TWI458727B - 作為激酶抑制劑之吡咯并吡啶 - Google Patents

Info

Publication number

TWI458727B

TWI458727B TW098115906A TW98115906A TWI458727B TW I458727 B TWI458727 B TW I458727B TW 098115906 A TW098115906 A TW 098115906A TW 98115906 A TW98115906 A TW 98115906A TW I458727 B TWI458727 B TW I458727B

Authority

TW

Taiwan

Prior art keywords

alkyl

pyrrolo

pyridin

bromo

group

Prior art date

2008-05-13

Links

• Espacenet
• Global Dossier
• Discuss

• 229940043355 kinase inhibitor Drugs 0.000 title description 2
• 239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
• 150000005255 pyrrolopyridines Chemical class 0.000 title 1
• 229910052739 hydrogen Inorganic materials 0.000 claims description 310
• 239000001257 hydrogen Substances 0.000 claims description 310
• -1 6-methylpyridin-3-yl Chemical group 0.000 claims description 266
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 246
• 150000001875 compounds Chemical class 0.000 claims description 215
• 150000002431 hydrogen Chemical class 0.000 claims description 186
• 229910052736 halogen Inorganic materials 0.000 claims description 174
• 150000002367 halogens Chemical class 0.000 claims description 138
• 125000004429 atom Chemical group 0.000 claims description 131
• 238000006243 chemical reaction Methods 0.000 claims description 120
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 118
• 125000001072 heteroaryl group Chemical group 0.000 claims description 115
• 238000000034 method Methods 0.000 claims description 115
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 104
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 99
• 125000003118 aryl group Chemical group 0.000 claims description 98
• 125000000217 alkyl group Chemical group 0.000 claims description 96
• 229920006395 saturated elastomer Polymers 0.000 claims description 95
• 125000000468 ketone group Chemical group 0.000 claims description 91
• 125000000623 heterocyclic group Chemical group 0.000 claims description 80
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 75
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 63
• 125000005843 halogen group Chemical group 0.000 claims description 61
• 229930194542 Keto Natural products 0.000 claims description 57
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 56
• 206010028980 Neoplasm Diseases 0.000 claims description 47
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 41
• 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 38
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 38
• 150000001408 amides Chemical class 0.000 claims description 38
• 150000003839 salts Chemical class 0.000 claims description 38
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 36
• 238000011282 treatment Methods 0.000 claims description 36
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 35
• 201000011510 cancer Diseases 0.000 claims description 35
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 34
• 229910052731 fluorine Inorganic materials 0.000 claims description 32
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 31
• 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 claims description 30
• 201000010099 disease Diseases 0.000 claims description 30
• 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 claims description 29
• 229910052799 carbon Inorganic materials 0.000 claims description 29
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 26
• 230000003463 hyperproliferative effect Effects 0.000 claims description 24
• 125000002619 bicyclic group Chemical group 0.000 claims description 22
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 22
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 21
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 20
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
• 229910052801 chlorine Inorganic materials 0.000 claims description 19
• 239000012623 DNA damaging agent Substances 0.000 claims description 18
• 125000006239 protecting group Chemical group 0.000 claims description 18
• 125000001424 substituent group Chemical group 0.000 claims description 18
• 125000005842 heteroatom Chemical group 0.000 claims description 16
• 239000008194 pharmaceutical composition Substances 0.000 claims description 15
• 125000004076 pyridyl group Chemical group 0.000 claims description 15
• 229910052794 bromium Inorganic materials 0.000 claims description 14
• 239000003814 drug Substances 0.000 claims description 13
• 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 11
• 150000001412 amines Chemical class 0.000 claims description 11
• 238000004519 manufacturing process Methods 0.000 claims description 11
• 125000003342 alkenyl group Chemical group 0.000 claims description 10
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
• 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 claims description 9
• 235000005152 nicotinamide Nutrition 0.000 claims description 9
• 239000011570 nicotinamide Substances 0.000 claims description 9
• 229960003966 nicotinamide Drugs 0.000 claims description 9
• 238000005859 coupling reaction Methods 0.000 claims description 8
• 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 claims description 8
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
• 229960005277 gemcitabine Drugs 0.000 claims description 7
• 229960004768 irinotecan Drugs 0.000 claims description 7
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 7
• 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 6
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 6
• 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 claims description 6
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 6
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 claims description 6
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 5
• GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 5
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 5
• 229960004316 cisplatin Drugs 0.000 claims description 5
• GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 4
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 4
• BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 4
• KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 4
• 229960004117 capecitabine Drugs 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 229960002949 fluorouracil Drugs 0.000 claims description 4
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 claims description 4
• 230000002265 prevention Effects 0.000 claims description 4
• 238000006467 substitution reaction Methods 0.000 claims description 4
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• 125000001847 2-phenylcyclopropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1([H])C([H])([H])C1([H])* 0.000 claims description 3
• 125000004811 3-methylpropylene group Chemical group [H]C([H])([H])C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 3
• KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 3
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
• 230000002152 alkylating effect Effects 0.000 claims description 3
• 229940127093 camptothecin Drugs 0.000 claims description 3
• VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 3
• VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims description 3
• 229960004964 temozolomide Drugs 0.000 claims description 3
• NUUMHIQSZZZWTQ-LLVKDONJSA-N 4-[(3R)-3-aminopiperidin-1-yl]-5-bromo-N-(2-methylpropyl)-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound CC(C)CNc1c[nH]c2ncc(Br)c(N3CCC[C@@H](N)C3)c12 NUUMHIQSZZZWTQ-LLVKDONJSA-N 0.000 claims description 2
• 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 2
• LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 2
• TYVVHZCTNCPUMP-GFCCVEGCSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-methyl-6-oxopyridine-3-carboxamide Chemical compound C1=CC(=O)N(C)C=C1C(=O)NC1=CNC2=NC=C(Br)C(N3C[C@H](N)CCC3)=C12 TYVVHZCTNCPUMP-GFCCVEGCSA-N 0.000 claims description 2
• HXPJIUNKSDFFOE-CYBMUJFWSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]benzamide Chemical compound C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C=1C=CC=CC=1)=CN2 HXPJIUNKSDFFOE-CYBMUJFWSA-N 0.000 claims description 2
• BAZRWWGASYWYGB-SNVBAGLBSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]cyclopropanecarboxamide Chemical compound C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1CC1)=CN2 BAZRWWGASYWYGB-SNVBAGLBSA-N 0.000 claims description 2
• KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 claims 12
• BSEXNZMHLUMQKR-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1.NC(=O)C1CC1 BSEXNZMHLUMQKR-UHFFFAOYSA-N 0.000 claims 5
• REERVHUCEUHPPB-TZMCWYRMSA-N CC(C)CNC1=CNC2=NC=C(C(=C12)N3CC[C@H]([C@@H](C3)N)OC)Br Chemical compound CC(C)CNC1=CNC2=NC=C(C(=C12)N3CC[C@H]([C@@H](C3)N)OC)Br REERVHUCEUHPPB-TZMCWYRMSA-N 0.000 claims 3
• DRRCSIQELQJXPM-NXEZZACHSA-N (2r)-n-[4-[(3r)-3-aminopiperidin-1-yl]-5-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-methoxypropanamide Chemical compound C=12C(NC(=O)[C@@H](C)OC)=CNC2=NC=C(F)C=1N1CCC[C@@H](N)C1 DRRCSIQELQJXPM-NXEZZACHSA-N 0.000 claims 2
• YRVLYGRBEAECRM-LLVKDONJSA-N CCCCNC1=CNC2=NC=C(C(=C12)N3CCC[C@H](C3)N)Cl Chemical compound CCCCNC1=CNC2=NC=C(C(=C12)N3CCC[C@H](C3)N)Cl YRVLYGRBEAECRM-LLVKDONJSA-N 0.000 claims 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims 2
• OJEYDZBIAYMFFD-UHFFFAOYSA-N cyclopentanecarboxamide Chemical compound NC(=O)C1C[CH]CC1 OJEYDZBIAYMFFD-UHFFFAOYSA-N 0.000 claims 2
• OFHOYTWEUIWHBB-NXEZZACHSA-N (2r)-n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-methoxypropanamide Chemical compound C=12C(NC(=O)[C@@H](C)OC)=CNC2=NC=C(Br)C=1N1CCC[C@@H](N)C1 OFHOYTWEUIWHBB-NXEZZACHSA-N 0.000 claims 1
• MNBQTKFHXBYTRZ-NXEZZACHSA-N (2r)-n-[4-[(3r)-3-aminopiperidin-1-yl]-5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-methoxypropanamide Chemical compound C=12C(NC(=O)[C@@H](C)OC)=CNC2=NC=C(Cl)C=1N1CCC[C@@H](N)C1 MNBQTKFHXBYTRZ-NXEZZACHSA-N 0.000 claims 1
• GZCQXIZJIMCERG-RKDXNWHRSA-N (2r)-n-[4-[(3r)-3-aminopyrrolidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-methoxypropanamide Chemical compound C=12C(NC(=O)[C@@H](C)OC)=CNC2=NC=C(Br)C=1N1CC[C@@H](N)C1 GZCQXIZJIMCERG-RKDXNWHRSA-N 0.000 claims 1
• MNBQTKFHXBYTRZ-VHSXEESVSA-N (2s)-n-[4-[(3r)-3-aminopiperidin-1-yl]-5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-methoxypropanamide Chemical compound C=12C(NC(=O)[C@H](C)OC)=CNC2=NC=C(Cl)C=1N1CCC[C@@H](N)C1 MNBQTKFHXBYTRZ-VHSXEESVSA-N 0.000 claims 1
• LZXUKFLAVHQLAO-WDEREUQCSA-N (2s)-n-[4-[(3r)-3-aminopiperidin-1-yl]-5-methylsulfanyl-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-methoxypropanamide Chemical compound C=12C(NC(=O)[C@H](C)OC)=CNC2=NC=C(SC)C=1N1CCC[C@@H](N)C1 LZXUKFLAVHQLAO-WDEREUQCSA-N 0.000 claims 1
• YYQUIXZYASIUSD-JGVFFNPUSA-N (2s)-n-[4-[(3r)-3-aminopyrrolidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-hydroxypropanamide Chemical compound C=12C(NC(=O)[C@@H](O)C)=CNC2=NC=C(Br)C=1N1CC[C@@H](N)C1 YYQUIXZYASIUSD-JGVFFNPUSA-N 0.000 claims 1
• GZCQXIZJIMCERG-DTWKUNHWSA-N (2s)-n-[4-[(3r)-3-aminopyrrolidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-methoxypropanamide Chemical compound C=12C(NC(=O)[C@H](C)OC)=CNC2=NC=C(Br)C=1N1CC[C@@H](N)C1 GZCQXIZJIMCERG-DTWKUNHWSA-N 0.000 claims 1
• GPCDGGKVBPVZCT-UHFFFAOYSA-N 1,1-difluorocyclopropane Chemical compound FC1(F)CC1 GPCDGGKVBPVZCT-UHFFFAOYSA-N 0.000 claims 1
• WRWPPGUCZBJXKX-UHFFFAOYSA-N 1-fluoro-4-methylbenzene Chemical compound CC1=CC=C(F)C=C1 WRWPPGUCZBJXKX-UHFFFAOYSA-N 0.000 claims 1
