1
- XNFKNFZALCXNBT-UHFFFAOYSA-N C(#N)C1=CC(=CC=2N(C=3N(N=CC=3C(=O)N3CCN(CC3)C(=O)OC(C)(C)C)C=21)COCC[Si](C)(C)C)F Chemical compound C(#N)C1=CC(=CC=2N(C=3N(N=CC=3C(=O)N3CCN(CC3)C(=O)OC(C)(C)C)C=21)COCC[Si](C)(C)C)F XNFKNFZALCXNBT-UHFFFAOYSA-N 0.000 description 1
- BGAGLDHDKUJNGM-UHFFFAOYSA-N C(#N)C1=CC(=CC=2NC=3N(N=C(C=3C3(CCN(CC3)C(=O)OC(C)(C)C)C)C)C=21)F Chemical compound C(#N)C1=CC(=CC=2NC=3N(N=C(C=3C3(CCN(CC3)C(=O)OC(C)(C)C)C)C)C=21)F BGAGLDHDKUJNGM-UHFFFAOYSA-N 0.000 description 1
- PBVVXWSQSXNHFN-UHFFFAOYSA-N C(#N)C1=CC(=CC=2NC=3N(N=C(C=3C3(CCN(CC3)C(=O)OC(C)(C)C)C)OC)C=21)F Chemical compound C(#N)C1=CC(=CC=2NC=3N(N=C(C=3C3(CCN(CC3)C(=O)OC(C)(C)C)C)OC)C=21)F PBVVXWSQSXNHFN-UHFFFAOYSA-N 0.000 description 1
- XYKGGJCCEJIWCR-UHFFFAOYSA-N C(#N)C1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)C(=O)OC(C)(C)C)C)C=21)F Chemical compound C(#N)C1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)C(=O)OC(C)(C)C)C)C=21)F XYKGGJCCEJIWCR-UHFFFAOYSA-N 0.000 description 1
- DKXJBTBCCMKNSR-UHFFFAOYSA-N C(#N)C1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)C(=O)OC(C)(C)C)CO)C=21)F Chemical compound C(#N)C1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)C(=O)OC(C)(C)C)CO)C=21)F DKXJBTBCCMKNSR-UHFFFAOYSA-N 0.000 description 1
- SFIODHRGCOELET-UHFFFAOYSA-N C(#N)CCN1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(#N)CCN1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F SFIODHRGCOELET-UHFFFAOYSA-N 0.000 description 1
- LEMDWDSFJMVUQA-UHFFFAOYSA-N C(C)(C)(C)OC(N(C)CC1=CC(=C(C=C1)B1OC(C(O1)(C)C)(C)C)F)=O Chemical compound C(C)(C)(C)OC(N(C)CC1=CC(=C(C=C1)B1OC(C(O1)(C)C)(C)C)F)=O LEMDWDSFJMVUQA-UHFFFAOYSA-N 0.000 description 1
- MMODRSWQQZEHQG-UHFFFAOYSA-N C(C)N1C(CC(CC1)(C)C1=C2N(N=C1C)C1=C(N2)C=C(C=C1C(=O)N)F)C Chemical compound C(C)N1C(CC(CC1)(C)C1=C2N(N=C1C)C1=C(N2)C=C(C=C1C(=O)N)F)C MMODRSWQQZEHQG-UHFFFAOYSA-N 0.000 description 1
- HTCZKIKMCWMUFP-UHFFFAOYSA-N C(C)N1C(CCC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1C(CCC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F HTCZKIKMCWMUFP-UHFFFAOYSA-N 0.000 description 1
- RJIXLEQEDRMAAH-UHFFFAOYSA-N C(C)N1CC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F RJIXLEQEDRMAAH-UHFFFAOYSA-N 0.000 description 1
- XIJKHEVWVPPDKV-UHFFFAOYSA-N C(C)N1CC(CC1)(C)C1=C2N(N=C1C)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CC(CC1)(C)C1=C2N(N=C1C)C1=C(N2)C=C(C=C1C(=O)N)F XIJKHEVWVPPDKV-UHFFFAOYSA-N 0.000 description 1
- QXPXSLDVFGZHCP-UHFFFAOYSA-N C(C)N1CC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F QXPXSLDVFGZHCP-UHFFFAOYSA-N 0.000 description 1
- LNFDOSNZQOXGKQ-UHFFFAOYSA-N C(C)N1CC(CCC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CC(CCC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F LNFDOSNZQOXGKQ-UHFFFAOYSA-N 0.000 description 1
- FYBQVZIZPBVPSJ-UHFFFAOYSA-N C(C)N1CC2(CC2C1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CC2(CC2C1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F FYBQVZIZPBVPSJ-UHFFFAOYSA-N 0.000 description 1
- AAIBVPSWZRMTMN-UHFFFAOYSA-N C(C)N1CC2C(C2C1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CC2C(C2C1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F AAIBVPSWZRMTMN-UHFFFAOYSA-N 0.000 description 1
- QIJCSIVKSXICPP-UHFFFAOYSA-N C(C)N1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F QIJCSIVKSXICPP-UHFFFAOYSA-N 0.000 description 1
- JMYDZRAEDACWNW-UHFFFAOYSA-N C(C)N1CCC(CC1)(C)C1=C2N(N=C1C)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CCC(CC1)(C)C1=C2N(N=C1C)C1=C(N2)C=C(C=C1C(=O)N)F JMYDZRAEDACWNW-UHFFFAOYSA-N 0.000 description 1
- ZAOUQUQFTPFWSO-UHFFFAOYSA-N C(C)N1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F ZAOUQUQFTPFWSO-UHFFFAOYSA-N 0.000 description 1
- NETMLKKSMZDURS-UHFFFAOYSA-N C(C)N1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=CC=C1C(=O)N Chemical compound C(C)N1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=CC=C1C(=O)N NETMLKKSMZDURS-UHFFFAOYSA-N 0.000 description 1
- MZDKWNRRBQVIJH-UHFFFAOYSA-N C(C)N1CCC(CC1)C=1C=C2N(N=1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CCC(CC1)C=1C=C2N(N=1)C1=C(N2)C=C(C=C1C(=O)N)F MZDKWNRRBQVIJH-UHFFFAOYSA-N 0.000 description 1
- OKTHNTHYFGPXNN-UHFFFAOYSA-N C(C)N1CCC(CC1)CN1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CCC(CC1)CN1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F OKTHNTHYFGPXNN-UHFFFAOYSA-N 0.000 description 1
- RXAYWAHWZYKWQY-UHFFFAOYSA-N C(C)N1CCC(CC1)N1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CCC(CC1)N1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F RXAYWAHWZYKWQY-UHFFFAOYSA-N 0.000 description 1
- IPIJSNGEQYYBCV-UHFFFAOYSA-N C(C1=CC=CC=C1)N1C2=C(N3N=CC(=C31)C1CCN(CC1)C(=O)OC(C)(C)C)C(=CC(=C2)F)C(N)=O Chemical compound C(C1=CC=CC=C1)N1C2=C(N3N=CC(=C31)C1CCN(CC1)C(=O)OC(C)(C)C)C(=CC(=C2)F)C(N)=O IPIJSNGEQYYBCV-UHFFFAOYSA-N 0.000 description 1
- FAVKSQVMARUFMV-UHFFFAOYSA-N C(C1=CC=CC=C1)N1C2=C(N3N=CC(=C31)C1CCN(CC1)CC(C)(C)F)C(=CC(=C2)F)C(=O)N Chemical compound C(C1=CC=CC=C1)N1C2=C(N3N=CC(=C31)C1CCN(CC1)CC(C)(C)F)C(=CC(=C2)F)C(=O)N FAVKSQVMARUFMV-UHFFFAOYSA-N 0.000 description 1
