AU2013213954B2 - 1H-pyrrolo[2,3-b] pyridine derivatives and their use as kinase inhibitors - Google Patents
1H-pyrrolo[2,3-b] pyridine derivatives and their use as kinase inhibitors Download PDFInfo
- Publication number
- AU2013213954B2 AU2013213954B2 AU2013213954A AU2013213954A AU2013213954B2 AU 2013213954 B2 AU2013213954 B2 AU 2013213954B2 AU 2013213954 A AU2013213954 A AU 2013213954A AU 2013213954 A AU2013213954 A AU 2013213954A AU 2013213954 B2 AU2013213954 B2 AU 2013213954B2
- Authority
- AU
- Australia
- Prior art keywords
- pyrrolo
- pyrazole
- carboxylic acid
- amide
- benzyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 150000005258 1H-pyrrolo(2,3-b)pyridines Chemical class 0.000 title description 5
- 229940043355 kinase inhibitor Drugs 0.000 title description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 365
- KGDOHXYALMXHLF-UHFFFAOYSA-N 1-benzylpyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=CC=C1 KGDOHXYALMXHLF-UHFFFAOYSA-N 0.000 claims description 128
- 239000000203 mixture Substances 0.000 claims description 68
- 238000000034 method Methods 0.000 claims description 66
- -1 pyrrolo[2,3-b]pyridin-4-yl Chemical group 0.000 claims description 59
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 28
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- AKKPGUPOFLAXRN-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=C(F)C=C1 AKKPGUPOFLAXRN-UHFFFAOYSA-N 0.000 claims description 23
- 206010028980 Neoplasm Diseases 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical group 0.000 claims description 20
- 125000003107 substituted aryl group Chemical group 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- RJAFVJZCUMEOBR-UHFFFAOYSA-N 1-(pyridin-4-ylmethyl)pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=NC=C1 RJAFVJZCUMEOBR-UHFFFAOYSA-N 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 11
- 230000000694 effects Effects 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- WCMWZVWZYCRAIW-UHFFFAOYSA-N 1-(pyridin-3-ylmethyl)pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=CN=C1 WCMWZVWZYCRAIW-UHFFFAOYSA-N 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 10
- 239000000460 chlorine Chemical group 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 7
- 102000001253 Protein Kinase Human genes 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 7
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 108060006633 protein kinase Proteins 0.000 claims description 7
- SOUZKMFQFRDGKE-UHFFFAOYSA-N 1-(pyridin-2-ylmethyl)pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=CC=N1 SOUZKMFQFRDGKE-UHFFFAOYSA-N 0.000 claims description 6
- UORKPBOZTFYKBG-UHFFFAOYSA-N 1-benzyl-n-(5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound C12=CC(Br)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 UORKPBOZTFYKBG-UHFFFAOYSA-N 0.000 claims description 6
- 125000004450 alkenylene group Chemical group 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 6
- ACKKVNVNGUYIAR-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]pyrazole-4-carboxylic acid Chemical compound COC1=CC=CC(CN2N=CC(=C2)C(O)=O)=C1 ACKKVNVNGUYIAR-UHFFFAOYSA-N 0.000 claims description 5
- IKIIMRKHGIWFEP-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=C(Cl)C=C1 IKIIMRKHGIWFEP-UHFFFAOYSA-N 0.000 claims description 5
- JMWJJDKQQMMJRG-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methyl]pyrazole-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1CN1N=CC(C(O)=O)=C1 JMWJJDKQQMMJRG-UHFFFAOYSA-N 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical class C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 125000000732 arylene group Chemical group 0.000 claims description 5
- MPVDXIMFBOLMNW-UHFFFAOYSA-N chembl1615565 Chemical compound OC1=CC=C2C=C(S(O)(=O)=O)C=C(S(O)(=O)=O)C2=C1N=NC1=CC=CC=C1 MPVDXIMFBOLMNW-UHFFFAOYSA-N 0.000 claims description 5
- 125000005549 heteroarylene group Chemical group 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000005717 substituted cycloalkylene group Chemical group 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- ALSCRMRUUIZZBO-UHFFFAOYSA-N 1-[(2-cyanophenyl)methyl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=CC=C1C#N ALSCRMRUUIZZBO-UHFFFAOYSA-N 0.000 claims description 3