• OCQGNFXFQNUNSG-GFCCVEGCSA-N CC(C)CCNC1=CNC2=NC=C(C(=C12)N3CCC[C@H](C3)N)Br Chemical compound CC(C)CCNC1=CNC2=NC=C(C(=C12)N3CCC[C@H](C3)N)Br OCQGNFXFQNUNSG-GFCCVEGCSA-N 0.000 claims 1
• JSOIZHDKUVDYSH-GFCCVEGCSA-N CC(C)CCNC1=CNC2=NC=C(C(=C12)N3CCC[C@H](C3)N)Cl Chemical compound CC(C)CCNC1=CNC2=NC=C(C(=C12)N3CCC[C@H](C3)N)Cl JSOIZHDKUVDYSH-GFCCVEGCSA-N 0.000 claims 1
• XVAKFEOWMVEGMI-CQSZACIVSA-N CC(C)CNC1=CNC2=NC=C(C(=C12)N3CCC[C@H](C3)N)C(=C)C Chemical compound CC(C)CNC1=CNC2=NC=C(C(=C12)N3CCC[C@H](C3)N)C(=C)C XVAKFEOWMVEGMI-CQSZACIVSA-N 0.000 claims 1
• MLIALPZBBRKBMF-NWDGAFQWSA-N CCCCNC1=CNC2=NC=C(C(=C12)N3CC[C@@H]([C@@H](C3)N)F)Br Chemical compound CCCCNC1=CNC2=NC=C(C(=C12)N3CC[C@@H]([C@@H](C3)N)F)Br MLIALPZBBRKBMF-NWDGAFQWSA-N 0.000 claims 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims 1
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims 1
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims 1
• 229930182817 methionine Natural products 0.000 claims 1
• GEYMAAFJXNDRCT-UHFFFAOYSA-N n-[4-(3-amino-3-methylpiperidin-1-yl)-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-methoxyacetamide Chemical compound C=12C(NC(=O)COC)=CNC2=NC=C(Br)C=1N1CCCC(C)(N)C1 GEYMAAFJXNDRCT-UHFFFAOYSA-N 0.000 claims 1
• LZXRQHOELAKEDX-GOSISDBHSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-(6-methylpyridin-3-yl)-1h-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide Chemical compound C1=NC(C)=CC=C1C1=CN=C(NC=C2NC(=O)C=3C=NC=CC=3)C2=C1N1C[C@H](N)CCC1 LZXRQHOELAKEDX-GOSISDBHSA-N 0.000 claims 1
• MTFAYOZCJDTATA-SECBINFHSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-(trifluoromethyl)cyclopropane-1-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1(CC1)C(F)(F)F)=CN2 MTFAYOZCJDTATA-SECBINFHSA-N 0.000 claims 1
• JJLVBOHJGOEWRU-SNVBAGLBSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-methoxycyclopropane-1-carboxamide Chemical compound C=1NC2=NC=C(Br)C(N3C[C@H](N)CCC3)=C2C=1NC(=O)C1(OC)CC1 JJLVBOHJGOEWRU-SNVBAGLBSA-N 0.000 claims 1
• HMEOVMONLFHTQW-SNVBAGLBSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-methylcyclopropane-1-carboxamide Chemical compound C=1NC2=NC=C(Br)C(N3C[C@H](N)CCC3)=C2C=1NC(=O)C1(C)CC1 HMEOVMONLFHTQW-SNVBAGLBSA-N 0.000 claims 1
• PKEACBQJQHBPIJ-LLVKDONJSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-methylpyrazole-4-carboxamide Chemical compound C1=NN(C)C=C1C(=O)NC1=CNC2=NC=C(Br)C(N3C[C@H](N)CCC3)=C12 PKEACBQJQHBPIJ-LLVKDONJSA-N 0.000 claims 1
• ALPUWAAWAXSURU-SNVBAGLBSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1h-pyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1=CNN=C1)=CN2 ALPUWAAWAXSURU-SNVBAGLBSA-N 0.000 claims 1
• UHSXQNOKVGZUBN-SNVBAGLBSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2,2-dimethylpropanamide Chemical compound C=12C(NC(=O)C(C)(C)C)=CNC2=NC=C(Br)C=1N1CCC[C@@H](N)C1 UHSXQNOKVGZUBN-SNVBAGLBSA-N 0.000 claims 1
• KNLYIIWNKWDLJV-LLVKDONJSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-cyclopropylacetamide Chemical compound C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)CC1CC1)=CN2 KNLYIIWNKWDLJV-LLVKDONJSA-N 0.000 claims 1
• NZYVTUQMAUQELZ-SNVBAGLBSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-ethoxyacetamide Chemical compound C=12C(NC(=O)COCC)=CNC2=NC=C(Br)C=1N1CCC[C@@H](N)C1 NZYVTUQMAUQELZ-SNVBAGLBSA-N 0.000 claims 1
• IIITWENPMJEWKO-GFCCVEGCSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-fluoro-5-methylbenzamide Chemical compound CC1=CC=C(F)C(C(=O)NC=2C3=C(N4C[C@H](N)CCC4)C(Br)=CN=C3NC=2)=C1 IIITWENPMJEWKO-GFCCVEGCSA-N 0.000 claims 1
• KTXZOTWLOACDOB-SECBINFHSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-hydroxy-2-methylpropanamide Chemical compound C=12C(NC(=O)C(C)(O)C)=CNC2=NC=C(Br)C=1N1CCC[C@@H](N)C1 KTXZOTWLOACDOB-SECBINFHSA-N 0.000 claims 1
• UHLKQHNFDMCOSQ-SECBINFHSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-methoxyacetamide Chemical compound C=12C(NC(=O)COC)=CNC2=NC=C(Br)C=1N1CCC[C@@H](N)C1 UHLKQHNFDMCOSQ-SECBINFHSA-N 0.000 claims 1
• STNWPYOQKDDRKN-GFCCVEGCSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-methylpyridine-3-carboxamide Chemical compound CC1=NC=CC=C1C(=O)NC1=CNC2=NC=C(Br)C(N3C[C@H](N)CCC3)=C12 STNWPYOQKDDRKN-GFCCVEGCSA-N 0.000 claims 1
• AKMCAGXGDNMYSQ-SECBINFHSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-methylsulfonylacetamide Chemical compound C=12C(NC(=O)CS(=O)(=O)C)=CNC2=NC=C(Br)C=1N1CCC[C@@H](N)C1 AKMCAGXGDNMYSQ-SECBINFHSA-N 0.000 claims 1
• KFUKGJHXXOVWCY-CQSZACIVSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-phenylacetamide Chemical compound C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)CC=1C=CC=CC=1)=CN2 KFUKGJHXXOVWCY-CQSZACIVSA-N 0.000 claims 1
• ZGMBGVLBKKPCGN-LLVKDONJSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-3-chloro-4-fluorobenzamide Chemical compound C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C=1C=C(Cl)C(F)=CC=1)=CN2 ZGMBGVLBKKPCGN-LLVKDONJSA-N 0.000 claims 1
• MYXOXPOEYNDIGN-GFCCVEGCSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-3-fluoro-4-methoxybenzamide Chemical compound C1=C(F)C(OC)=CC=C1C(=O)NC1=CNC2=NC=C(Br)C(N3C[C@H](N)CCC3)=C12 MYXOXPOEYNDIGN-GFCCVEGCSA-N 0.000 claims 1
• GFUXVUPUMNRCJW-CYBMUJFWSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-3-fluorobenzamide Chemical compound C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C=1C=C(F)C=CC=1)=CN2 GFUXVUPUMNRCJW-CYBMUJFWSA-N 0.000 claims 1
• OMTGGXBIKNLZAN-SNVBAGLBSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-3-methoxypropanamide Chemical compound C=12C(NC(=O)CCOC)=CNC2=NC=C(Br)C=1N1CCC[C@@H](N)C1 OMTGGXBIKNLZAN-SNVBAGLBSA-N 0.000 claims 1
• WECQJDQTLMUNKS-CQSZACIVSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-3-methylbenzamide Chemical compound CC1=CC=CC(C(=O)NC=2C3=C(N4C[C@H](N)CCC4)C(Br)=CN=C3NC=2)=C1 WECQJDQTLMUNKS-CQSZACIVSA-N 0.000 claims 1
• YGKVCYDJTMDWFD-GFCCVEGCSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-5-ethylpyrimidine-2-carboxamide Chemical compound N1=CC(CC)=CN=C1C(=O)NC1=CNC2=NC=C(Br)C(N3C[C@H](N)CCC3)=C12 YGKVCYDJTMDWFD-GFCCVEGCSA-N 0.000 claims 1
• RKBQUHFNFSKTIC-SECBINFHSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]acetamide Chemical compound C=12C(NC(=O)C)=CNC2=NC=C(Br)C=1N1CCC[C@@H](N)C1 RKBQUHFNFSKTIC-SECBINFHSA-N 0.000 claims 1
• GIUZGERWUATYGE-SECBINFHSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-hydroxy-2-methylpropanamide Chemical compound C=12C(NC(=O)C(C)(O)C)=CNC2=NC=C(Cl)C=1N1CCC[C@@H](N)C1 GIUZGERWUATYGE-SECBINFHSA-N 0.000 claims 1
• NKYHUGNXYLRUGZ-LLVKDONJSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-propan-2-yloxyacetamide Chemical compound C=12C(NC(=O)COC(C)C)=CNC2=NC=C(Cl)C=1N1CCC[C@@H](N)C1 NKYHUGNXYLRUGZ-LLVKDONJSA-N 0.000 claims 1
• QSCMIOPZJILKKZ-CYBMUJFWSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl]-5-methylpyridine-3-carboxamide Chemical compound CC1=CN=CC(C(=O)NC=2C3=C(N4C[C@H](N)CCC4)C(Cl)=CN=C3NC=2)=C1 QSCMIOPZJILKKZ-CYBMUJFWSA-N 0.000 claims 1
• LZPOXMQSBIJZGZ-SNVBAGLBSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl]cyclopropanecarboxamide Chemical compound C1[C@H](N)CCCN1C1=C(Cl)C=NC2=C1C(NC(=O)C1CC1)=CN2 LZPOXMQSBIJZGZ-SNVBAGLBSA-N 0.000 claims 1
• WCLCXCDIPAFMMJ-GFCCVEGCSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-ethylsulfanyl-1h-pyrrolo[2,3-b]pyridin-3-yl]cyclopropanecarboxamide Chemical compound C12=C(N3C[C@H](N)CCC3)C(SCC)=CN=C2NC=C1NC(=O)C1CC1 WCLCXCDIPAFMMJ-GFCCVEGCSA-N 0.000 claims 1
• COZGOLJZEZGYPY-SECBINFHSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-hydroxy-2-methylpropanamide Chemical compound C=12C(NC(=O)C(C)(O)C)=CNC2=NC=C(F)C=1N1CCC[C@@H](N)C1 COZGOLJZEZGYPY-SECBINFHSA-N 0.000 claims 1
• MLSFOTDQXORALM-SNVBAGLBSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl]cyclopropanecarboxamide Chemical compound C1[C@H](N)CCCN1C1=C(F)C=NC2=C1C(NC(=O)C1CC1)=CN2 MLSFOTDQXORALM-SNVBAGLBSA-N 0.000 claims 1
• RPTGNIGPVISKBZ-GFCCVEGCSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(F)C=NC2=C1C(NC(=O)C=1C=NC=CC=1)=CN2 RPTGNIGPVISKBZ-GFCCVEGCSA-N 0.000 claims 1
• WRLCRUFOHMCNTL-GFCCVEGCSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl]cyclopropanecarboxamide Chemical compound C12=C(N3C[C@H](N)CCC3)C(C)=CN=C2NC=C1NC(=O)C1CC1 WRLCRUFOHMCNTL-GFCCVEGCSA-N 0.000 claims 1
• UFYMBKRCTCBSJF-CYBMUJFWSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-propan-2-yl-1h-pyrrolo[2,3-b]pyridin-3-yl]cyclopropanecarboxamide Chemical compound C12=C(N3C[C@H](N)CCC3)C(C(C)C)=CN=C2NC=C1NC(=O)C1CC1 UFYMBKRCTCBSJF-CYBMUJFWSA-N 0.000 claims 1
• QHLBLKLHJNCROG-CYBMUJFWSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-propan-2-ylsulfanyl-1h-pyrrolo[2,3-b]pyridin-3-yl]cyclopropanecarboxamide Chemical compound C12=C(N3C[C@H](N)CCC3)C(SC(C)C)=CN=C2NC=C1NC(=O)C1CC1 QHLBLKLHJNCROG-CYBMUJFWSA-N 0.000 claims 1
• IGIVUEDKQBXAGD-QMMMGPOBSA-N n-[4-[(3s)-3-aminopyrrolidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]acetamide Chemical compound C=12C(NC(=O)C)=CNC2=NC=C(Br)C=1N1CC[C@H](N)C1 IGIVUEDKQBXAGD-QMMMGPOBSA-N 0.000 claims 1
• AANBDJTVWPOXPS-GFCCVEGCSA-N n-[5-bromo-4-[(3r)-3-(2-fluoroethylamino)piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]cyclopropanecarboxamide Chemical compound C1[C@H](NCCF)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1CC1)=CN2 AANBDJTVWPOXPS-GFCCVEGCSA-N 0.000 claims 1
• RQVSJBLBFGBVAJ-CYBMUJFWSA-N n-[5-bromo-4-[(3r)-3-(2-hydroxyethylamino)piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]-3-chloro-4-fluorobenzamide Chemical compound C1[C@H](NCCO)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C=1C=C(Cl)C(F)=CC=1)=CN2 RQVSJBLBFGBVAJ-CYBMUJFWSA-N 0.000 claims 1
• VLQITELRYDTIIX-CYBMUJFWSA-N n-[5-bromo-4-[(3r)-3-(2-methoxyethylamino)piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]cyclopropanecarboxamide Chemical compound C1[C@H](NCCOC)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1CC1)=CN2 VLQITELRYDTIIX-CYBMUJFWSA-N 0.000 claims 1
• NRMYZJZIDQULMU-CYBMUJFWSA-N n-[5-bromo-4-[(3r)-3-(ethylamino)piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-cyclopropylacetamide Chemical compound C1[C@H](NCC)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)CC1CC1)=CN2 NRMYZJZIDQULMU-CYBMUJFWSA-N 0.000 claims 1
• OIONZBAXXSNKIQ-GFCCVEGCSA-N n-[5-bromo-4-[(3r)-3-(ethylamino)piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]cyclopropanecarboxamide Chemical compound C1[C@H](NCC)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1CC1)=CN2 OIONZBAXXSNKIQ-GFCCVEGCSA-N 0.000 claims 1
• AYGXAXKQGVXYEP-GFCCVEGCSA-N n-[5-bromo-4-[(3r)-3-(methylamino)piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-propan-2-yloxyacetamide Chemical compound C1[C@H](NC)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)COC(C)C)=CN2 AYGXAXKQGVXYEP-GFCCVEGCSA-N 0.000 claims 1
• UZYJPIURZUFBHJ-LLVKDONJSA-N n-[5-chloro-4-[(3r)-3-(methylamino)piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]cyclopropanecarboxamide Chemical compound C1[C@H](NC)CCCN1C1=C(Cl)C=NC2=C1C(NC(=O)C1CC1)=CN2 UZYJPIURZUFBHJ-LLVKDONJSA-N 0.000 claims 1
• DUXPFRRFZLRICX-UHFFFAOYSA-N oxolane-3-carboxamide Chemical compound NC(=O)C1CCOC1 DUXPFRRFZLRICX-UHFFFAOYSA-N 0.000 claims 1
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims 1
• FUXJMHXHGDAHPD-UHFFFAOYSA-N pyrimidine-2-carboxamide Chemical compound NC(=O)C1=NC=CC=N1 FUXJMHXHGDAHPD-UHFFFAOYSA-N 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 298
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 149
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 144
• 235000019439 ethyl acetate Nutrition 0.000 description 138
• 239000007787 solid Substances 0.000 description 138