- APIXNDSALFYMTH-UHFFFAOYSA-N C(C1=CC=CC=C1)N1C2=C(N3N=CC(=C31)C1CCN(CC1)CC(C)(C)O)C(=CC(=C2)F)C(=O)N Chemical compound C(C1=CC=CC=C1)N1C2=C(N3N=CC(=C31)C1CCN(CC1)CC(C)(C)O)C(=CC(=C2)F)C(=O)N APIXNDSALFYMTH-UHFFFAOYSA-N 0.000 description 1
- KHDPPMACKSAZLZ-UHFFFAOYSA-N C(C1=CC=CC=C1)N1C2=C(N3N=CC(=C31)C1CCNCC1)C(=CC(=C2)F)C(=O)N Chemical compound C(C1=CC=CC=C1)N1C2=C(N3N=CC(=C31)C1CCNCC1)C(=CC(=C2)F)C(=O)N KHDPPMACKSAZLZ-UHFFFAOYSA-N 0.000 description 1
- GOMCMRUWXASSKV-UHFFFAOYSA-N C(C1=CC=CC=C1)OC1=NN(C(=C1C1(CCNCC1)C)N)C1=C(C=C(C=C1Br)F)Br Chemical compound C(C1=CC=CC=C1)OC1=NN(C(=C1C1(CCNCC1)C)N)C1=C(C=C(C=C1Br)F)Br GOMCMRUWXASSKV-UHFFFAOYSA-N 0.000 description 1
- WDRQDBJZHMEAPQ-UHFFFAOYSA-N C(N)(=O)C1=CC(=CC=2N(C=3N(N=CC=3C(=O)N3CCN(CC3)C(=O)OC(C)(C)C)C=21)COCC[Si](C)(C)C)F Chemical compound C(N)(=O)C1=CC(=CC=2N(C=3N(N=CC=3C(=O)N3CCN(CC3)C(=O)OC(C)(C)C)C=21)COCC[Si](C)(C)C)F WDRQDBJZHMEAPQ-UHFFFAOYSA-N 0.000 description 1
- WTYMASCVVZDINH-UHFFFAOYSA-N C(N)(=O)C1=CC(=CC=2N(C=3N(N=CC=3C3CCN(CC3)C(=O)OC(C)(C)C)C=21)C)F Chemical compound C(N)(=O)C1=CC(=CC=2N(C=3N(N=CC=3C3CCN(CC3)C(=O)OC(C)(C)C)C=21)C)F WTYMASCVVZDINH-UHFFFAOYSA-N 0.000 description 1
- WTVQUFGRAFCAIJ-UHFFFAOYSA-N C(N)(=O)C1=CC(=CC=2NC=3N(N=C(C=3)C3CCN(CC3)C(=O)OC(C)(C)C)C=21)F Chemical compound C(N)(=O)C1=CC(=CC=2NC=3N(N=C(C=3)C3CCN(CC3)C(=O)OC(C)(C)C)C=21)F WTVQUFGRAFCAIJ-UHFFFAOYSA-N 0.000 description 1
- QXXTVTFTVVORLD-UHFFFAOYSA-N C(N)(=O)C1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)C(=O)OC(C)(C)C)C)C=21)F Chemical compound C(N)(=O)C1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)C(=O)OC(C)(C)C)C)C=21)F QXXTVTFTVVORLD-UHFFFAOYSA-N 0.000 description 1
- RILQXFYXIONPOA-UHFFFAOYSA-N C(N)(=O)C1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)CC3C(C3)C(=O)OCC)C)C=21)F Chemical compound C(N)(=O)C1=CC(=CC=2NC=3N(N=CC=3C3(CCN(CC3)CC3C(C3)C(=O)OCC)C)C=21)F RILQXFYXIONPOA-UHFFFAOYSA-N 0.000 description 1
- GPJXSWDKCHCBNC-UHFFFAOYSA-N C(N)(=O)C1=CC(=CC=2NC=3N(N=CC=3C3CCN(CC3)C(=O)OC(C)(C)C)C=21)F Chemical compound C(N)(=O)C1=CC(=CC=2NC=3N(N=CC=3C3CCN(CC3)C(=O)OC(C)(C)C)C=21)F GPJXSWDKCHCBNC-UHFFFAOYSA-N 0.000 description 1
- JESSAIHVOLAWGN-UHFFFAOYSA-N C1(CC1)C(=O)N1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F JESSAIHVOLAWGN-UHFFFAOYSA-N 0.000 description 1
- NWBDARPJZPJEBC-UHFFFAOYSA-N C1(CC1)CN1CC(CC1)(C)C1=C2N(N=C1C)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C1(CC1)CN1CC(CC1)(C)C1=C2N(N=C1C)C1=C(N2)C=C(C=C1C(=O)N)F NWBDARPJZPJEBC-UHFFFAOYSA-N 0.000 description 1
- UJXPUOSNGOJFGI-UHFFFAOYSA-N C1(CC1)CN1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C1(CC1)CN1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F UJXPUOSNGOJFGI-UHFFFAOYSA-N 0.000 description 1
- ULBRRCANLFATTG-UHFFFAOYSA-N C1(CC1)N1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C1(CC1)N1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F ULBRRCANLFATTG-UHFFFAOYSA-N 0.000 description 1
- SYWPJGWIIQPORA-UHFFFAOYSA-N C1(CC1)N1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C1(CC1)N1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F SYWPJGWIIQPORA-UHFFFAOYSA-N 0.000 description 1
- KISWSHALCLGQQD-UHFFFAOYSA-N C1(CCC1)N1CC2(CC2C1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C1(CCC1)N1CC2(CC2C1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F KISWSHALCLGQQD-UHFFFAOYSA-N 0.000 description 1
- OPYJYBHKOUCYGW-UHFFFAOYSA-N C12(CNCC2C1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C12(CNCC2C1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F OPYJYBHKOUCYGW-UHFFFAOYSA-N 0.000 description 1
- NBLAJPKHKNAMIV-UHFFFAOYSA-N CC(C)(C)OC(=O)N1CCC(=CC1)C1=C2N(N=C1)C1=C(C=C(F)C=C1C2(F)F)C(N)=O Chemical compound CC(C)(C)OC(=O)N1CCC(=CC1)C1=C2N(N=C1)C1=C(C=C(F)C=C1C2(F)F)C(N)=O NBLAJPKHKNAMIV-UHFFFAOYSA-N 0.000 description 1
- AQDQFCWXQBCVFO-UHFFFAOYSA-N CC(C)(C)OC(=O)N1CCC(=CC1)C1=C2N(N=C1)C1=C(C=C(F)C=C1C2=O)C(N)=O Chemical compound CC(C)(C)OC(=O)N1CCC(=CC1)C1=C2N(N=C1)C1=C(C=C(F)C=C1C2=O)C(N)=O AQDQFCWXQBCVFO-UHFFFAOYSA-N 0.000 description 1
- NPMUPKBXCPNZRZ-UHFFFAOYSA-N CC(C)(C)OC(=O)N1CCC(CC1)C1=C2C(O)C3=CC(F)=CC(C(N)=O)=C3N2N=C1 Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)C1=C2C(O)C3=CC(F)=CC(C(N)=O)=C3N2N=C1 NPMUPKBXCPNZRZ-UHFFFAOYSA-N 0.000 description 1
- COBKYKDJHIIYLW-UHFFFAOYSA-N CC(C)(C)OC(=O)N1CCC(CC1)C1=C2N(N=C1)C1=C(C=C(F)C=C1C2(F)F)C(N)=O Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)C1=C2N(N=C1)C1=C(C=C(F)C=C1C2(F)F)C(N)=O COBKYKDJHIIYLW-UHFFFAOYSA-N 0.000 description 1
- POPQXTGADMPRIM-UHFFFAOYSA-N CN(C)CC1C(C1)CN1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound CN(C)CC1C(C1)CN1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F POPQXTGADMPRIM-UHFFFAOYSA-N 0.000 description 1
- KFUIHIBIRILOBM-UHFFFAOYSA-N CN(CCN1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F)C Chemical compound CN(CCN1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F)C KFUIHIBIRILOBM-UHFFFAOYSA-N 0.000 description 1