- SEVWRBACKOQREE-UHFFFAOYSA-N 1-[(2-fluorophenyl)methyl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=CC=C1F SEVWRBACKOQREE-UHFFFAOYSA-N 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000001959 radiotherapy Methods 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- OETDPVHIOQFDBI-UHFFFAOYSA-N 1-benzyl-n-(4-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound C1=2C(Br)=CC=NC=2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 OETDPVHIOQFDBI-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 206010052779 Transplant rejections Diseases 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 206010025135 lupus erythematosus Diseases 0.000 claims description 2
- DUAGZNPOPXJGOT-UHFFFAOYSA-N n-(5-bromo-1h-pyrrolo[2,3-b]pyridin-3-yl)-1-(1h-pyrrol-2-ylmethyl)pyrazole-4-carboxamide Chemical compound C12=CC(Br)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=CN1 DUAGZNPOPXJGOT-UHFFFAOYSA-N 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 150000003053 piperidines Chemical class 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 229910052727 yttrium Inorganic materials 0.000 claims description 2
- 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 claims 2
- 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 claims 2
- WMEWWDFWHBMCBM-UHFFFAOYSA-N 1-benzyl-n-(1h-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound C=1NC2=NC=CC=C2C=1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 WMEWWDFWHBMCBM-UHFFFAOYSA-N 0.000 claims 1
- VAZGKVZODODPDU-UHFFFAOYSA-N 1-benzyl-n-(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound C12=CC(C)=CN=C2NC=C1NC(=O)C(=C1)C=NN1CC1=CC=CC=C1 VAZGKVZODODPDU-UHFFFAOYSA-N 0.000 claims 1
- FBLBZRLTZBPZFA-UHFFFAOYSA-N 1-benzyl-n-(5-phenyl-1h-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C1=CC=CC=C1 FBLBZRLTZBPZFA-UHFFFAOYSA-N 0.000 claims 1
- QPLMQVLSVQFQTH-UHFFFAOYSA-N 1-benzyl-n-(5-piperidin-1-yl-1h-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2N1CCCCC1 QPLMQVLSVQFQTH-UHFFFAOYSA-N 0.000 claims 1
- LNYMJXVFIFMSOW-UHFFFAOYSA-N 1-benzylpyrazole-4-carboxamide Chemical compound C1=C(C(=O)N)C=NN1CC1=CC=CC=C1 LNYMJXVFIFMSOW-UHFFFAOYSA-N 0.000 claims 1
- ZVXKYWHJBYIYNI-UHFFFAOYSA-N 1h-pyrazole-4-carboxamide Chemical compound NC(=O)C=1C=NNC=1 ZVXKYWHJBYIYNI-UHFFFAOYSA-N 0.000 claims 1
- RTADYVMNEDWFEV-SSDOTTSWSA-N 4-[(3R)-3-aminopiperidin-1-yl]-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1[C@H](N)CCCN1C1=C(C(F)(F)F)C=NC2=C1C(N)=CN2 RTADYVMNEDWFEV-SSDOTTSWSA-N 0.000 claims 1
- KTMVCQFCIUKKDQ-OGFXRTJISA-N 4-[(3R)-3-aminopiperidin-1-yl]-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-amine 1-(pyridin-2-ylmethyl)pyrazole-4-carboxylic acid Chemical compound N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1C(F)(F)F.OC(C1=CN(CC2=NC=CC=C2)N=C1)=O KTMVCQFCIUKKDQ-OGFXRTJISA-N 0.000 claims 1
- MKXNTQZPJNTKGC-OGFXRTJISA-N 4-[(3R)-3-aminopiperidin-1-yl]-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-amine 1-(pyridin-3-ylmethyl)pyrazole-4-carboxylic acid Chemical compound N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1C(F)(F)F.OC(C1=CN(CC2=CC=CN=C2)N=C1)=O MKXNTQZPJNTKGC-OGFXRTJISA-N 0.000 claims 1
- SPVXSBKORLMTPI-OGFXRTJISA-N 4-[(3R)-3-aminopiperidin-1-yl]-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-amine 1-benzylpyrazole-4-carboxylic acid Chemical compound N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1C(F)(F)F.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O SPVXSBKORLMTPI-OGFXRTJISA-N 0.000 claims 1
- TYOAKDISSULLGZ-SSDOTTSWSA-N 4-[(3R)-3-aminopiperidin-1-yl]-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1[C@H](N)CCCN1C1=C(Br)C=NC2=C1C(N)=CN2 TYOAKDISSULLGZ-SSDOTTSWSA-N 0.000 claims 1
- SAWFSXLXKNVUBQ-ZMBIFBSDSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.BrC=1C(=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)N2C[C@@H](CCC2)NCC(C)(C)C Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.BrC=1C(=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)N2C[C@@H](CCC2)NCC(C)(C)C SAWFSXLXKNVUBQ-ZMBIFBSDSA-N 0.000 claims 1
- XBMFSGXLIPBRKO-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN(CC(COC=1C=C(C=CC1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)(C)C)C Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN(CC(COC=1C=C(C=CC1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)(C)C)C XBMFSGXLIPBRKO-UHFFFAOYSA-N 0.000 claims 1
- SLPPVGYPELTOKU-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN1N=CC(=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN1N=CC(=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 SLPPVGYPELTOKU-UHFFFAOYSA-N 0.000 claims 1