• 239000000203 mixture Substances 0.000 description 101
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 100
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 84
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 80
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 77
• 239000000243 solution Substances 0.000 description 69
• 238000005481 NMR spectroscopy Methods 0.000 description 66
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 64
• 239000002904 solvent Substances 0.000 description 64
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 58
• 238000003818 flash chromatography Methods 0.000 description 51
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 44
• 239000012071 phase Substances 0.000 description 40
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
• 230000014759 maintenance of location Effects 0.000 description 37
• 239000002585 base Substances 0.000 description 33
• 238000001914 filtration Methods 0.000 description 32
• 230000002441 reversible effect Effects 0.000 description 31
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 30
• 239000003112 inhibitor Substances 0.000 description 27
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 27
• 239000003921 oil Substances 0.000 description 26
• 241000124008 Mammalia Species 0.000 description 25
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 24
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 24
• 239000012267 brine Substances 0.000 description 22
• 238000004587 chromatography analysis Methods 0.000 description 22
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 22
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
• 210000004027 cell Anatomy 0.000 description 21
• 229910052757 nitrogen Inorganic materials 0.000 description 21
• 239000011541 reaction mixture Substances 0.000 description 21
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 19
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
• 229910052938 sodium sulfate Inorganic materials 0.000 description 19
• 235000011152 sodium sulphate Nutrition 0.000 description 19
• 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 18
• 239000012044 organic layer Substances 0.000 description 17
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical group CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 17
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 16
• 101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 description 16
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 16
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 16
• KCZYHRFGDUTYKG-MRVPVSSYSA-N C(C)(C)(C)OC(NN[C@H]1CNC=CC1)=O Chemical compound C(C)(C)(C)OC(NN[C@H]1CNC=CC1)=O KCZYHRFGDUTYKG-MRVPVSSYSA-N 0.000 description 15
• 102100031075 Serine/threonine-protein kinase Chk2 Human genes 0.000 description 15
• 238000003756 stirring Methods 0.000 description 15
• MMWRGWQTAMNAFC-UHFFFAOYSA-N 1,2-dihydropyridine Chemical compound C1NC=CC=C1 MMWRGWQTAMNAFC-UHFFFAOYSA-N 0.000 description 14
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 14
• 208000024891 symptom Diseases 0.000 description 14
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
• 239000003795 chemical substances by application Substances 0.000 description 13
• 239000000706 filtrate Substances 0.000 description 13
• 238000000746 purification Methods 0.000 description 13
• QOBUCUTUULGTCS-MRVPVSSYSA-N tert-butyl N-[[(3R)-piperidin-3-yl]amino]carbamate Chemical compound CC(C)(C)OC(=O)NN[C@@H]1CCCNC1 QOBUCUTUULGTCS-MRVPVSSYSA-N 0.000 description 13
• 206010025323 Lymphomas Diseases 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 239000001301 oxygen Substances 0.000 description 12
• 229910052760 oxygen Inorganic materials 0.000 description 12
• 239000000725 suspension Substances 0.000 description 12
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
• 208000009956 adenocarcinoma Diseases 0.000 description 11
• 208000035475 disorder Diseases 0.000 description 11
• 239000012074 organic phase Substances 0.000 description 11
• 206010039491 Sarcoma Diseases 0.000 description 10
• ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 10
• 239000002244 precipitate Substances 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• 238000003786 synthesis reaction Methods 0.000 description 10
• KLDLRDSRCMJKGM-UHFFFAOYSA-N 3-[chloro-(2-oxo-1,3-oxazolidin-3-yl)phosphoryl]-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1P(=O)(Cl)N1CCOC1=O KLDLRDSRCMJKGM-UHFFFAOYSA-N 0.000 description 9
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 239000003153 chemical reaction reagent Substances 0.000 description 9
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 9
• 235000001968 nicotinic acid Nutrition 0.000 description 9
• 239000011664 nicotinic acid Substances 0.000 description 9
• 238000002360 preparation method Methods 0.000 description 9
• 108020004414 DNA Proteins 0.000 description 8
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• 208000027418 Wounds and injury Diseases 0.000 description 8
• 230000002159 abnormal effect Effects 0.000 description 8
• 239000002246 antineoplastic agent Substances 0.000 description 8
• 208000014674 injury Diseases 0.000 description 8
• 239000010410 layer Substances 0.000 description 8
• 238000000926 separation method Methods 0.000 description 8
• IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 description 7
• 108091000080 Phosphotransferase Proteins 0.000 description 7
• 239000008346 aqueous phase Substances 0.000 description 7
• 208000006990 cholangiocarcinoma Diseases 0.000 description 7
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 7
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
• 102000020233 phosphotransferase Human genes 0.000 description 7
• 206010041823 squamous cell carcinoma Diseases 0.000 description 7
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
• MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical class C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 6
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
• 206010009944 Colon cancer Diseases 0.000 description 6
• 206010033128 Ovarian cancer Diseases 0.000 description 6
• 206010061535 Ovarian neoplasm Diseases 0.000 description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
• 230000006378 damage Effects 0.000 description 6
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 6
• 239000000543 intermediate Substances 0.000 description 6
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 6
• 235000018102 proteins Nutrition 0.000 description 6
• 102000004169 proteins and genes Human genes 0.000 description 6
• 108090000623 proteins and genes Proteins 0.000 description 6
• 238000004007 reversed phase HPLC Methods 0.000 description 6
• 239000011593 sulfur Chemical group 0.000 description 6
• 229910052717 sulfur Chemical group 0.000 description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
• 206010001233 Adenoma benign Diseases 0.000 description 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 5
• 208000032612 Glial tumor Diseases 0.000 description 5
• 206010018338 Glioma Diseases 0.000 description 5
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 5
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• 239000012298 atmosphere Substances 0.000 description 5
• 230000010261 cell growth Effects 0.000 description 5
• 238000004440 column chromatography Methods 0.000 description 5
• 239000012065 filter cake Substances 0.000 description 5
• 238000009472 formulation Methods 0.000 description 5
• 201000011066 hemangioma Diseases 0.000 description 5
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
• 201000010260 leiomyoma Diseases 0.000 description 5
• WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 5
• 201000007270 liver cancer Diseases 0.000 description 5
• 208000014018 liver neoplasm Diseases 0.000 description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 description 5
• 201000002528 pancreatic cancer Diseases 0.000 description 5
• 239000000741 silica gel Substances 0.000 description 5
• 229910002027 silica gel Inorganic materials 0.000 description 5
• 229910000104 sodium hydride Inorganic materials 0.000 description 5
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 5
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 4
• XZERBDMTFISXSV-UHFFFAOYSA-N 1-o-benzyl 3-o-methyl 3-methylpyrrolidine-1,3-dicarboxylate Chemical compound C1C(C(=O)OC)(C)CCN1C(=O)OCC1=CC=CC=C1 XZERBDMTFISXSV-UHFFFAOYSA-N 0.000 description 4
• XWIYUCRMWCHYJR-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical compound C1=CC=C2NC=CC2=N1 XWIYUCRMWCHYJR-UHFFFAOYSA-N 0.000 description 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 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 4
• 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 4
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
• 208000003200 Adenoma Diseases 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• WPFFDHHULJZMCO-UHFFFAOYSA-N CC(C)C(CCCCCCCCCN1C2=NC=CC(F)=C2C=C1)(C(C)C)C(C)C Chemical compound CC(C)C(CCCCCCCCCN1C2=NC=CC(F)=C2C=C1)(C(C)C)C(C)C WPFFDHHULJZMCO-UHFFFAOYSA-N 0.000 description 4
• 201000009030 Carcinoma Diseases 0.000 description 4
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
• 206010041067 Small cell lung cancer Diseases 0.000 description 4
• 208000005718 Stomach Neoplasms Diseases 0.000 description 4
• MCNHVBWLINLGIB-UHFFFAOYSA-N [Li].CC(CCCCCCCCCNCCCCCCCCCC(C)(C)C)(C)C Chemical compound [Li].CC(CCCCCCCCCNCCCCCCCCCC(C)(C)C)(C)C MCNHVBWLINLGIB-UHFFFAOYSA-N 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
• TUWZZXGAUMSUOB-UHFFFAOYSA-N benzyl piperidine-1-carboxylate Chemical compound C1CCCCN1C(=O)OCC1=CC=CC=C1 TUWZZXGAUMSUOB-UHFFFAOYSA-N 0.000 description 4
• GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 4
• HTRXGEPDTFSKLI-UHFFFAOYSA-N butanoic acid;ethyl acetate Chemical compound CCCC(O)=O.CCOC(C)=O HTRXGEPDTFSKLI-UHFFFAOYSA-N 0.000 description 4
• 239000003054 catalyst Substances 0.000 description 4
• 229940125797 compound 12 Drugs 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 125000004122 cyclic group Chemical group 0.000 description 4
• 229940127089 cytotoxic agent Drugs 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• 239000000284 extract Substances 0.000 description 4
• 206010017758 gastric cancer Diseases 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• 208000032839 leukemia Diseases 0.000 description 4
• 210000004185 liver Anatomy 0.000 description 4
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• DBAOFQCSAQXIIN-UHFFFAOYSA-N n-(5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)pyridine-3-carboxamide Chemical compound C1=2C(F)=C(Br)C=NC=2NC=C1NC(=O)C1=CC=CN=C1 DBAOFQCSAQXIIN-UHFFFAOYSA-N 0.000 description 4
• 229960002715 nicotine Drugs 0.000 description 4
• 238000011275 oncology therapy Methods 0.000 description 4
• 230000003287 optical effect Effects 0.000 description 4
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
• 208000008443 pancreatic carcinoma Diseases 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 230000005855 radiation Effects 0.000 description 4
• 238000001959 radiotherapy Methods 0.000 description 4
• 208000000587 small cell lung carcinoma Diseases 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 201000011549 stomach cancer Diseases 0.000 description 4
• 230000004083 survival effect Effects 0.000 description 4
• 238000012360 testing method Methods 0.000 description 4
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 3