- PRWRQZFPPHHJRL-UHFFFAOYSA-N CN1C(=NC=C1CN1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F)C Chemical compound CN1C(=NC=C1CN1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F)C PRWRQZFPPHHJRL-UHFFFAOYSA-N 0.000 description 1
- RXFKNSAWUSNQRF-UHFFFAOYSA-N CN1CC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound CN1CC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F RXFKNSAWUSNQRF-UHFFFAOYSA-N 0.000 description 1
- CVLRIRNJCVMRSG-UHFFFAOYSA-N CN1CCC(CC1)(C)C1=C2N(N=C1C)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound CN1CCC(CC1)(C)C1=C2N(N=C1C)C1=C(N2)C=C(C=C1C(=O)N)F CVLRIRNJCVMRSG-UHFFFAOYSA-N 0.000 description 1
- IMDZTPGDODDKBE-UHFFFAOYSA-N COC(=O)C1=C2N3N=CC(Br)=C3C3(SCCS3)C2=CC(F)=C1 Chemical compound COC(=O)C1=C2N3N=CC(Br)=C3C3(SCCS3)C2=CC(F)=C1 IMDZTPGDODDKBE-UHFFFAOYSA-N 0.000 description 1
- AEJDGZFSTGREBK-UHFFFAOYSA-N COC(=O)C1=C2N3N=CC=C3C(=O)C2=CC(F)=C1 Chemical compound COC(=O)C1=C2N3N=CC=C3C(=O)C2=CC(F)=C1 AEJDGZFSTGREBK-UHFFFAOYSA-N 0.000 description 1
- PKTFPWGPOBPLJT-UHFFFAOYSA-N COC(=O)C1=C2N3N=CC=C3C3(SCCS3)C2=CC(F)=C1 Chemical compound COC(=O)C1=C2N3N=CC=C3C3(SCCS3)C2=CC(F)=C1 PKTFPWGPOBPLJT-UHFFFAOYSA-N 0.000 description 1
- QJVUSBHZEUCBJM-UHFFFAOYSA-N COC(=O)C1=CC(F)=CC2=C1N1N=CC(Br)=C1C2(F)F Chemical compound COC(=O)C1=CC(F)=CC2=C1N1N=CC(Br)=C1C2(F)F QJVUSBHZEUCBJM-UHFFFAOYSA-N 0.000 description 1
- NLQLYAFJFPDGAF-UHFFFAOYSA-N COC(=O)C1=CC(F)=CC2=C1N1N=CC(Br)=C1C2=O Chemical compound COC(=O)C1=CC(F)=CC2=C1N1N=CC(Br)=C1C2=O NLQLYAFJFPDGAF-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- JAKZGUXITYHQED-UHFFFAOYSA-N ClCC12CN(CC2C1)C(=O)OC(C)(C)C Chemical compound ClCC12CN(CC2C1)C(=O)OC(C)(C)C JAKZGUXITYHQED-UHFFFAOYSA-N 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
- YPZMPEPLWKRVLD-PJEQPVAWSA-N D-Glycero-D-gulo-Heptose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C=O YPZMPEPLWKRVLD-PJEQPVAWSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 102000008158 DNA Ligase ATP Human genes 0.000 description 1
- 108010060248 DNA Ligase ATP Proteins 0.000 description 1
- 102000001996 DNA Polymerase beta Human genes 0.000 description 1
- 108010001132 DNA Polymerase beta Proteins 0.000 description 1
- 239000012624 DNA alkylating agent Substances 0.000 description 1
- 230000008265 DNA repair mechanism Effects 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 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
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- XXRCUYVCPSWGCC-UHFFFAOYSA-N Ethyl pyruvate Chemical compound CCOC(=O)C(C)=O XXRCUYVCPSWGCC-UHFFFAOYSA-N 0.000 description 1
- ZWAWFPGLEPZERJ-UHFFFAOYSA-N FC1(C(C1)CN1CC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F)F Chemical compound FC1(C(C1)CN1CC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F)F ZWAWFPGLEPZERJ-UHFFFAOYSA-N 0.000 description 1
- MRUDQBCNBQUVPD-UHFFFAOYSA-N FC1=CC(Br)=C2N3N=CC=C3C(=O)C2=C1 Chemical compound FC1=CC(Br)=C2N3N=CC=C3C(=O)C2=C1 MRUDQBCNBQUVPD-UHFFFAOYSA-N 0.000 description 1
- HVRROQGMCKYUQQ-UHFFFAOYSA-N FC=1C=C(C2=C(N(C=3N2N=CC=3)COCC[Si](C)(C)C)C=1)C(=O)OC Chemical compound FC=1C=C(C2=C(N(C=3N2N=CC=3)COCC[Si](C)(C)C)C=1)C(=O)OC HVRROQGMCKYUQQ-UHFFFAOYSA-N 0.000 description 1
- GIIPHLQVMLRTKW-UHFFFAOYSA-N FC=1C=C(C2=C(N(C=3N2N=CC=3C2=CC=C(C=C2)F)COCC[Si](C)(C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(N(C=3N2N=CC=3C2=CC=C(C=C2)F)COCC[Si](C)(C)C)C=1)C(=O)N GIIPHLQVMLRTKW-UHFFFAOYSA-N 0.000 description 1
- OORULQANFKFDQA-UHFFFAOYSA-N FC=1C=C(C2=C(N(C=3N2N=CC=3C2CCNCC2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(N(C=3N2N=CC=3C2CCNCC2)C)C=1)C(=O)N OORULQANFKFDQA-UHFFFAOYSA-N 0.000 description 1
- FTDQWOQNIHGUGT-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=C(C=3C2(CCN(CC2)C(C)C)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=C(C=3C2(CCN(CC2)C(C)C)C)C)C=1)C(=O)N FTDQWOQNIHGUGT-UHFFFAOYSA-N 0.000 description 1
- SBWBVEBNJBOOKS-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=C(C=3C2(CCN(CC2)CC(C)(C)O)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=C(C=3C2(CCN(CC2)CC(C)(C)O)C)C)C=1)C(=O)N SBWBVEBNJBOOKS-UHFFFAOYSA-N 0.000 description 1
- GLXFXQCGWRQLJC-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=C(C=3C2(CCN(CC2)CC(C)C)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=C(C=3C2(CCN(CC2)CC(C)C)C)C)C=1)C(=O)N GLXFXQCGWRQLJC-UHFFFAOYSA-N 0.000 description 1
- BCGDFKIJCNZYJZ-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=C(C=3C2(CCNCC2)C)OC)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=C(C=3C2(CCNCC2)C)OC)C=1)C(=O)N BCGDFKIJCNZYJZ-UHFFFAOYSA-N 0.000 description 1
- LEQYNFWNANKJLS-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=C(C=3C2(CN(CC2)C(C)C)C)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=C(C=3C2(CN(CC2)C(C)C)C)C)C=1)C(=O)N LEQYNFWNANKJLS-UHFFFAOYSA-N 0.000 description 1
- ITISQRYDKIQXMN-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C(=O)N2CCNCC2)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C(=O)N2CCNCC2)C=1)C(=O)N ITISQRYDKIQXMN-UHFFFAOYSA-N 0.000 description 1