- UGGAJCLMYNPURU-PKLMIRHRSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.N[C@H]1CN(CC1)C1=C2C(=NC=C1Br)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.N[C@H]1CN(CC1)C1=C2C(=NC=C1Br)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 UGGAJCLMYNPURU-PKLMIRHRSA-N 0.000 claims 1
- MHIAXZIRPYHGAF-DDWIOCJRSA-N CC1=C(CN2N=CC(C(O)=O)=C2)C=CC=C1.COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N Chemical compound CC1=C(CN2N=CC(C(O)=O)=C2)C=CC=C1.COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N MHIAXZIRPYHGAF-DDWIOCJRSA-N 0.000 claims 1
- DVQDRSRXPMVYEC-OGFXRTJISA-N CC1=CC=C(CN2N=CC(C(O)=O)=C2)C=C1.N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br Chemical compound CC1=CC=C(CN2N=CC(C(O)=O)=C2)C=C1.N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br DVQDRSRXPMVYEC-OGFXRTJISA-N 0.000 claims 1
- MYKLZOYZOPHBGF-GMUIIQOCSA-N CC=1C=C(CN2N=CC(=C2)C(=O)O)C=CC1.N[C@H]1CN(CCC1)C1=C2C(=NC=C1OC)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=C(C=C2)F Chemical compound CC=1C=C(CN2N=CC(=C2)C(=O)O)C=CC1.N[C@H]1CN(CCC1)C1=C2C(=NC=C1OC)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=C(C=C2)F MYKLZOYZOPHBGF-GMUIIQOCSA-N 0.000 claims 1
- APZUKNZNPKHHJL-SBSPUUFOSA-N CCN[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O Chemical compound CCN[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O APZUKNZNPKHHJL-SBSPUUFOSA-N 0.000 claims 1
- XHZDDRBDQDQSQE-UHFFFAOYSA-N CN1CC(COC2=CC=CC(C(C=C34)=CN=C3NC=C4N)=C2)CCC1.O=C(C1=CN(CC2=CC=CC=C2)N=C1)NC(C1=C2)=CNC1=NC=C2C1=CC(OC2COC2)=CC=C1 Chemical compound CN1CC(COC2=CC=CC(C(C=C34)=CN=C3NC=C4N)=C2)CCC1.O=C(C1=CN(CC2=CC=CC=C2)N=C1)NC(C1=C2)=CNC1=NC=C2C1=CC(OC2COC2)=CC=C1 XHZDDRBDQDQSQE-UHFFFAOYSA-N 0.000 claims 1
- PKDQBCMMGWHXSG-DDWIOCJRSA-N CN[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O Chemical compound CN[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O PKDQBCMMGWHXSG-DDWIOCJRSA-N 0.000 claims 1
- IPRXOEHKXRAEKQ-DDWIOCJRSA-N COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC(C=C2)=CC=C2F)N=C1)=O Chemical compound COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC(C=C2)=CC=C2F)N=C1)=O IPRXOEHKXRAEKQ-DDWIOCJRSA-N 0.000 claims 1
- PRAUREVGHZSSDV-DDWIOCJRSA-N COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC(C=CC=C2)=C2Cl)N=C1)=O Chemical compound COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC(C=CC=C2)=C2Cl)N=C1)=O PRAUREVGHZSSDV-DDWIOCJRSA-N 0.000 claims 1
- MSIWZVCYOPLFBZ-DDWIOCJRSA-N COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC2=CC(F)=CC=C2)N=C1)=O Chemical compound COC(C(N(CCC1)C[C@@H]1N)=C12)=CN=C1NC=C2N.OC(C1=CN(CC2=CC(F)=CC=C2)N=C1)=O MSIWZVCYOPLFBZ-DDWIOCJRSA-N 0.000 claims 1
- GFXCEZXCSDIYRL-OGFXRTJISA-N COC1=CC=C(CN2N=CC(C(O)=O)=C2)C=C1.N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br Chemical compound COC1=CC=C(CN2N=CC(C(O)=O)=C2)C=C1.N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br GFXCEZXCSDIYRL-OGFXRTJISA-N 0.000 claims 1
- FTRJQLBPISGMTR-UHFFFAOYSA-N COC1=CC=CC(CN2N=CC(C(O)=O)=C2)=C1.NC(C1=C2)=CNC1=NC=C2C1=CC=NC=C1.O=C(C1=CN(CC2=CC=CC=C2)N=C1)NC(C1=C2)=CNC1=NC=C2C1=CC=CN=C1 Chemical compound COC1=CC=CC(CN2N=CC(C(O)=O)=C2)=C1.NC(C1=C2)=CNC1=NC=C2C1=CC=NC=C1.O=C(C1=CN(CC2=CC=CC=C2)N=C1)NC(C1=C2)=CNC1=NC=C2C1=CC=CN=C1 FTRJQLBPISGMTR-UHFFFAOYSA-N 0.000 claims 1
- LPBCCMHKOCJHPN-DGXMUYMBSA-N N-[4-[(3R,4R)-3-amino-4-cyclopropylpiperidin-1-yl]-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide 1-benzylpyrazole-4-carboxylic acid Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.N[C@H]1CN(CC[C@@H]1C1CC1)C1=C2C(=NC=C1Br)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 LPBCCMHKOCJHPN-DGXMUYMBSA-N 0.000 claims 1
- XWRYPFPSCKPQSB-UHFFFAOYSA-N NC(C1=C2)=CNC1=NC=C2C(C=CC(CN1CCCC1)=C1)=C1F.O=C(C1=CN(CC2=CC=CC=C2)N=C1)NC(C1=C2)=CNC1=NC=C2C1=CC(N2CCCC2)=CC=C1 Chemical compound NC(C1=C2)=CNC1=NC=C2C(C=CC(CN1CCCC1)=C1)=C1F.O=C(C1=CN(CC2=CC=CC=C2)N=C1)NC(C1=C2)=CNC1=NC=C2C1=CC(N2CCCC2)=CC=C1 XWRYPFPSCKPQSB-UHFFFAOYSA-N 0.000 claims 1
- WDIHOGKPAMVSOE-UHFFFAOYSA-N NC(C1=C2)=CNC1=NC=C2C1=CC(OCCCN2CCOCC2)=CC=C1.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O Chemical compound NC(C1=C2)=CNC1=NC=C2C1=CC(OCCCN2CCOCC2)=CC=C1.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O WDIHOGKPAMVSOE-UHFFFAOYSA-N 0.000 claims 1
- CKAACKNQKCXNMS-IGLJFSGRSA-N NC(C1=C2N(CC3)C[C@@H]3O)=CNC1=NC=C2Br.O[C@H](CCC1)CN1C1=C(C(NC(C2=CN(CC3=CC=CC=C3)N=C2)=O)=CN2)C2=NC=C1Br Chemical compound NC(C1=C2N(CC3)C[C@@H]3O)=CNC1=NC=C2Br.O[C@H](CCC1)CN1C1=C(C(NC(C2=CN(CC3=CC=CC=C3)N=C2)=O)=CN2)C2=NC=C1Br CKAACKNQKCXNMS-IGLJFSGRSA-N 0.000 claims 1