• DWXCAYCYQNEZLL-UHFFFAOYSA-N 1-hydroxypyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2N(O)C=CC2=C1 DWXCAYCYQNEZLL-UHFFFAOYSA-N 0.000 description 3
• JFARWSFILDKQQJ-UHFFFAOYSA-N 1-o-benzyl 3-o-ethyl 3-methylpiperidine-1,3-dicarboxylate Chemical compound C1C(C(=O)OCC)(C)CCCN1C(=O)OCC1=CC=CC=C1 JFARWSFILDKQQJ-UHFFFAOYSA-N 0.000 description 3
• NJRONXOELMBCSE-UHFFFAOYSA-N 1-o-benzyl 3-o-ethyl piperidine-1,3-dicarboxylate Chemical compound C1C(C(=O)OCC)CCCN1C(=O)OCC1=CC=CC=C1 NJRONXOELMBCSE-UHFFFAOYSA-N 0.000 description 3
• CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 3
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
• IHVZRADTOCTZIA-UHFFFAOYSA-N 4,5-difluoro-1h-pyrrolo[2,3-b]pyridine Chemical compound FC1=CN=C2NC=CC2=C1F IHVZRADTOCTZIA-UHFFFAOYSA-N 0.000 description 3
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 3
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 3
• 108020004491 Antisense DNA Proteins 0.000 description 3
• 108020005544 Antisense RNA Proteins 0.000 description 3
• ADJXJKPSKLKHLW-UHFFFAOYSA-N CC(C)C(CCCCCCCCCN1C=CC2=C(C(=CN=C21)Cl)F)(C(C)C)C(C)C Chemical compound CC(C)C(CCCCCCCCCN1C=CC2=C(C(=CN=C21)Cl)F)(C(C)C)C(C)C ADJXJKPSKLKHLW-UHFFFAOYSA-N 0.000 description 3
• 229940123587 Cell cycle inhibitor Drugs 0.000 description 3
• 108010019243 Checkpoint Kinase 2 Proteins 0.000 description 3
• 102000006457 Checkpoint Kinase 2 Human genes 0.000 description 3
• 230000033616 DNA repair Effects 0.000 description 3
• 201000008808 Fibrosarcoma Diseases 0.000 description 3
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 3
• 208000017604 Hodgkin disease Diseases 0.000 description 3
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 3
• 206010024612 Lipoma Diseases 0.000 description 3
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 3
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 3
• 206010060862 Prostate cancer Diseases 0.000 description 3
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 3
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
• 208000031320 Teratogenesis Diseases 0.000 description 3
• 239000002168 alkylating agent Substances 0.000 description 3
• 229940100198 alkylating agent Drugs 0.000 description 3
• 239000004037 angiogenesis inhibitor Substances 0.000 description 3
• 229940121369 angiogenesis inhibitor Drugs 0.000 description 3
• 239000003242 anti bacterial agent Substances 0.000 description 3
• 239000000051 antiandrogen Substances 0.000 description 3
• 239000013059 antihormonal agent Substances 0.000 description 3
• 239000003816 antisense DNA Substances 0.000 description 3
• QUQOGTDJUKKSQL-UHFFFAOYSA-N benzyl chlorate Chemical compound Cl(=O)(=O)OCC1=CC=CC=C1 QUQOGTDJUKKSQL-UHFFFAOYSA-N 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 210000000845 cartilage Anatomy 0.000 description 3
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 3
• 238000002648 combination therapy Methods 0.000 description 3
• 239000003184 complementary RNA Substances 0.000 description 3
• 229940125773 compound 10 Drugs 0.000 description 3
• 229940126543 compound 14 Drugs 0.000 description 3
• 229940126214 compound 3 Drugs 0.000 description 3
• 238000001816 cooling Methods 0.000 description 3
• 239000013058 crude material Substances 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• 229960000684 cytarabine Drugs 0.000 description 3
• 230000000593 degrading effect Effects 0.000 description 3
• 239000003534 dna topoisomerase inhibitor Substances 0.000 description 3
• 230000000694 effects Effects 0.000 description 3
• 239000002532 enzyme inhibitor Substances 0.000 description 3
• 238000001640 fractional crystallisation Methods 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 239000003102 growth factor Substances 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 3
• 239000000367 immunologic factor Substances 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 3
• 230000003211 malignant effect Effects 0.000 description 3
• 201000001441 melanoma Diseases 0.000 description 3
• 206010027191 meningioma Diseases 0.000 description 3
• 239000002480 mineral oil Substances 0.000 description 3
• 235000010446 mineral oil Nutrition 0.000 description 3
• 230000004048 modification Effects 0.000 description 3
• 238000012986 modification Methods 0.000 description 3
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
• 229960003512 nicotinic acid Drugs 0.000 description 3
• HNKLPNDFOVJIFG-UHFFFAOYSA-N oxalic acid;platinum Chemical compound [Pt].OC(=O)C(O)=O HNKLPNDFOVJIFG-UHFFFAOYSA-N 0.000 description 3
• 229910052763 palladium Inorganic materials 0.000 description 3
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
• 125000000168 pyrrolyl group Chemical group 0.000 description 3
• 102000027483 retinoid hormone receptors Human genes 0.000 description 3
• 108091008679 retinoid hormone receptors Proteins 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 239000012312 sodium hydride Substances 0.000 description 3
• VDJQDKIUIIFWJD-UHFFFAOYSA-N tert-butyl pyrrolo[2,3-c]pyridine-1-carboxylate Chemical compound C1=NC=C2N(C(=O)OC(C)(C)C)C=CC2=C1 VDJQDKIUIIFWJD-UHFFFAOYSA-N 0.000 description 3
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 229940044693 topoisomerase inhibitor Drugs 0.000 description 3
• 239000003558 transferase inhibitor Substances 0.000 description 3
• 210000004881 tumor cell Anatomy 0.000 description 3
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
• KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 2
• QJQGMOIUEXCUOH-UHFFFAOYSA-N 1,3-oxazole;1h-pyrrole Chemical compound C=1C=CNC=1.C1=COC=N1 QJQGMOIUEXCUOH-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
• XLKDJOPOOHHZAN-UHFFFAOYSA-N 1h-pyrrolo[2,3-c]pyridine Chemical compound C1=NC=C2NC=CC2=C1 XLKDJOPOOHHZAN-UHFFFAOYSA-N 0.000 description 2
• YIRNNHURQFNQDX-UHFFFAOYSA-N 3,6-dihydro-2h-pyridine-1-carboxylic acid Chemical compound OC(=O)N1CCC=CC1 YIRNNHURQFNQDX-UHFFFAOYSA-N 0.000 description 2
• VTRVUNGMWPPWGP-UHFFFAOYSA-N 3-methyl-1-phenylmethoxycarbonylpiperidine-3-carboxylic acid Chemical compound C1C(C)(C(O)=O)CCCN1C(=O)OCC1=CC=CC=C1 VTRVUNGMWPPWGP-UHFFFAOYSA-N 0.000 description 2
• PVHTZUOXJDYNBQ-UHFFFAOYSA-N 3-methyl-1-phenylmethoxycarbonylpyrrolidine-3-carboxylic acid Chemical compound C1C(C)(C(O)=O)CCN1C(=O)OCC1=CC=CC=C1 PVHTZUOXJDYNBQ-UHFFFAOYSA-N 0.000 description 2
• GUPWUZXHKUBUIK-UHFFFAOYSA-N 4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=CC(F)=C2C(N)=CNC2=N1 GUPWUZXHKUBUIK-UHFFFAOYSA-N 0.000 description 2
• OURXRFYZEOUCRM-UHFFFAOYSA-N 4-hydroxymorpholine Chemical compound ON1CCOCC1 OURXRFYZEOUCRM-UHFFFAOYSA-N 0.000 description 2
• DJDHHXDFKSLEQY-UHFFFAOYSA-N 5-methylpyridine-3-carboxylic acid Chemical group CC1=CN=CC(C(O)=O)=C1 DJDHHXDFKSLEQY-UHFFFAOYSA-N 0.000 description 2
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
• 239000005695 Ammonium acetate Substances 0.000 description 2
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
• 239000005711 Benzoic acid Substances 0.000 description 2
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
• ONNVELFGUOJYRK-UHFFFAOYSA-N BrC1=C2C(=NC=C1)N(C=C2)CCCCCCCCCC(C(C)C)(C(C)C)C(C)C Chemical compound BrC1=C2C(=NC=C1)N(C=C2)CCCCCCCCCC(C(C)C)(C(C)C)C(C)C ONNVELFGUOJYRK-UHFFFAOYSA-N 0.000 description 2
• 206010055113 Breast cancer metastatic Diseases 0.000 description 2
• DZJWHUQKZNCVGP-UHFFFAOYSA-N CN(C)C(CCC1)CN1C1=C(C(N(C2)C=CC=C2C(O)=O)=CN2)C2=NC=C1Br Chemical compound CN(C)C(CCC1)CN1C1=C(C(N(C2)C=CC=C2C(O)=O)=CN2)C2=NC=C1Br DZJWHUQKZNCVGP-UHFFFAOYSA-N 0.000 description 2
• RZFNMBAAABQDBA-UHFFFAOYSA-N COCC1=CC=CC=[N+]1NC(C1=C2F)=CNC1=NC=C2Br Chemical compound COCC1=CC=CC=[N+]1NC(C1=C2F)=CNC1=NC=C2Br RZFNMBAAABQDBA-UHFFFAOYSA-N 0.000 description 2
• 206010008342 Cervix carcinoma Diseases 0.000 description 2
• 108010019244 Checkpoint Kinase 1 Proteins 0.000 description 2
• 102000006459 Checkpoint Kinase 1 Human genes 0.000 description 2
• 201000005262 Chondroma Diseases 0.000 description 2
• 208000006332 Choriocarcinoma Diseases 0.000 description 2
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
• 229940126657 Compound 17 Drugs 0.000 description 2
• VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 2
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
• 230000005778 DNA damage Effects 0.000 description 2
• 231100000277 DNA damage Toxicity 0.000 description 2
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
• MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 2
• 206010058314 Dysplasia Diseases 0.000 description 2
• 206010014733 Endometrial cancer Diseases 0.000 description 2
• 206010014759 Endometrial neoplasm Diseases 0.000 description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
• 208000022072 Gallbladder Neoplasms Diseases 0.000 description 2
• 206010018691 Granuloma Diseases 0.000 description 2
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 2
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
• QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
• 208000018142 Leiomyosarcoma Diseases 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• 229940121849 Mitotic inhibitor Drugs 0.000 description 2
• 208000034578 Multiple myelomas Diseases 0.000 description 2
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
• XKTABYOWTSPKHT-UHFFFAOYSA-N N1=CC=CC2=CC=CC=C21.N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 Chemical compound N1=CC=CC2=CC=CC=C21.N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 XKTABYOWTSPKHT-UHFFFAOYSA-N 0.000 description 2
• OWRQJDDKMITVJJ-UHFFFAOYSA-N N1CC(CCC1)NNC(O)=O Chemical compound N1CC(CCC1)NNC(O)=O OWRQJDDKMITVJJ-UHFFFAOYSA-N 0.000 description 2
• XMKCDONBAISGMA-GFCCVEGCSA-N N[C@H](CCC1)CN1C1=C(C([N+]2=CC=CC=C2)=CN2)C2=NC=C1Br Chemical compound N[C@H](CCC1)CN1C1=C(C([N+]2=CC=CC=C2)=CN2)C2=NC=C1Br XMKCDONBAISGMA-GFCCVEGCSA-N 0.000 description 2
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• 206010035226 Plasma cell myeloma Diseases 0.000 description 2
• 102000001253 Protein Kinase Human genes 0.000 description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
• LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
• 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 2
• 208000024313 Testicular Neoplasms Diseases 0.000 description 2
• 206010057644 Testis cancer Diseases 0.000 description 2
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
• 229940123468 Transferase inhibitor Drugs 0.000 description 2
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical group OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
• LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 210000002945 adventitial reticular cell Anatomy 0.000 description 2
• 235000019257 ammonium acetate Nutrition 0.000 description 2
• 229940043376 ammonium acetate Drugs 0.000 description 2
• 235000019270 ammonium chloride Nutrition 0.000 description 2
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
• 230000001093 anti-cancer Effects 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
• 235000010233 benzoic acid Nutrition 0.000 description 2
• QUKGYYKBILRGFE-UHFFFAOYSA-N benzyl acetate Chemical compound CC(=O)OCC1=CC=CC=C1 QUKGYYKBILRGFE-UHFFFAOYSA-N 0.000 description 2
• GCTPMLUUWLLESL-UHFFFAOYSA-N benzyl prop-2-enoate Chemical compound C=CC(=O)OCC1=CC=CC=C1 GCTPMLUUWLLESL-UHFFFAOYSA-N 0.000 description 2