- NRGUNFVOMCDGBV-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CCF)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCN(CC2)CCF)C)C=1)C(=O)N NRGUNFVOMCDGBV-UHFFFAOYSA-N 0.000 description 1
- JSKWIQOWIIRLJS-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCNCC2)CO)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCNCC2)CO)C=1)C(=O)N JSKWIQOWIIRLJS-UHFFFAOYSA-N 0.000 description 1
- AHNAMGZYQGIEKZ-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2=C(C=CC(=C2)CNC)F)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2=C(C=CC(=C2)CNC)F)C=1)C(=O)N AHNAMGZYQGIEKZ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 101001113440 Homo sapiens Poly [ADP-ribose] polymerase 2 Proteins 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-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
- 241001465754 Metazoa Species 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- VLPNATUWHZMARG-UHFFFAOYSA-N N1C2=CC=CC=C2N2C1=CC=N2 Chemical class N1C2=CC=CC=C2N2C1=CC=N2 VLPNATUWHZMARG-UHFFFAOYSA-N 0.000 description 1
- FJAWQHUTRAQOBP-UHFFFAOYSA-N NC(=O)C1=C2N3N=CC(C4CCN(CC5CC5)CC4)=C3C(F)(F)C2=CC(F)=C1 Chemical compound NC(=O)C1=C2N3N=CC(C4CCN(CC5CC5)CC4)=C3C(F)(F)C2=CC(F)=C1 FJAWQHUTRAQOBP-UHFFFAOYSA-N 0.000 description 1
- FSSGFBWWNXMCSR-UHFFFAOYSA-N NC(=O)C1=C2N3N=CC(C4CCNCC4)=C3C(F)(F)C2=CC(F)=C1 Chemical compound NC(=O)C1=C2N3N=CC(C4CCNCC4)=C3C(F)(F)C2=CC(F)=C1 FSSGFBWWNXMCSR-UHFFFAOYSA-N 0.000 description 1
- BFDQCKHYUKKFEY-UHFFFAOYSA-N NC(=O)C1=C2N3N=CC(C4CCNCC4)=C3C(O)C2=CC(F)=C1 Chemical compound NC(=O)C1=C2N3N=CC(C4CCNCC4)=C3C(O)C2=CC(F)=C1 BFDQCKHYUKKFEY-UHFFFAOYSA-N 0.000 description 1
- GRBYSMRWZGGMAN-UHFFFAOYSA-N NC1(CC1)CN1CC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound NC1(CC1)CN1CC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F GRBYSMRWZGGMAN-UHFFFAOYSA-N 0.000 description 1
- AYGSDRYSFIFNOJ-UHFFFAOYSA-N NC1(CC1)CN1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound NC1(CC1)CN1CCC(CC1)(C)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F AYGSDRYSFIFNOJ-UHFFFAOYSA-N 0.000 description 1
- FDDDHOHNQVGJOR-UHFFFAOYSA-N NC1=C(C(=NN1C1=C(C=C(C=C1Br)F)Br)C)C1(CCN(CC1)C(=O)OC(C)(C)C)C Chemical compound NC1=C(C(=NN1C1=C(C=C(C=C1Br)F)Br)C)C1(CCN(CC1)C(=O)OC(C)(C)C)C FDDDHOHNQVGJOR-UHFFFAOYSA-N 0.000 description 1
- JFOAVCGDQOZOAR-UHFFFAOYSA-N NC1=C(C(=NN1C1=C(C=C(C=C1Br)F)Br)O)C1(CCN(CC1)C(=O)OC(C)(C)C)C Chemical compound NC1=C(C(=NN1C1=C(C=C(C=C1Br)F)Br)O)C1(CCN(CC1)C(=O)OC(C)(C)C)C JFOAVCGDQOZOAR-UHFFFAOYSA-N 0.000 description 1
- QEVQJKNWLKQVCR-UHFFFAOYSA-N NC1=C(C(=NN1C1=C(C=C(C=C1Br)F)Br)OC)C1(CCN(CC1)C(=O)OC(C)(C)C)C Chemical compound NC1=C(C(=NN1C1=C(C=C(C=C1Br)F)Br)OC)C1(CCN(CC1)C(=O)OC(C)(C)C)C QEVQJKNWLKQVCR-UHFFFAOYSA-N 0.000 description 1
- WYFGPIGCNGEYRN-UHFFFAOYSA-N NC1=C(C(=NN1C1=C(C=C(C=C1Br)F)Br)OCC1=CC=CC=C1)C1(CCN(CC1)C(=O)OC(C)(C)C)C Chemical compound NC1=C(C(=NN1C1=C(C=C(C=C1Br)F)Br)OCC1=CC=CC=C1)C1(CCN(CC1)C(=O)OC(C)(C)C)C WYFGPIGCNGEYRN-UHFFFAOYSA-N 0.000 description 1
- JNHQVHIHHMBEJM-UHFFFAOYSA-N NC1=C(C=NN1C1=C(C=C(C=C1Br)F)Br)C#N Chemical compound NC1=C(C=NN1C1=C(C=C(C=C1Br)F)Br)C#N JNHQVHIHHMBEJM-UHFFFAOYSA-N 0.000 description 1
- XFJMWGABDHNXDY-UHFFFAOYSA-N NC1=C(C=NN1C1=C(C=C(C=C1Br)F)Br)C(=O)OCC Chemical compound NC1=C(C=NN1C1=C(C=C(C=C1Br)F)Br)C(=O)OCC XFJMWGABDHNXDY-UHFFFAOYSA-N 0.000 description 1
- LAWFEMLASVTYPL-UHFFFAOYSA-N NC1=C(C=NN1C1=C(C=C(C=C1Br)F)Br)C1(CCN(CC1)C(=O)OC(C)(C)C)C Chemical compound NC1=C(C=NN1C1=C(C=C(C=C1Br)F)Br)C1(CCN(CC1)C(=O)OC(C)(C)C)C LAWFEMLASVTYPL-UHFFFAOYSA-N 0.000 description 1
- CDVWWDPTHGNTRQ-UHFFFAOYSA-N NC1=C(C=NN1C1=C(C=C(C=C1Br)F)Br)C1(CCN(CC1)C(=O)OC(C)(C)C)C#N Chemical compound NC1=C(C=NN1C1=C(C=C(C=C1Br)F)Br)C1(CCN(CC1)C(=O)OC(C)(C)C)C#N CDVWWDPTHGNTRQ-UHFFFAOYSA-N 0.000 description 1
- OVSQNNFEGBDAOR-UHFFFAOYSA-N NC1=C(C=NN1C1=C(C=C(C=C1Br)F)Br)C1CCN(CC1)C(=O)OC(C)(C)C Chemical compound NC1=C(C=NN1C1=C(C=C(C=C1Br)F)Br)C1CCN(CC1)C(=O)OC(C)(C)C OVSQNNFEGBDAOR-UHFFFAOYSA-N 0.000 description 1
- LWAWGDARQUVNKR-UHFFFAOYSA-N NC1=CC(=NN1C1=C(C=C(C=C1Br)F)Br)C1CCN(CC1)C(=O)OC(C)(C)C Chemical compound NC1=CC(=NN1C1=C(C=C(C=C1Br)F)Br)C1CCN(CC1)C(=O)OC(C)(C)C LWAWGDARQUVNKR-UHFFFAOYSA-N 0.000 description 1
- 108700019961 Neoplasm Genes Proteins 0.000 description 1
- 102000048850 Neoplasm Genes Human genes 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 102000015087 Poly (ADP-Ribose) Polymerase-1 Human genes 0.000 description 1
- 102100023652 Poly [ADP-ribose] polymerase 2 Human genes 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 229910006124 SOCl2 Inorganic materials 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 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
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- BBAWTPDTGRXPDG-UHFFFAOYSA-N [1,3]thiazolo[4,5-b]pyridine Chemical compound C1=CC=C2SC=NC2=N1 BBAWTPDTGRXPDG-UHFFFAOYSA-N 0.000 description 1
- PNDPGZBMCMUPRI-XXSWNUTMSA-N [125I][125I] Chemical compound [125I][125I] PNDPGZBMCMUPRI-XXSWNUTMSA-N 0.000 description 1