- DIQULVRWKMNRKU-RFVHGSKJSA-N NC(C1=C2N(CCC3)C[C@@H]3NCC3CC3)=CNC1=NC=C2Br.OC(C1=CN(CC(C=C2)=CC=C2F)N=C1)=O Chemical compound NC(C1=C2N(CCC3)C[C@@H]3NCC3CC3)=CNC1=NC=C2Br.OC(C1=CN(CC(C=C2)=CC=C2F)N=C1)=O DIQULVRWKMNRKU-RFVHGSKJSA-N 0.000 claims 1
- XTCMXISUSSDVBQ-OGFXRTJISA-N N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br.OC(C1=CN(CC(C=C2)=CC=C2Cl)N=C1)=O Chemical compound N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br.OC(C1=CN(CC(C=C2)=CC=C2Cl)N=C1)=O XTCMXISUSSDVBQ-OGFXRTJISA-N 0.000 claims 1
- IFMJQMPEPSQUES-OGFXRTJISA-N N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br.OC(C1=CN(CC2=NC=CC=C2)N=C1)=O Chemical compound N[C@H](CCC1)CN1C1=C(C(N)=CN2)C2=NC=C1Br.OC(C1=CN(CC2=NC=CC=C2)N=C1)=O IFMJQMPEPSQUES-OGFXRTJISA-N 0.000 claims 1
- 238000002512 chemotherapy Methods 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- SHUUEBOBDREAPE-UHFFFAOYSA-N n-(5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridin-3-yl)-1-[(4-methoxyphenyl)methyl]pyrazole-4-carboxamide Chemical compound C1=CC(OC)=CC=C1CN1N=CC(C(=O)NC=2C3=C(F)C(Br)=CN=C3NC=2)=C1 SHUUEBOBDREAPE-UHFFFAOYSA-N 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 317
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 282
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 200
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 138
- 239000007787 solid Substances 0.000 description 121
- 238000002360 preparation method Methods 0.000 description 105
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 104
- 235000019439 ethyl acetate Nutrition 0.000 description 100
- 238000005481 NMR spectroscopy Methods 0.000 description 99
- 239000000243 solution Substances 0.000 description 99
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 97
- 229920006395 saturated elastomer Polymers 0.000 description 95
- 238000006243 chemical reaction Methods 0.000 description 86
- 239000002904 solvent Substances 0.000 description 70
- 239000011541 reaction mixture Substances 0.000 description 69
- 239000011780 sodium chloride Substances 0.000 description 69
- 239000000047 product Substances 0.000 description 65
- 238000004440 column chromatography Methods 0.000 description 50
- 239000013058 crude material Substances 0.000 description 47
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
- 239000000843 powder Substances 0.000 description 37
- 238000007792 addition Methods 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 29
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 26
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 26
- 239000000463 material Substances 0.000 description 26
- 125000000217 alkyl group Chemical group 0.000 description 24
- 238000001914 filtration Methods 0.000 description 23
- 239000003921 oil Substances 0.000 description 23
- 235000019198 oils Nutrition 0.000 description 23
- 238000003756 stirring Methods 0.000 description 22
- 239000006071 cream Substances 0.000 description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
- 239000000284 extract Substances 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 238000002953 preparative HPLC Methods 0.000 description 18
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 17
- 238000003818 flash chromatography Methods 0.000 description 17
- 238000000746 purification Methods 0.000 description 17
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 17
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 14
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical class [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
- 235000011114 ammonium hydroxide Nutrition 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000003112 inhibitor Substances 0.000 description 12
- WUOQXNWMYLFAHT-MRVPVSSYSA-N tert-butyl n-[(3r)-piperidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCCNC1 WUOQXNWMYLFAHT-MRVPVSSYSA-N 0.000 description 12
- 102000006459 Checkpoint Kinase 1 Human genes 0.000 description 11
- 108010019244 Checkpoint Kinase 1 Proteins 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 238000005516 engineering process Methods 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 241000400611 Eucalyptus deanei Species 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- 235000011121 sodium hydroxide Nutrition 0.000 description 10
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000007821 HATU Substances 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 125000003545 alkoxy group Chemical group 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000011521 glass Substances 0.000 description 9