• 230000003115 biocidal effect Effects 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• PNTZVNQIKCEBNZ-UHFFFAOYSA-N butyl n,n-dibutylcarbamate Chemical compound CCCCOC(=O)N(CCCC)CCCC PNTZVNQIKCEBNZ-UHFFFAOYSA-N 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 230000025084 cell cycle arrest Effects 0.000 description 2
• 230000030833 cell death Effects 0.000 description 2
• 230000004640 cellular pathway Effects 0.000 description 2
• 201000010881 cervical cancer Diseases 0.000 description 2
• 229940125898 compound 5 Drugs 0.000 description 2
• 239000010779 crude oil Substances 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 229950011148 cyclopropane Drugs 0.000 description 2
• AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 description 2
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 230000002950 deficient Effects 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 239000012039 electrophile Substances 0.000 description 2
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
• 229960000752 etoposide phosphate Drugs 0.000 description 2
• LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=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 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 2
• 206010016629 fibroma Diseases 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 2
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 235000003599 food sweetener Nutrition 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 201000010175 gallbladder cancer Diseases 0.000 description 2
• 239000007789 gas Substances 0.000 description 2
• 230000002496 gastric effect Effects 0.000 description 2
• 231100000024 genotoxic Toxicity 0.000 description 2
• 230000001738 genotoxic effect Effects 0.000 description 2
• 208000005017 glioblastoma Diseases 0.000 description 2
• 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 2
• VHHHONWQHHHLTI-UHFFFAOYSA-N hexachloroethane Chemical compound ClC(Cl)(Cl)C(Cl)(Cl)Cl VHHHONWQHHHLTI-UHFFFAOYSA-N 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 238000006138 lithiation reaction Methods 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
• 235000019341 magnesium sulphate Nutrition 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 229940102396 methyl bromide Drugs 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• VZCGKSSRLUIALP-UHFFFAOYSA-N n-(4,5-difluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)pyridine-3-carboxamide Chemical compound C12=C(F)C(F)=CN=C2NC=C1NC(=O)C1=CC=CN=C1 VZCGKSSRLUIALP-UHFFFAOYSA-N 0.000 description 2
• CUZIPFGAGCVNAB-UHFFFAOYSA-N n-(5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)-2,2-dimethylpropanamide Chemical compound C1=C(Br)C(F)=C2C(NC(=O)C(C)(C)C)=CNC2=N1 CUZIPFGAGCVNAB-UHFFFAOYSA-N 0.000 description 2
• NNQXLZDUZAKWEM-UHFFFAOYSA-N n-(5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)-3-fluorobenzamide Chemical compound FC1=CC=CC(C(=O)NC=2C3=C(F)C(Br)=CN=C3NC=2)=C1 NNQXLZDUZAKWEM-UHFFFAOYSA-N 0.000 description 2
• GLTFDQRVCAVPNR-UHFFFAOYSA-N n-(5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)cyclopentanecarboxamide Chemical compound C1=2C(F)=C(Br)C=NC=2NC=C1NC(=O)C1CCCC1 GLTFDQRVCAVPNR-UHFFFAOYSA-N 0.000 description 2
• FXRIROWCAQFUKO-UHFFFAOYSA-N n-(5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-2-carboxamide Chemical compound C1=2C(F)=C(Br)C=NC=2NC=C1NC(=O)C1=NC=CC=N1 FXRIROWCAQFUKO-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
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• 210000005036 nerve Anatomy 0.000 description 2
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
• 210000000929 nociceptor Anatomy 0.000 description 2
• 108091008700 nociceptors Proteins 0.000 description 2
• 239000004533 oil dispersion Substances 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 201000008968 osteosarcoma Diseases 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• WBXPDJSOTKVWSJ-ZDUSSCGKSA-N pemetrexed Chemical compound C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 WBXPDJSOTKVWSJ-ZDUSSCGKSA-N 0.000 description 2
• 239000000825 pharmaceutical preparation Substances 0.000 description 2
• SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 2
• 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 2
• 229920001296 polysiloxane Polymers 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 108060006633 protein kinase Proteins 0.000 description 2
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000006722 reduction reaction Methods 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
• 230000001235 sensitizing effect Effects 0.000 description 2
• 230000019491 signal transduction Effects 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical class [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
• 210000002784 stomach Anatomy 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 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 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
• QOBUCUTUULGTCS-UHFFFAOYSA-N tert-butyl n-(piperidin-3-ylamino)carbamate Chemical compound CC(C)(C)OC(=O)NNC1CCCNC1 QOBUCUTUULGTCS-UHFFFAOYSA-N 0.000 description 2
• 201000003120 testicular cancer Diseases 0.000 description 2
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical group BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 2
• 239000003643 water by type Substances 0.000 description 2
• GNLJBJNONOOOQC-UHFFFAOYSA-N $l^{3}-carbane;magnesium Chemical compound [Mg]C GNLJBJNONOOOQC-UHFFFAOYSA-N 0.000 description 1
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
• ICPWFHKNYYRBSZ-VKHMYHEASA-N (2s)-2-methoxypropanoic acid Chemical compound CO[C@@H](C)C(O)=O ICPWFHKNYYRBSZ-VKHMYHEASA-N 0.000 description 1
• AUVSTZHSHHMCJB-YFKPBYRVSA-N (2s)-n-(5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxypropanamide Chemical compound C1=C(Br)C(F)=C2C(NC(=O)[C@H](C)OC)=CNC2=N1 AUVSTZHSHHMCJB-YFKPBYRVSA-N 0.000 description 1
• OFHOYTWEUIWHBB-VHSXEESVSA-N (2s)-n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2-methoxypropanamide Chemical compound C=12C(NC(=O)[C@H](C)OC)=CNC2=NC=C(Br)C=1N1CCC[C@@H](N)C1 OFHOYTWEUIWHBB-VHSXEESVSA-N 0.000 description 1
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
• DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 1
• YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
• KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 1
• WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
• SKCBKBCACWDALV-UHFFFAOYSA-N 1-(trifluoromethyl)cyclopropane-1-carboxylic acid Chemical compound OC(=O)C1(C(F)(F)F)CC1 SKCBKBCACWDALV-UHFFFAOYSA-N 0.000 description 1
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
• VSSLMOXCHCJREU-UHFFFAOYSA-N 1-fluoropyrrolo[2,3-b]pyridin-3-amine Chemical compound FN1C=C(C=2C1=NC=CC=2)N VSSLMOXCHCJREU-UHFFFAOYSA-N 0.000 description 1
• RGZCKPXTNJAWMR-UHFFFAOYSA-N 1-methyl-6-oxopyridine-3-carboxylic acid Chemical compound CN1C=C(C(O)=O)C=CC1=O RGZCKPXTNJAWMR-UHFFFAOYSA-N 0.000 description 1
• YBFIKNNFQIBIQZ-UHFFFAOYSA-N 1-methyl-pyrazole-3-carboxylic acid Chemical compound CN1C=CC(C(O)=O)=N1 YBFIKNNFQIBIQZ-UHFFFAOYSA-N 0.000 description 1
• JZDIVDBVWXFEMR-UHFFFAOYSA-N 1-o-benzyl 3-o-methyl pyrrolidine-1,3-dicarboxylate Chemical compound C1C(C(=O)OC)CCN1C(=O)OCC1=CC=CC=C1 JZDIVDBVWXFEMR-UHFFFAOYSA-N 0.000 description 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• VYDQUABHDFWIIX-UHFFFAOYSA-N 2,2-difluoro-2-fluorosulfonylacetic acid Chemical compound OC(=O)C(F)(F)S(F)(=O)=O VYDQUABHDFWIIX-UHFFFAOYSA-N 0.000 description 1
• ARDGQYVTLGUJII-UHFFFAOYSA-N 2,2-dimethylpropanimidamide;hydrochloride Chemical compound Cl.CC(C)(C)C(N)=N ARDGQYVTLGUJII-UHFFFAOYSA-N 0.000 description 1
• VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 1
• WOGXHNJBKGZMHV-UHFFFAOYSA-N 2-methoxypropanamide Chemical compound COC(C)C(N)=O WOGXHNJBKGZMHV-UHFFFAOYSA-N 0.000 description 1
• STXABSODTGKUAK-UHFFFAOYSA-N 2-pyrrolidin-3-ylpyridine Chemical compound C1NCCC1C1=CC=CC=N1 STXABSODTGKUAK-UHFFFAOYSA-N 0.000 description 1
• PYNDVWZZEOHSPX-UHFFFAOYSA-N 3-aminobutylcarbamic acid Chemical compound CC(N)CCNC(O)=O PYNDVWZZEOHSPX-UHFFFAOYSA-N 0.000 description 1
• HSHKYRFNBSPIAV-UHFFFAOYSA-N 3-chloro-2-(trifluoromethyl)-1H-pyrrole Chemical compound ClC1=C(NC=C1)C(F)(F)F HSHKYRFNBSPIAV-UHFFFAOYSA-N 0.000 description 1
• LULAYUGMBFYYEX-UHFFFAOYSA-M 3-chlorobenzoate Chemical compound [O-]C(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-M 0.000 description 1
• MXNBDFWNYRNIBH-UHFFFAOYSA-N 3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1 MXNBDFWNYRNIBH-UHFFFAOYSA-N 0.000 description 1
• JWQSTMYPGUOZFW-UHFFFAOYSA-N 3-methylpiperidine-1,3-dicarboxylic acid Chemical compound OC(=O)C1(C)CCCN(C(O)=O)C1 JWQSTMYPGUOZFW-UHFFFAOYSA-N 0.000 description 1
• LMHIBYREWJHKNZ-UHFFFAOYSA-N 3-methylpyridine-2-carboxylic acid Chemical compound CC1=CC=CN=C1C(O)=O LMHIBYREWJHKNZ-UHFFFAOYSA-N 0.000 description 1
• UWFACSVBWAXADE-UHFFFAOYSA-N 4,5-difluoro-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=C(F)C(F)=C2C(N)=CNC2=N1 UWFACSVBWAXADE-UHFFFAOYSA-N 0.000 description 1
• SPGCMKRVEAQIME-UHFFFAOYSA-N 4,5-difluoro-3-nitro-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=C(F)C(F)=C2C([N+](=O)[O-])=CNC2=N1 SPGCMKRVEAQIME-UHFFFAOYSA-N 0.000 description 1
• HNTZVGMWXCFCTA-UHFFFAOYSA-N 4-chloro-1h-pyrrolo[2,3-b]pyridine Chemical compound ClC1=CC=NC2=C1C=CN2 HNTZVGMWXCFCTA-UHFFFAOYSA-N 0.000 description 1
• QXSHSRLNQIYBIU-UHFFFAOYSA-N 4-chloro-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=C(C(F)(F)F)C(Cl)=C2C(N)=CNC2=N1 QXSHSRLNQIYBIU-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• VNDHYTGVCGVETQ-UHFFFAOYSA-N 4-fluorobenzamide Chemical compound NC(=O)C1=CC=C(F)C=C1 VNDHYTGVCGVETQ-UHFFFAOYSA-N 0.000 description 1
• NJHGVAYLDHROPT-UHFFFAOYSA-N 5-(trifluoromethyl)pyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(C(F)(F)F)C=N1 NJHGVAYLDHROPT-UHFFFAOYSA-N 0.000 description 1
• PUJVSTYUTMVCSG-UHFFFAOYSA-N 5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridine Chemical class FC1=C(Br)C=NC2=C1C=CN2 PUJVSTYUTMVCSG-UHFFFAOYSA-N 0.000 description 1
• ZUOPKGTYJJCCND-UHFFFAOYSA-N 5-bromo-4-fluoro-3-nitro-1h-pyrrolo[2,3-b]pyridine Chemical class C1=C(Br)C(F)=C2C([N+](=O)[O-])=CNC2=N1 ZUOPKGTYJJCCND-UHFFFAOYSA-N 0.000 description 1
• WFJVLHMDAOKGPA-UHFFFAOYSA-N 5-chloro-n-(5-chloro-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)pyridine-3-carboxamide Chemical compound C1=2C(F)=C(Cl)C=NC=2NC=C1NC(=O)C1=CN=CC(Cl)=C1 WFJVLHMDAOKGPA-UHFFFAOYSA-N 0.000 description 1
• GJLOKYIYZIOIPN-UHFFFAOYSA-N 5-chloropyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Cl)C=N1 GJLOKYIYZIOIPN-UHFFFAOYSA-N 0.000 description 1
• XYLPLVUYPAPCML-UHFFFAOYSA-N 5-chloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC(Cl)=C1 XYLPLVUYPAPCML-UHFFFAOYSA-N 0.000 description 1
• RZOKQIPOABEQAM-UHFFFAOYSA-N 6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)C=N1 RZOKQIPOABEQAM-UHFFFAOYSA-N 0.000 description 1
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
• PQJUJGAVDBINPI-UHFFFAOYSA-N 9H-thioxanthene Chemical compound C1=CC=C2CC3=CC=CC=C3SC2=C1 PQJUJGAVDBINPI-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 241000349731 Afzelia bipindensis Species 0.000 description 1
• 206010061424 Anal cancer Diseases 0.000 description 1
• 206010002329 Aneurysm Diseases 0.000 description 1
• 201000003076 Angiosarcoma Diseases 0.000 description 1
• 241000156724 Antirhea Species 0.000 description 1
• 208000007860 Anus Neoplasms Diseases 0.000 description 1
• 206010003571 Astrocytoma Diseases 0.000 description 1
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 206010004146 Basal cell carcinoma Diseases 0.000 description 1