- SEHNWAWVQGNEKM-UHFFFAOYSA-N [4-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexen-1-yl] trifluoromethanesulfonate Chemical compound CC(C)(C)OC(=O)NC1CCC(OS(=O)(=O)C(F)(F)F)=CC1 SEHNWAWVQGNEKM-UHFFFAOYSA-N 0.000 description 1
- CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical group [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 229940124650 anti-cancer therapies Drugs 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical group 0.000 description 1
- 125000005101 aryl methoxy carbonyl group Chemical group 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
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 description 1
- 230000033590 base-excision repair Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004935 benzoxazolinyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000000872 buffer 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
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000004623 carbolinyl group Chemical group 0.000 description 1
- OSQPUMRCKZAIOZ-UHFFFAOYSA-N carbon dioxide;ethanol Chemical compound CCO.O=C=O OSQPUMRCKZAIOZ-UHFFFAOYSA-N 0.000 description 1
- OEERIBPGRSLGEK-UHFFFAOYSA-N carbon dioxide;methanol Chemical compound OC.O=C=O OEERIBPGRSLGEK-UHFFFAOYSA-N 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- HWGQMRYQVZSGDQ-HZPDHXFCSA-N chembl3137320 Chemical compound CN1N=CN=C1[C@H]([C@H](N1)C=2C=CC(F)=CC=2)C2=NNC(=O)C3=C2C1=CC(F)=C3 HWGQMRYQVZSGDQ-HZPDHXFCSA-N 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229940112669 cuprous oxide Drugs 0.000 description 1
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-M cyclopropanecarboxylate Chemical compound [O-]C(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-M 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000005782 double-strand break Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- KTMGNAIGXYODKQ-VOTSOKGWSA-N ethyl (e)-2-cyano-3-ethoxyprop-2-enoate Chemical compound CCO\C=C(/C#N)C(=O)OCC KTMGNAIGXYODKQ-VOTSOKGWSA-N 0.000 description 1
- GTCBVGDJIQFBFF-AATRIKPKSA-N ethyl (e)-4-(dimethylamino)-2-oxobut-3-enoate Chemical compound CCOC(=O)C(=O)\C=C\N(C)C GTCBVGDJIQFBFF-AATRIKPKSA-N 0.000 description 1
- JXEUGJMMTIWQIF-UHFFFAOYSA-N ethyl 1-benzyl-2,5-dihydropyrrole-3-carboxylate Chemical compound C1C(C(=O)OCC)=CCN1CC1=CC=CC=C1 JXEUGJMMTIWQIF-UHFFFAOYSA-N 0.000 description 1
- MSPOSRHJXMILNK-UHFFFAOYSA-N ethyl 1h-pyrazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=NN1 MSPOSRHJXMILNK-UHFFFAOYSA-N 0.000 description 1
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
- SFFQYGDIFWFUAF-UHFFFAOYSA-N ethyl 3-benzyl-2,4-dioxo-3-azabicyclo[3.1.0]hexane-6-carboxylate Chemical compound CCOC(=O)C1C(C2=O)C1C(=O)N2CC1=CC=CC=C1 SFFQYGDIFWFUAF-UHFFFAOYSA-N 0.000 description 1
- UFLBURFPRRPJQT-UHFFFAOYSA-N ethyl 3-benzyl-3-azabicyclo[3.1.0]hexane-1-carboxylate Chemical compound C1C2(C(=O)OCC)CC2CN1CC1=CC=CC=C1 UFLBURFPRRPJQT-UHFFFAOYSA-N 0.000 description 1
- FMVJYQGSRWVMQV-UHFFFAOYSA-N ethyl propiolate Chemical compound CCOC(=O)C#C FMVJYQGSRWVMQV-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000001640 fractional crystallisation Methods 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
- 125000003838 furazanyl group Chemical group 0.000 description 1
- JVZRCNQLWOELDU-UHFFFAOYSA-N gamma-Phenylpyridine Natural products C1=CC=CC=C1C1=CC=NC=C1 JVZRCNQLWOELDU-UHFFFAOYSA-N 0.000 description 1
- 229910052732 germanium Inorganic materials 0.000 description 1
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 125000004474 heteroalkylene group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229940044173 iodine-125 Drugs 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- 238000012423 maintenance Methods 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical group CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
- ISGGVCWFTPTHIX-UHFFFAOYSA-N n'-(2-hydroxy-3-piperidin-1-ylpropoxy)pyridine-3-carboximidamide;dihydrochloride Chemical compound Cl.Cl.C1CCCCN1CC(O)CONC(=N)C1=CC=CN=C1 ISGGVCWFTPTHIX-UHFFFAOYSA-N 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- REPVNSJSTLRQEQ-UHFFFAOYSA-N n,n-dimethylacetamide;n,n-dimethylformamide Chemical compound CN(C)C=O.CN(C)C(C)=O REPVNSJSTLRQEQ-UHFFFAOYSA-N 0.000 description 1
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
- RPZAAFUKDPKTKP-UHFFFAOYSA-N n-(methoxymethyl)-1-phenyl-n-(trimethylsilylmethyl)methanamine Chemical compound COCN(C[Si](C)(C)C)CC1=CC=CC=C1 RPZAAFUKDPKTKP-UHFFFAOYSA-N 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- LAIZPRYFQUWUBN-UHFFFAOYSA-L nickel chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Ni+2] LAIZPRYFQUWUBN-UHFFFAOYSA-L 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- QNNHQVPFZIFNFK-UHFFFAOYSA-N oxazolo[4,5-b]pyridine Chemical compound C1=CC=C2OC=NC2=N1 QNNHQVPFZIFNFK-UHFFFAOYSA-N 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 125000004095 oxindolyl group Chemical group N1(C(CC2=CC=CC=C12)=O)* 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 229960004838 phosphoric acid Drugs 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 125000004928 piperidonyl group Chemical group 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000009666 routine test Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 150000003413 spiro compounds Chemical class 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000006253 t-butylcarbonyl group Chemical group [H]C([H])([H])C(C(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000001648 tannin Substances 0.000 description 1
