HUE035332T2 - 1H-pyrrolo [2,3-b] pyridine derivatives and their use as kinase inhibitors - Google Patents

Info

Publication number

HUE035332T2

HUE035332T2 HUE13703121A HUE13703121A HUE035332T2 HU E035332 T2 HUE035332 T2 HU E035332T2 HU E13703121 A HUE13703121 A HU E13703121A HU E13703121 A HUE13703121 A HU E13703121A HU E035332 T2 HUE035332 T2 HU E035332T2

Authority

HU

Hungary

Prior art keywords

pyrrolo

pyridin

benzyl

pyrazole

amide

Prior art date

2012-01-30

Links

• Espacenet
• Global Dossier
• Discuss

• 150000005258 1H-pyrrolo(2,3-b)pyridines Chemical class 0.000 title description 4
• 229940043355 kinase inhibitor Drugs 0.000 title 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 343
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 107
• -1 mercapto, mercapto Chemical class 0.000 claims description 71
• 239000000203 mixture Substances 0.000 claims description 69
• 238000000034 method Methods 0.000 claims description 59
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 31
• 229910052736 halogen Inorganic materials 0.000 claims description 27
• 125000000623 heterocyclic group Chemical group 0.000 claims description 27
• 150000002367 halogens Chemical class 0.000 claims description 26
• 125000000217 alkyl group Chemical group 0.000 claims description 25
• 206010028980 Neoplasm Diseases 0.000 claims description 24
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 20
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
• 150000003839 salts Chemical class 0.000 claims description 19
• 125000001072 heteroaryl group Chemical group 0.000 claims description 18
• 125000003107 substituted aryl group Chemical group 0.000 claims description 18
• 201000011510 cancer Diseases 0.000 claims description 14
• 229910052739 hydrogen Inorganic materials 0.000 claims description 14
• 239000002253 acid Substances 0.000 claims description 13
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
• 125000001424 substituent group Chemical group 0.000 claims description 13
• 238000011282 treatment Methods 0.000 claims description 11
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
• 125000003118 aryl group Chemical group 0.000 claims description 10
• 239000001257 hydrogen Substances 0.000 claims description 10
• 229910052757 nitrogen Inorganic materials 0.000 claims description 10
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
• 125000004432 carbon atom Chemical group C* 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 9
• 239000000126 substance Substances 0.000 claims description 9
• 229910052799 carbon Inorganic materials 0.000 claims description 8
• 239000002244 precipitate Substances 0.000 claims description 8
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 7
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 7
• 125000003545 alkoxy group Chemical group 0.000 claims description 6
• 150000001412 amines Chemical class 0.000 claims description 6
• 102000004190 Enzymes Human genes 0.000 claims description 5
• 108090000790 Enzymes Proteins 0.000 claims description 5
• 125000004450 alkenylene group Chemical group 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 125000004193 piperazinyl group Chemical group 0.000 claims description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
• 238000002560 therapeutic procedure Methods 0.000 claims description 5
• 125000002947 alkylene group Chemical group 0.000 claims description 4
• 125000000732 arylene group Chemical group 0.000 claims description 4
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
• 229910052794 bromium Inorganic materials 0.000 claims description 4
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 125000005549 heteroarylene group Chemical group 0.000 claims description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
• 102000004169 proteins and genes Human genes 0.000 claims description 4
• 108090000623 proteins and genes Proteins 0.000 claims description 4
• 125000005717 substituted cycloalkylene group Chemical group 0.000 claims description 4
• 208000023275 Autoimmune disease Diseases 0.000 claims description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
• 150000002431 hydrogen Chemical class 0.000 claims description 3
• 150000003053 piperidines Chemical class 0.000 claims description 3
• 229910006074 SO2NH2 Inorganic materials 0.000 claims description 2
• 239000011230 binding agent Substances 0.000 claims description 2
• 238000002512 chemotherapy Methods 0.000 claims description 2
• 230000006378 damage Effects 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 150000001408 amides Chemical class 0.000 claims 11
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 10
• IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 claims 3
• WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical class C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 claims 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 2
• 125000001246 bromo group Chemical group Br* 0.000 claims 2
• 150000001735 carboxylic acids Chemical class 0.000 claims 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
• 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims 1
• PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 claims 1
• UZEFHQIOSJWWSB-UHFFFAOYSA-N 4-azidobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(N=[N+]=[N-])C=C1 UZEFHQIOSJWWSB-UHFFFAOYSA-N 0.000 claims 1
• 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims 1
• 101100439253 Arabidopsis thaliana CHI3 gene Proteins 0.000 claims 1
• 241000726103 Atta Species 0.000 claims 1
• 101100087530 Caenorhabditis elegans rom-1 gene Proteins 0.000 claims 1
• 101100426970 Caenorhabditis elegans ttr-1 gene Proteins 0.000 claims 1
• QXKAIJAYHKCRRA-JJYYJPOSSA-N D-arabinonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C(O)=O QXKAIJAYHKCRRA-JJYYJPOSSA-N 0.000 claims 1
• 101100456896 Drosophila melanogaster metl gene Proteins 0.000 claims 1
• 241000196324 Embryophyta Species 0.000 claims 1
• OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims 1
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
• 239000005977 Ethylene Substances 0.000 claims 1
• 235000010044 Hernandia moerenhoutiana Nutrition 0.000 claims 1
• 244000084296 Hernandia moerenhoutiana Species 0.000 claims 1
• 101100305983 Mus musculus Rom1 gene Proteins 0.000 claims 1
• IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims 1
• QPFYXYFORQJZEC-FOCLMDBBSA-N Phenazopyridine Chemical compound NC1=NC(N)=CC=C1\N=N\C1=CC=CC=C1 QPFYXYFORQJZEC-FOCLMDBBSA-N 0.000 claims 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 1
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 claims 1
• 101100097319 Schizosaccharomyces pombe (strain 972 / ATCC 24843) ala1 gene Proteins 0.000 claims 1
• 235000001484 Trigonella foenum graecum Nutrition 0.000 claims 1
• 244000250129 Trigonella foenum graecum Species 0.000 claims 1
• 230000002730 additional effect Effects 0.000 claims 1
• 125000006323 alkenyl amino group Chemical group 0.000 claims 1
• 125000005002 aryl methyl group Chemical group 0.000 claims 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
• 210000004556 brain Anatomy 0.000 claims 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims 1
• 150000007942 carboxylates Chemical class 0.000 claims 1
• 125000003963 dichloro group Chemical group Cl* 0.000 claims 1
• 235000011389 fruit/vegetable juice Nutrition 0.000 claims 1
• ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 claims 1
• 230000003394 haemopoietic effect Effects 0.000 claims 1
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims 1
• HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims 1
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims 1
• 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
• 125000006504 o-cyanobenzyl group Chemical group [H]C1=C([H])C(C#N)=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims 1
• LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 claims 1
• KXXXUIKPSVVSAW-UHFFFAOYSA-K pyranine Chemical compound [Na+].[Na+].[Na+].C1=C2C(O)=CC(S([O-])(=O)=O)=C(C=C3)C2=C2C3=C(S([O-])(=O)=O)C=C(S([O-])(=O)=O)C2=C1 KXXXUIKPSVVSAW-UHFFFAOYSA-K 0.000 claims 1
• WHYQCQRHPQBZHM-UHFFFAOYSA-N pyrazole-1-carboxylic acid Chemical compound OC(=O)N1C=CC=N1 WHYQCQRHPQBZHM-UHFFFAOYSA-N 0.000 claims 1
• 229940070891 pyridium Drugs 0.000 claims 1
• 239000004094 surface-active agent Substances 0.000 claims 1
• 108010036387 trimethionine Proteins 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 308
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 276
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 200
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 140
• 239000007787 solid Substances 0.000 description 121
• 229910001868 water Inorganic materials 0.000 description 112
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 108
• 238000002360 preparation method Methods 0.000 description 105
• 235000019439 ethyl acetate Nutrition 0.000 description 100
• 239000000243 solution Substances 0.000 description 99
• 238000005160 1H NMR spectroscopy Methods 0.000 description 97
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 97
• 229920006395 saturated elastomer Polymers 0.000 description 95
• 238000006243 chemical reaction Methods 0.000 description 84
• KGDOHXYALMXHLF-UHFFFAOYSA-N 1-benzylpyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=CC=C1 KGDOHXYALMXHLF-UHFFFAOYSA-N 0.000 description 74
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 74
• 239000011541 reaction mixture Substances 0.000 description 71
• 239000011780 sodium chloride Substances 0.000 description 70
• 239000002904 solvent Substances 0.000 description 64
• 239000000047 product Substances 0.000 description 63
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
• 238000004440 column chromatography Methods 0.000 description 52
• 239000013058 crude material Substances 0.000 description 49
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
• 239000000843 powder Substances 0.000 description 37
• 238000007792 addition Methods 0.000 description 30
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 28
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 26
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 26
• 229910000027 potassium carbonate Inorganic materials 0.000 description 26
• AKKPGUPOFLAXRN-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=C(F)C=C1 AKKPGUPOFLAXRN-UHFFFAOYSA-N 0.000 description 24
• 238000001914 filtration Methods 0.000 description 23
• 239000000463 material Substances 0.000 description 23
• 239000003921 oil Substances 0.000 description 23
• 235000019198 oils Nutrition 0.000 description 23
• 238000003756 stirring Methods 0.000 description 22
• 239000006071 cream Substances 0.000 description 21
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
• 239000000284 extract Substances 0.000 description 20
• 238000003818 flash chromatography Methods 0.000 description 20
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
• 238000002953 preparative HPLC Methods 0.000 description 18
• 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 17
• 238000000746 purification Methods 0.000 description 17
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 16
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 15
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
• 102000006459 Checkpoint Kinase 1 Human genes 0.000 description 14
• 108010019244 Checkpoint Kinase 1 Proteins 0.000 description 14
• 239000012044 organic layer Substances 0.000 description 14
• LGRLJNBPDMHSOL-UHFFFAOYSA-N 1-benzyl-n-[5-bromo-1-(4-methylphenyl)sulfonylpyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=NC=C(Br)C=C2C(NC(=O)C2=CN(CC=3C=CC=CC=3)N=C2)=C1 LGRLJNBPDMHSOL-UHFFFAOYSA-N 0.000 description 13
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical class [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
• 235000011114 ammonium hydroxide Nutrition 0.000 description 13
• 239000000706 filtrate Substances 0.000 description 13
• WUOQXNWMYLFAHT-MRVPVSSYSA-N tert-butyl n-[(3r)-piperidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCCNC1 WUOQXNWMYLFAHT-MRVPVSSYSA-N 0.000 description 13
• UORKPBOZTFYKBG-UHFFFAOYSA-N 1-benzyl-n-(5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound C12=CC(Br)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 UORKPBOZTFYKBG-UHFFFAOYSA-N 0.000 description 12
• JMCVFWQJWKRMHW-UHFFFAOYSA-N 5-bromo-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=C(Br)C=C2C(N)=CNC2=N1 JMCVFWQJWKRMHW-UHFFFAOYSA-N 0.000 description 12
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• RJAFVJZCUMEOBR-UHFFFAOYSA-N 1-(pyridin-4-ylmethyl)pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=NC=C1 RJAFVJZCUMEOBR-UHFFFAOYSA-N 0.000 description 11
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
• 238000005516 engineering process Methods 0.000 description 11
• 238000010438 heat treatment Methods 0.000 description 11
• 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 11
• 239000003112 inhibitor Substances 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
• GNRWXAUPOYGSJF-MRVPVSSYSA-N 4-[(3R)-3-aminopiperidin-1-yl]-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound COC1=CN=C2NC=C(N)C2=C1N1CCC[C@@H](N)C1 GNRWXAUPOYGSJF-MRVPVSSYSA-N 0.000 description 10