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
• 206010004593 Bile duct cancer Diseases 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 206010073106 Bone giant cell tumour malignant Diseases 0.000 description 1
• ISOWLIVREWWHIE-WHCXFUJUSA-N BrC=1C(=C2C(=NC1)NC=C2N2CC=CC(=C2)[C@@H]2N(C)CCC2)N2CC(CCC2)NC Chemical compound BrC=1C(=C2C(=NC1)NC=C2N2CC=CC(=C2)[C@@H]2N(C)CCC2)N2CC(CCC2)NC ISOWLIVREWWHIE-WHCXFUJUSA-N 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• 206010006417 Bronchial carcinoma Diseases 0.000 description 1
• OFINIVMMBPEROE-QMMMGPOBSA-N C(C)(C)(C)OC(NNC[C@@H]1CNCC1)=O Chemical compound C(C)(C)(C)OC(NNC[C@@H]1CNCC1)=O OFINIVMMBPEROE-QMMMGPOBSA-N 0.000 description 1
• YQDWBUAKCFLSNI-SSDOTTSWSA-N C(C)(C)(C)OC(NN[C@H]1CNCC1)=O Chemical compound C(C)(C)(C)OC(NN[C@H]1CNCC1)=O YQDWBUAKCFLSNI-SSDOTTSWSA-N 0.000 description 1
• ZHKMBQUHASLQCU-UHFFFAOYSA-N C(C1=CC=CC=C1)OC(=O)C1(CC2C(C2CC1)=O)[N+](=O)[O-] Chemical compound C(C1=CC=CC=C1)OC(=O)C1(CC2C(C2CC1)=O)[N+](=O)[O-] ZHKMBQUHASLQCU-UHFFFAOYSA-N 0.000 description 1
• GOLSZYBAGXAMKI-UHFFFAOYSA-N C1=CC=[N+](C=C1)C2=CNC3=NC=C(C(=C23)Cl)C(F)(F)F Chemical compound C1=CC=[N+](C=C1)C2=CNC3=NC=C(C(=C23)Cl)C(F)(F)F GOLSZYBAGXAMKI-UHFFFAOYSA-N 0.000 description 1
• CCMJDGDZDHGMRZ-UHFFFAOYSA-N C1=CC=[N+](C=C1)NCC2=CNC3=NC=C(C(=C23)Cl)C(F)(F)F Chemical compound C1=CC=[N+](C=C1)NCC2=CNC3=NC=C(C(=C23)Cl)C(F)(F)F CCMJDGDZDHGMRZ-UHFFFAOYSA-N 0.000 description 1
• RWJPJVSSIKNDPQ-UHFFFAOYSA-N C1C(=CC=CN1C2=CNC3=NC=C(C(=C23)F)Br)C(=O)O Chemical compound C1C(=CC=CN1C2=CNC3=NC=C(C(=C23)F)Br)C(=O)O RWJPJVSSIKNDPQ-UHFFFAOYSA-N 0.000 description 1
• QSDHFYYYIGBUSC-UHFFFAOYSA-N C1C=CC=CN1CC2=CNC3=NC=C(C(=C23)Cl)C(F)(F)F Chemical compound C1C=CC=CN1CC2=CNC3=NC=C(C(=C23)Cl)C(F)(F)F QSDHFYYYIGBUSC-UHFFFAOYSA-N 0.000 description 1
• STJQFDFUSHFLET-UHFFFAOYSA-N C1CN(C2C1CNC2)C3=C4C(=CNC4=NC=C3Br)N5CC(=CC=C5)C(=O)O Chemical compound C1CN(C2C1CNC2)C3=C4C(=CNC4=NC=C3Br)N5CC(=CC=C5)C(=O)O STJQFDFUSHFLET-UHFFFAOYSA-N 0.000 description 1
• HXBGUDQDKIKBAY-NSHDSACASA-N C1CN(C[C@@H]1CN)C2=C3C(=CNC3=NC=C2Br)N4CC(=CC=C4)C(=O)O Chemical compound C1CN(C[C@@H]1CN)C2=C3C(=CNC3=NC=C2Br)N4CC(=CC=C4)C(=O)O HXBGUDQDKIKBAY-NSHDSACASA-N 0.000 description 1
• DIRBFWWDJOQSTM-CYBMUJFWSA-N C1CN(C[C@@H]1N)C2=C3C(=CNC3=NC=C2Br)CC4=CN=CC=C4 Chemical compound C1CN(C[C@@H]1N)C2=C3C(=CNC3=NC=C2Br)CC4=CN=CC=C4 DIRBFWWDJOQSTM-CYBMUJFWSA-N 0.000 description 1
• RRQDCTHMBOTVCK-LLVKDONJSA-N C1CN(C[C@@H]1N)C2=C3C(=CNC3=NC=C2Br)N4CC(=CC=C4)C(=O)O Chemical compound C1CN(C[C@@H]1N)C2=C3C(=CNC3=NC=C2Br)N4CC(=CC=C4)C(=O)O RRQDCTHMBOTVCK-LLVKDONJSA-N 0.000 description 1
• XGQQHSFUMWEVEG-LBPRGKRZSA-N C1C[C@@H](CN(C1)C2=C3C(=CNC3=NC=C2Br)N4CC(=CC=C4)C(=O)O)N Chemical compound C1C[C@@H](CN(C1)C2=C3C(=CNC3=NC=C2Br)N4CC(=CC=C4)C(=O)O)N XGQQHSFUMWEVEG-LBPRGKRZSA-N 0.000 description 1
• WMVQNQNNHXFOMB-CQSZACIVSA-N C1C[C@H](CN(C1)C2=C3C(=CNC3=NC=C2Br)NCC4=CC(=CC=C4)F)N Chemical compound C1C[C@H](CN(C1)C2=C3C(=CNC3=NC=C2Br)NCC4=CC(=CC=C4)F)N WMVQNQNNHXFOMB-CQSZACIVSA-N 0.000 description 1
• DFMSSBZRVVVHMZ-CQSZACIVSA-N C1C[C@H](CN(C1)C2=C3C(=CNC3=NC=C2Br)NCC4=CC=C(C=C4)F)N Chemical compound C1C[C@H](CN(C1)C2=C3C(=CNC3=NC=C2Br)NCC4=CC=C(C=C4)F)N DFMSSBZRVVVHMZ-CQSZACIVSA-N 0.000 description 1
• WQWUBMOLPYJNHI-LLVKDONJSA-N C1C[C@H](CN(C1)C2=C3C(=CNC3=NC=C2C(F)(F)F)NC4=CC=CC=N4)N Chemical compound C1C[C@H](CN(C1)C2=C3C(=CNC3=NC=C2C(F)(F)F)NC4=CC=CC=N4)N WQWUBMOLPYJNHI-LLVKDONJSA-N 0.000 description 1
• HOJZPEHMCWBXDN-OAHLLOKOSA-N C1C[C@H](CN(C1)C2=C3C(=CNC3=NC=C2C4CC4)N5CC(=CC=C5)C(=O)O)N Chemical compound C1C[C@H](CN(C1)C2=C3C(=CNC3=NC=C2C4CC4)N5CC(=CC=C5)C(=O)O)N HOJZPEHMCWBXDN-OAHLLOKOSA-N 0.000 description 1
• BACSDVITGVANKG-GFCCVEGCSA-N C1C[C@H](CN(C1)C2=C3C(=CNC3=NC=C2Cl)N4CC(=CC(=C4)Cl)C(=O)O)N Chemical compound C1C[C@H](CN(C1)C2=C3C(=CNC3=NC=C2Cl)N4CC(=CC(=C4)Cl)C(=O)O)N BACSDVITGVANKG-GFCCVEGCSA-N 0.000 description 1
• VOMFXRHNQPQGMO-GFCCVEGCSA-N C1C[C@H](CN(C1)C2=C3C(=CNC3=NC=C2Cl)N4CC(=CC=C4)C(=O)O)N Chemical compound C1C[C@H](CN(C1)C2=C3C(=CNC3=NC=C2Cl)N4CC(=CC=C4)C(=O)O)N VOMFXRHNQPQGMO-GFCCVEGCSA-N 0.000 description 1
• BCSZOCKSMXKOJY-UHFFFAOYSA-N CC(C)(C)OC(=O)NNC1(CN=CC=C1)O Chemical compound CC(C)(C)OC(=O)NNC1(CN=CC=C1)O BCSZOCKSMXKOJY-UHFFFAOYSA-N 0.000 description 1
• VZCGPMDXHDVJFP-RKDXNWHRSA-N CC(C)(C)OC(=O)NN[C@@H]1CNCC[C@H]1OC Chemical compound CC(C)(C)OC(=O)NN[C@@H]1CNCC[C@H]1OC VZCGPMDXHDVJFP-RKDXNWHRSA-N 0.000 description 1
• LIUKCQYLWATTNM-UHFFFAOYSA-N CC(C)(C)OC(N(CC1CC2)CC1N2C1=C(C(CC2=CN=CC=C2)=CN2)C2=NC=C1Br)=O Chemical compound CC(C)(C)OC(N(CC1CC2)CC1N2C1=C(C(CC2=CN=CC=C2)=CN2)C2=NC=C1Br)=O LIUKCQYLWATTNM-UHFFFAOYSA-N 0.000 description 1
• IJOKXZZWJGCCLG-UHFFFAOYSA-N CC(C)CNC1=CNC2=NC=C(C(=C12)F)Br Chemical compound CC(C)CNC1=CNC2=NC=C(C(=C12)F)Br IJOKXZZWJGCCLG-UHFFFAOYSA-N 0.000 description 1
• JZCNEEJNYNERTR-VGAJERRHSA-N CC(C)NC1CCCN(C1)C2=C3C(=CNC3=NC=C2Cl)N4CC=CC(=C4)[C@H]5CCCN5C Chemical compound CC(C)NC1CCCN(C1)C2=C3C(=CNC3=NC=C2Cl)N4CC=CC(=C4)[C@H]5CCCN5C JZCNEEJNYNERTR-VGAJERRHSA-N 0.000 description 1
• SBKPRJUTNYGGHW-AWEZNQCLSA-N CC(C)NC[C@@H]1CCN(C1)C2=C3C(=CNC3=NC=C2Br)N4CC(=CC=C4)C(=O)O Chemical compound CC(C)NC[C@@H]1CCN(C1)C2=C3C(=CNC3=NC=C2Br)N4CC(=CC=C4)C(=O)O SBKPRJUTNYGGHW-AWEZNQCLSA-N 0.000 description 1
• PSSKSNVUDZNVAX-UHFFFAOYSA-N CC1(CCCNC1)NNC(=O)OC(C)(C)C Chemical compound CC1(CCCNC1)NNC(=O)OC(C)(C)C PSSKSNVUDZNVAX-UHFFFAOYSA-N 0.000 description 1
• GBSPSCCJTFLEPM-UHFFFAOYSA-N CC1(CCN(C1)C2=C3C(=CNC3=NC=C2Br)N4CC(=CC=C4)C(=O)O)N Chemical compound CC1(CCN(C1)C2=C3C(=CNC3=NC=C2Br)N4CC(=CC=C4)C(=O)O)N GBSPSCCJTFLEPM-UHFFFAOYSA-N 0.000 description 1
• BZNCSLCSJPOFGE-UHFFFAOYSA-N CC1(CCN(C1)C2=C3C(=CNC3=NC=C2Br)N4CC=CC(=C4)C5CCCN5C)N Chemical compound CC1(CCN(C1)C2=C3C(=CNC3=NC=C2Br)N4CC=CC(=C4)C5CCCN5C)N BZNCSLCSJPOFGE-UHFFFAOYSA-N 0.000 description 1
• MNDUPKBIWWXTIU-UHFFFAOYSA-N CC1=C(C(=NC=C1)C(=O)NC2=CNC3=NC=C(C(=C23)F)Br)C Chemical compound CC1=C(C(=NC=C1)C(=O)NC2=CNC3=NC=C(C(=C23)F)Br)C MNDUPKBIWWXTIU-UHFFFAOYSA-N 0.000 description 1
• LQDPNIDFTZSPCR-CQSZACIVSA-N CC1=C([N+](=CC=C1)C2=CNC3=NC=C(C(=C23)N4CCC[C@H](C4)N)Br)C Chemical compound CC1=C([N+](=CC=C1)C2=CNC3=NC=C(C(=C23)N4CCC[C@H](C4)N)Br)C LQDPNIDFTZSPCR-CQSZACIVSA-N 0.000 description 1
• HMRWBQSMNNYCJI-UHFFFAOYSA-N CC1=C([N+](=CC=C1)NC2=CNC3=NC=C(C(=C23)F)Br)C Chemical compound CC1=C([N+](=CC=C1)NC2=CNC3=NC=C(C(=C23)F)Br)C HMRWBQSMNNYCJI-UHFFFAOYSA-N 0.000 description 1
• CQCCKJFMSMJGEN-OAHLLOKOSA-N CC1=CC(=CC=C1)CNC2=CNC3=NC=C(C(=C23)N4CCC[C@H](C4)N)Br Chemical compound CC1=CC(=CC=C1)CNC2=CNC3=NC=C(C(=C23)N4CCC[C@H](C4)N)Br CQCCKJFMSMJGEN-OAHLLOKOSA-N 0.000 description 1
• DEIYYJSORJYGNS-GFCCVEGCSA-N CC1=CC(=CN=C1C(=O)NC2=CNC3=NC=C(C(=C23)N4CCC[C@H](C4)N)Br)C(F)(F)F Chemical compound CC1=CC(=CN=C1C(=O)NC2=CNC3=NC=C(C(=C23)N4CCC[C@H](C4)N)Br)C(F)(F)F DEIYYJSORJYGNS-GFCCVEGCSA-N 0.000 description 1
• YLDUWAPTJFRAGV-CYBMUJFWSA-N CC1=[N+](C=C(C=C1)Cl)C2=CNC3=NC=C(C(=C23)N4CCC[C@H](C4)N)Br Chemical compound CC1=[N+](C=C(C=C1)Cl)C2=CNC3=NC=C(C(=C23)N4CCC[C@H](C4)N)Br YLDUWAPTJFRAGV-CYBMUJFWSA-N 0.000 description 1
• GPVKBMVYWQQIGZ-UHFFFAOYSA-N CCC(C)NNC(O)=O Chemical compound CCC(C)NNC(O)=O GPVKBMVYWQQIGZ-UHFFFAOYSA-N 0.000 description 1
• LHRYYWJNUBMUQZ-UHFFFAOYSA-N CCCCCCCCCCCC(CNC1=C2C(=CNC2=NC=C1Br)N3CC(=CC=C3)C(=O)O)N Chemical compound CCCCCCCCCCCC(CNC1=C2C(=CNC2=NC=C1Br)N3CC(=CC=C3)C(=O)O)N LHRYYWJNUBMUQZ-UHFFFAOYSA-N 0.000 description 1
• UCVBPLKCMWEJGB-XMMPIXPASA-N CCCCOC(=O)C(C(=O)OCCCC)(C(=O)OCCCC)N[C@@H]1CCCN(C1)C(=O)OCC2=CC=CC=C2 Chemical compound CCCCOC(=O)C(C(=O)OCCCC)(C(=O)OCCCC)N[C@@H]1CCCN(C1)C(=O)OCC2=CC=CC=C2 UCVBPLKCMWEJGB-XMMPIXPASA-N 0.000 description 1
• HVIRMNXKLHTDOT-RUZDIDTESA-N CCCCOC(=O)C(CN[C@@H]1CCCN(C1)C(=O)OCC2=CC=CC=C2)(C(=O)OCCCC)C(=O)OCCCC Chemical compound CCCCOC(=O)C(CN[C@@H]1CCCN(C1)C(=O)OCC2=CC=CC=C2)(C(=O)OCCCC)C(=O)OCCCC HVIRMNXKLHTDOT-RUZDIDTESA-N 0.000 description 1
• ZJJBZKCUKUFSOV-SSDOTTSWSA-N CCN(C(O)=O)[C@@H]1CCCNC1 Chemical compound CCN(C(O)=O)[C@@H]1CCCNC1 ZJJBZKCUKUFSOV-SSDOTTSWSA-N 0.000 description 1
• UHDABDFQKNWRIN-KPMSDPLLSA-N CN1CCC[C@@H]1C2=CN(CC=C2)C3=CNC4=NC=C(C(=C34)N5CCC(C5)CN)Br Chemical compound CN1CCC[C@@H]1C2=CN(CC=C2)C3=CNC4=NC=C(C(=C34)N5CCC(C5)CN)Br UHDABDFQKNWRIN-KPMSDPLLSA-N 0.000 description 1
• YQAVMOUDPLOINC-UHUGOGIASA-N CN1CCC[C@@H]1C2=CN(CC=C2)C3=CNC4=NC=C(C(=C34)N5CCCC(C5)N)C(F)(F)F Chemical compound CN1CCC[C@@H]1C2=CN(CC=C2)C3=CNC4=NC=C(C(=C34)N5CCCC(C5)N)C(F)(F)F YQAVMOUDPLOINC-UHUGOGIASA-N 0.000 description 1
• UHDABDFQKNWRIN-PKHIMPSTSA-N CN1CCC[C@H]1C2=CN(CC=C2)C3=CNC4=NC=C(C(=C34)N5CCC(C5)CN)Br Chemical compound CN1CCC[C@H]1C2=CN(CC=C2)C3=CNC4=NC=C(C(=C34)N5CCC(C5)CN)Br UHDABDFQKNWRIN-PKHIMPSTSA-N 0.000 description 1
• MQJIZGDYHFRMSO-UHFFFAOYSA-N CNC1CCN(C1)C2=C3C(=CNC3=NC=C2Br)N4CC(=CC=C4)C(=O)O Chemical compound CNC1CCN(C1)C2=C3C(=CNC3=NC=C2Br)N4CC(=CC=C4)C(=O)O MQJIZGDYHFRMSO-UHFFFAOYSA-N 0.000 description 1
• VUDSJYCEMIXGQZ-UHFFFAOYSA-N COC1=CC=CC(=C1)C(=NC2=CNC3=NC=C(C(=C23)F)Br)N Chemical compound COC1=CC=CC(=C1)C(=NC2=CNC3=NC=C(C(=C23)F)Br)N VUDSJYCEMIXGQZ-UHFFFAOYSA-N 0.000 description 1
• ISHBQHQRYVVIQR-PHDIDXHHSA-N C[C@@H]1CCNC[C@H]1NNC(=O)O Chemical compound C[C@@H]1CCNC[C@H]1NNC(=O)O ISHBQHQRYVVIQR-PHDIDXHHSA-N 0.000 description 1
• 101100220616 Caenorhabditis elegans chk-2 gene Proteins 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
• 208000006029 Cardiomegaly Diseases 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 206010008263 Cervical dysplasia Diseases 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 208000005243 Chondrosarcoma Diseases 0.000 description 1
• 201000009047 Chordoma Diseases 0.000 description 1
• 235000001258 Cinchona calisaya Nutrition 0.000 description 1
• IFTSZOWRCBJSSJ-UHFFFAOYSA-N ClC(C(C(C)C)(C(C)C)C(C)C)CCCCCCCC Chemical compound ClC(C(C(C)C)(C(C)C)C(C)C)CCCCCCCC IFTSZOWRCBJSSJ-UHFFFAOYSA-N 0.000 description 1
• GIVGSCVCLMYMNY-UHFFFAOYSA-N ClC1=C2C(=NC=C1)N(C=C2)CCCCCCCCCC(C(C)C)(C(C)C)C(C)C Chemical compound ClC1=C2C(=NC=C1)N(C=C2)CCCCCCCCCC(C(C)C)(C(C)C)C(C)C GIVGSCVCLMYMNY-UHFFFAOYSA-N 0.000 description 1
• 206010048832 Colon adenoma Diseases 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 230000012746 DNA damage checkpoint Effects 0.000 description 1
• MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
• 206010061818 Disease progression Diseases 0.000 description 1
• 206010014967 Ependymoma Diseases 0.000 description 1
• 208000006168 Ewing Sarcoma Diseases 0.000 description 1
• RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 208000007659 Fibroadenoma Diseases 0.000 description 1
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
• 230000005526 G1 to G0 transition Effects 0.000 description 1
• 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
• 208000007569 Giant Cell Tumors Diseases 0.000 description 1
• 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 208000001258 Hemangiosarcoma Diseases 0.000 description 1
• 206010019629 Hepatic adenoma Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
• 208000008839 Kidney Neoplasms Diseases 0.000 description 1
• 239000005909 Kieselgur Substances 0.000 description 1
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
• 208000002404 Liver Cell Adenoma Diseases 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
• 230000027311 M phase Effects 0.000 description 1
• 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
• 208000032271 Malignant tumor of penis Diseases 0.000 description 1