- 235000018553 tannin Nutrition 0.000 description 1
- 229920001864 tannin Polymers 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- MBAADMFGYWKMMF-UHFFFAOYSA-N tert-butyl 1-(1-cyano-2-hydroxyethenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C(#N)C(=CO)C12CN(CC2C1)C(=O)OC(C)(C)C MBAADMFGYWKMMF-UHFFFAOYSA-N 0.000 description 1
- DOPRDXHHOYTKGU-UHFFFAOYSA-N tert-butyl 1-(cyanomethyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2CC21CC#N DOPRDXHHOYTKGU-UHFFFAOYSA-N 0.000 description 1
- BTWDGFQQIGGAPU-UHFFFAOYSA-N tert-butyl 1-(hydroxymethyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2CC21CO BTWDGFQQIGGAPU-UHFFFAOYSA-N 0.000 description 1
- GTYSZKBZNYJZOS-UHFFFAOYSA-N tert-butyl 1-[1-cyano-2-(dimethylamino)ethenyl]-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C(#N)C(=CN(C)C)C12CN(CC2C1)C(=O)OC(C)(C)C GTYSZKBZNYJZOS-UHFFFAOYSA-N 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- OMMHAHKCMUUEOY-UHFFFAOYSA-N tert-butyl 3-(hydroxymethyl)-3-methylpyrrolidine-1-carboxylate Chemical group CC(C)(C)OC(=O)N1CCC(C)(CO)C1 OMMHAHKCMUUEOY-UHFFFAOYSA-N 0.000 description 1
- WPHYDBXMMSEFTR-UHFFFAOYSA-N tert-butyl 3-(hydroxymethyl)-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1C(CO)CC2CCC1N2C(=O)OC(C)(C)C WPHYDBXMMSEFTR-UHFFFAOYSA-N 0.000 description 1
- OJCLHERKFHHUTB-UHFFFAOYSA-N tert-butyl 3-(hydroxymethyl)piperidine-1-carboxylate Chemical group CC(C)(C)OC(=O)N1CCCC(CO)C1 OJCLHERKFHHUTB-UHFFFAOYSA-N 0.000 description 1
- NLUNJBHKDGTAAA-UHFFFAOYSA-N tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC1C1=CC=C(B2OC(C)(C)C(C)(C)O2)C=C1 NLUNJBHKDGTAAA-UHFFFAOYSA-N 0.000 description 1
- UVURMTGIVKSLEM-UHFFFAOYSA-N tert-butyl 3-cyano-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1C(C#N)CC2CCC1N2C(=O)OC(C)(C)C UVURMTGIVKSLEM-UHFFFAOYSA-N 0.000 description 1
- MENILFUADYEXNU-UHFFFAOYSA-N tert-butyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1C(=O)CC2CCC1N2C(=O)OC(C)(C)C MENILFUADYEXNU-UHFFFAOYSA-N 0.000 description 1
- QBQXRKGENOPPKW-UHFFFAOYSA-N tert-butyl 4-(1-cyano-2-ethoxy-2-oxoethyl)-4-ethylpiperidine-1-carboxylate Chemical compound CCOC(=O)C(C#N)C1(CC)CCN(C(=O)OC(C)(C)C)CC1 QBQXRKGENOPPKW-UHFFFAOYSA-N 0.000 description 1
- LVNPCKNJAKRMKN-UHFFFAOYSA-N tert-butyl 4-(1-cyano-2-ethoxy-2-oxoethyl)-4-methylpiperidine-1-carboxylate Chemical compound CCOC(=O)C(C#N)C1(C)CCN(C(=O)OC(C)(C)C)CC1 LVNPCKNJAKRMKN-UHFFFAOYSA-N 0.000 description 1
- NBSHVKMXTRWGLJ-UHFFFAOYSA-N tert-butyl 4-(1-cyano-2-oxoethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C(C=O)C#N)CC1 NBSHVKMXTRWGLJ-UHFFFAOYSA-N 0.000 description 1
- VSLLBQBSHAGKLC-UHFFFAOYSA-N tert-butyl 4-(2-cyanoacetyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C(=O)CC#N)CC1 VSLLBQBSHAGKLC-UHFFFAOYSA-N 0.000 description 1
- VVDCRJGWILREQH-UHFFFAOYSA-N tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(B2OC(C)(C)C(C)(C)O2)=C1 VVDCRJGWILREQH-UHFFFAOYSA-N 0.000 description 1
- PRMYRRODTPOYIU-UHFFFAOYSA-N tert-butyl 4-(cyanomethyl)-4-methylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C)(CC#N)CC1 PRMYRRODTPOYIU-UHFFFAOYSA-N 0.000 description 1
- LARQASBBVGBMDA-UHFFFAOYSA-N tert-butyl 4-(cyanomethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC#N)CC1 LARQASBBVGBMDA-UHFFFAOYSA-N 0.000 description 1
- DARTVAOOTJKHQW-UHFFFAOYSA-N tert-butyl 4-[(4-methylphenyl)sulfonyloxymethyl]piperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1CCN(C(=O)OC(C)(C)C)CC1 DARTVAOOTJKHQW-UHFFFAOYSA-N 0.000 description 1
- WUJJEYHIEPKVKT-UHFFFAOYSA-N tert-butyl 4-[1-cyano-2-[(2,6-dibromo-4-fluorophenyl)hydrazinylidene]propyl]-4-methylpiperidine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1CCC(CC1)(C)C(C(C)=NNC1=C(C=C(C=C1Br)F)Br)C#N WUJJEYHIEPKVKT-UHFFFAOYSA-N 0.000 description 1
- BKQNVBOBIVKLOZ-UHFFFAOYSA-N tert-butyl 4-[C-(cyanomethyl)-N-(2,6-dibromo-4-fluoroanilino)carbonimidoyl]piperidine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1CCC(CC1)C(CC#N)=NNC1=C(C=C(C=C1Br)F)Br BKQNVBOBIVKLOZ-UHFFFAOYSA-N 0.000 description 1
- NFWFWDHQKIZYSJ-UHFFFAOYSA-N tert-butyl 4-[tert-butyl(diphenyl)silyl]oxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound C1C(CO)N(C(=O)OC(C)(C)C)CC1O[Si](C(C)(C)C)(C=1C=CC=CC=1)C1=CC=CC=C1 NFWFWDHQKIZYSJ-UHFFFAOYSA-N 0.000 description 1
- JVIDPFGQYMFQDZ-UHFFFAOYSA-N tert-butyl 6-(hydroxymethyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2C(CO)C21 JVIDPFGQYMFQDZ-UHFFFAOYSA-N 0.000 description 1