• 241000400611 Eucalyptus deanei Species 0.000 description 10
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
• 238000003556 assay Methods 0.000 description 10
• 238000001035 drying Methods 0.000 description 10
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
• WCMWZVWZYCRAIW-UHFFFAOYSA-N 1-(pyridin-3-ylmethyl)pyrazole-4-carboxylic acid Chemical group C1=C(C(=O)O)C=NN1CC1=CC=CN=C1 WCMWZVWZYCRAIW-UHFFFAOYSA-N 0.000 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• 239000007821 HATU Substances 0.000 description 9
• 239000003795 chemical substances by application Substances 0.000 description 9
• 239000011521 glass Substances 0.000 description 9
• 238000005342 ion exchange Methods 0.000 description 9
• 235000011121 sodium hydroxide Nutrition 0.000 description 9
• LCTSAPFWCLXWNS-HXUWFJFHSA-N tert-butyl n-[(3r)-1-[3-[(1-benzylpyrazole-4-carbonyl)amino]-5-bromo-1h-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 LCTSAPFWCLXWNS-HXUWFJFHSA-N 0.000 description 9
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
• RLIKCTSDMAQFES-UHFFFAOYSA-N 1-benzyl-N-[1-(4-methylphenyl)sulfonyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound Cc1ccc(cc1)S(=O)(=O)n1cc(NC(=O)c2cnn(Cc3ccccc3)c2)c2cc(cnc12)B1OC(C)(C)C(C)(C)O1 RLIKCTSDMAQFES-UHFFFAOYSA-N 0.000 description 8
• TYOAKDISSULLGZ-SSDOTTSWSA-N 4-[(3R)-3-aminopiperidin-1-yl]-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(N)=CN2 TYOAKDISSULLGZ-SSDOTTSWSA-N 0.000 description 8
• WPZRLMSKIZPOBF-UHFFFAOYSA-N 5-chloro-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=C(Cl)C=C2C(N)=CNC2=N1 WPZRLMSKIZPOBF-UHFFFAOYSA-N 0.000 description 8
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical class C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• 235000019270 ammonium chloride Nutrition 0.000 description 8
• 101150113535 chek1 gene Proteins 0.000 description 8
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
• 230000002829 reductive effect Effects 0.000 description 8
• SOUZKMFQFRDGKE-UHFFFAOYSA-N 1-(pyridin-2-ylmethyl)pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=CC=N1 SOUZKMFQFRDGKE-UHFFFAOYSA-N 0.000 description 7
• PUJVSTYUTMVCSG-UHFFFAOYSA-N 5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridine Chemical compound FC1=C(Br)C=NC2=C1C=CN2 PUJVSTYUTMVCSG-UHFFFAOYSA-N 0.000 description 7
• 101150050673 CHK1 gene Proteins 0.000 description 7
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 7
• 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 7
• HLZOIFAAAWCMOG-UHFFFAOYSA-N Fc1c(Br)cnc2[nH]cc(NC(=O)c3cnn(Cc4ccccc4)c3)c12 Chemical compound Fc1c(Br)cnc2[nH]cc(NC(=O)c3cnn(Cc4ccccc4)c3)c12 HLZOIFAAAWCMOG-UHFFFAOYSA-N 0.000 description 7
• 210000004027 cell Anatomy 0.000 description 7
• 239000012065 filter cake Substances 0.000 description 7
• 229960005277 gemcitabine Drugs 0.000 description 7
• 239000012074 organic phase Substances 0.000 description 7
• ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 7
• 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 7
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
• 238000001665 trituration Methods 0.000 description 7
• 238000010626 work up procedure Methods 0.000 description 7
• HJBGZJMKTOMQRR-UHFFFAOYSA-N (3-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C=O)=C1 HJBGZJMKTOMQRR-UHFFFAOYSA-N 0.000 description 6
• GUYKTJJGCNDECQ-NEPJUHHUSA-N (3R,4R)-4-cyclopropyl-N-diethoxyphosphorylpiperidin-3-amine Chemical compound CCOP(=O)(OCC)N[C@H]1CNCC[C@@H]1C1CC1 GUYKTJJGCNDECQ-NEPJUHHUSA-N 0.000 description 6
• YESANHMKGXGZLQ-UHFFFAOYSA-N (4-fluoropyrrolo[2,3-b]pyridin-1-yl)-tri(propan-2-yl)silane Chemical compound C1=CN=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1F YESANHMKGXGZLQ-UHFFFAOYSA-N 0.000 description 6
• OETDPVHIOQFDBI-UHFFFAOYSA-N 1-benzyl-n-(4-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound C1=2C(Br)=CC=NC=2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 OETDPVHIOQFDBI-UHFFFAOYSA-N 0.000 description 6
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
• GRAATXNNMKWDDS-SSDOTTSWSA-N N[C@@H]1CCCN(C1)c1c(Cl)cnc2[nH]cc(N)c12 Chemical compound N[C@@H]1CCCN(C1)c1c(Cl)cnc2[nH]cc(N)c12 GRAATXNNMKWDDS-SSDOTTSWSA-N 0.000 description 6
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
• 239000002246 antineoplastic agent Substances 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 6
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 6
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 6
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
• FKVTXXBRIXJUQQ-UHFFFAOYSA-N 1-benzyl-n-[5-[3-(2-morpholin-4-ylethoxy)phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(C=1)=CC=CC=1OCCN1CCOCC1 FKVTXXBRIXJUQQ-UHFFFAOYSA-N 0.000 description 5
• XVRJHIDTMLOKPU-UHFFFAOYSA-N 1-benzyl-n-[5-[3-(2-pyrrolidin-1-ylethoxy)phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(C=1)=CC=CC=1OCCN1CCCC1 XVRJHIDTMLOKPU-UHFFFAOYSA-N 0.000 description 5
• UEATVVZEWOUJKH-UHFFFAOYSA-N 1-benzyl-n-[5-[3-[(dimethylamino)methyl]phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound CN(C)CC1=CC=CC(C=2C=C3C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)=CNC3=NC=2)=C1 UEATVVZEWOUJKH-UHFFFAOYSA-N 0.000 description 5
• ZUOPKGTYJJCCND-UHFFFAOYSA-N 5-bromo-4-fluoro-3-nitro-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=C(Br)C(F)=C2C([N+](=O)[O-])=CNC2=N1 ZUOPKGTYJJCCND-UHFFFAOYSA-N 0.000 description 5
• 108091000080 Phosphotransferase Proteins 0.000 description 5
• 239000012043 crude product Substances 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 230000001965 increasing effect Effects 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• 125000002757 morpholinyl group Chemical group 0.000 description 5
• ABZYQTQZJDCXJQ-QGZVFWFLSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(Cl)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 ABZYQTQZJDCXJQ-QGZVFWFLSA-N 0.000 description 5
• WPIMBSFJUGQKSO-GOSISDBHSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-methoxy-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide Chemical compound C12=C(N3C[C@H](N)CCC3)C(OC)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 WPIMBSFJUGQKSO-GOSISDBHSA-N 0.000 description 5
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 5
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 102000020233 phosphotransferase Human genes 0.000 description 5
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 5
• 235000011118 potassium hydroxide Nutrition 0.000 description 5
• GSXCRDCXKUWXJK-UHFFFAOYSA-M potassium;1-(1h-pyrrol-2-ylmethyl)pyrazole-4-carboxylate Chemical group [K+].C1=C(C(=O)[O-])C=NN1CC1=CC=CN1 GSXCRDCXKUWXJK-UHFFFAOYSA-M 0.000 description 5
• 150000003254 radicals Chemical class 0.000 description 5
• 235000017557 sodium bicarbonate Nutrition 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• 229910000029 sodium carbonate Inorganic materials 0.000 description 5
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 5
• ALENDSSETVVANF-LLVKDONJSA-N tert-butyl n-[(3r)-1-(3-amino-5-methoxy-1h-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl]carbamate Chemical compound COC1=CN=C2NC=C(N)C2=C1N1CCC[C@@H](NC(=O)OC(C)(C)C)C1 ALENDSSETVVANF-LLVKDONJSA-N 0.000 description 5
• YMSXGXBENOJJLW-UHFFFAOYSA-N (4-fluoro-3-nitro-1h-pyrrolo[2,3-b]pyridin-5-yl) 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC1=CN=C2NC=C([N+]([O-])=O)C2=C1F YMSXGXBENOJJLW-UHFFFAOYSA-N 0.000 description 4
• ACKKVNVNGUYIAR-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]pyrazole-4-carboxylic acid Chemical compound COC1=CC=CC(CN2N=CC(=C2)C(O)=O)=C1 ACKKVNVNGUYIAR-UHFFFAOYSA-N 0.000 description 4
• IKIIMRKHGIWFEP-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=C(Cl)C=C1 IKIIMRKHGIWFEP-UHFFFAOYSA-N 0.000 description 4
• GJVFRIBDYISNDD-UHFFFAOYSA-N 1-benzyl-n-(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound C12=CC(Cl)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 GJVFRIBDYISNDD-UHFFFAOYSA-N 0.000 description 4
• FBLBZRLTZBPZFA-UHFFFAOYSA-N 1-benzyl-n-(5-phenyl-1h-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C1=CC=CC=C1 FBLBZRLTZBPZFA-UHFFFAOYSA-N 0.000 description 4
• MVQKTQBUBSANNZ-UHFFFAOYSA-N 1-benzyl-n-[1-(4-methylphenyl)sulfonyl-5-[3-(2-morpholin-4-ylethoxy)phenyl]pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=NC=C(C=3C=C(OCCN4CCOCC4)C=CC=3)C=C2C(NC(=O)C2=CN(CC=3C=CC=CC=3)N=C2)=C1 MVQKTQBUBSANNZ-UHFFFAOYSA-N 0.000 description 4
• XKZWGEUABLHBNY-UHFFFAOYSA-N 1-benzyl-n-[5-(4-formylphenyl)-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=CC(C=O)=CC=C1C1=CN=C(NC=C2NC(=O)C3=CN(CC=4C=CC=CC=4)N=C3)C2=C1 XKZWGEUABLHBNY-UHFFFAOYSA-N 0.000 description 4
• IHPXFCQAPBYVLG-VWLOTQADSA-N 1-benzyl-n-[5-[3-[[(2s)-1-methylpyrrolidin-2-yl]methoxy]phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound CN1CCC[C@H]1COC1=CC=CC(C=2C=C3C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)=CNC3=NC=2)=C1 IHPXFCQAPBYVLG-VWLOTQADSA-N 0.000 description 4
• WQTCAALJJAUNEH-UHFFFAOYSA-N 2-(4-bromopyrazol-1-yl)-n,n-diethylethanamine Chemical compound CCN(CC)CCN1C=C(Br)C=N1 WQTCAALJJAUNEH-UHFFFAOYSA-N 0.000 description 4
• NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 4
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
• RTADYVMNEDWFEV-SSDOTTSWSA-N 4-[(3R)-3-aminopiperidin-1-yl]-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1[C@H](N)CCCN1C1=C(C(F)(F)F)C=NC2=C1C(N)=CN2 RTADYVMNEDWFEV-SSDOTTSWSA-N 0.000 description 4
• RWOSDAABDCYOQZ-UHFFFAOYSA-N 4-bromo-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=CC(Br)=C2C(N)=CNC2=N1 RWOSDAABDCYOQZ-UHFFFAOYSA-N 0.000 description 4
• LIMWPGZSXIVMIU-UHFFFAOYSA-N 4-fluoro-1-tri(propan-2-yl)silylindol-5-ol Chemical compound OC1=CC=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1F LIMWPGZSXIVMIU-UHFFFAOYSA-N 0.000 description 4
• LPTVWZSQAIDCEB-UHFFFAOYSA-N 5-bromo-1h-pyrrolo[2,3-b]pyridine Chemical compound BrC1=CN=C2NC=CC2=C1 LPTVWZSQAIDCEB-UHFFFAOYSA-N 0.000 description 4
• 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 4
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
• 102000010111 Ezrin/radixin/moesin Human genes 0.000 description 4
• 108050001788 Ezrin/radixin/moesin Proteins 0.000 description 4
• 229910017711 NHRa Inorganic materials 0.000 description 4
• 229910003827 NRaRb Inorganic materials 0.000 description 4
• 102000001253 Protein Kinase Human genes 0.000 description 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
• SIMJJYIGUQFXCG-UHFFFAOYSA-N [4-fluoro-1-tri(propan-2-yl)silylpyrrolo[2,3-b]pyridin-5-yl] 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC1=CN=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1F SIMJJYIGUQFXCG-UHFFFAOYSA-N 0.000 description 4
• WJEIYVAPNMUNIU-UHFFFAOYSA-N [Na].OC(O)=O Chemical compound [Na].OC(O)=O WJEIYVAPNMUNIU-UHFFFAOYSA-N 0.000 description 4
• PWVDWURTOBCLJW-UHFFFAOYSA-N benzyl 3-azido-4-hydroxypiperidine-1-carboxylate Chemical compound C1C(N=[N+]=[N-])C(O)CCN1C(=O)OCC1=CC=CC=C1 PWVDWURTOBCLJW-UHFFFAOYSA-N 0.000 description 4
• 229910000024 caesium carbonate Inorganic materials 0.000 description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
• MPVDXIMFBOLMNW-UHFFFAOYSA-N chembl1615565 Chemical compound OC1=CC=C2C=C(S(O)(=O)=O)C=C(S(O)(=O)=O)C2=C1N=NC1=CC=CC=C1 MPVDXIMFBOLMNW-UHFFFAOYSA-N 0.000 description 4
• 239000013078 crystal Substances 0.000 description 4
• VELDYOPRLMJFIK-UHFFFAOYSA-N cyclopentanecarbaldehyde Chemical compound O=CC1CCCC1 VELDYOPRLMJFIK-UHFFFAOYSA-N 0.000 description 4
• 231100000433 cytotoxic Toxicity 0.000 description 4
• 229940127089 cytotoxic agent Drugs 0.000 description 4
• 230000001472 cytotoxic effect Effects 0.000 description 4
• 239000006185 dispersion Substances 0.000 description 4
• 229940088598 enzyme Drugs 0.000 description 4
• 235000019441 ethanol Nutrition 0.000 description 4
• 235000019253 formic acid Nutrition 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 125000005842 heteroatom Chemical group 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 4
• 239000002480 mineral oil Substances 0.000 description 4
• 235000010446 mineral oil Nutrition 0.000 description 4
• DUAGZNPOPXJGOT-UHFFFAOYSA-N n-(5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl)-1-(1h-pyrrol-2-ylmethyl)pyrazole-4-carboxamide Chemical compound C12=CC(Br)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=CN1 DUAGZNPOPXJGOT-UHFFFAOYSA-N 0.000 description 4
• XBPPJNNXAGYWRI-QGZVFWFLSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-methoxy-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-(pyridin-4-ylmethyl)pyrazole-4-carboxamide Chemical compound C12=C(N3C[C@H](N)CCC3)C(OC)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=NC=C1 XBPPJNNXAGYWRI-QGZVFWFLSA-N 0.000 description 4
• HBFUKTPVCNGAFU-GOSISDBHSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-methoxy-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-[(4-fluorophenyl)methyl]pyrazole-4-carboxamide Chemical compound C12=C(N3C[C@H](N)CCC3)C(OC)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=C(F)C=C1 HBFUKTPVCNGAFU-GOSISDBHSA-N 0.000 description 4
• PJOWZRBEUFUWFG-HSZRJFAPSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-phenyl-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(C=2C=CC=CC=2)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 PJOWZRBEUFUWFG-HSZRJFAPSA-N 0.000 description 4