• 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• 208000019695 Migraine disease Diseases 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 208000014767 Myeloproliferative disease Diseases 0.000 description 1
• NUGPIZCTELGDOS-QHCPKHFHSA-N N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclopentanecarboxamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CC[C@@H](C=1C=NC=CC=1)NC(=O)C1CCCC1)C NUGPIZCTELGDOS-QHCPKHFHSA-N 0.000 description 1
• OWRQJDDKMITVJJ-RXMQYKEDSA-N N1C[C@@H](CCC1)NNC(O)=O Chemical class N1C[C@@H](CCC1)NNC(O)=O OWRQJDDKMITVJJ-RXMQYKEDSA-N 0.000 description 1
• 241000475481 Nebula Species 0.000 description 1
• 238000006411 Negishi coupling reaction Methods 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 208000009905 Neurofibromatoses Diseases 0.000 description 1
• 239000006057 Non-nutritive feed additive Substances 0.000 description 1
• QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 1
• 201000010133 Oligodendroglioma Diseases 0.000 description 1
• 208000002193 Pain Diseases 0.000 description 1
• 208000002471 Penile Neoplasms Diseases 0.000 description 1
• 206010034299 Penile cancer Diseases 0.000 description 1
• 241000018646 Pinus brutia Species 0.000 description 1
• 239000004743 Polypropylene Substances 0.000 description 1
• 206010036790 Productive cough Diseases 0.000 description 1
• GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 208000015634 Rectal Neoplasms Diseases 0.000 description 1
• 206010038389 Renal cancer Diseases 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• 208000005678 Rhabdomyoma Diseases 0.000 description 1
• 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 1
• 206010061934 Salivary gland cancer Diseases 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• 208000000097 Sertoli-Leydig cell tumor Diseases 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 229920004890 Triton X-100 Polymers 0.000 description 1
• 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 208000002495 Uterine Neoplasms Diseases 0.000 description 1
• 206010046798 Uterine leiomyoma Diseases 0.000 description 1
• 208000008383 Wilms tumor Diseases 0.000 description 1
• 206010048214 Xanthoma Diseases 0.000 description 1
• 206010048215 Xanthomatosis Diseases 0.000 description 1
• HJWOWXPYUDERMA-VXGBXAGGSA-N [(3R,4R)-4-azidopiperidin-3-yl] phenylmethanesulfonate Chemical compound C1CNC[C@H]([C@@H]1N=[N+]=[N-])OS(=O)(=O)CC2=CC=CC=C2 HJWOWXPYUDERMA-VXGBXAGGSA-N 0.000 description 1
• 229940022663 acetate Drugs 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 210000004100 adrenal gland Anatomy 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 229940110282 alimta Drugs 0.000 description 1
• 150000001335 aliphatic alkanes Chemical class 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• WYTGDNHDOZPMIW-RCBQFDQVSA-N alstonine Natural products C1=CC2=C3C=CC=CC3=NC2=C2N1C[C@H]1[C@H](C)OC=C(C(=O)OC)[C@H]1C2 WYTGDNHDOZPMIW-RCBQFDQVSA-N 0.000 description 1
• 125000006242 amine protecting group Chemical group 0.000 description 1
• 235000001014 amino acid Nutrition 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 1
• 229940025084 amphetamine Drugs 0.000 description 1
• 229940124650 anti-cancer therapies Drugs 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 238000011319 anticancer therapy Methods 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 201000011165 anus cancer Diseases 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 125000003943 azolyl group Chemical group 0.000 description 1
• WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 1
• 229910001626 barium chloride Inorganic materials 0.000 description 1
• 230000037429 base substitution Effects 0.000 description 1
• QSKXWLBDBBHPNU-RTBURBONSA-N benzyl (3R,4R)-3-azido-4-benzylsulfonyloxypiperidine-1-carboxylate Chemical compound C(C1=CC=CC=C1)OC(=O)N1C[C@H]([C@@H](CC1)OS(=O)(=O)CC1=CC=CC=C1)N=[N+]=[N-] QSKXWLBDBBHPNU-RTBURBONSA-N 0.000 description 1
• PWVDWURTOBCLJW-VXGBXAGGSA-N benzyl (3r,4r)-3-azido-4-hydroxypiperidine-1-carboxylate Chemical compound C1[C@@H](N=[N+]=[N-])[C@H](O)CCN1C(=O)OCC1=CC=CC=C1 PWVDWURTOBCLJW-VXGBXAGGSA-N 0.000 description 1
• 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 1
• NMGQSFWNPZDFBS-UHFFFAOYSA-N benzyl 7-oxo-3-azabicyclo[4.1.0]heptane-3-carboxylate Chemical compound C(C1=CC=CC=C1)OC(=O)N1CC2C(C2CC1)=O NMGQSFWNPZDFBS-UHFFFAOYSA-N 0.000 description 1
• 229940007550 benzyl acetate Drugs 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 201000000053 blastoma Diseases 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 201000003149 breast fibroadenoma Diseases 0.000 description 1
• 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
• 201000002143 bronchus adenoma Diseases 0.000 description 1
• 239000004067 bulking agent Substances 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 229940088954 camptosar Drugs 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• CSJDPVWYKSCJME-UHFFFAOYSA-N carbonochloridic acid;cyclopropane Chemical compound C1CC1.OC(Cl)=O CSJDPVWYKSCJME-UHFFFAOYSA-N 0.000 description 1
• 229960004562 carboplatin Drugs 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 230000012820 cell cycle checkpoint Effects 0.000 description 1
• 230000006369 cell cycle progression Effects 0.000 description 1
• 210000003679 cervix uteri Anatomy 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
• 229960005091 chloramphenicol Drugs 0.000 description 1
• 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 1
• AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
• 238000002983 circular dichroism Methods 0.000 description 1
• 208000009060 clear cell adenocarcinoma Diseases 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 229940125758 compound 15 Drugs 0.000 description 1
• 229940126142 compound 16 Drugs 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
• 150000001924 cycloalkanes Chemical class 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• YMGUBTXCNDTFJI-UHFFFAOYSA-M cyclopropanecarboxylate Chemical compound [O-]C(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-M 0.000 description 1
• WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 1
• KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
• 229960000975 daunorubicin Drugs 0.000 description 1
• RMKNCYHVESPYFD-UHFFFAOYSA-N decan-1-amine;hydrochloride Chemical compound [Cl-].CCCCCCCCCC[NH3+] RMKNCYHVESPYFD-UHFFFAOYSA-N 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 230000006866 deterioration Effects 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 150000004683 dihydrates Chemical class 0.000 description 1
• 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
• 125000005052 dihydropyrazolyl group Chemical group N1(NCC=C1)* 0.000 description 1
• 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
• 230000005750 disease progression Effects 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• 229960004679 doxorubicin Drugs 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 210000005069 ears Anatomy 0.000 description 1
• 229920001971 elastomer Polymers 0.000 description 1
• 229940120655 eloxatin Drugs 0.000 description 1
• 201000008184 embryoma Diseases 0.000 description 1
• 208000014616 embryonal neoplasm Diseases 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000002357 endometrial effect Effects 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 238000001952 enzyme assay Methods 0.000 description 1
• 229940125532 enzyme inhibitor Drugs 0.000 description 1
• 229960002179 ephedrine Drugs 0.000 description 1
• 210000003238 esophagus Anatomy 0.000 description 1
• XIWBSOUNZWSFKU-UHFFFAOYSA-N ethyl piperidine-3-carboxylate Chemical compound CCOC(=O)C1CCCNC1 XIWBSOUNZWSFKU-UHFFFAOYSA-N 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
• 230000005284 excitation Effects 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
• 201000010934 exostosis Diseases 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 238000007306 functionalization reaction Methods 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 229940020967 gemzar Drugs 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 210000004392 genitalia Anatomy 0.000 description 1
• 210000004602 germ cell Anatomy 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 201000010536 head and neck cancer Diseases 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 201000002735 hepatocellular adenoma Diseases 0.000 description 1
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
• 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
• 102000048620 human CHEK1 Human genes 0.000 description 1
• 229940088013 hycamtin Drugs 0.000 description 1
• OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
• IKGLACJFEHSFNN-UHFFFAOYSA-N hydron;triethylazanium;trifluoride Chemical compound F.F.F.CCN(CC)CC IKGLACJFEHSFNN-UHFFFAOYSA-N 0.000 description 1
• 201000001421 hyperglycemia Diseases 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 229910017053 inorganic salt Inorganic materials 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 208000020082 intraepithelial neoplasia Diseases 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 230000009545 invasion Effects 0.000 description 1
• 208000030776 invasive breast carcinoma Diseases 0.000 description 1
• 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 1
• 201000010985 invasive ductal carcinoma Diseases 0.000 description 1
• 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• 238000005342 ion exchange Methods 0.000 description 1
• 238000006317 isomerization reaction Methods 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 229960003299 ketamine Drugs 0.000 description 1
• 201000010982 kidney cancer Diseases 0.000 description 1
• 230000002147 killing effect Effects 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 210000002429 large intestine Anatomy 0.000 description 1
• 206010024627 liposarcoma Diseases 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 1
• 238000003819 low-pressure liquid chromatography Methods 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 201000005249 lung adenocarcinoma Diseases 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 210000005265 lung cell Anatomy 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 201000004593 malignant giant cell tumor Diseases 0.000 description 1
• 210000001161 mammalian embryo Anatomy 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 210000002418 meninge Anatomy 0.000 description 1
• LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
• 238000001465 metallisation Methods 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
• IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 1
• RMIODHQZRUFFFF-UHFFFAOYSA-N methoxyacetic acid Chemical compound COCC(O)=O RMIODHQZRUFFFF-UHFFFAOYSA-N 0.000 description 1
• 229940050176 methyl chloride Drugs 0.000 description 1
• VVBSXSVVMNGQIN-UHFFFAOYSA-N methyl pyrrolidine-3-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1CCNC1 VVBSXSVVMNGQIN-UHFFFAOYSA-N 0.000 description 1
• 206010027599 migraine Diseases 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004001 molecular interaction Effects 0.000 description 1
• 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
• 208000025113 myeloid leukemia Diseases 0.000 description 1
• 208000009091 myxoma Diseases 0.000 description 1
• NMGVIZJUIPNHLI-UHFFFAOYSA-N n,n-dimethylpiperidin-3-amine Chemical compound CN(C)C1CCCNC1 NMGVIZJUIPNHLI-UHFFFAOYSA-N 0.000 description 1