- 238000005342 ion exchange Methods 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- LGRLJNBPDMHSOL-UHFFFAOYSA-N 1-benzyl-n-[5-bromo-1-(4-methylphenyl)sulfonylpyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=NC=C(Br)C=C2C(NC(=O)C2=CN(CC=3C=CC=CC=3)N=C2)=C1 LGRLJNBPDMHSOL-UHFFFAOYSA-N 0.000 description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 101150113535 chek1 gene Proteins 0.000 description 8
- 229960005277 gemcitabine Drugs 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 101150050673 CHK1 gene Proteins 0.000 description 7
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 7
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 7
- 235000019270 ammonium chloride Nutrition 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000012065 filter cake Substances 0.000 description 7
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 7
- 238000001665 trituration Methods 0.000 description 7
- 238000010626 work up procedure Methods 0.000 description 7
- HJBGZJMKTOMQRR-UHFFFAOYSA-N (3-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C=O)=C1 HJBGZJMKTOMQRR-UHFFFAOYSA-N 0.000 description 6
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
- PUJVSTYUTMVCSG-UHFFFAOYSA-N 5-bromo-4-fluoro-1h-pyrrolo[2,3-b]pyridine Chemical compound FC1=C(Br)C=NC2=C1C=CN2 PUJVSTYUTMVCSG-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 6
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 6
- GUYKTJJGCNDECQ-NEPJUHHUSA-N (3R,4R)-4-cyclopropyl-N-diethoxyphosphorylpiperidin-3-amine Chemical compound CCOP(=O)(OCC)N[C@H]1CNCC[C@@H]1C1CC1 GUYKTJJGCNDECQ-NEPJUHHUSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 235000011118 potassium hydroxide Nutrition 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 5
- LCTSAPFWCLXWNS-HXUWFJFHSA-N tert-butyl n-[(3r)-1-[3-[(1-benzylpyrazole-4-carbonyl)amino]-5-bromo-1h-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCCN1C1=C(Br)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 LCTSAPFWCLXWNS-HXUWFJFHSA-N 0.000 description 5
- YESANHMKGXGZLQ-UHFFFAOYSA-N (4-fluoropyrrolo[2,3-b]pyridin-1-yl)-tri(propan-2-yl)silane Chemical compound C1=CN=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1F YESANHMKGXGZLQ-UHFFFAOYSA-N 0.000 description 4
- HYBRAUPLUXQZEG-UHFFFAOYSA-N 1-[(4-methylphenyl)methyl]pyrazole-4-carboxylic acid Chemical compound C1=CC(C)=CC=C1CN1N=CC(C(O)=O)=C1 HYBRAUPLUXQZEG-UHFFFAOYSA-N 0.000 description 4
- NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 4
- ZUOPKGTYJJCCND-UHFFFAOYSA-N 5-bromo-4-fluoro-3-nitro-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=C(Br)C(F)=C2C([N+](=O)[O-])=CNC2=N1 ZUOPKGTYJJCCND-UHFFFAOYSA-N 0.000 description 4
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000010111 Ezrin/radixin/moesin Human genes 0.000 description 4
- 108050001788 Ezrin/radixin/moesin Proteins 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
- FXKSFAVNDYZPFN-CYBMUJFWSA-N [3-amino-4-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-5-yl] 2,2-dimethylpropanoate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCCN1C1=C(OC(=O)C(C)(C)C)C=NC2=C1C(N)=CN2 FXKSFAVNDYZPFN-CYBMUJFWSA-N 0.000 description 4
- WJEIYVAPNMUNIU-UHFFFAOYSA-N [Na].OC(O)=O Chemical compound [Na].OC(O)=O WJEIYVAPNMUNIU-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- VELDYOPRLMJFIK-UHFFFAOYSA-N cyclopentanecarbaldehyde Chemical compound O=CC1CCCC1 VELDYOPRLMJFIK-UHFFFAOYSA-N 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 229940127089 cytotoxic agent Drugs 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 4
- 229960004768 irinotecan Drugs 0.000 description 4
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 4
- 239000002480 mineral oil Substances 0.000 description 4
- 235000010446 mineral oil Nutrition 0.000 description 4
- 125000002757 morpholinyl group Chemical group 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 239000003039 volatile agent Substances 0.000 description 4
- YMSXGXBENOJJLW-UHFFFAOYSA-N (4-fluoro-3-nitro-1h-pyrrolo[2,3-b]pyridin-5-yl) 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC1=CN=C2NC=C([N+]([O-])=O)C2=C1F YMSXGXBENOJJLW-UHFFFAOYSA-N 0.000 description 3
- RLIKCTSDMAQFES-UHFFFAOYSA-N 1-benzyl-N-[1-(4-methylphenyl)sulfonyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound Cc1ccc(cc1)S(=O)(=O)n1cc(NC(=O)c2cnn(Cc3ccccc3)c2)c2cc(cnc12)B1OC(C)(C)C(C)(C)O1 RLIKCTSDMAQFES-UHFFFAOYSA-N 0.000 description 3