• IFNPVACASQSGQR-MRXNPFEDSA-N n-[4-[(3r)-3-aminopyrrolidin-1-yl]-5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide Chemical compound C1[C@H](N)CCN1C1=C(Cl)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 IFNPVACASQSGQR-MRXNPFEDSA-N 0.000 description 4
• 230000037361 pathway Effects 0.000 description 4
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
• 125000003386 piperidinyl group Chemical group 0.000 description 4
• 108060006633 protein kinase Proteins 0.000 description 4
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 4
• 229910052717 sulfur Inorganic materials 0.000 description 4
• 238000003786 synthesis reaction Methods 0.000 description 4
• 239000006188 syrup Substances 0.000 description 4
• 235000020357 syrup Nutrition 0.000 description 4
• 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 4
• 239000003981 vehicle Substances 0.000 description 4
• 239000003039 volatile agent Substances 0.000 description 4
• 229910052727 yttrium Inorganic materials 0.000 description 4
• RYNNPVYRYQJPEO-HNNXBMFYSA-N (2s)-1-methyl-2-[[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl]pyrrolidine Chemical compound CN1CCC[C@H]1COC1=CC=CC(B2OC(C)(C)C(C)(C)O2)=C1 RYNNPVYRYQJPEO-HNNXBMFYSA-N 0.000 description 3
• QSEMMUYKUYKNBI-UHFFFAOYSA-N (4-bromopyrrolo[2,3-b]pyridin-1-yl)-tri(propan-2-yl)silane Chemical compound C1=CN=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1Br QSEMMUYKUYKNBI-UHFFFAOYSA-N 0.000 description 3
• RRAXPOIWTUEFDD-UHFFFAOYSA-N (4-fluoro-1h-pyrrolo[2,3-b]pyridin-5-yl) 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC1=CN=C2NC=CC2=C1F RRAXPOIWTUEFDD-UHFFFAOYSA-N 0.000 description 3
• QEYOHUBBPSKXMV-UHFFFAOYSA-N (4-fluoro-5-methoxypyrrolo[2,3-b]pyridin-1-yl)-tri(propan-2-yl)silane Chemical compound COC1=CN=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1F QEYOHUBBPSKXMV-UHFFFAOYSA-N 0.000 description 3
• AIJAFOFKGPWSSO-UHFFFAOYSA-N (5-bromo-4-fluoropyrrolo[2,3-b]pyridin-1-yl)-tri(propan-2-yl)silane Chemical compound BrC1=CN=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1F AIJAFOFKGPWSSO-UHFFFAOYSA-N 0.000 description 3
• FDWUFDIEKNWJQX-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-chloro-5-(trifluoromethyl)pyrrolo[2,3-b]pyridine Chemical compound C1=CC2=C(Cl)C(C(F)(F)F)=CN=C2N1S(=O)(=O)C1=CC=CC=C1 FDWUFDIEKNWJQX-UHFFFAOYSA-N 0.000 description 3
• HYBRAUPLUXQZEG-UHFFFAOYSA-N 1-[(4-methylphenyl)methyl]pyrazole-4-carboxylic acid Chemical group C1=CC(C)=CC=C1CN1N=CC(C(O)=O)=C1 HYBRAUPLUXQZEG-UHFFFAOYSA-N 0.000 description 3
• KMOFOKGTZRFKEM-UHFFFAOYSA-N 1-[2-(3-bromophenoxy)ethyl]pyrrolidine Chemical compound BrC1=CC=CC(OCCN2CCCC2)=C1 KMOFOKGTZRFKEM-UHFFFAOYSA-N 0.000 description 3
• XEEBVHGZQKYBCD-UHFFFAOYSA-N 1-benzyl-N-(4-fluoro-5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound Cc1cnc2[nH]cc(NC(=O)c3cnn(Cc4ccccc4)c3)c2c1F XEEBVHGZQKYBCD-UHFFFAOYSA-N 0.000 description 3
• HLYSRDACCKXGKI-UHFFFAOYSA-N 1-benzyl-N-(5-chloro-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound Fc1c(Cl)cnc2[nH]cc(NC(=O)c3cnn(Cc4ccccc4)c3)c12 HLYSRDACCKXGKI-UHFFFAOYSA-N 0.000 description 3
• XFPUFBHANVVZFG-UHFFFAOYSA-N 1-benzyl-N-[5-[4-[3-(dimethylamino)propoxy]phenyl]-1-(4-methylphenyl)sulfonylpyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound CN(CCCOC1=CC=C(C=C1)C=1C=C2C(=NC1)N(C=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)S(=O)(=O)C2=CC=C(C=C2)C)C XFPUFBHANVVZFG-UHFFFAOYSA-N 0.000 description 3
• SKBZOZUZPJPMOH-UHFFFAOYSA-N 1-benzyl-n-[5-[1-[2-(diethylamino)ethyl]pyrazol-4-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CCN(CC)CC)C=C1C1=CN=C(NC=C2NC(=O)C3=CN(CC=4C=CC=CC=4)N=C3)C2=C1 SKBZOZUZPJPMOH-UHFFFAOYSA-N 0.000 description 3
• LIJLRHBIIZMMKG-UHFFFAOYSA-N 1-benzyl-n-[5-[3-(1-methylpiperidin-3-yl)oxyphenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1N(C)CCCC1OC1=CC=CC(C=2C=C3C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)=CNC3=NC=2)=C1 LIJLRHBIIZMMKG-UHFFFAOYSA-N 0.000 description 3
• MPFNQGRSVYQEGR-UHFFFAOYSA-N 1-benzyl-n-[5-[3-(3-morpholin-4-ylpropoxy)phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(C=1)=CC=CC=1OCCCN1CCOCC1 MPFNQGRSVYQEGR-UHFFFAOYSA-N 0.000 description 3
• OOTMYPYUUUELHQ-UHFFFAOYSA-N 1-benzyl-n-[5-[3-(oxetan-3-yloxy)phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(C=1)=CC=CC=1OC1COC1 OOTMYPYUUUELHQ-UHFFFAOYSA-N 0.000 description 3
• SJEDDYYAUFEAIO-UHFFFAOYSA-N 1-benzyl-n-[5-[3-[(3,3-difluoropiperidin-1-yl)methyl]phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1C(F)(F)CCCN1CC1=CC=CC(C=2C=C3C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)=CNC3=NC=2)=C1 SJEDDYYAUFEAIO-UHFFFAOYSA-N 0.000 description 3
• BJJLYPIQEQCYLS-UHFFFAOYSA-N 1-benzyl-n-[5-[4-(piperidin-1-ylmethyl)phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(C=C1)=CC=C1CN1CCCCC1 BJJLYPIQEQCYLS-UHFFFAOYSA-N 0.000 description 3
• ZWCOYOQJKYJBIG-UHFFFAOYSA-N 1-benzyl-n-[5-[4-[3-(dimethylamino)propoxy]phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=CC(OCCCN(C)C)=CC=C1C1=CN=C(NC=C2NC(=O)C3=CN(CC=4C=CC=CC=4)N=C3)C2=C1 ZWCOYOQJKYJBIG-UHFFFAOYSA-N 0.000 description 3
• XDRUKDNFTVGUGB-UHFFFAOYSA-N 1-benzyl-n-[5-[4-[[2-methoxyethyl(methyl)amino]methyl]phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=CC(CN(C)CCOC)=CC=C1C1=CN=C(NC=C2NC(=O)C3=CN(CC=4C=CC=CC=4)N=C3)C2=C1 XDRUKDNFTVGUGB-UHFFFAOYSA-N 0.000 description 3
• VCNOSUOVNNJQAB-UHFFFAOYSA-N 1-benzyl-n-[5-[5-(pyrrolidin-1-ylmethyl)thiophen-2-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(S1)=CC=C1CN1CCCC1 VCNOSUOVNNJQAB-UHFFFAOYSA-N 0.000 description 3
• KISRVFPBFBJTPK-UHFFFAOYSA-N 1-benzyl-n-[5-[5-(pyrrolidin-1-ylmethyl)thiophen-3-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(C=1)=CSC=1CN1CCCC1 KISRVFPBFBJTPK-UHFFFAOYSA-N 0.000 description 3
• NHOBBIVFUQBEMI-UHFFFAOYSA-N 1-methylsulfonylpyrrole-2-carbaldehyde Chemical compound CS(=O)(=O)N1C=CC=C1C=O NHOBBIVFUQBEMI-UHFFFAOYSA-N 0.000 description 3
• KOHBEDRJXKOYHL-UHFFFAOYSA-N 2-methoxy-n-methylethanamine Chemical compound CNCCOC KOHBEDRJXKOYHL-UHFFFAOYSA-N 0.000 description 3
• QLCHXZVEEOWYHL-UHFFFAOYSA-N 3-chloro-n,n,2,2-tetramethylpropan-1-amine;hydrochloride Chemical compound Cl.CN(C)CC(C)(C)CCl QLCHXZVEEOWYHL-UHFFFAOYSA-N 0.000 description 3
• BEPFGDZUAZYOHN-UHFFFAOYSA-N 4-bromo-3-nitro-7-azaindole Chemical compound C1=CC(Br)=C2C([N+](=O)[O-])=CNC2=N1 BEPFGDZUAZYOHN-UHFFFAOYSA-N 0.000 description 3
• VPSJPRMYBKNGOI-UHFFFAOYSA-N 4-chloro-3-nitro-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=C(C(F)(F)F)C(Cl)=C2C([N+](=O)[O-])=CNC2=N1 VPSJPRMYBKNGOI-UHFFFAOYSA-N 0.000 description 3
• ATLADCFKPSZUNL-UHFFFAOYSA-N 4-chloro-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridine Chemical compound FC(F)(F)C1=CN=C2NC=CC2=C1Cl ATLADCFKPSZUNL-UHFFFAOYSA-N 0.000 description 3
• HHPQMGPENICAAD-UHFFFAOYSA-N 4-chloro-5-iodo-1h-pyrrolo[2,3-b]pyridine Chemical compound ClC1=C(I)C=NC2=C1C=CN2 HHPQMGPENICAAD-UHFFFAOYSA-N 0.000 description 3
• HIODJZBVHNCROX-UHFFFAOYSA-N 4-fluoro-5-methoxy-1h-pyrrolo[2,3-b]pyridine Chemical compound COC1=CN=C2NC=CC2=C1F HIODJZBVHNCROX-UHFFFAOYSA-N 0.000 description 3
• MHQHNMJVQKUNEQ-UHFFFAOYSA-N 4-fluoro-5-methoxy-3-nitro-1h-pyrrolo[2,3-b]pyridine Chemical compound COC1=CN=C2NC=C([N+]([O-])=O)C2=C1F MHQHNMJVQKUNEQ-UHFFFAOYSA-N 0.000 description 3
• DOXBRKCMQZDRGY-UHFFFAOYSA-N 4-fluoro-5-methyl-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound CC1=CN=C2NC=C(N)C2=C1F DOXBRKCMQZDRGY-UHFFFAOYSA-N 0.000 description 3
• FBLZOAQGIMCKEK-UHFFFAOYSA-N 4-fluoro-5-methyl-1h-pyrrolo[2,3-b]pyridine Chemical compound CC1=CN=C2NC=CC2=C1F FBLZOAQGIMCKEK-UHFFFAOYSA-N 0.000 description 3
• YYMPANVNHSGRDP-UHFFFAOYSA-N 4-fluoro-5-methyl-3-nitro-1h-pyrrolo[2,3-b]pyridine Chemical compound CC1=CN=C2NC=C([N+]([O-])=O)C2=C1F YYMPANVNHSGRDP-UHFFFAOYSA-N 0.000 description 3
• AOTXEIQACILNKS-UHFFFAOYSA-N 5-chloro-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=C(Cl)C(F)=C2C(N)=CNC2=N1 AOTXEIQACILNKS-UHFFFAOYSA-N 0.000 description 3
• NXFUJGIWFYKQGK-UHFFFAOYSA-N 5-chloro-4-fluoro-1h-pyrrolo[2,3-b]pyridine Chemical compound FC1=C(Cl)C=NC2=C1C=CN2 NXFUJGIWFYKQGK-UHFFFAOYSA-N 0.000 description 3
• YPMLOIUVRSZLKG-UHFFFAOYSA-N 5-chloro-4-fluoro-3-nitro-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=C(Cl)C(F)=C2C([N+](=O)[O-])=CNC2=N1 YPMLOIUVRSZLKG-UHFFFAOYSA-N 0.000 description 3
• GHHWPSOGKLMSCJ-UHFFFAOYSA-N 507462-26-2 Chemical compound C1=C(Br)C=C2C([N+](=O)[O-])=CNC2=N1 GHHWPSOGKLMSCJ-UHFFFAOYSA-N 0.000 description 3
• SCGIEJZHILIERP-LLVKDONJSA-N CC(C)(C)CN[C@@H]1CCCN(C1)c1c(Br)cnc2[nH]cc(N)c12 Chemical compound CC(C)(C)CN[C@@H]1CCCN(C1)c1c(Br)cnc2[nH]cc(N)c12 SCGIEJZHILIERP-LLVKDONJSA-N 0.000 description 3
• BCGFDXHWKWLNQL-UHFFFAOYSA-N CN1N=CC(=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound CN1N=CC(=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 BCGFDXHWKWLNQL-UHFFFAOYSA-N 0.000 description 3
• 229910014455 Ca-Cb Inorganic materials 0.000 description 3
• VLZMDADZTOITSH-UHFFFAOYSA-N Cc1ccc(cc1)S(=O)(=O)n1cc(NC(=O)c2cnn(Cc3ccccc3)c2)c2cc(cnc12)-c1cccc(OCCN2CCCC2)c1 Chemical compound Cc1ccc(cc1)S(=O)(=O)n1cc(NC(=O)c2cnn(Cc3ccccc3)c2)c2cc(cnc12)-c1cccc(OCCN2CCCC2)c1 VLZMDADZTOITSH-UHFFFAOYSA-N 0.000 description 3
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
• JHQKHJMEWNLYMX-UHFFFAOYSA-N N-(5-chloro-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1-(pyridin-4-ylmethyl)pyrazole-4-carboxamide Chemical compound Fc1c(Cl)cnc2[nH]cc(NC(=O)c3cnn(Cc4ccncc4)c3)c12 JHQKHJMEWNLYMX-UHFFFAOYSA-N 0.000 description 3
• LCMOAKKJWRIJPH-UHFFFAOYSA-N Nc1c[nH]c2ncc(cc12)-c1cccc(CN2CCC2)c1 Chemical compound Nc1c[nH]c2ncc(cc12)-c1cccc(CN2CCC2)c1 LCMOAKKJWRIJPH-UHFFFAOYSA-N 0.000 description 3
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-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
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• OPJPCDCKLCWJON-HSZRJFAPSA-N [3-[(1-benzylpyrazole-4-carbonyl)amino]-4-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-5-yl] 2,2-dimethylpropanoate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCCN1C1=C(OC(=O)C(C)(C)C)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 OPJPCDCKLCWJON-HSZRJFAPSA-N 0.000 description 3
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 239000002585 base Substances 0.000 description 3
• JPEMPGCPBAKNKS-MOPGFXCFSA-N benzyl (3r,4r)-4-cyclopropyl-3-(diethoxyphosphorylamino)piperidine-1-carboxylate Chemical compound C1([C@H]2CCN(C[C@@H]2NP(=O)(OCC)OCC)C(=O)OCC=2C=CC=CC=2)CC1 JPEMPGCPBAKNKS-MOPGFXCFSA-N 0.000 description 3
• LXLUFXYWZIVHSF-UHFFFAOYSA-N benzyl 3-(diethoxyphosphorylamino)-4-(4-methylphenyl)sulfonyloxypiperidine-1-carboxylate Chemical compound CCOP(=O)(OCC)NC1CN(C(=O)OCC=2C=CC=CC=2)CCC1OS(=O)(=O)C1=CC=C(C)C=C1 LXLUFXYWZIVHSF-UHFFFAOYSA-N 0.000 description 3
• AHVUFKFGWHXUDC-UHFFFAOYSA-N benzyl 4-azido-3-(4-methylphenyl)sulfonyloxypiperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1C(N=[N+]=[N-])CCN(C(=O)OCC=2C=CC=CC=2)C1 AHVUFKFGWHXUDC-UHFFFAOYSA-N 0.000 description 3
• XOCCDWVWMPSHJU-UHFFFAOYSA-N benzyl 4-azido-3-hydroxypiperidine-1-carboxylate Chemical compound C1CC(N=[N+]=[N-])C(O)CN1C(=O)OCC1=CC=CC=C1 XOCCDWVWMPSHJU-UHFFFAOYSA-N 0.000 description 3
• BOZPVLJVKMWARN-UHFFFAOYSA-N benzyl 7-diethoxyphosphoryl-4,7-diazabicyclo[4.1.0]heptane-4-carboxylate Chemical compound C1C2N(P(=O)(OCC)OCC)C2CCN1C(=O)OCC1=CC=CC=C1 BOZPVLJVKMWARN-UHFFFAOYSA-N 0.000 description 3
• PHSSLYCBJRMEEV-UHFFFAOYSA-N benzyl 7-oxa-4-azabicyclo[4.1.0]heptane-4-carboxylate Chemical compound C1CC2OC2CN1C(=O)OCC1=CC=CC=C1 PHSSLYCBJRMEEV-UHFFFAOYSA-N 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• 230000022131 cell cycle Effects 0.000 description 3
• 229940044683 chemotherapy drug Drugs 0.000 description 3
• 238000010511 deprotection reaction Methods 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• OPTPGWNYYFAYHY-UHFFFAOYSA-N ethyl 1-[(1-methylsulfonylpyrrol-2-yl)methyl]pyrazole-4-carboxylate Chemical compound C1=C(C(=O)OCC)C=NN1CC1=CC=CN1S(C)(=O)=O OPTPGWNYYFAYHY-UHFFFAOYSA-N 0.000 description 3
• KACZQOKEFKFNDB-UHFFFAOYSA-N ethyl 1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NNC=1 KACZQOKEFKFNDB-UHFFFAOYSA-N 0.000 description 3
• FDLDWKIEWAWOSL-UHFFFAOYSA-N ethyl acetate;2-methylpentane Chemical compound CCCC(C)C.CCOC(C)=O FDLDWKIEWAWOSL-UHFFFAOYSA-N 0.000 description 3
• 150000004675 formic acid derivatives Chemical class 0.000 description 3
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 3
• 229960004768 irinotecan Drugs 0.000 description 3
• 125000000842 isoxazolyl group Chemical group 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• SHUUEBOBDREAPE-UHFFFAOYSA-N n-(5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)-1-[(4-methoxyphenyl)methyl]pyrazole-4-carboxamide Chemical compound C1=CC(OC)=CC=C1CN1N=CC(C(=O)NC=2C3=C(F)C(Br)=CN=C3NC=2)=C1 SHUUEBOBDREAPE-UHFFFAOYSA-N 0.000 description 3
• CFLVRAZWHBQIGQ-QGZVFWFLSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(C(F)(F)F)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 CFLVRAZWHBQIGQ-QGZVFWFLSA-N 0.000 description 3
• XCPWMFLYGXCEGF-QGZVFWFLSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-hydroxy-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(O)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 XCPWMFLYGXCEGF-QGZVFWFLSA-N 0.000 description 3