• VMHKLVCWJQISTH-UHFFFAOYSA-N n-(5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)-1-(trifluoromethyl)cyclopropane-1-carboxamide Chemical compound C1=2C(F)=C(Br)C=NC=2NC=C1NC(=O)C1(C(F)(F)F)CC1 VMHKLVCWJQISTH-UHFFFAOYSA-N 0.000 description 1
• HIEGYRSDXDTCKS-UHFFFAOYSA-N n-(5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxyacetamide Chemical compound C1=C(Br)C(F)=C2C(NC(=O)COC)=CNC2=N1 HIEGYRSDXDTCKS-UHFFFAOYSA-N 0.000 description 1
• NAHBKERQINVKSR-UHFFFAOYSA-N n-(5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NC=2C3=C(F)C(Br)=CN=C3NC=2)=C1 NAHBKERQINVKSR-UHFFFAOYSA-N 0.000 description 1
• NFULGMLGXKXIJF-UHFFFAOYSA-N n-(5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)-3-methylbenzamide Chemical compound CC1=CC=CC(C(=O)NC=2C3=C(F)C(Br)=CN=C3NC=2)=C1 NFULGMLGXKXIJF-UHFFFAOYSA-N 0.000 description 1
• NJQKETMCYRDMEH-UHFFFAOYSA-N n-(5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)benzamide Chemical compound C1=2C(F)=C(Br)C=NC=2NC=C1NC(=O)C1=CC=CC=C1 NJQKETMCYRDMEH-UHFFFAOYSA-N 0.000 description 1
• RLGYMHWBBLLUNX-UHFFFAOYSA-N n-(5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)cyclopropanecarboxamide Chemical compound C1=2C(F)=C(Br)C=NC=2NC=C1NC(=O)C1CC1 RLGYMHWBBLLUNX-UHFFFAOYSA-N 0.000 description 1
• QMAVAETYUZAQDW-UHFFFAOYSA-N n-[4-(1,2,3,3a,4,5,7,7a-octahydropyrrolo[2,3-c]pyridin-6-yl)-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide Chemical compound C12=C(N3CC4NCCC4CC3)C(Br)=CN=C2NC=C1NC(=O)C1=CC=CN=C1 QMAVAETYUZAQDW-UHFFFAOYSA-N 0.000 description 1
• XEEMHUAWQDDHFY-UHFFFAOYSA-N n-[4-(3-aminopiperidin-1-yl)-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide Chemical compound C1C(N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C=1C=NC=CC=1)=CN2 XEEMHUAWQDDHFY-UHFFFAOYSA-N 0.000 description 1
• NVKRLDFNLSIROE-SBSPUUFOSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-(trifluoromethyl)cyclopropane-1-carboxamide;hydrochloride Chemical compound Cl.C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1(CC1)C(F)(F)F)=CN2 NVKRLDFNLSIROE-SBSPUUFOSA-N 0.000 description 1
• KZHFUBOLXWIOFY-UTONKHPSSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-methyl-6-oxopyridine-3-carboxamide;hydrochloride Chemical compound Cl.C1=CC(=O)N(C)C=C1C(=O)NC1=CNC2=NC=C(Br)C(N3C[C@H](N)CCC3)=C12 KZHFUBOLXWIOFY-UTONKHPSSA-N 0.000 description 1
• OPRMEDUJSFVHGE-HNCPQSOCSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-methylpyrazole-3-carboxamide;hydrochloride Chemical compound Cl.CN1C=CC(C(=O)NC=2C3=C(N4C[C@H](N)CCC4)C(Br)=CN=C3NC=2)=N1 OPRMEDUJSFVHGE-HNCPQSOCSA-N 0.000 description 1
• GLVAXFGIKUABQD-HNCPQSOCSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-2,2-dimethylpropanamide;hydrochloride Chemical compound Cl.C=12C(NC(=O)C(C)(C)C)=CNC2=NC=C(Br)C=1N1CCC[C@@H](N)C1 GLVAXFGIKUABQD-HNCPQSOCSA-N 0.000 description 1
• UMEQUCCVDMNKRC-BTQNPOSSSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-3-fluorobenzamide;hydrochloride Chemical compound Cl.C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C=1C=C(F)C=CC=1)=CN2 UMEQUCCVDMNKRC-BTQNPOSSSA-N 0.000 description 1
• QBOYYYXAQNINAJ-PFEQFJNWSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-3-methylbenzamide;hydrochloride Chemical compound Cl.CC1=CC=CC(C(=O)NC=2C3=C(N4C[C@H](N)CCC4)C(Br)=CN=C3NC=2)=C1 QBOYYYXAQNINAJ-PFEQFJNWSA-N 0.000 description 1
• FRXOKGPYWNXRQP-BTQNPOSSSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]-4-fluorobenzamide;hydrochloride Chemical compound Cl.C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C=1C=CC(F)=CC=1)=CN2 FRXOKGPYWNXRQP-BTQNPOSSSA-N 0.000 description 1
• QKKMSVOWPYQVPA-BTQNPOSSSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]benzamide;hydrochloride Chemical compound Cl.C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C=1C=CC=CC=1)=CN2 QKKMSVOWPYQVPA-BTQNPOSSSA-N 0.000 description 1
• VQHDZIYCOTVXHI-HNCPQSOCSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrimidine-2-carboxamide;hydrochloride Chemical compound Cl.C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C=1N=CC=CN=1)=CN2 VQHDZIYCOTVXHI-HNCPQSOCSA-N 0.000 description 1
• UWVMMXGLDOULIA-UHFFFAOYSA-N n-[5-bromo-4-(3-pyridin-2-ylpyrrolidin-1-yl)-1h-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide Chemical compound C12=C(N3CC(CC3)C=3N=CC=CC=3)C(Br)=CN=C2NC=C1NC(=O)C1=CC=CN=C1 UWVMMXGLDOULIA-UHFFFAOYSA-N 0.000 description 1
• ARALVOCHONNTCN-OAHLLOKOSA-N n-[5-chloro-4-[(3r)-3-(propan-2-ylamino)piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide Chemical compound C1[C@H](NC(C)C)CCCN1C1=C(Cl)C=NC2=C1C(NC(=O)C=1C=NC=CC=1)=CN2 ARALVOCHONNTCN-OAHLLOKOSA-N 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 208000007538 neurilemmoma Diseases 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 201000004662 neurofibroma of spinal cord Diseases 0.000 description 1
• 201000004931 neurofibromatosis Diseases 0.000 description 1
• 125000000627 niacin group Chemical group 0.000 description 1
• 238000006396 nitration reaction Methods 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 210000003250 oocyst Anatomy 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 208000003388 osteoid osteoma Diseases 0.000 description 1
• 208000008798 osteoma Diseases 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 210000003101 oviduct Anatomy 0.000 description 1
• 125000000466 oxiranyl group Chemical group 0.000 description 1
• BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 229960005079 pemetrexed Drugs 0.000 description 1
• 201000002628 peritoneum cancer Diseases 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 229940127557 pharmaceutical product Drugs 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• MVXXTYYBNQKGKT-UHFFFAOYSA-N phenylsulfanium;chloride Chemical compound [Cl-].[SH2+]C1=CC=CC=C1 MVXXTYYBNQKGKT-UHFFFAOYSA-N 0.000 description 1
• XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• GMCGYLIRFCDMPS-UHFFFAOYSA-N piperidin-3-ylcarbamic acid Chemical compound OC(=O)NC1CCCNC1 GMCGYLIRFCDMPS-UHFFFAOYSA-N 0.000 description 1
• 229920001155 polypropylene Polymers 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 230000032029 positive regulation of DNA repair Effects 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 239000003909 protein kinase inhibitor Substances 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• OBLVPWTUALCMGD-UHFFFAOYSA-N pyridin-1-ium-3-carboxamide;chloride Chemical compound Cl.NC(=O)C1=CC=CN=C1 OBLVPWTUALCMGD-UHFFFAOYSA-N 0.000 description 1
• ZFCHNZDUMIOWFV-UHFFFAOYSA-N pyrimidine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=N1 ZFCHNZDUMIOWFV-UHFFFAOYSA-N 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• ADPQWEGXWVSSKZ-UHFFFAOYSA-N pyrrolidine-1,3-dicarboxylic acid Chemical compound OC(=O)C1CCN(C(O)=O)C1 ADPQWEGXWVSSKZ-UHFFFAOYSA-N 0.000 description 1
• 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
• 229960000948 quinine Drugs 0.000 description 1
• 206010038038 rectal cancer Diseases 0.000 description 1
• 201000001275 rectum cancer Diseases 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000008439 repair process Effects 0.000 description 1
• 239000013557 residual solvent Substances 0.000 description 1
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
• YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 1
• 229930182490 saponin Natural products 0.000 description 1
• 150000007949 saponins Chemical class 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 208000037968 sinus cancer Diseases 0.000 description 1
• 201000000849 skin cancer Diseases 0.000 description 1
• 210000003625 skull Anatomy 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 239000000779 smoke Substances 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 235000015096 spirit Nutrition 0.000 description 1
• 125000003003 spiro group Chemical group 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 208000024794 sputum Diseases 0.000 description 1
• 210000003802 sputum Anatomy 0.000 description 1
• 208000017572 squamous cell neoplasm Diseases 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 210000002536 stromal cell Anatomy 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 238000000859 sublimation Methods 0.000 description 1
• 230000008022 sublimation Effects 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 229940061353 temodar Drugs 0.000 description 1
• 229960001278 teniposide Drugs 0.000 description 1
• 208000001608 teratocarcinoma Diseases 0.000 description 1
• FZAKOAFETOZBLC-HTQZYQBOSA-N tert-butyl (3r,4r)-4-fluoro-3-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](F)[C@H](O)C1 FZAKOAFETOZBLC-HTQZYQBOSA-N 0.000 description 1
• NYGXZCRPVBPJTA-UHFFFAOYSA-N tert-butyl 2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[2,3-c]pyrrole-5-carboxylate Chemical compound C1CNC2CN(C(=O)OC(C)(C)C)CC21 NYGXZCRPVBPJTA-UHFFFAOYSA-N 0.000 description 1
• HPPARSNAMZJAPZ-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.4]nonane-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC11CNCC1 HPPARSNAMZJAPZ-UHFFFAOYSA-N 0.000 description 1
• FCTYQLDARMKVAB-UHFFFAOYSA-N tert-butyl 7-oxo-4-azabicyclo[4.1.0]heptane-4-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2C(=O)C12 FCTYQLDARMKVAB-UHFFFAOYSA-N 0.000 description 1
• RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
• WIEJVMZWPIUWHO-QMMMGPOBSA-N tert-butyl n-[[(3s)-pyrrolidin-3-yl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NC[C@H]1CCNC1 WIEJVMZWPIUWHO-QMMMGPOBSA-N 0.000 description 1
• NVISSTNTBKVSPW-SNVBAGLBSA-N tert-butyl n-ethyl-n-[(3r)-piperidin-3-yl]carbamate Chemical compound 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 compound CC(C)(C)OC(=O)N(C)[C@@H]1CCCNC1 RTXNDTNDOHQMTI-SECBINFHSA-N 0.000 description 1
• XYKYUXYNQDXZTD-UHFFFAOYSA-N tert-butyl n-methyl-n-pyrrolidin-3-ylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)C1CCNC1 XYKYUXYNQDXZTD-UHFFFAOYSA-N 0.000 description 1
• JHLVEBNWCCKSGY-UHFFFAOYSA-N tert-butyl n-methylcarbamate Chemical compound CNC(=O)OC(C)(C)C JHLVEBNWCCKSGY-UHFFFAOYSA-N 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000002381 testicular Effects 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
• 125000003554 tetrahydropyrrolyl group Chemical group 0.000 description 1
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• VOVUARRWDCVURC-UHFFFAOYSA-N thiirane Chemical compound C1CS1 VOVUARRWDCVURC-UHFFFAOYSA-N 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 150000003568 thioethers Chemical class 0.000 description 1
• XDLNRRRJZOJTRW-UHFFFAOYSA-N thiohypochlorous acid Chemical compound ClS XDLNRRRJZOJTRW-UHFFFAOYSA-N 0.000 description 1
• DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 229960000303 topotecan Drugs 0.000 description 1
• 230000026683 transduction Effects 0.000 description 1
• 238000010361 transduction Methods 0.000 description 1
• 230000016596 traversing start control point of mitotic cell cycle Effects 0.000 description 1
• WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
• 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 208000022271 tubular adenoma Diseases 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 210000003708 urethra Anatomy 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 206010046766 uterine cancer Diseases 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 210000001215 vagina Anatomy 0.000 description 1
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
• JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 239000000052 vinegar Substances 0.000 description 1
• 235000021419 vinegar Nutrition 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 229940053867 xeloda Drugs 0.000 description 1