- WQTCAALJJAUNEH-UHFFFAOYSA-N 2-(4-bromopyrazol-1-yl)-n,n-diethylethanamine Chemical compound CCN(CC)CCN1C=C(Br)C=N1 WQTCAALJJAUNEH-UHFFFAOYSA-N 0.000 description 3
- KOHBEDRJXKOYHL-UHFFFAOYSA-N 2-methoxy-n-methylethanamine Chemical compound CNCCOC KOHBEDRJXKOYHL-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- LIMWPGZSXIVMIU-UHFFFAOYSA-N 4-fluoro-1-tri(propan-2-yl)silylindol-5-ol Chemical compound OC1=CC=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1F LIMWPGZSXIVMIU-UHFFFAOYSA-N 0.000 description 3
- MHQHNMJVQKUNEQ-UHFFFAOYSA-N 4-fluoro-5-methoxy-3-nitro-1h-pyrrolo[2,3-b]pyridine Chemical compound COC1=CN=C2NC=C([N+]([O-])=O)C2=C1F MHQHNMJVQKUNEQ-UHFFFAOYSA-N 0.000 description 3
- JMCVFWQJWKRMHW-UHFFFAOYSA-N 5-bromo-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=C(Br)C=C2C(N)=CNC2=N1 JMCVFWQJWKRMHW-UHFFFAOYSA-N 0.000 description 3
- LPTVWZSQAIDCEB-UHFFFAOYSA-N 5-bromo-1h-pyrrolo[2,3-b]pyridine Chemical compound BrC1=CN=C2NC=CC2=C1 LPTVWZSQAIDCEB-UHFFFAOYSA-N 0.000 description 3
- 101100220616 Caenorhabditis elegans chk-2 gene Proteins 0.000 description 3
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 3
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- HLZOIFAAAWCMOG-UHFFFAOYSA-N Fc1c(Br)cnc2[nH]cc(NC(=O)c3cnn(Cc4ccccc4)c3)c12 Chemical compound Fc1c(Br)cnc2[nH]cc(NC(=O)c3cnn(Cc4ccccc4)c3)c12 HLZOIFAAAWCMOG-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- QFCNHLDVIBPZKC-CYBMUJFWSA-N [4-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]piperidin-1-yl]-3-nitro-1h-pyrrolo[2,3-b]pyridin-5-yl] 2,2-dimethylpropanoate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCCN1C1=C(OC(=O)C(C)(C)C)C=NC2=C1C([N+]([O-])=O)=CN2 QFCNHLDVIBPZKC-CYBMUJFWSA-N 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 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 3
- AHVUFKFGWHXUDC-UHFFFAOYSA-N benzyl 4-azido-3-(4-methylphenyl)sulfonyloxypiperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1C(N=[N+]=[N-])CCN(C(=O)OCC=2C=CC=CC=2)C1 AHVUFKFGWHXUDC-UHFFFAOYSA-N 0.000 description 3
- PHSSLYCBJRMEEV-UHFFFAOYSA-N benzyl 7-oxa-4-azabicyclo[4.1.0]heptane-4-carboxylate Chemical compound C1CC2OC2CN1C(=O)OCC1=CC=CC=C1 PHSSLYCBJRMEEV-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 230000022131 cell cycle Effects 0.000 description 3
- 229940044683 chemotherapy drug Drugs 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- FDLDWKIEWAWOSL-UHFFFAOYSA-N ethyl acetate;2-methylpentane Chemical compound CCCC(C)C.CCOC(C)=O FDLDWKIEWAWOSL-UHFFFAOYSA-N 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 150000004675 formic acid derivatives Chemical class 0.000 description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 3
- 125000000842 isoxazolyl group Chemical group 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 125000004193 piperazinyl group Chemical group 0.000 description 3
- 125000003386 piperidinyl group Chemical group 0.000 description 3
- GSXCRDCXKUWXJK-UHFFFAOYSA-M potassium;1-(1h-pyrrol-2-ylmethyl)pyrazole-4-carboxylate Chemical group [K+].C1=C(C(=O)[O-])C=NN1CC1=CC=CN1 GSXCRDCXKUWXJK-UHFFFAOYSA-M 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- ALENDSSETVVANF-LLVKDONJSA-N tert-butyl n-[(3r)-1-(3-amino-5-methoxy-1h-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl]carbamate Chemical compound COC1=CN=C2NC=C(N)C2=C1N1CCC[C@@H](NC(=O)OC(C)(C)C)C1 ALENDSSETVVANF-LLVKDONJSA-N 0.000 description 3
- PXPBIKLQGJBGRG-HXUWFJFHSA-N tert-butyl n-[(3r)-1-[3-[[1-[(4-fluorophenyl)methyl]pyrazole-4-carbonyl]amino]-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCCN1C1=C(C(F)(F)F)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC(F)=CC=3)N=C1)=CN2 PXPBIKLQGJBGRG-HXUWFJFHSA-N 0.000 description 3
- LRZZXMQRQHIQAQ-SNVBAGLBSA-N tert-butyl n-[(3r)-1-[3-amino-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCCN1C1=C(C(F)(F)F)C=NC2=C1C(N)=CN2 LRZZXMQRQHIQAQ-SNVBAGLBSA-N 0.000 description 3
- RYNNPVYRYQJPEO-HNNXBMFYSA-N (2s)-1-methyl-2-[[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl]pyrrolidine Chemical compound CN1CCC[C@H]1COC1=CC=CC(B2OC(C)(C)C(C)(C)O2)=C1 RYNNPVYRYQJPEO-HNNXBMFYSA-N 0.000 description 2
- QSEMMUYKUYKNBI-UHFFFAOYSA-N (4-bromopyrrolo[2,3-b]pyridin-1-yl)-tri(propan-2-yl)silane Chemical compound C1=CN=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1Br QSEMMUYKUYKNBI-UHFFFAOYSA-N 0.000 description 2