• NFVCVYOJNDBBOX-CTNGQTDRSA-N n-[4-[(3r,4r)-3-amino-4-cyclopropylpiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide Chemical compound C1([C@H]2CCN(C[C@@H]2N)C=2C=3C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)=CNC=3N=CC=2Br)CC1 NFVCVYOJNDBBOX-CTNGQTDRSA-N 0.000 description 3
• 150000002825 nitriles Chemical class 0.000 description 3
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
• 125000004043 oxo group Chemical group O=* 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 108090000765 processed proteins & peptides Proteins 0.000 description 3
• 125000004076 pyridyl group Chemical group 0.000 description 3
• 125000000168 pyrrolyl group Chemical group 0.000 description 3
• 238000001959 radiotherapy Methods 0.000 description 3
• 230000008439 repair process Effects 0.000 description 3
• 230000010076 replication Effects 0.000 description 3
• 239000012279 sodium borohydride Substances 0.000 description 3
• 229910000033 sodium borohydride Inorganic materials 0.000 description 3
• 239000012453 solvate Substances 0.000 description 3
• 239000000600 sorbitol Substances 0.000 description 3
• 235000010356 sorbitol Nutrition 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• GWIXKKVUKDHQOY-LLVKDONJSA-N tert-butyl n-[(3r)-1-(5-methoxy-3-nitro-1h-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl]carbamate Chemical compound COC1=CN=C2NC=C([N+]([O-])=O)C2=C1N1CCC[C@@H](NC(=O)OC(C)(C)C)C1 GWIXKKVUKDHQOY-LLVKDONJSA-N 0.000 description 3
• LRZZXMQRQHIQAQ-SNVBAGLBSA-N tert-butyl n-[(3r)-1-[3-amino-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCCN1C1=C(C(F)(F)F)C=NC2=C1C(N)=CN2 LRZZXMQRQHIQAQ-SNVBAGLBSA-N 0.000 description 3
• OGPCSYUFPBVGKD-SNVBAGLBSA-N tert-butyl n-[(3r)-1-[3-nitro-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCCN1C1=C(C(F)(F)F)C=NC2=C1C([N+]([O-])=O)=CN2 OGPCSYUFPBVGKD-SNVBAGLBSA-N 0.000 description 3
• GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 3
• FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
• HSMLARVFJADZQS-UHFFFAOYSA-N (4-chloropyrrolo[2,3-b]pyridin-1-yl)-tri(propan-2-yl)silane Chemical compound C1=CN=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1Cl HSMLARVFJADZQS-UHFFFAOYSA-N 0.000 description 2
• COIQUVGFTILYGA-UHFFFAOYSA-N (4-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=C(O)C=C1 COIQUVGFTILYGA-UHFFFAOYSA-N 0.000 description 2
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 2
• FSNGFFWICFYWQC-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine;hydron;chloride Chemical compound Cl.ClCCN1CCCC1 FSNGFFWICFYWQC-UHFFFAOYSA-N 0.000 description 2
• VXWPLQTVHINTNQ-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-chloro-5-iodopyrrolo[2,3-b]pyridine Chemical compound C1=CC=2C(Cl)=C(I)C=NC=2N1S(=O)(=O)C1=CC=CC=C1 VXWPLQTVHINTNQ-UHFFFAOYSA-N 0.000 description 2
• CUDHNDFUGXHTRN-UHFFFAOYSA-N 1-[(2-chlorophenyl)methyl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=CC=C1Cl CUDHNDFUGXHTRN-UHFFFAOYSA-N 0.000 description 2
• JMWJJDKQQMMJRG-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methyl]pyrazole-4-carboxylic acid Chemical group C1=CC(OC)=CC=C1CN1N=CC(C(O)=O)=C1 JMWJJDKQQMMJRG-UHFFFAOYSA-N 0.000 description 2
• OUHKYWQKHLTDBH-UHFFFAOYSA-N 1-[fluoro(phenyl)methyl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1C(F)C1=CC=CC=C1 OUHKYWQKHLTDBH-UHFFFAOYSA-N 0.000 description 2
• VGAFMEAQTYKXFH-UHFFFAOYSA-N 1-benzyl-N-[5-[1-[2-(diethylamino)ethyl]pyrazol-4-yl]-1-(4-methylphenyl)sulfonylpyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C(C)N(CCN1N=CC(=C1)C=1C=C2C(=NC1)N(C=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)S(=O)(=O)C2=CC=C(C=C2)C)CC VGAFMEAQTYKXFH-UHFFFAOYSA-N 0.000 description 2
• HPJSOTCSLFGBGU-UHFFFAOYSA-N 1-benzyl-N-[5-[3-[(dimethylamino)methyl]phenyl]-1-(4-methylphenyl)sulfonylpyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound CN(C)CC=1C=C(C=CC1)C=1C=C2C(=NC1)N(C=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)S(=O)(=O)C2=CC=C(C=C2)C HPJSOTCSLFGBGU-UHFFFAOYSA-N 0.000 description 2
• WMEWWDFWHBMCBM-UHFFFAOYSA-N 1-benzyl-n-(1h-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound C=1NC2=NC=CC=C2C=1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 WMEWWDFWHBMCBM-UHFFFAOYSA-N 0.000 description 2
• QPLMQVLSVQFQTH-UHFFFAOYSA-N 1-benzyl-n-(5-piperidin-1-yl-1h-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2N1CCCCC1 QPLMQVLSVQFQTH-UHFFFAOYSA-N 0.000 description 2
• XVAVLCVWQVUKSR-UHFFFAOYSA-N 1-benzyl-n-(5-pyridin-3-yl-1h-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C1=CC=CN=C1 XVAVLCVWQVUKSR-UHFFFAOYSA-N 0.000 description 2
• YGPFFZKSUPWOQT-UHFFFAOYSA-N 1-benzyl-n-(5-pyridin-4-yl-1h-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C1=CC=NC=C1 YGPFFZKSUPWOQT-UHFFFAOYSA-N 0.000 description 2
• LYXOBSZCHAQLCV-UHFFFAOYSA-N 1-benzyl-n-[5-[5-[(3,3-difluoroazetidin-1-yl)methyl]thiophen-3-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1C(F)(F)CN1CC1=CC(C=2C=C3C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)=CNC3=NC=2)=CS1 LYXOBSZCHAQLCV-UHFFFAOYSA-N 0.000 description 2
• BNGITRCRSAWPSZ-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2N[C]=CC2=C1 BNGITRCRSAWPSZ-UHFFFAOYSA-N 0.000 description 2
• UWLHXRTWYGHNEM-UHFFFAOYSA-N 2-(chloromethyl)-1-methylsulfonylpyrrole Chemical compound CS(=O)(=O)N1C=CC=C1CCl UWLHXRTWYGHNEM-UHFFFAOYSA-N 0.000 description 2
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
• CDBAEFXTCRKJPZ-UHFFFAOYSA-N 3,3-difluoroazetidine;hydron;chloride Chemical group Cl.FC1(F)CNC1 CDBAEFXTCRKJPZ-UHFFFAOYSA-N 0.000 description 2
• MUKIFYQKIZOYKT-UHFFFAOYSA-N 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC(O)=C1 MUKIFYQKIZOYKT-UHFFFAOYSA-N 0.000 description 2
• RDJUBLSLAULIAT-UHFFFAOYSA-N 3-fluoropiperidine;hydrochloride Chemical group Cl.FC1CCCNC1 RDJUBLSLAULIAT-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• LEZHTYOQWQEBLH-UHFFFAOYSA-N 4-bromo-1h-pyrrolo[2,3-b]pyridine Chemical compound BrC1=CC=NC2=C1C=CN2 LEZHTYOQWQEBLH-UHFFFAOYSA-N 0.000 description 2
• UMRGFHCHWMHAET-UHFFFAOYSA-N 4-fluoro-5-methoxy-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound COC1=CN=C2NC=C(N)C2=C1F UMRGFHCHWMHAET-UHFFFAOYSA-N 0.000 description 2
• SAVKOAJJSOGDHL-UHFFFAOYSA-N 5-[4-[3-(dimethylamino)propoxy]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=CC(OCCCN(C)C)=CC=C1C1=CN=C(NC=C2N)C2=C1 SAVKOAJJSOGDHL-UHFFFAOYSA-N 0.000 description 2
• TXNYLFGVDKRUOT-LLVKDONJSA-N 5-bromo-4-[(3R)-3-(cyclopropylmethylamino)piperidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound N([C@@H]1CCCN(C1)C=1C(Br)=CN=C2NC=C(C=12)N)CC1CC1 TXNYLFGVDKRUOT-LLVKDONJSA-N 0.000 description 2
• VZHJRYVFKSFRKL-UHFFFAOYSA-N 5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=C(Br)C(F)=C2C(N)=CNC2=N1 VZHJRYVFKSFRKL-UHFFFAOYSA-N 0.000 description 2
• UVDDIZSAAWVACA-UHFFFAOYSA-N 5-methyl-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical group CC1=CN=C2NC=C(N)C2=C1 UVDDIZSAAWVACA-UHFFFAOYSA-N 0.000 description 2
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 2
• TXRPBOFZDDOMNM-UHFFFAOYSA-N BrC=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC(=CC=C2)OC.N2=CC(=CC=C2)C=2C=C1C(=NC2)NC=C1NC(=O)C=1C=NN(C1)CC1=CC=CC=C1 Chemical compound BrC=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC(=CC=C2)OC.N2=CC(=CC=C2)C=2C=C1C(=NC2)NC=C1NC(=O)C=1C=NN(C1)CC1=CC=CC=C1 TXRPBOFZDDOMNM-UHFFFAOYSA-N 0.000 description 2
• 101100220616 Caenorhabditis elegans chk-2 gene Proteins 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• YLXXAERIKGIGMP-SECBINFHSA-N Cc1cnc2[nH]cc(N)c2c1N1CCC[C@@H](N)C1 Chemical compound Cc1cnc2[nH]cc(N)c2c1N1CCC[C@@H](N)C1 YLXXAERIKGIGMP-SECBINFHSA-N 0.000 description 2
• 230000033616 DNA repair Effects 0.000 description 2
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
• 240000007472 Leucaena leucocephala Species 0.000 description 2
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• 238000005481 NMR spectroscopy Methods 0.000 description 2
• HBIQGRBURSCEDY-OGFXRTJISA-N N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Cl.OC(C1=CN(CC2=CC=NC=C2)N=C1)=O Chemical compound N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Cl.OC(C1=CN(CC2=CC=NC=C2)N=C1)=O HBIQGRBURSCEDY-OGFXRTJISA-N 0.000 description 2
• HVQFBMREBFMHEW-ZCFIWIBFSA-N Nc1c[nH]c2ncc(Br)c(N3CC[C@@H](O)C3)c12 Chemical compound Nc1c[nH]c2ncc(Br)c(N3CC[C@@H](O)C3)c12 HVQFBMREBFMHEW-ZCFIWIBFSA-N 0.000 description 2
• 235000019502 Orange oil Nutrition 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
• FXKSFAVNDYZPFN-CYBMUJFWSA-N [3-amino-4-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-5-yl] 2,2-dimethylpropanoate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCCN1C1=C(OC(=O)C(C)(C)C)C=NC2=C1C(N)=CN2 FXKSFAVNDYZPFN-CYBMUJFWSA-N 0.000 description 2
• 229960000583 acetic acid Drugs 0.000 description 2
• 125000004414 alkyl thio group Chemical group 0.000 description 2
• 150000001413 amino acids Chemical group 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• MVXVYAKCVDQRLW-UHFFFAOYSA-N azain Natural products C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 2
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
• YWKYQRWNOXUYJK-UHFFFAOYSA-N benzyl 3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1CC=CCN1C(=O)OCC1=CC=CC=C1 YWKYQRWNOXUYJK-UHFFFAOYSA-N 0.000 description 2
• 239000004305 biphenyl Substances 0.000 description 2
• IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 125000002837 carbocyclic group Chemical group 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 230000012820 cell cycle checkpoint Effects 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
• 230000002950 deficient Effects 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 2
• 238000007865 diluting Methods 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 239000012636 effector Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 238000001952 enzyme assay Methods 0.000 description 2
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• 150000002430 hydrocarbons Chemical group 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 239000012535 impurity Substances 0.000 description 2
• 125000001041 indolyl group Chemical group 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 230000005865 ionizing radiation Effects 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• 125000001786 isothiazolyl group Chemical group 0.000 description 2
• 231100000225 lethality Toxicity 0.000 description 2
• IOOMXAQUNPWDLL-UHFFFAOYSA-M lissamine rhodamine anion Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S([O-])(=O)=O)C=C1S([O-])(=O)=O IOOMXAQUNPWDLL-UHFFFAOYSA-M 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 231100000682 maximum tolerated dose Toxicity 0.000 description 2
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
• 238000012544 monitoring process Methods 0.000 description 2
• 101150071637 mre11 gene Proteins 0.000 description 2
• XRZNJPQJASFALN-UHFFFAOYSA-N n-(5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl)-1-[(2-cyanophenyl)methyl]pyrazole-4-carboxamide Chemical compound C12=CC(Br)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1C#N XRZNJPQJASFALN-UHFFFAOYSA-N 0.000 description 2
• ASLYMEOTMCLKLQ-UHFFFAOYSA-N n-(5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl)-1-[(2-fluorophenyl)methyl]pyrazole-4-carboxamide Chemical compound FC1=CC=CC=C1CN1N=CC(C(=O)NC=2C3=CC(Br)=CN=C3NC=2)=C1 ASLYMEOTMCLKLQ-UHFFFAOYSA-N 0.000 description 2
• JHZHSQCMNHPMQR-UHFFFAOYSA-N n-(5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl)-1-[(4-fluorophenyl)methyl]pyrazole-4-carboxamide Chemical compound C1=CC(F)=CC=C1CN1N=CC(C(=O)NC=2C3=CC(Br)=CN=C3NC=2)=C1 JHZHSQCMNHPMQR-UHFFFAOYSA-N 0.000 description 2
• YSEIJTJGIBDVBU-UHFFFAOYSA-N n-(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)-1-[(4-fluorophenyl)methyl]pyrazole-4-carboxamide Chemical compound C1=CC(F)=CC=C1CN1N=CC(C(=O)NC=2C3=CC(Cl)=CN=C3NC=2)=C1 YSEIJTJGIBDVBU-UHFFFAOYSA-N 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
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
• AHTMQORKLQAAMI-MRXNPFEDSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-(pyridin-3-ylmethyl)pyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1=CN(CC=3C=NC=CC=3)N=C1)=CN2 AHTMQORKLQAAMI-MRXNPFEDSA-N 0.000 description 2
• KWBOHFWRWKIONX-MRXNPFEDSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-(pyridin-4-ylmethyl)pyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CN=CC=3)N=C1)=CN2 KWBOHFWRWKIONX-MRXNPFEDSA-N 0.000 description 2
• MZRXXLIYVNTBDV-QGZVFWFLSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-[(4-methoxyphenyl)methyl]pyrazole-4-carboxamide Chemical compound C1=CC(OC)=CC=C1CN1N=CC(C(=O)NC=2C3=C(N4C[C@H](N)CCC4)C(Br)=CN=C3NC=2)=C1 MZRXXLIYVNTBDV-QGZVFWFLSA-N 0.000 description 2
• ZWZKABMEGYEOBX-MRXNPFEDSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-(pyridin-4-ylmethyl)pyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(Cl)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CN=CC=3)N=C1)=CN2 ZWZKABMEGYEOBX-MRXNPFEDSA-N 0.000 description 2
• PHEWWHHWHGYFGW-QGZVFWFLSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(F)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 PHEWWHHWHGYFGW-QGZVFWFLSA-N 0.000 description 2