- XAQOLIIGQHXQAB-UHFFFAOYSA-N tert-butyl N-[(4-bromo-3-fluorophenyl)methyl]-N-methylcarbamate Chemical compound BrC1=C(C=C(CN(C(OC(C)(C)C)=O)C)C=C1)F XAQOLIIGQHXQAB-UHFFFAOYSA-N 0.000 description 1
- WYVFPGFWUKBXPZ-UHFFFAOYSA-N tert-butyl n-(4-oxocyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(=O)CC1 WYVFPGFWUKBXPZ-UHFFFAOYSA-N 0.000 description 1
- BQDDQHLYCAQNMX-UHFFFAOYSA-N tert-butyl n-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-en-1-yl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CCC(B2OC(C)(C)C(C)(C)O2)=C1 BQDDQHLYCAQNMX-UHFFFAOYSA-N 0.000 description 1
- JHLVEBNWCCKSGY-UHFFFAOYSA-N tert-butyl n-methylcarbamate Chemical compound CNC(=O)OC(C)(C)C JHLVEBNWCCKSGY-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 1
- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- OVRJVKCZJCNSOW-UHFFFAOYSA-N thian-4-one Chemical compound O=C1CCSCC1 OVRJVKCZJCNSOW-UHFFFAOYSA-N 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 150000003573 thiols Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- JNAHVYVRKWKWKQ-CYBMUJFWSA-N veliparib Chemical compound N=1C2=CC=CC(C(N)=O)=C2NC=1[C@@]1(C)CCCN1 JNAHVYVRKWKWKQ-CYBMUJFWSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
Claims (19)
Priority Applications (23)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410144173.0A CN104974161B (zh) | 2014-04-10 | 2014-04-10 | 作为PARP抑制剂的4H-吡唑并[1,5-α]苯并咪唑化合物的类似物 |
SG11201608438YA SG11201608438YA (en) | 2014-04-10 | 2015-03-30 | Analogs of 4h-pyrazolo[1,5-α]benzimidazole compounds as parp inhibitors |
CN201580017657.1A CN106459057B (zh) | 2014-04-10 | 2015-03-30 | 作为PARP抑制剂的4H-吡唑并[1,5-α]苯并咪唑化合物的类似物 |
BR112016023397-2A BR112016023397B1 (pt) | 2014-04-10 | 2015-03-30 | Composto da fórmula ou um sal farmaceuticamente aceitável |
HUE15777444A HUE047410T2 (hu) | 2014-04-10 | 2015-03-30 | 4H-Pirazolo[1,5-a]benzimidazol vegyület analógjai, mint PARP inhibitorok |
CA2944801A CA2944801C (en) | 2014-04-10 | 2015-03-30 | Analogs of 4h-pyrazolo[1,5-a]benzimidazole compounds as parp inhibitors |
PT157774449T PT3130592T (pt) | 2014-04-10 | 2015-03-30 | Análogos do composto 4h-pirazolo[1,5-]benzimidazole como inibidores de parp |
PL15777444T PL3130592T3 (pl) | 2014-04-10 | 2015-03-30 | Analogi związków 4h-pirazolo[1,5-α]benzimidazolowych jako inhibitory PARP |
EP15777444.9A EP3130592B1 (en) | 2014-04-10 | 2015-03-30 | Analogues of 4h-pyrazolo[1,5- ]benzimidazole compound as parp inhibitors |
US15/302,588 US9856262B2 (en) | 2014-04-10 | 2015-03-30 | Analogues of 4H-pyrazolo[1,5-a] benzimidazole compound as PARP inhibitors |
PCT/CN2015/075363 WO2015154630A1 (zh) | 2014-04-10 | 2015-03-30 | 作为PARP抑制剂的4H-吡唑并[1,5-α]苯并咪唑化合物的类似物 |
NZ725165A NZ725165A (en) | 2014-04-10 | 2015-03-30 | Analogues of 4h-pyrazolo[1,5-α]benzimidazole compound as parp inhibitors |
AU2015245786A AU2015245786B2 (en) | 2014-04-10 | 2015-03-30 | Analogues of 4H-pyrazolo[1,5-a]benzimidazole compound as PARP inhibitors |
DK15777444T DK3130592T3 (da) | 2014-04-10 | 2015-03-30 | ANALOGER AF 4H-PYRAZOLO[1,5-á]BENZIMIDAZOL-FORBINDELSER SOM PARPINHIBITORER |
JP2017504223A JP6359175B2 (ja) | 2014-04-10 | 2015-03-30 | PARP阻害剤としての4H‐ピラゾロ[1,5‐α]ベンゾイミダゾール化合物のアナログ |
KR1020167031520A KR101921486B1 (ko) | 2014-04-10 | 2015-03-30 | PARP억제제인 4H-피라졸로[1,5-a]벤즈이미다졸 화합물의 아날로그 |
MX2016013265A MX368496B (es) | 2014-04-10 | 2015-03-30 | Análogos de compuestos de 4h-pirazolo[1,5-a]bencimidazol como inhibidores parp. |
ES15777444T ES2754590T3 (es) | 2014-04-10 | 2015-03-30 | An¿¢logos de compuestos de 4h-pirazolo[1,5-¿A]bencimidazol como inhibidores de las PARP |
RU2016144202A RU2672722C2 (ru) | 2014-04-10 | 2015-03-30 | Аналоги соединений 4н-пиразоло[1,5-а]бензимидазола в качестве ингибиторов parp |
TW104111236A TWI671301B (zh) | 2014-04-10 | 2015-04-08 | 作為PARP抑制劑的4H-吡唑並[1,5-α]苯並咪唑化合物的類似物 |
IL248258A IL248258B (en) | 2014-04-10 | 2016-10-09 | Analogues of 4h-pyrazolo[5,1-a]benzimidazole compounds as PARP inhibitors |
SA516380051A SA516380051B1 (ar) | 2014-04-10 | 2016-10-10 | نظائر مركبات من 4h- بيرازولو [1، 5-a] بنزوميدازول مثل مثبطات parp (بولي ريبوز بوليمرات adp) |
ZA2016/07736A ZA201607736B (en) | 2014-04-10 | 2016-11-09 | Analogs of 4h-pyrazolo[1,5-a]benzimidazole compounds as parp inhibitors |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410144173.0A CN104974161B (zh) | 2014-04-10 | 2014-04-10 | 作为PARP抑制剂的4H-吡唑并[1,5-α]苯并咪唑化合物的类似物 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN104974161A CN104974161A (zh) | 2015-10-14 |
CN104974161B true CN104974161B (zh) | 2019-11-01 |
Family
ID=54271172
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201410144173.0A Active CN104974161B (zh) | 2014-04-10 | 2014-04-10 | 作为PARP抑制剂的4H-吡唑并[1,5-α]苯并咪唑化合物的类似物 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN104974161B (zh) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT3130592T (pt) | 2014-04-10 | 2019-11-21 | Hubei Bio Pharmaceutical Industrial Tech Institute Inc | Análogos do composto 4h-pirazolo[1,5-]benzimidazole como inibidores de parp |