- HSMLARVFJADZQS-UHFFFAOYSA-N (4-chloropyrrolo[2,3-b]pyridin-1-yl)-tri(propan-2-yl)silane Chemical compound C1=CN=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1Cl HSMLARVFJADZQS-UHFFFAOYSA-N 0.000 description 2
- RRAXPOIWTUEFDD-UHFFFAOYSA-N (4-fluoro-1h-pyrrolo[2,3-b]pyridin-5-yl) 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC1=CN=C2NC=CC2=C1F RRAXPOIWTUEFDD-UHFFFAOYSA-N 0.000 description 2
- COIQUVGFTILYGA-UHFFFAOYSA-N (4-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=C(O)C=C1 COIQUVGFTILYGA-UHFFFAOYSA-N 0.000 description 2
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 2
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 2
- FSNGFFWICFYWQC-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine;hydron;chloride Chemical compound Cl.ClCCN1CCCC1 FSNGFFWICFYWQC-UHFFFAOYSA-N 0.000 description 2
- VXWPLQTVHINTNQ-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-chloro-5-iodopyrrolo[2,3-b]pyridine Chemical compound C1=CC=2C(Cl)=C(I)C=NC=2N1S(=O)(=O)C1=CC=CC=C1 VXWPLQTVHINTNQ-UHFFFAOYSA-N 0.000 description 2
- CUDHNDFUGXHTRN-UHFFFAOYSA-N 1-[(2-chlorophenyl)methyl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=CC=C1Cl CUDHNDFUGXHTRN-UHFFFAOYSA-N 0.000 description 2
- QELIFVMICKIPRJ-UHFFFAOYSA-N 1-[(2-methylphenyl)methyl]pyrazole-4-carboxylic acid Chemical compound CC1=CC=CC=C1CN1N=CC(C(O)=O)=C1 QELIFVMICKIPRJ-UHFFFAOYSA-N 0.000 description 2
- IVDPFMFNQXHGNX-UHFFFAOYSA-N 1-[(3-fluorophenyl)methyl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=CC(F)=C1 IVDPFMFNQXHGNX-UHFFFAOYSA-N 0.000 description 2
- PBGWCCZEAHKYKB-UHFFFAOYSA-N 1-[(3-methylphenyl)methyl]pyrazole-4-carboxylic acid Chemical compound CC1=CC=CC(CN2N=CC(=C2)C(O)=O)=C1 PBGWCCZEAHKYKB-UHFFFAOYSA-N 0.000 description 2
- OUHKYWQKHLTDBH-UHFFFAOYSA-N 1-[fluoro(phenyl)methyl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1C(F)C1=CC=CC=C1 OUHKYWQKHLTDBH-UHFFFAOYSA-N 0.000 description 2
- MVQKTQBUBSANNZ-UHFFFAOYSA-N 1-benzyl-n-[1-(4-methylphenyl)sulfonyl-5-[3-(2-morpholin-4-ylethoxy)phenyl]pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=NC=C(C=3C=C(OCCN4CCOCC4)C=CC=3)C=C2C(NC(=O)C2=CN(CC=3C=CC=CC=3)N=C2)=C1 MVQKTQBUBSANNZ-UHFFFAOYSA-N 0.000 description 2
- CSGLYJVSUTZITP-UHFFFAOYSA-N 1-fluoropiperidine;hydrochloride Chemical compound Cl.FN1CCCCC1 CSGLYJVSUTZITP-UHFFFAOYSA-N 0.000 description 2
- NHOBBIVFUQBEMI-UHFFFAOYSA-N 1-methylsulfonylpyrrole-2-carbaldehyde Chemical compound CS(=O)(=O)N1C=CC=C1C=O NHOBBIVFUQBEMI-UHFFFAOYSA-N 0.000 description 2
- UWLHXRTWYGHNEM-UHFFFAOYSA-N 2-(chloromethyl)-1-methylsulfonylpyrrole Chemical compound CS(=O)(=O)N1C=CC=C1CCl UWLHXRTWYGHNEM-UHFFFAOYSA-N 0.000 description 2
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- HLMHCDKXKXBKQK-UHFFFAOYSA-N 2-bromoethyl(diethyl)azanium;bromide Chemical compound Br.CCN(CC)CCBr HLMHCDKXKXBKQK-UHFFFAOYSA-N 0.000 description 2
- CDBAEFXTCRKJPZ-UHFFFAOYSA-N 3,3-difluoroazetidine;hydron;chloride Chemical group Cl.FC1(F)CNC1 CDBAEFXTCRKJPZ-UHFFFAOYSA-N 0.000 description 2
- MUKIFYQKIZOYKT-UHFFFAOYSA-N 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC(O)=C1 MUKIFYQKIZOYKT-UHFFFAOYSA-N 0.000 description 2
- QLCHXZVEEOWYHL-UHFFFAOYSA-N 3-chloro-n,n,2,2-tetramethylpropan-1-amine;hydrochloride Chemical compound Cl.CN(C)CC(C)(C)CCl QLCHXZVEEOWYHL-UHFFFAOYSA-N 0.000 description 2
- IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- RWOSDAABDCYOQZ-UHFFFAOYSA-N 4-bromo-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound C1=CC(Br)=C2C(N)=CNC2=N1 RWOSDAABDCYOQZ-UHFFFAOYSA-N 0.000 description 2
- BEPFGDZUAZYOHN-UHFFFAOYSA-N 4-bromo-3-nitro-7-azaindole Chemical compound C1=CC(Br)=C2C([N+](=O)[O-])=CNC2=N1 BEPFGDZUAZYOHN-UHFFFAOYSA-N 0.000 description 2
- 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 2
- UMRGFHCHWMHAET-UHFFFAOYSA-N 4-fluoro-5-methoxy-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound COC1=CN=C2NC=C(N)C2=C1F UMRGFHCHWMHAET-UHFFFAOYSA-N 0.000 description 2
- HIODJZBVHNCROX-UHFFFAOYSA-N 4-fluoro-5-methoxy-1h-pyrrolo[2,3-b]pyridine Chemical compound COC1=CN=C2NC=CC2=C1F HIODJZBVHNCROX-UHFFFAOYSA-N 0.000 description 2
- FBLZOAQGIMCKEK-UHFFFAOYSA-N 4-fluoro-5-methyl-1h-pyrrolo[2,3-b]pyridine Chemical compound CC1=CN=C2NC=CC2=C1F FBLZOAQGIMCKEK-UHFFFAOYSA-N 0.000 description 2
- YYMPANVNHSGRDP-UHFFFAOYSA-N 4-fluoro-5-methyl-3-nitro-1h-pyrrolo[2,3-b]pyridine Chemical compound CC1=CN=C2NC=C([N+]([O-])=O)C2=C1F YYMPANVNHSGRDP-UHFFFAOYSA-N 0.000 description 2
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 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 2