• LGOPTKMIOURNCV-LJQANCHMSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-methoxy-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-[(2-methylphenyl)methyl]pyrazole-4-carboxamide Chemical compound C12=C(N3C[C@H](N)CCC3)C(OC)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1C LGOPTKMIOURNCV-LJQANCHMSA-N 0.000 description 2
• OYIXCSYMSNDXOH-GOSISDBHSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-methoxy-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-[(3-fluorophenyl)methyl]pyrazole-4-carboxamide Chemical compound C12=C(N3C[C@H](N)CCC3)C(OC)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=CC(F)=C1 OYIXCSYMSNDXOH-GOSISDBHSA-N 0.000 description 2
• MPWNBGYRKVPEDL-LJQANCHMSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-methoxy-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-[(3-methylphenyl)methyl]pyrazole-4-carboxamide Chemical compound C12=C(N3C[C@H](N)CCC3)C(OC)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=CC(C)=C1 MPWNBGYRKVPEDL-LJQANCHMSA-N 0.000 description 2
• BWALUAWCEKXXCM-GOSISDBHSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-(pyridin-3-ylmethyl)pyrazole-4-carboxamide Chemical compound C12=C(N3C[C@H](N)CCC3)C(C)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=CN=C1 BWALUAWCEKXXCM-GOSISDBHSA-N 0.000 description 2
• ASUJIXSPTFXYHQ-GOSISDBHSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-(pyridin-4-ylmethyl)pyrazole-4-carboxamide Chemical compound C12=C(N3C[C@H](N)CCC3)C(C)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=NC=C1 ASUJIXSPTFXYHQ-GOSISDBHSA-N 0.000 description 2
• 239000012299 nitrogen atmosphere Substances 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 239000010502 orange oil Substances 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• 125000002971 oxazolyl group Chemical group 0.000 description 2
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
• 230000026731 phosphorylation Effects 0.000 description 2
• 238000006366 phosphorylation reaction Methods 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
• 125000003226 pyrazolyl group Chemical group 0.000 description 2
• QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 239000000741 silica gel Substances 0.000 description 2
• 229910002027 silica gel Inorganic materials 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• 229960001866 silicon dioxide Drugs 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 238000000527 sonication Methods 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 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 2
• PXPBIKLQGJBGRG-HXUWFJFHSA-N tert-butyl n-[(3r)-1-[3-[[1-[(4-fluorophenyl)methyl]pyrazole-4-carbonyl]amino]-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCCN1C1=C(C(F)(F)F)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC(F)=CC=3)N=C1)=CN2 PXPBIKLQGJBGRG-HXUWFJFHSA-N 0.000 description 2
• MBSRUUCAYDFSGF-OAQYLSRUSA-N tert-butyl n-[(3r)-1-[3-[[1-[(4-fluorophenyl)methyl]pyrazole-4-carbonyl]amino]-5-methoxy-1h-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-yl]carbamate Chemical compound C12=C(N3C[C@@H](CCC3)NC(=O)OC(C)(C)C)C(OC)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=C(F)C=C1 MBSRUUCAYDFSGF-OAQYLSRUSA-N 0.000 description 2
• DQQJBEAXSOOCPG-SSDOTTSWSA-N tert-butyl n-[(3r)-pyrrolidin-3-yl]carbamate Chemical group CC(C)(C)OC(=O)N[C@@H]1CCNC1 DQQJBEAXSOOCPG-SSDOTTSWSA-N 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 125000001113 thiadiazolyl group Chemical group 0.000 description 2
• 125000000335 thiazolyl group Chemical group 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
• 210000004881 tumor cell Anatomy 0.000 description 2
• GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 2
• VLECDMDGMKPUSK-NUBCRITNSA-N (3r)-piperidin-3-ol;hydrochloride Chemical group Cl.O[C@@H]1CCCNC1 VLECDMDGMKPUSK-NUBCRITNSA-N 0.000 description 1
• JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical group O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 1
• VXWBQOJISHAKKM-UHFFFAOYSA-N (4-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)C=C1 VXWBQOJISHAKKM-UHFFFAOYSA-N 0.000 description 1
• DEQOVKFWRPOPQP-UHFFFAOYSA-N (5-formylthiophen-2-yl)boronic acid Chemical group OB(O)C1=CC=C(C=O)S1 DEQOVKFWRPOPQP-UHFFFAOYSA-N 0.000 description 1
• ZCUFJAORCNFWOF-UHFFFAOYSA-N (5-formylthiophen-3-yl)boronic acid Chemical group OB(O)C1=CSC(C=O)=C1 ZCUFJAORCNFWOF-UHFFFAOYSA-N 0.000 description 1
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
• ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
• NVNPLEPBDPJYRZ-UHFFFAOYSA-N 1-(bromomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CBr)C=C1 NVNPLEPBDPJYRZ-UHFFFAOYSA-N 0.000 description 1
• ALSCRMRUUIZZBO-UHFFFAOYSA-N 1-[(2-cyanophenyl)methyl]pyrazole-4-carboxylic acid Chemical group C1=C(C(=O)O)C=NN1CC1=CC=CC=C1C#N ALSCRMRUUIZZBO-UHFFFAOYSA-N 0.000 description 1
• SEVWRBACKOQREE-UHFFFAOYSA-N 1-[(2-fluorophenyl)methyl]pyrazole-4-carboxylic acid Chemical group C1=C(C(=O)O)C=NN1CC1=CC=CC=C1F SEVWRBACKOQREE-UHFFFAOYSA-N 0.000 description 1
• QELIFVMICKIPRJ-UHFFFAOYSA-N 1-[(2-methylphenyl)methyl]pyrazole-4-carboxylic acid Chemical group CC1=CC=CC=C1CN1N=CC(C(O)=O)=C1 QELIFVMICKIPRJ-UHFFFAOYSA-N 0.000 description 1
• IVDPFMFNQXHGNX-UHFFFAOYSA-N 1-[(3-fluorophenyl)methyl]pyrazole-4-carboxylic acid Chemical group C1=C(C(=O)O)C=NN1CC1=CC=CC(F)=C1 IVDPFMFNQXHGNX-UHFFFAOYSA-N 0.000 description 1
• PBGWCCZEAHKYKB-UHFFFAOYSA-N 1-[(3-methylphenyl)methyl]pyrazole-4-carboxylic acid Chemical group CC1=CC=CC(CN2N=CC(=C2)C(O)=O)=C1 PBGWCCZEAHKYKB-UHFFFAOYSA-N 0.000 description 1
• ATWXYVDFJLESJV-UHFFFAOYSA-N 1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrrolidine Chemical group O1C(C)(C)C(C)(C)OB1C1=CC=CC(N2CCCC2)=C1 ATWXYVDFJLESJV-UHFFFAOYSA-N 0.000 description 1
• SYYBDNPGDKKJDU-ZDUSSCGKSA-N 1-[5-bromo-4-methyl-2-[[(2S)-2-morpholinyl]methoxy]phenyl]-3-(5-methyl-2-pyrazinyl)urea Chemical compound C1=NC(C)=CN=C1NC(=O)NC1=CC(Br)=C(C)C=C1OC[C@H]1OCCNC1 SYYBDNPGDKKJDU-ZDUSSCGKSA-N 0.000 description 1
• 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
• FNUNODOPANYPJX-UHFFFAOYSA-N 1-benzyl-N-[1-(4-methylphenyl)sulfonyl-5-[3-(1-methylpiperidin-3-yl)oxyphenyl]pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound CN1CC(CCC1)OC=1C=C(C=CC1)C=1C=C2C(=NC1)N(C=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)S(=O)(=O)C2=CC=C(C=C2)C FNUNODOPANYPJX-UHFFFAOYSA-N 0.000 description 1
• IIWWOSRETZGKGC-HKBQPEDESA-N 1-benzyl-N-[1-(4-methylphenyl)sulfonyl-5-[3-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]phenyl]pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound CN1CCC[C@H]1COc1cccc(c1)-c1cnc2n(cc(NC(=O)c3cnn(Cc4ccccc4)c3)c2c1)S(=O)(=O)c1ccc(C)cc1 IIWWOSRETZGKGC-HKBQPEDESA-N 0.000 description 1
• ZXPMQTKJDAVJIN-UHFFFAOYSA-N 1-benzyl-N-[5-(5-formylthiophen-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C(=O)C1=CC=C(S1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 ZXPMQTKJDAVJIN-UHFFFAOYSA-N 0.000 description 1
• DLSLDFAQJNGMKK-UHFFFAOYSA-N 1-benzyl-N-[5-[3-[(3,3-difluoropiperidin-1-yl)methyl]phenyl]-1-(4-methylphenyl)sulfonylpyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound FC1(CN(CCC1)CC=1C=C(C=CC=1)C=1C=C2C(=NC=1)N(C=C2NC(=O)C=1C=NN(C=1)CC1=CC=CC=C1)S(=O)(=O)C1=CC=C(C=C1)C)F DLSLDFAQJNGMKK-UHFFFAOYSA-N 0.000 description 1
• VRHKTPMCIVSRJQ-UHFFFAOYSA-N 1-benzyl-n-[5-(3-pyrrolidin-1-ylphenyl)-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(C=1)=CC=CC=1N1CCCC1 VRHKTPMCIVSRJQ-UHFFFAOYSA-N 0.000 description 1
• KPNGWKHUIVRLGR-UHFFFAOYSA-N 1-benzyl-n-[5-[1-(2-pyrrolidin-1-ylethyl)pyrazol-4-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(=C1)C=NN1CCN1CCCC1 KPNGWKHUIVRLGR-UHFFFAOYSA-N 0.000 description 1
• HLZMBGHAGVCGKD-UHFFFAOYSA-N 1-benzyl-n-[5-[2-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C=1C=C(C=2C=C3C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)=CNC3=NC=2)C(F)=CC=1CN1CCCC1 HLZMBGHAGVCGKD-UHFFFAOYSA-N 0.000 description 1
• FKVNJWFPVGBMHU-UHFFFAOYSA-N 1-benzyl-n-[5-[3-(pyrrolidin-1-ylmethyl)phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(C=1)=CC=CC=1CN1CCCC1 FKVNJWFPVGBMHU-UHFFFAOYSA-N 0.000 description 1
• SXYOIQPOSWUZHF-UHFFFAOYSA-N 1-benzyl-n-[5-[3-[(3,3-difluoroazetidin-1-yl)methyl]phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1C(F)(F)CN1CC1=CC=CC(C=2C=C3C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)=CNC3=NC=2)=C1 SXYOIQPOSWUZHF-UHFFFAOYSA-N 0.000 description 1
• SFIBYAJMZBUDEP-UHFFFAOYSA-N 1-benzyl-n-[5-[3-[(3-fluoropiperidin-1-yl)methyl]phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1C(F)CCCN1CC1=CC=CC(C=2C=C3C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)=CNC3=NC=2)=C1 SFIBYAJMZBUDEP-UHFFFAOYSA-N 0.000 description 1
• RCKUZUSNWYHRIU-UHFFFAOYSA-N 1-benzyl-n-[5-[3-[3-(dimethylamino)-2,2-dimethylpropoxy]phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound CN(C)CC(C)(C)COC1=CC=CC(C=2C=C3C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)=CNC3=NC=2)=C1 RCKUZUSNWYHRIU-UHFFFAOYSA-N 0.000 description 1
• COGQQFNLQDLLDI-UHFFFAOYSA-N 1-benzyl-n-[5-[4-(methylaminomethyl)phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=CC(CNC)=CC=C1C1=CN=C(NC=C2NC(=O)C3=CN(CC=4C=CC=CC=4)N=C3)C2=C1 COGQQFNLQDLLDI-UHFFFAOYSA-N 0.000 description 1
• IQBWEJGHTHXWAW-UHFFFAOYSA-N 1-benzyl-n-[5-[4-(morpholin-4-ylmethyl)phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(C=C1)=CC=C1CN1CCOCC1 IQBWEJGHTHXWAW-UHFFFAOYSA-N 0.000 description 1
• ZMCSBUCSRQVLBA-UHFFFAOYSA-N 1-benzyl-n-[5-[4-(pyrrolidin-1-ylmethyl)phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(C=C1)=CC=C1CN1CCCC1 ZMCSBUCSRQVLBA-UHFFFAOYSA-N 0.000 description 1
• BLLXERLFSOJNOT-UHFFFAOYSA-N 1-benzyl-n-[5-[4-[(3,3-difluoropyrrolidin-1-yl)methyl]phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1C(F)(F)CCN1CC1=CC=C(C=2C=C3C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)=CNC3=NC=2)C=C1 BLLXERLFSOJNOT-UHFFFAOYSA-N 0.000 description 1
• WRVVBGFYPHYTGJ-UHFFFAOYSA-N 1-benzyl-n-[5-[4-[(3-fluoropiperidin-1-yl)methyl]phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1C(F)CCCN1CC1=CC=C(C=2C=C3C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)=CNC3=NC=2)C=C1 WRVVBGFYPHYTGJ-UHFFFAOYSA-N 0.000 description 1
• JENONEIRHGQXAF-UHFFFAOYSA-N 1-benzyl-n-[5-[4-[(4-fluoropiperidin-1-yl)methyl]phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1CC(F)CCN1CC1=CC=C(C=2C=C3C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)=CNC3=NC=2)C=C1 JENONEIRHGQXAF-UHFFFAOYSA-N 0.000 description 1
• HUEAWOHEOVJAGH-UHFFFAOYSA-N 1-benzyl-n-[5-[4-[(dimethylamino)methyl]phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=CC(CN(C)C)=CC=C1C1=CN=C(NC=C2NC(=O)C3=CN(CC=4C=CC=CC=4)N=C3)C2=C1 HUEAWOHEOVJAGH-UHFFFAOYSA-N 0.000 description 1
• VNMIEOYDXHEBID-OAQYLSRUSA-N 1-benzyl-n-[5-bromo-4-[(3r)-3-(2-methylpropylamino)piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1[C@H](NCC(C)C)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 VNMIEOYDXHEBID-OAQYLSRUSA-N 0.000 description 1
• QZQBBQDPZSEQAX-LJQANCHMSA-N 1-benzyl-n-[5-bromo-4-[(3r)-3-(ethylamino)piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1[C@H](NCC)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 QZQBBQDPZSEQAX-LJQANCHMSA-N 0.000 description 1
• YJMRDASTXLIUJT-GOSISDBHSA-N 1-benzyl-n-[5-bromo-4-[(3r)-3-(methylamino)piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1[C@H](NC)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 YJMRDASTXLIUJT-GOSISDBHSA-N 0.000 description 1
• XUNIQFSPDUAMQG-QGZVFWFLSA-N 1-benzyl-n-[5-bromo-4-[(3r)-3-hydroxypiperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1[C@H](O)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 XUNIQFSPDUAMQG-QGZVFWFLSA-N 0.000 description 1
• UOOLXMHPWCOLLX-MRXNPFEDSA-N 1-benzyl-n-[5-bromo-4-[(3r)-3-hydroxypyrrolidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1[C@H](O)CCN1C1=C(Br)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 UOOLXMHPWCOLLX-MRXNPFEDSA-N 0.000 description 1
• MBURDEXNWSTAFU-UHFFFAOYSA-N 1-benzyl-n-[5-bromo-4-[3-(dimethylamino)piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1C(N(C)C)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 MBURDEXNWSTAFU-UHFFFAOYSA-N 0.000 description 1
• RBYWKNNPGORGMC-UHFFFAOYSA-N 1-benzylpyrazole-4-carboxylic acid 5-[5-[(3,3-difluoroazetidin-1-yl)methyl]thiophen-3-yl]-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound NC(C1=C2)=CNC1=NC=C2C1=CSC(CN(C2)CC2(F)F)=C1.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O RBYWKNNPGORGMC-UHFFFAOYSA-N 0.000 description 1
• UCNGGGYMLHAMJG-UHFFFAOYSA-N 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical group C1=NN(C)C=C1B1OC(C)(C)C(C)(C)O1 UCNGGGYMLHAMJG-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• HCTKTFWOSSBSIL-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=CC=C2C(N)=CNC2=N1 HCTKTFWOSSBSIL-UHFFFAOYSA-N 0.000 description 1
• JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
• IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
• HLMHCDKXKXBKQK-UHFFFAOYSA-N 2-bromoethyl(diethyl)azanium;bromide Chemical compound Br.CCN(CC)CCBr HLMHCDKXKXBKQK-UHFFFAOYSA-N 0.000 description 1
• ILJKKAIQFPEIBL-UHFFFAOYSA-N 2-cyclopropyl-2-hydroxyacetonitrile Chemical group N#CC(O)C1CC1 ILJKKAIQFPEIBL-UHFFFAOYSA-N 0.000 description 1
• CTRPRMNBTVRDFH-UHFFFAOYSA-N 2-n-methyl-1,3,5-triazine-2,4,6-triamine Chemical compound CNC1=NC(N)=NC(N)=N1 CTRPRMNBTVRDFH-UHFFFAOYSA-N 0.000 description 1