KR102664193B1 (ko) * | 2015-09-30 | 2024-05-10 | 후베이 바이오-파마슈티컬 인더스트리얼 테크놀로지컬 인스티튜트 인크. | 4H-피라졸로[1,5-α]벤즈이미다졸계 화합물의 염형, 결정형 및 이의 제조방법과 중간체 |
CN105837579A (zh) * | 2016-05-30 | 2016-08-10 | 青岛科技大学 | 一种多取代苯并[4,5]咪唑并[1,2-b]吡唑衍生物的制备方法 |
CN106187865A (zh) * | 2016-07-08 | 2016-12-07 | 武汉工程大学 | (r)‑1‑叔丁氧羰基‑3‑苄基‑3‑甲酸哌啶的合成及手性拆分方法 |
CN107964012B (zh) * | 2016-10-19 | 2020-04-24 | 广州丹康医药生物有限公司 | 作为parp抑制剂的化合物及其用途 |
WO2018192445A1 (zh) * | 2017-04-17 | 2018-10-25 | 广州丹康医药生物有限公司 | 作为parp抑制活性的多环化合物及其用途 |
CN114072410B (zh) * | 2019-08-01 | 2023-08-01 | 正大天晴药业集团股份有限公司 | 作为parp抑制剂吲哚并七元酰肟化合物 |
CN116969954B (zh) * | 2023-09-21 | 2023-11-28 | 广东省农业科学院农业质量标准与监测技术研究所 | 一类含内酰胺的三环稠合杂环化合物及其应用 |
CN117534677B (zh) * | 2024-01-09 | 2024-03-12 | 广东省农业科学院农业质量标准与监测技术研究所 | 一类含亚胺的三环稠合杂环化合物及其应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101506214A (zh) * | 2006-06-20 | 2009-08-12 | 艾博特公司 | 作为parp抑制剂的吡唑并喹唑啉酮 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT3130592T (pt) * | 2014-04-10 | 2019-11-21 | Hubei Bio Pharmaceutical Industrial Tech Institute Inc | Análogos do composto 4h-pirazolo[1,5-]benzimidazole como inibidores de parp |
-
2014
- 2014-04-10 CN CN201410144173.0A patent/CN104974161B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101506214A (zh) * | 2006-06-20 | 2009-08-12 | 艾博特公司 | 作为parp抑制剂的吡唑并喹唑啉酮 |
Non-Patent Citations (2)
Title |
---|
Design and Synthesis of New Templates Derived from Pyrrolopyrimidine as Selective Multidrug-Resistance-Associated Protein Inhibitors in Multidrug Resistance;Shouming Wang, et al.;《J. Med. Chem.》;20040207;第47卷(第6期);第1339-1350页 * |
Synthesis and Evaluation of a New Generation of Orally Efficacious Benzimidazole-Based Poly(ADP-ribose) Polymerase-1 (PARP-1) Inhibitors as Anticancer Agents;Yunsong Tong, et al.;《Journal of Medicinal Chemistry》;20091021;第52卷(第21期);第6803-6813页 * |
Also Published As
Publication number | Publication date |
---|---|
CN104974161A (zh) | 2015-10-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN104974161B (zh) | 作为PARP抑制剂的4H-吡唑并[1,5-α]苯并咪唑化合物的类似物 | |
CN106459057B (zh) | 作为PARP抑制剂的4H-吡唑并[1,5-α]苯并咪唑化合物的类似物 | |
EP2124951B1 (en) | 5-cyan0-4- (pyrrolo[2, 3b]pyridine-3-yl) -pyrimidine derivatives useful as protein kinase inhibitors | |
EP2678338B1 (en) | Pyrazolo[1,5-a]pyridines as trk inhibitors | |
JP2022024019A (ja) | Rock阻害剤としてのスピロヘプタンサリチルアミドおよび関連性化合物 | |
TWI676622B (zh) | 作為rho激酶抑制劑的異喹啉磺醯衍生物 | |
CN110869363A (zh) | 作为rock抑制剂的5元和二环杂环酰胺 | |
WO2012034095A1 (en) | Compounds and compositions as trk inhibitors | |
EP2614062A1 (en) | Imidazo [1, 2]pyridazin compounds and compositions as trk inhibitors | |
CN102089307A (zh) | 作为激酶抑制剂的吡咯并吡啶 | |
JP2018514551A (ja) | Jak阻害剤 | |
CN111471059A (zh) | Pde9抑制剂及其用途 | |
KR20160086930A (ko) | 피롤로피롤론 유도체 및 bet 억제제로서의 그의 용도 | |
CN116354957A (zh) | Cdk9抑制剂及其用途 | |
JP2019518052A (ja) | Akt阻害剤としてのジヒドロピラゾロアゼピン系化合物 | |
TW202214634A (zh) | 雜環化合物及其衍生物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C41 | Transfer of patent application or patent right or utility model | ||
CB03 | Change of inventor or designer information |
Inventor after: Wang Xuehai Inventor after: Zhang Zhibo Inventor after: Chen Haijing Inventor after: Sun Wenjie Inventor after: Huang Lu Inventor after: Ding Zhaozhong Inventor after: Xu Yong Inventor after: Chen Shuhui Inventor after: Li Lie Inventor after: Li Gang Inventor after: Tu Ronghua Inventor after: Wang Cailin Inventor after: Le Yang Inventor before: Ding Zhaozhong Inventor before: Chen Shuhui Inventor before: Li Gang Inventor before: Wang Cailin Inventor before: Zhang Zhibo |
|
COR | Change of bibliographic data | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20151210 Address after: 430075 East Lake high tech Development Zone, Hubei Province, high and new avenue, No. 666, No. Applicant after: Hubei company limited of Bio-pharmaceutical Industry Institute for Research and Technology Applicant after: Ren Fu Pharmaceutical Group stock company Applicant after: NANJING MINGDE NEW DRUG RESEARCH AND DEVELOPMENT CO., LTD. Address before: 210032 Jiangsu city of Nanjing province Nanjing high tech Development Zone of High Road No. 9 business office building room 218 Applicant before: NANJING MINGDE NEW DRUG RESEARCH AND DEVELOPMENT CO., LTD. |
|
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20190201 Address after: 430075 No. 666 High-tech Avenue, Donghu High-tech Development Zone, Wuhan City, Hubei Province Applicant after: Hubei company limited of Bio-pharmaceutical Industry Institute for Research and Technology Applicant after: Humanwell Pharmaceutical Group Limited by Share Ltd Address before: 430075 No. 666 High-tech Avenue, Donghu High-tech Development Zone, Wuhan City, Hubei Province Applicant before: Hubei company limited of Bio-pharmaceutical Industry Institute for Research and Technology Applicant before: Ren Fu Pharmaceutical Group stock company Applicant before: NANJING MINGDE NEW DRUG RESEARCH AND DEVELOPMENT CO., LTD. |
|
TA01 | Transfer of patent application right | ||
GR01 | Patent grant | ||
GR01 | Patent grant |