• LEHHIPIDKQVNEV-UHFFFAOYSA-N 3,3-difluoropiperidine;hydrochloride Chemical group Cl.FC1(F)CCCNC1 LEHHIPIDKQVNEV-UHFFFAOYSA-N 0.000 description 1
• YYVPZQADFREIFR-UHFFFAOYSA-N 3,3-difluoropyrrolidine;hydrochloride Chemical group [Cl-].FC1(F)CC[NH2+]C1 YYVPZQADFREIFR-UHFFFAOYSA-N 0.000 description 1
• XEZLBMHDUXSICI-UHFFFAOYSA-N 3-(1-ethylpiperidin-4-yl)oxy-5,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaene-4-carbonitrile Chemical compound C1CN(CC)CCC1OC1=C(C#N)N=CC2=C1C1=CC=CN=C1N2 XEZLBMHDUXSICI-UHFFFAOYSA-N 0.000 description 1
• VZYZKPJAXWDZFT-UHFFFAOYSA-N 3-(bromomethyl)-1-methylpiperidine Chemical group CN1CCCC(CBr)C1 VZYZKPJAXWDZFT-UHFFFAOYSA-N 0.000 description 1
• IAYGCINLNONXHY-LBPRGKRZSA-N 3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-3-piperidinyl]-2-thiophenecarboxamide Chemical compound NC(=O)NC=1C=C(C=2C=C(F)C=CC=2)SC=1C(=O)N[C@H]1CCCNC1 IAYGCINLNONXHY-LBPRGKRZSA-N 0.000 description 1
• PYEWZDAEJUUIJX-UHFFFAOYSA-N 3-(dimethylamino)-2,2-dimethylpropan-1-ol Chemical compound CN(C)CC(C)(C)CO PYEWZDAEJUUIJX-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• MNOJRWOWILAHAV-UHFFFAOYSA-N 3-bromophenol Chemical compound OC1=CC=CC(Br)=C1 MNOJRWOWILAHAV-UHFFFAOYSA-N 0.000 description 1
• LJQNMDZRCXJETK-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine;hydron;chloride Chemical compound Cl.CN(C)CCCCl LJQNMDZRCXJETK-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• KBEIFKMKVCDETC-UHFFFAOYSA-N 3-iodooxetane Chemical group IC1COC1 KBEIFKMKVCDETC-UHFFFAOYSA-N 0.000 description 1
• FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 1
• ZAPMTSHEXFEPSD-UHFFFAOYSA-N 4-(2-chloroethyl)morpholine Chemical compound ClCCN1CCOCC1 ZAPMTSHEXFEPSD-UHFFFAOYSA-N 0.000 description 1
• PIAZYBLGBSMNLX-UHFFFAOYSA-N 4-(3-chloropropyl)morpholine Chemical group ClCCCN1CCOCC1 PIAZYBLGBSMNLX-UHFFFAOYSA-N 0.000 description 1
• HXWHKHVVPMTTLJ-CYBMUJFWSA-N 4-[(3R)-3-aminopiperidin-1-yl]-5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1[C@H](N)CCCN1C1=C(C=2C=CC=CC=2)C=NC2=C1C(N)=CN2 HXWHKHVVPMTTLJ-CYBMUJFWSA-N 0.000 description 1
• SZDGCPAAQKHPFH-ZCFIWIBFSA-N 4-[(3R)-3-aminopyrrolidin-1-yl]-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1[C@H](N)CCN1C1=C(Cl)C=NC2=C1C(N)=CN2 SZDGCPAAQKHPFH-ZCFIWIBFSA-N 0.000 description 1
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
• BZBNGPXWPOQJPT-UHFFFAOYSA-N 4-bromo-1,2-dihydropyrrolo[3,2-b]pyridine Chemical compound BrN1C=CC=C2NCC=C12 BZBNGPXWPOQJPT-UHFFFAOYSA-N 0.000 description 1
• WVGCPEDBFHEHEZ-UHFFFAOYSA-N 4-bromo-1h-pyrazole Chemical compound BrC=1C=NNC=1 WVGCPEDBFHEHEZ-UHFFFAOYSA-N 0.000 description 1
• HNTZVGMWXCFCTA-UHFFFAOYSA-N 4-chloro-1h-pyrrolo[2,3-b]pyridine Chemical group ClC1=CC=NC2=C1C=CN2 HNTZVGMWXCFCTA-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• IXENWFQXVCOHAZ-UHFFFAOYSA-N 4-fluoropiperidine;hydrochloride Chemical group Cl.FC1CCNCC1 IXENWFQXVCOHAZ-UHFFFAOYSA-N 0.000 description 1
• CAIZJLPXHFFJFO-UHFFFAOYSA-N 5-[1-(2-pyrrolidin-1-ylethyl)pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=C2C(N)=CNC2=NC=C1C(=C1)C=NN1CCN1CCCC1 CAIZJLPXHFFJFO-UHFFFAOYSA-N 0.000 description 1
• OEHQEMWNVNXSPE-UHFFFAOYSA-N 5-[3-(2-morpholin-4-ylethoxy)phenyl]-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=C2C(N)=CNC2=NC=C1C(C=1)=CC=CC=1OCCN1CCOCC1 OEHQEMWNVNXSPE-UHFFFAOYSA-N 0.000 description 1
• JTIFJTIBYDWWJO-UHFFFAOYSA-N 5-[3-[(1-methylpiperidin-3-yl)methoxy]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1N(C)CCCC1COC1=CC=CC(C=2C=C3C(N)=CNC3=NC=2)=C1 JTIFJTIBYDWWJO-UHFFFAOYSA-N 0.000 description 1
• QZIVPSUZFSQBKH-UHFFFAOYSA-N 5-[3-[(3,3-difluoropiperidin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=C2C(N)=CNC2=NC=C1C(C=1)=CC=CC=1CN1CCCC(F)(F)C1 QZIVPSUZFSQBKH-UHFFFAOYSA-N 0.000 description 1
• XOEZQJWSGXVJAB-UHFFFAOYSA-N 5-[4-[(3-fluoropiperidin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=C2C(N)=CNC2=NC=C1C(C=C1)=CC=C1CN1CCCC(F)C1 XOEZQJWSGXVJAB-UHFFFAOYSA-N 0.000 description 1
• KHWHOZAZVCZUJJ-UHFFFAOYSA-N 5-[4-[(4-fluoropiperidin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=C2C(N)=CNC2=NC=C1C(C=C1)=CC=C1CN1CCC(F)CC1 KHWHOZAZVCZUJJ-UHFFFAOYSA-N 0.000 description 1
• ANNXLXWBHJQDHZ-UHFFFAOYSA-N 5-[5-[(3,3-difluoroazetidin-1-yl)methyl]thiophen-3-yl]-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=C2C(N)=CNC2=NC=C1C(C=1)=CSC=1CN1CC(F)(F)C1 ANNXLXWBHJQDHZ-UHFFFAOYSA-N 0.000 description 1
• YALUKZAGHLPXPO-CYBMUJFWSA-N 5-bromo-4-[(3R)-3-(cyclopentylmethylamino)piperidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound N([C@@H]1CCCN(C1)C=1C(Br)=CN=C2NC=C(C=12)N)CC1CCCC1 YALUKZAGHLPXPO-CYBMUJFWSA-N 0.000 description 1
• MFZQJIKENSPRSJ-UHFFFAOYSA-N 5-chloro-1h-pyrrolo[2,3-b]pyridine Chemical group ClC1=CN=C2NC=CC2=C1 MFZQJIKENSPRSJ-UHFFFAOYSA-N 0.000 description 1
• DEZAIQUWOITSPT-UHFFFAOYSA-N 5-chloro-3-nitro-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=C(Cl)C=C2C([N+](=O)[O-])=CNC2=N1 DEZAIQUWOITSPT-UHFFFAOYSA-N 0.000 description 1
• DJCJHFFRHKGOCQ-UHFFFAOYSA-N 5-methyl-1h-pyrrolo[2,3-b]pyridine Chemical group CC1=CN=C2NC=CC2=C1 DJCJHFFRHKGOCQ-UHFFFAOYSA-N 0.000 description 1
• OWGGSXQRLHNDGC-UHFFFAOYSA-N 5-methyl-3-nitro-1h-pyrrolo[2,3-b]pyridine Chemical group CC1=CN=C2NC=C([N+]([O-])=O)C2=C1 OWGGSXQRLHNDGC-UHFFFAOYSA-N 0.000 description 1
• FABOGBCGXOXMKJ-UHFFFAOYSA-N 5-phenyl-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=C2C(N)=CNC2=NC=C1C1=CC=CC=C1 FABOGBCGXOXMKJ-UHFFFAOYSA-N 0.000 description 1
• GMIZZEXBPRLVIV-SECBINFHSA-N 6-bromo-3-(1-methylpyrazol-4-yl)-5-[(3r)-piperidin-3-yl]pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=NN(C)C=C1C1=C2N=C([C@H]3CNCCC3)C(Br)=C(N)N2N=C1 GMIZZEXBPRLVIV-SECBINFHSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 239000012099 Alexa Fluor family Substances 0.000 description 1
• 235000019489 Almond oil Nutrition 0.000 description 1
• 108010024976 Asparaginase Proteins 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 241000937413 Axia Species 0.000 description 1
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• LLOQOEIEKWFHRV-UHFFFAOYSA-N BrC=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=C(C=CC=C2)C#N.BrC=2C=C1C(=NC2)NC=C1NC(=O)C=1C=NN(C1)CC1=C(C=CC=C1)F Chemical compound BrC=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=C(C=CC=C2)C#N.BrC=2C=C1C(=NC2)NC=C1NC(=O)C=1C=NN(C1)CC1=C(C=CC=C1)F LLOQOEIEKWFHRV-UHFFFAOYSA-N 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• OGMPGWHSCRAOJC-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.BrC=1C(=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)N2CC(CCC2)N(C)C Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.BrC=1C(=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)N2CC(CCC2)N(C)C OGMPGWHSCRAOJC-UHFFFAOYSA-N 0.000 description 1
• BMGLURLQYUOSQF-FSRHSHDFSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.BrC=1C(=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)N2C[C@@H](CCC2)NCC Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.BrC=1C(=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)N2C[C@@H](CCC2)NCC BMGLURLQYUOSQF-FSRHSHDFSA-N 0.000 description 1
• CLOWZCJCZNXHOG-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.C(C)N(CCN1N=CC(=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)CC Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.C(C)N(CCN1N=CC(=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)CC CLOWZCJCZNXHOG-UHFFFAOYSA-N 0.000 description 1
• PCTMORGVTOSOJE-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN(C)CC=1C=C(C=CC1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN(C)CC=1C=C(C=CC1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 PCTMORGVTOSOJE-UHFFFAOYSA-N 0.000 description 1
• XBMFSGXLIPBRKO-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN(CC(COC=1C=C(C=CC1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)(C)C)C Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN(CC(COC=1C=C(C=CC1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)(C)C)C XBMFSGXLIPBRKO-UHFFFAOYSA-N 0.000 description 1
• PKVCTXDIQCVNNP-UQIIZPHYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN1[C@@H](CCC1)COC=1C=C(C=CC1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN1[C@@H](CCC1)COC=1C=C(C=CC1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 PKVCTXDIQCVNNP-UQIIZPHYSA-N 0.000 description 1
• IUEZQVCAQYRAFK-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.FC1CN(CCC1)CC1=CC=C(C=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.FC1CN(CCC1)CC1=CC=C(C=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 IUEZQVCAQYRAFK-UHFFFAOYSA-N 0.000 description 1
• XBOFWHNVUMQWFJ-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.N1(CCCC1)CC1=CC=C(C=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.N1(CCCC1)CC1=CC=C(C=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 XBOFWHNVUMQWFJ-UHFFFAOYSA-N 0.000 description 1
• QLEAMDSDDJDRHO-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.N1(CCCC1)CC1=CC=C(S1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.N1(CCCC1)CC1=CC=C(S1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 QLEAMDSDDJDRHO-UHFFFAOYSA-N 0.000 description 1
• UGGAJCLMYNPURU-PKLMIRHRSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.N[C@H]1CN(CC1)C1=C2C(=NC=C1Br)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.N[C@H]1CN(CC1)C1=C2C(=NC=C1Br)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 UGGAJCLMYNPURU-PKLMIRHRSA-N 0.000 description 1
• GXMZVJHJKMXIIA-GNAFDRTKSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.N[C@H]1CN(CCC1)C1=C2C(=NC=C1C1=CC=CC=C1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.N[C@H]1CN(CCC1)C1=C2C(=NC=C1C1=CC=CC=C1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 GXMZVJHJKMXIIA-GNAFDRTKSA-N 0.000 description 1
• AMIUXBXGZNSUEB-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.O1CC(C1)OC=1C=C(C=CC1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.O1CC(C1)OC=1C=C(C=CC1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 AMIUXBXGZNSUEB-UHFFFAOYSA-N 0.000 description 1
• HWNDZLSNNWFFEJ-SBSPUUFOSA-N CC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC(C=C2)=CC=C2F)N=C1)=O Chemical compound CC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC(C=C2)=CC=C2F)N=C1)=O HWNDZLSNNWFFEJ-SBSPUUFOSA-N 0.000 description 1
• OMJAUIMFWRLBAY-SBSPUUFOSA-N CC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC2=CC=CN=C2)N=C1)=O Chemical compound CC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC2=CC=CN=C2)N=C1)=O OMJAUIMFWRLBAY-SBSPUUFOSA-N 0.000 description 1
• DVQDRSRXPMVYEC-OGFXRTJISA-N CC1=CC=C(CN2N=CC(C(O)=O)=C2)C=C1.N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br Chemical compound CC1=CC=C(CN2N=CC(C(O)=O)=C2)C=C1.N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br DVQDRSRXPMVYEC-OGFXRTJISA-N 0.000 description 1
• NQDDPBXCTLBGRZ-DDWIOCJRSA-N CC1=CC=CC(CN2N=CC(C(O)=O)=C2)=C1.COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N Chemical compound CC1=CC=CC(CN2N=CC(C(O)=O)=C2)=C1.COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N NQDDPBXCTLBGRZ-DDWIOCJRSA-N 0.000 description 1
• LFPNOJWVMMWSOD-UHFFFAOYSA-N CN(C)C1CCCN(C1)c1c(Br)cnc2[nH]cc(N)c12 Chemical compound CN(C)C1CCCN(C1)c1c(Br)cnc2[nH]cc(N)c12 LFPNOJWVMMWSOD-UHFFFAOYSA-N 0.000 description 1
• UGLULSBFXMGBTB-UHFFFAOYSA-N CN(C)CC(C=C1)=CC=C1C(C=C12)=CN=C1NC=C2NC(C1=CN(CC2=CC=CC=C2)N=C1)=O.NC(C1=C2)=CNC1=NC=C2C1=CC=C(CN(CC2)CCC2F)C=C1 Chemical compound CN(C)CC(C=C1)=CC=C1C(C=C12)=CN=C1NC=C2NC(C1=CN(CC2=CC=CC=C2)N=C1)=O.NC(C1=C2)=CNC1=NC=C2C1=CC=C(CN(CC2)CCC2F)C=C1 UGLULSBFXMGBTB-UHFFFAOYSA-N 0.000 description 1
• YUVPCMAVSSSYSQ-UHFFFAOYSA-N CN(C)CCCOC(C=C1)=CC=C1C(C=C12)=CN=C1NC=C2NC(C1=CN(CC2=CC=CC=C2)N=C1)=O.CN(CCC1)CC1OC1=CC=CC(C(C=C23)=CN=C2NC=C3N)=C1 Chemical compound CN(C)CCCOC(C=C1)=CC=C1C(C=C12)=CN=C1NC=C2NC(C1=CN(CC2=CC=CC=C2)N=C1)=O.CN(CCC1)CC1OC1=CC=CC(C(C=C23)=CN=C2NC=C3N)=C1 YUVPCMAVSSSYSQ-UHFFFAOYSA-N 0.000 description 1
• LWAFCCQSFGQAQC-UHFFFAOYSA-N CN(C)Cc1ccc(cc1)-c1cnc2[nH]cc(N)c2c1 Chemical compound CN(C)Cc1ccc(cc1)-c1cnc2[nH]cc(N)c2c1 LWAFCCQSFGQAQC-UHFFFAOYSA-N 0.000 description 1
• AOWKUNXVSWMTSM-UHFFFAOYSA-N CN(C)Cc1cccc(c1)-c1cnc2[nH]cc(N)c2c1 Chemical compound CN(C)Cc1cccc(c1)-c1cnc2[nH]cc(N)c2c1 AOWKUNXVSWMTSM-UHFFFAOYSA-N 0.000 description 1
• WFSOVBYUZOGEBY-UHFFFAOYSA-N CNCC(C=C1)=CC=C1C(C=C12)=CN=C1NC=C2N.O=C(C1=CN(CC2=CC=CC=C2)N=C1)NC(C1=C2)=CNC1=NC=C2C1=CC=C(CN2CCOCC2)C=C1 Chemical compound CNCC(C=C1)=CC=C1C(C=C12)=CN=C1NC=C2N.O=C(C1=CN(CC2=CC=CC=C2)N=C1)NC(C1=C2)=CNC1=NC=C2C1=CC=C(CN2CCOCC2)C=C1 WFSOVBYUZOGEBY-UHFFFAOYSA-N 0.000 description 1
• PKOCEBONEXDTFY-UHFFFAOYSA-N CNCc1ccc(cc1)-c1cnc2[nH]cc(N)c2c1 Chemical compound CNCc1ccc(cc1)-c1cnc2[nH]cc(N)c2c1 PKOCEBONEXDTFY-UHFFFAOYSA-N 0.000 description 1
• KKKORGHFBPSQCN-MRVPVSSYSA-N CN[C@@H]1CCCN(C1)c1c(Br)cnc2[nH]cc(N)c12 Chemical compound CN[C@@H]1CCCN(C1)c1c(Br)cnc2[nH]cc(N)c12 KKKORGHFBPSQCN-MRVPVSSYSA-N 0.000 description 1
• PRAUREVGHZSSDV-DDWIOCJRSA-N COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC(C=CC=C2)=C2Cl)N=C1)=O Chemical compound COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC(C=CC=C2)=C2Cl)N=C1)=O PRAUREVGHZSSDV-DDWIOCJRSA-N 0.000 description 1
• MSIWZVCYOPLFBZ-DDWIOCJRSA-N COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC2=CC(F)=CC=C2)N=C1)=O Chemical compound COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC2=CC(F)=CC=C2)N=C1)=O MSIWZVCYOPLFBZ-DDWIOCJRSA-N 0.000 description 1
• WVVQPKJIHXFHBG-DDWIOCJRSA-N COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O Chemical compound COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O WVVQPKJIHXFHBG-DDWIOCJRSA-N 0.000 description 1
• ZYRXZOXZXSVHIU-DDWIOCJRSA-N COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC2=CC=CN=C2)N=C1)=O Chemical compound COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC2=CC=CN=C2)N=C1)=O ZYRXZOXZXSVHIU-DDWIOCJRSA-N 0.000 description 1
• HZCMGDNELYYKMH-DDWIOCJRSA-N COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC2=NC=CC=C2)N=C1)=O Chemical compound COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC2=NC=CC=C2)N=C1)=O HZCMGDNELYYKMH-DDWIOCJRSA-N 0.000 description 1
• GFXCEZXCSDIYRL-OGFXRTJISA-N COC1=CC=C(CN2N=CC(C(O)=O)=C2)C=C1.N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br Chemical compound COC1=CC=C(CN2N=CC(C(O)=O)=C2)C=C1.N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br GFXCEZXCSDIYRL-OGFXRTJISA-N 0.000 description 1
• FDZAMAJPQHUQHJ-OGFXRTJISA-N COC1=CC=C(CN2N=CC(C(O)=O)=C2)C=C1.N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Cl Chemical compound COC1=CC=C(CN2N=CC(C(O)=O)=C2)C=C1.N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Cl FDZAMAJPQHUQHJ-OGFXRTJISA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• WHVNAKCUXVQYBR-UNTBIKODSA-N ClC1=CC=C(CN2N=CC(=C2)C(=O)O)C=C1.N[C@H]1CN(CCC1)C1=C2C(=NC=C1Br)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=C(C=C2)F Chemical compound ClC1=CC=C(CN2N=CC(=C2)C(=O)O)C=C1.N[C@H]1CN(CCC1)C1=C2C(=NC=C1Br)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=C(C=C2)F WHVNAKCUXVQYBR-UNTBIKODSA-N 0.000 description 1
• RGKKQRUIVBGXJF-UHFFFAOYSA-N Cn1cc(cn1)-c1cnc2[nH]cc(N)c2c1 Chemical compound Cn1cc(cn1)-c1cnc2[nH]cc(N)c2c1 RGKKQRUIVBGXJF-UHFFFAOYSA-N 0.000 description 1
• 206010053138 Congenital aplastic anaemia Diseases 0.000 description 1
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• 230000007118 DNA alkylation Effects 0.000 description 1
• 230000005778 DNA damage Effects 0.000 description 1
• 231100000277 DNA damage Toxicity 0.000 description 1
• 230000012746 DNA damage checkpoint Effects 0.000 description 1
• 239000012623 DNA damaging agent Substances 0.000 description 1
• 230000004543 DNA replication Effects 0.000 description 1
• BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 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
• 239000004150 EU approved colour Substances 0.000 description 1
• 229910052693 Europium Inorganic materials 0.000 description 1
• KWTYBNKTSQXYLV-GMUIIQOCSA-N FC1=CC=C(CN2N=CC(=C2)C(=O)O)C=C1.N[C@H]1CN(CCC1)C1=C2C(=NC=C1Cl)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=C(C=C2)C Chemical compound FC1=CC=C(CN2N=CC(=C2)C(=O)O)C=C1.N[C@H]1CN(CCC1)C1=C2C(=NC=C1Cl)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=C(C=C2)C KWTYBNKTSQXYLV-GMUIIQOCSA-N 0.000 description 1
• FRFJACSMYUFDEM-FSRHSHDFSA-N FC1=CC=C(CN2N=CC(=C2)C(=O)O)C=C1.N[C@H]1CN(CCC1)C1=C2C(=NC=C1OC)NC=C2NC(=O)C=2C=NN(C2)CC2=C(C=CC=C2)C Chemical compound FC1=CC=C(CN2N=CC(=C2)C(=O)O)C=C1.N[C@H]1CN(CCC1)C1=C2C(=NC=C1OC)NC=C2NC(=O)C=2C=NN(C2)CC2=C(C=CC=C2)C FRFJACSMYUFDEM-FSRHSHDFSA-N 0.000 description 1
• 201000004939 Fanconi anemia Diseases 0.000 description 1
• 230000010337 G2 phase Effects 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
• 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
• 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 description 1
• VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
• 102000014150 Interferons Human genes 0.000 description 1
• 108010050904 Interferons Proteins 0.000 description 1
• 102000000588 Interleukin-2 Human genes 0.000 description 1
• 108010002350 Interleukin-2 Proteins 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
• 235000019759 Maize starch Nutrition 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
• YSGWATGYKAQJOL-UNTBIKODSA-N N1=CC(=CC=C1)CN1N=CC(=C1)C(=O)O.N[C@H]1CN(CCC1)C1=C2C(=NC=C1OC)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=NC=C2 Chemical compound N1=CC(=CC=C1)CN1N=CC(=C1)C(=O)O.N[C@H]1CN(CCC1)C1=C2C(=NC=C1OC)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=NC=C2 YSGWATGYKAQJOL-UNTBIKODSA-N 0.000 description 1
• XGYQOIJLMURDNT-UHFFFAOYSA-N N1=CC=C(C=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2.CN2N=CC(=C2)C=2C=C1C(=NC2)NC=C1NC(=O)C=1C=NN(C1)CC1=CC=CC=C1 Chemical compound N1=CC=C(C=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2.CN2N=CC(=C2)C=2C=C1C(=NC2)NC=C1NC(=O)C=1C=NN(C1)CC1=CC=CC=C1 XGYQOIJLMURDNT-UHFFFAOYSA-N 0.000 description 1
• 101150081841 NBN gene Proteins 0.000 description 1
• XWRYPFPSCKPQSB-UHFFFAOYSA-N NC(C1=C2)=CNC1=NC=C2C(C=CC(CN1CCCC1)=C1)=C1F.O=C(C1=CN(CC2=CC=CC=C2)N=C1)NC(C1=C2)=CNC1=NC=C2C1=CC(N2CCCC2)=CC=C1 Chemical compound NC(C1=C2)=CNC1=NC=C2C(C=CC(CN1CCCC1)=C1)=C1F.O=C(C1=CN(CC2=CC=CC=C2)N=C1)NC(C1=C2)=CNC1=NC=C2C1=CC(N2CCCC2)=CC=C1 XWRYPFPSCKPQSB-UHFFFAOYSA-N 0.000 description 1
• WDIHOGKPAMVSOE-UHFFFAOYSA-N NC(C1=C2)=CNC1=NC=C2C1=CC(OCCCN2CCOCC2)=CC=C1.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O Chemical compound NC(C1=C2)=CNC1=NC=C2C1=CC(OCCCN2CCOCC2)=CC=C1.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O WDIHOGKPAMVSOE-UHFFFAOYSA-N 0.000 description 1
• LPJBVNBESFYLCN-UHFFFAOYSA-N NC(C1=C2)=CNC1=NC=C2C1=CC(OCCN2CCCC2)=CC=C1.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O Chemical compound NC(C1=C2)=CNC1=NC=C2C1=CC(OCCN2CCCC2)=CC=C1.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O LPJBVNBESFYLCN-UHFFFAOYSA-N 0.000 description 1
• KDJRBWIMFMMRKI-UHFFFAOYSA-N NC(C1=C2)=CNC1=NC=C2C1=CSC(CN2CCCC2)=C1.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O Chemical compound NC(C1=C2)=CNC1=NC=C2C1=CSC(CN2CCCC2)=C1.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O KDJRBWIMFMMRKI-UHFFFAOYSA-N 0.000 description 1
• CKAACKNQKCXNMS-IGLJFSGRSA-N NC(C1=C2N(CC3)C[C@@H]3O)=CNC1=NC=C2Br.O[C@H](CCC1)CN1C1=C(C(NC(C2=CN(CC3=CC=CC=C3)N=C2)=O)=CN2)C2=NC=C1Br Chemical compound NC(C1=C2N(CC3)C[C@@H]3O)=CNC1=NC=C2Br.O[C@H](CCC1)CN1C1=C(C(NC(C2=CN(CC3=CC=CC=C3)N=C2)=O)=CN2)C2=NC=C1Br CKAACKNQKCXNMS-IGLJFSGRSA-N 0.000 description 1
• WYJCJMRFXOGRSK-SSDOTTSWSA-N N[C@@H]1CCCN(C1)c1c(F)cnc2[nH]cc(N)c12 Chemical compound N[C@@H]1CCCN(C1)c1c(F)cnc2[nH]cc(N)c12 WYJCJMRFXOGRSK-SSDOTTSWSA-N 0.000 description 1
• WFXGXSDTSFCUCZ-SSDOTTSWSA-N N[C@@H]1CCCN(C1)c1c(O)cnc2[nH]cc(N)c12 Chemical compound N[C@@H]1CCCN(C1)c1c(O)cnc2[nH]cc(N)c12 WFXGXSDTSFCUCZ-SSDOTTSWSA-N 0.000 description 1
• GWNXSSAWSXFAII-ZCFIWIBFSA-N N[C@@H]1CCN(C1)c1c(Br)cnc2[nH]cc(N)c12 Chemical compound N[C@@H]1CCN(C1)c1c(Br)cnc2[nH]cc(N)c12 GWNXSSAWSXFAII-ZCFIWIBFSA-N 0.000 description 1
• UGDLGCRRLJTBCC-OGFXRTJISA-N N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br.OC(C1=CN(CC2=CC=CN=C2)N=C1)=O Chemical compound N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br.OC(C1=CN(CC2=CC=CN=C2)N=C1)=O UGDLGCRRLJTBCC-OGFXRTJISA-N 0.000 description 1
• QPHJTKCDTAWPQT-OGFXRTJISA-N N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br.OC(C1=CN(CC2=CC=NC=C2)N=C1)=O Chemical compound N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br.OC(C1=CN(CC2=CC=NC=C2)N=C1)=O QPHJTKCDTAWPQT-OGFXRTJISA-N 0.000 description 1
• IFMJQMPEPSQUES-OGFXRTJISA-N N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br.OC(C1=CN(CC2=NC=CC=C2)N=C1)=O Chemical compound N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br.OC(C1=CN(CC2=NC=CC=C2)N=C1)=O IFMJQMPEPSQUES-OGFXRTJISA-N 0.000 description 1
• HIDJJTWMVARPOW-YYVQYPFISA-N N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1C#N.O=C(C1=CN(CC2=CC=CC=C2)N=C1)NC(C1=C2)=CNC1=NC=C2C1=CC(OCCN2CCOCC2)=CC=C1 Chemical compound N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1C#N.O=C(C1=CN(CC2=CC=CC=C2)N=C1)NC(C1=C2)=CNC1=NC=C2C1=CC(OCCN2CCOCC2)=CC=C1 HIDJJTWMVARPOW-YYVQYPFISA-N 0.000 description 1
• ATVHNFUCMKFGOK-OGFXRTJISA-N N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Cl.OC(C1=CN(CC(C=C2)=CC=C2Cl)N=C1)=O Chemical compound N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Cl.OC(C1=CN(CC(C=C2)=CC=C2Cl)N=C1)=O ATVHNFUCMKFGOK-OGFXRTJISA-N 0.000 description 1
• WJOWXXHOUGZAOP-OGFXRTJISA-N N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Cl.OC(C1=CN(CC2=NC=CC=C2)N=C1)=O Chemical compound N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Cl.OC(C1=CN(CC2=NC=CC=C2)N=C1)=O WJOWXXHOUGZAOP-OGFXRTJISA-N 0.000 description 1
• HETFFETWHDPVKB-QEKUCLETSA-N N[C@H](CCC1)CN1C1=C(C(NC(C2=CN(CC3=CC=CC=C3)N=C2)=O)=CN2)C2=NC=C1Cl.N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br Chemical compound N[C@H](CCC1)CN1C1=C(C(NC(C2=CN(CC3=CC=CC=C3)N=C2)=O)=CN2)C2=NC=C1Cl.N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br HETFFETWHDPVKB-QEKUCLETSA-N 0.000 description 1
• XCQMBHUTTXGWAY-UNTBIKODSA-N N[C@H](CCC1)CN1C1=C(C(NC(C2=CN(CC3=CC=CC=C3)N=C2)=O)=CN2)C2=NC=C1F.NC(C1=C2)=CNC1=NC=C2C1=CC(CN2CCCC2)=CC=C1 Chemical compound N[C@H](CCC1)CN1C1=C(C(NC(C2=CN(CC3=CC=CC=C3)N=C2)=O)=CN2)C2=NC=C1F.NC(C1=C2)=CNC1=NC=C2C1=CC(CN2CCCC2)=CC=C1 XCQMBHUTTXGWAY-UNTBIKODSA-N 0.000 description 1
• HUYFSOSSMCQTEE-SKDRFNHKSA-N N[C@H]1CN(CC[C@@H]1C1CC1)c1c(Br)cnc2[nH]cc(N)c12 Chemical compound N[C@H]1CN(CC[C@@H]1C1CC1)c1c(Br)cnc2[nH]cc(N)c12 HUYFSOSSMCQTEE-SKDRFNHKSA-N 0.000 description 1
• QOMMKHUMIWLGGK-SSDOTTSWSA-N Nc1c[nH]c2ncc(Br)c(N3CCC[C@@H](O)C3)c12 Chemical compound Nc1c[nH]c2ncc(Br)c(N3CCC[C@@H](O)C3)c12 QOMMKHUMIWLGGK-SSDOTTSWSA-N 0.000 description 1
• ZBBVVJLRFQMCIU-UHFFFAOYSA-N Nc1c[nH]c2ncc(cc12)-c1ccc(CN2CCCC2)cc1 Chemical compound Nc1c[nH]c2ncc(cc12)-c1ccc(CN2CCCC2)cc1 ZBBVVJLRFQMCIU-UHFFFAOYSA-N 0.000 description 1
• VEMXXFAYMSGLHS-UHFFFAOYSA-N Nc1c[nH]c2ncc(cc12)-c1ccc(CN2CCCC2)cc1F Chemical compound Nc1c[nH]c2ncc(cc12)-c1ccc(CN2CCCC2)cc1F VEMXXFAYMSGLHS-UHFFFAOYSA-N 0.000 description 1
• RWZIAHGUGHTSIE-UHFFFAOYSA-N Nc1c[nH]c2ncc(cc12)-c1ccc(CN2CCCC2)s1 Chemical compound Nc1c[nH]c2ncc(cc12)-c1ccc(CN2CCCC2)s1 RWZIAHGUGHTSIE-UHFFFAOYSA-N 0.000 description 1
• CGGNQVPFTZIXJZ-UHFFFAOYSA-N Nc1c[nH]c2ncc(cc12)-c1ccc(CN2CCOCC2)cc1 Chemical compound Nc1c[nH]c2ncc(cc12)-c1ccc(CN2CCOCC2)cc1 CGGNQVPFTZIXJZ-UHFFFAOYSA-N 0.000 description 1
• VCBIHBQQXNRKMP-UHFFFAOYSA-N Nc1c[nH]c2ncc(cc12)-c1cccc(CN2CCCC2)c1 Chemical compound Nc1c[nH]c2ncc(cc12)-c1cccc(CN2CCCC2)c1 VCBIHBQQXNRKMP-UHFFFAOYSA-N 0.000 description 1
• UXNHZYFYYPFIKD-UHFFFAOYSA-N Nc1c[nH]c2ncc(cc12)-c1cccc(OC2COC2)c1 Chemical compound Nc1c[nH]c2ncc(cc12)-c1cccc(OC2COC2)c1 UXNHZYFYYPFIKD-UHFFFAOYSA-N 0.000 description 1
• WZWLPKXQIBPPDW-UHFFFAOYSA-N Nc1c[nH]c2ncc(cc12)-c1cccc(OCCCN2CCOCC2)c1 Chemical compound Nc1c[nH]c2ncc(cc12)-c1cccc(OCCCN2CCOCC2)c1 WZWLPKXQIBPPDW-UHFFFAOYSA-N 0.000 description 1
• WWOMLKXHOUOXNN-UHFFFAOYSA-N Nc1c[nH]c2ncc(cc12)-c1csc(CN2CCCC2)c1 Chemical compound Nc1c[nH]c2ncc(cc12)-c1csc(CN2CCCC2)c1 WWOMLKXHOUOXNN-UHFFFAOYSA-N 0.000 description 1
• OBEYLKAMKXOMHV-UHFFFAOYSA-N Nc1c[nH]c2ncc(cc12)N1CCCCC1 Chemical compound Nc1c[nH]c2ncc(cc12)N1CCCCC1 OBEYLKAMKXOMHV-UHFFFAOYSA-N 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
• KEIXOXQZIIOWQD-UHFFFAOYSA-N OC=1C=C(C=CC=1)C=1C=C2C(=NC=1)N(C=C2NC(=O)C=1C=NN(C=1)CC1=CC=CC=C1)S(=O)(=O)C1=CC=C(C=C1)C Chemical compound OC=1C=C(C=CC=1)C=1C=C2C(=NC=1)N(C=C2NC(=O)C=1C=NN(C=1)CC1=CC=CC=C1)S(=O)(=O)C1=CC=C(C=C1)C KEIXOXQZIIOWQD-UHFFFAOYSA-N 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 229930012538 Paclitaxel Natural products 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 239000007868 Raney catalyst Substances 0.000 description 1
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
• 229910000564 Raney nickel Inorganic materials 0.000 description 1
• 102100031075 Serine/threonine-protein kinase Chk2 Human genes 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 239000004141 Sodium laurylsulphate Substances 0.000 description 1
• 239000004133 Sodium thiosulphate Substances 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
• 229940123237 Taxane Drugs 0.000 description 1
• 229910052771 Terbium Inorganic materials 0.000 description 1
• 101710183280 Topoisomerase Proteins 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 206010052779 Transplant rejections Diseases 0.000 description 1
• 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• QFCNHLDVIBPZKC-CYBMUJFWSA-N [4-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]piperidin-1-yl]-3-nitro-1h-pyrrolo[2,3-b]pyridin-5-yl] 2,2-dimethylpropanoate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCCN1C1=C(OC(=O)C(C)(C)C)C=NC2=C1C([N+]([O-])=O)=CN2 QFCNHLDVIBPZKC-CYBMUJFWSA-N 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 230000001780 adrenocortical effect Effects 0.000 description 1
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
• 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 239000008168 almond oil Substances 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 230000003444 anaesthetic effect Effects 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 208000036878 aneuploidy Diseases 0.000 description 1
• 231100001075 aneuploidy Toxicity 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000002280 anti-androgenic effect Effects 0.000 description 1
• 229940046836 anti-estrogen Drugs 0.000 description 1
• 230000001833 anti-estrogenic effect Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 239000000051 antiandrogen Substances 0.000 description 1
• 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 229940045686 antimetabolites antineoplastic purine analogs Drugs 0.000 description 1
• 229940045687 antimetabolites folic acid analogs Drugs 0.000 description 1
• 239000003080 antimitotic agent Substances 0.000 description 1
• 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
• 229940045688 antineoplastic antimetabolites pyrimidine analogues Drugs 0.000 description 1
• 230000005756 apoptotic signaling Effects 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 229910052788 barium Inorganic materials 0.000 description 1
• DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
• CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 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
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• SGNZKPPDOWTEPS-UHFFFAOYSA-N benzyl 3-azido-4-(4-methylphenyl)sulfonyloxypiperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1C(N=[N+]=[N-])CN(C(=O)OCC=2C=CC=CC=2)CC1 SGNZKPPDOWTEPS-UHFFFAOYSA-N 0.000 description 1
• XFFCBJRBTDUAFD-UHFFFAOYSA-N benzyl 4-(diethoxyphosphorylamino)-3-(4-methylphenyl)sulfonyloxypiperidine-1-carboxylate Chemical compound CCOP(=O)(OCC)NC1CCN(C(=O)OCC=2C=CC=CC=2)CC1OS(=O)(=O)C1=CC=C(C)C=C1 XFFCBJRBTDUAFD-UHFFFAOYSA-N 0.000 description 1
• XVIBCNQBYCYALT-UHFFFAOYSA-N benzyl 4-amino-3-(4-methylphenyl)sulfonyloxypiperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1C(N)CCN(C(=O)OCC=2C=CC=CC=2)C1 XVIBCNQBYCYALT-UHFFFAOYSA-N 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 229960002092 busulfan Drugs 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 244000309466 calf Species 0.000 description 1
• 235000013877 carbamide Nutrition 0.000 description 1
• 230000025084 cell cycle arrest Effects 0.000 description 1
• 230000006369 cell cycle progression Effects 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 210000003850 cellular structure Anatomy 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 230000000973 chemotherapeutic effect Effects 0.000 description 1
• 239000000460 chlorine Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 210000000349 chromosome Anatomy 0.000 description 1
• 230000024321 chromosome segregation Effects 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
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 125000006165 cyclic alkyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
• 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 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 1
• 229960000684 cytarabine Drugs 0.000 description 1
• 239000000824 cytostatic agent Substances 0.000 description 1
• 238000011393 cytotoxic chemotherapy Methods 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• 229960003901 dacarbazine Drugs 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 239000005547 deoxyribonucleotide Substances 0.000 description 1
• 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
• 238000001784 detoxification Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• MXFYYFVVIIWKFE-UHFFFAOYSA-N dicyclohexyl-[2-[2,6-di(propan-2-yloxy)phenyl]phenyl]phosphane Chemical group CC(C)OC1=CC=CC(OC(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 MXFYYFVVIIWKFE-UHFFFAOYSA-N 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 239000013024 dilution buffer Substances 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• 201000010099 disease Diseases 0.000 description 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
• 230000005782 double-strand break Effects 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 239000012039 electrophile Substances 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 229940011871 estrogen Drugs 0.000 description 1
• 239000000262 estrogen Substances 0.000 description 1
• 239000000328 estrogen antagonist Substances 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
• 229960005420 etoposide Drugs 0.000 description 1
• OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 150000002224 folic acids Chemical class 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000003193 general anesthetic agent Substances 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 230000002489 hematologic effect Effects 0.000 description 1
• 210000005096 hematological system Anatomy 0.000 description 1
• VHHHONWQHHHLTI-UHFFFAOYSA-N hexachloroethane Chemical compound ClC(Cl)(Cl)C(Cl)(Cl)Cl VHHHONWQHHHLTI-UHFFFAOYSA-N 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 1
• 229960001330 hydroxycarbamide Drugs 0.000 description 1
• 239000000367 immunologic factor Substances 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 239000003999 initiator Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 229910010272 inorganic material Inorganic materials 0.000 description 1
• 239000011147 inorganic material Substances 0.000 description 1
• 239000002198 insoluble material Substances 0.000 description 1
• 230000010354 integration Effects 0.000 description 1
• 229940079322 interferon Drugs 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 238000004255 ion exchange chromatography Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000010410 layer Substances 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 238000013332 literature search Methods 0.000 description 1
• 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 1
• WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 206010025135 lupus erythematosus Diseases 0.000 description 1
• VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical class [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
• 235000012254 magnesium hydroxide Nutrition 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• VFZXMEQGIIWBFJ-UHFFFAOYSA-M magnesium;cyclopropane;bromide Chemical compound [Mg+2].[Br-].C1C[CH-]1 VFZXMEQGIIWBFJ-UHFFFAOYSA-M 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 210000004962 mammalian cell Anatomy 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• GQJCAQADCPTHKN-UHFFFAOYSA-N methyl 2,2-difluoro-2-fluorosulfonylacetate Chemical compound COC(=O)C(F)(F)S(F)(=O)=O GQJCAQADCPTHKN-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
• KTMKRRPZPWUYKK-UHFFFAOYSA-N methylboronic acid Chemical compound CB(O)O KTMKRRPZPWUYKK-UHFFFAOYSA-N 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000017205 mitotic cell cycle checkpoint Effects 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• NMGVIZJUIPNHLI-UHFFFAOYSA-N n,n-dimethylpiperidin-3-amine Chemical group CN(C)C1CCCNC1 NMGVIZJUIPNHLI-UHFFFAOYSA-N 0.000 description 1
• KGAOIYHCFQTRKA-OAHLLOKOSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-(pyridin-2-ylmethyl)pyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(C(F)(F)F)C=NC2=C1C(NC(=O)C1=CN(CC=3N=CC=CC=3)N=C1)=CN2 KGAOIYHCFQTRKA-OAHLLOKOSA-N 0.000 description 1
• QTNWUWKATNIWLH-MRXNPFEDSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-(pyridin-3-ylmethyl)pyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(C(F)(F)F)C=NC2=C1C(NC(=O)C1=CN(CC=3C=NC=CC=3)N=C1)=CN2 QTNWUWKATNIWLH-MRXNPFEDSA-N 0.000 description 1
• HTOOLTNEQULOQS-QGZVFWFLSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-[(4-fluorophenyl)methyl]pyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(C(F)(F)F)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC(F)=CC=3)N=C1)=CN2 HTOOLTNEQULOQS-QGZVFWFLSA-N 0.000 description 1
• URRSARVIJHLNCX-QGZVFWFLSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-[(4-chlorophenyl)methyl]pyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC(Cl)=CC=3)N=C1)=CN2 URRSARVIJHLNCX-QGZVFWFLSA-N 0.000 description 1
• PJDLFZIKISOUET-QGZVFWFLSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-[(4-fluorophenyl)methyl]pyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC(F)=CC=3)N=C1)=CN2 PJDLFZIKISOUET-QGZVFWFLSA-N 0.000 description 1
• DQWQPMZVWDESPL-GOSISDBHSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-[(4-methylphenyl)methyl]pyrazole-4-carboxamide Chemical compound C1=CC(C)=CC=C1CN1N=CC(C(=O)NC=2C3=C(N4C[C@H](N)CCC4)C(Br)=CN=C3NC=2)=C1 DQWQPMZVWDESPL-GOSISDBHSA-N 0.000 description 1
• JYKZGECLJWFYMK-QGZVFWFLSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-[(4-chlorophenyl)methyl]pyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(Cl)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC(Cl)=CC=3)N=C1)=CN2 JYKZGECLJWFYMK-QGZVFWFLSA-N 0.000 description 1
• GIDXCMOSYBGJED-MRXNPFEDSA-N n-[4-[(3r)-3-aminopyrrolidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide Chemical compound C1[C@H](N)CCN1C1=C(Br)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 GIDXCMOSYBGJED-MRXNPFEDSA-N 0.000 description 1
• ISFUPDOATOAKAA-UHFFFAOYSA-N n-[5-[3-(azetidin-1-ylmethyl)phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(C=1)=CC=CC=1CN1CCC1 ISFUPDOATOAKAA-UHFFFAOYSA-N 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• 239000003956 nonsteroidal anti androgen Substances 0.000 description 1
• 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 229960001592 paclitaxel Drugs 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 239000003182 parenteral nutrition solution Substances 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
• 239000001120 potassium sulphate Substances 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
• 229960000624 procarbazine Drugs 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 239000000583 progesterone congener Substances 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
• 238000011321 prophylaxis Methods 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 235000013772 propylene glycol Nutrition 0.000 description 1
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical group OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
• AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridine hydrochloride Substances [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• ZSKGQVFRTSEPJT-UHFFFAOYSA-N pyrrole-2-carboxaldehyde Chemical compound O=CC1=CC=CN1 ZSKGQVFRTSEPJT-UHFFFAOYSA-N 0.000 description 1
• 150000005255 pyrrolopyridines Chemical class 0.000 description 1
• 101150010682 rad50 gene Proteins 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000003362 replicative effect Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 230000028617 response to DNA damage stimulus Effects 0.000 description 1
• SHGAZHPCJJPHSC-YCNIQYBTSA-N retinoic acid group Chemical class C\C(=C/C(=O)O)\C=C\C=C(\C=C\C1=C(CCCC1(C)C)C)/C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 125000006413 ring segment Chemical group 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
• 210000002966 serum Anatomy 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical class [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 235000010265 sodium sulphite Nutrition 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000001593 sorbitan monooleate Substances 0.000 description 1
• 235000011069 sorbitan monooleate Nutrition 0.000 description 1
• 229940035049 sorbitan monooleate Drugs 0.000 description 1
• 230000003595 spectral effect Effects 0.000 description 1
• 125000003003 spiro group Chemical group 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 229910021653 sulphate ion Inorganic materials 0.000 description 1
• 239000001117 sulphuric acid Substances 0.000 description 1
• 235000011149 sulphuric acid Nutrition 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 231100000057 systemic toxicity Toxicity 0.000 description 1
• 239000002278 tabletting lubricant Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 229960001603 tamoxifen Drugs 0.000 description 1
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
• 229960001278 teniposide Drugs 0.000 description 1
• GZCRRIHWUXGPOV-UHFFFAOYSA-N terbium atom Chemical compound [Tb] GZCRRIHWUXGPOV-UHFFFAOYSA-N 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• YHWGALVHDQPEOA-HXUWFJFHSA-N tert-butyl n-[(3r)-1-[5-bromo-3-[[1-[(4-methoxyphenyl)methyl]pyrazole-4-carbonyl]amino]-1h-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-yl]carbamate Chemical compound C1=CC(OC)=CC=C1CN1N=CC(C(=O)NC=2C3=C(N4C[C@@H](CCC4)NC(=O)OC(C)(C)C)C(Br)=CN=C3NC=2)=C1 YHWGALVHDQPEOA-HXUWFJFHSA-N 0.000 description 1
• NVISSTNTBKVSPW-SNVBAGLBSA-N tert-butyl n-ethyl-n-[(3r)-piperidin-3-yl]carbamate Chemical group CC(C)(C)OC(=O)N(CC)[C@@H]1CCCNC1 NVISSTNTBKVSPW-SNVBAGLBSA-N 0.000 description 1
• RTXNDTNDOHQMTI-SECBINFHSA-N tert-butyl n-methyl-n-[(3r)-piperidin-3-yl]carbamate Chemical group CC(C)(C)OC(=O)N(C)[C@@H]1CCCNC1 RTXNDTNDOHQMTI-SECBINFHSA-N 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 125000003396 thiol group Chemical class [H]S* 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
• 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 230000002463 transducing effect Effects 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• 230000016596 traversing start control point of mitotic cell cycle Effects 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• 150000003918 triazines Chemical class 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• 208000022679 triple-negative breast carcinoma Diseases 0.000 description 1
• 238000000825 ultraviolet detection Methods 0.000 description 1
• 150000003672 ureas Chemical class 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1