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 2
- FVLVBPDQNARYJU-XAHDHGMMSA-N C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O Chemical compound C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O FVLVBPDQNARYJU-XAHDHGMMSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
- VLZMDADZTOITSH-UHFFFAOYSA-N Cc1ccc(cc1)S(=O)(=O)n1cc(NC(=O)c2cnn(Cc3ccccc3)c2)c2cc(cnc12)-c1cccc(OCCN2CCCC2)c1 Chemical compound Cc1ccc(cc1)S(=O)(=O)n1cc(NC(=O)c2cnn(Cc3ccccc3)c2)c2cc(cnc12)-c1cccc(OCCN2CCCC2)c1 VLZMDADZTOITSH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
- 230000033616 DNA repair Effects 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- JHQKHJMEWNLYMX-UHFFFAOYSA-N N-(5-chloro-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1-(pyridin-4-ylmethyl)pyrazole-4-carboxamide Chemical compound Fc1c(Cl)cnc2[nH]cc(NC(=O)c3cnn(Cc4ccncc4)c3)c12 JHQKHJMEWNLYMX-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- JPEMPGCPBAKNKS-MOPGFXCFSA-N benzyl (3r,4r)-4-cyclopropyl-3-(diethoxyphosphorylamino)piperidine-1-carboxylate Chemical compound C1([C@H]2CCN(C[C@@H]2NP(=O)(OCC)OCC)C(=O)OCC=2C=CC=CC=2)CC1 JPEMPGCPBAKNKS-MOPGFXCFSA-N 0.000 description 2
- LXLUFXYWZIVHSF-UHFFFAOYSA-N benzyl 3-(diethoxyphosphorylamino)-4-(4-methylphenyl)sulfonyloxypiperidine-1-carboxylate Chemical compound CCOP(=O)(OCC)NC1CN(C(=O)OCC=2C=CC=CC=2)CCC1OS(=O)(=O)C1=CC=C(C)C=C1 LXLUFXYWZIVHSF-UHFFFAOYSA-N 0.000 description 2
- SGNZKPPDOWTEPS-UHFFFAOYSA-N benzyl 3-azido-4-(4-methylphenyl)sulfonyloxypiperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1C(N=[N+]=[N-])CN(C(=O)OCC=2C=CC=CC=2)CC1 SGNZKPPDOWTEPS-UHFFFAOYSA-N 0.000 description 2
- XFFCBJRBTDUAFD-UHFFFAOYSA-N benzyl 4-(diethoxyphosphorylamino)-3-(4-methylphenyl)sulfonyloxypiperidine-1-carboxylate Chemical compound CCOP(=O)(OCC)NC1CCN(C(=O)OCC=2C=CC=CC=2)CC1OS(=O)(=O)C1=CC=C(C)C=C1 XFFCBJRBTDUAFD-UHFFFAOYSA-N 0.000 description 2
- XVIBCNQBYCYALT-UHFFFAOYSA-N benzyl 4-amino-3-(4-methylphenyl)sulfonyloxypiperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1C(N)CCN(C(=O)OCC=2C=CC=CC=2)C1 XVIBCNQBYCYALT-UHFFFAOYSA-N 0.000 description 2
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000012820 cell cycle checkpoint Effects 0.000 description 2
- KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 229960000684 cytarabine Drugs 0.000 description 2
- 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 2
- 230000002950 deficient Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000001952 enzyme assay Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- KACZQOKEFKFNDB-UHFFFAOYSA-N ethyl 1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NNC=1 KACZQOKEFKFNDB-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 2
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000005865 ionizing radiation Effects 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 231100000225 lethality Toxicity 0.000 description 2
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 2
- IOOMXAQUNPWDLL-UHFFFAOYSA-M lissamine rhodamine anion Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S([O-])(=O)=O)C=C1S([O-])(=O)=O IOOMXAQUNPWDLL-UHFFFAOYSA-M 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 231100000682 maximum tolerated dose Toxicity 0.000 description 2
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 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
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 2
- 229960003440 semustine Drugs 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 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
- DQQJBEAXSOOCPG-SSDOTTSWSA-N tert-butyl n-[(3r)-pyrrolidin-3-yl]carbamate Chemical group CC(C)(C)OC(=O)N[C@@H]1CCNC1 DQQJBEAXSOOCPG-SSDOTTSWSA-N 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 2
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 2
- 230000000699 topical 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
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 2
- GBBJBUGPGFNISJ-UPACWWRESA-N (2r,8as)-(+)-(camphorylsulfonyl)oxaziridine Chemical compound C1S(=O)(=O)N2O[C@@]32CC2C(C)(C)[C@]13CC2 GBBJBUGPGFNISJ-UPACWWRESA-N 0.000 description 1
- VLECDMDGMKPUSK-NUBCRITNSA-N (3r)-piperidin-3-ol;hydrochloride Chemical group Cl.O[C@@H]1CCCNC1 VLECDMDGMKPUSK-NUBCRITNSA-N 0.000 description 1
- JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical group O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 1
- QEYOHUBBPSKXMV-UHFFFAOYSA-N (4-fluoro-5-methoxypyrrolo[2,3-b]pyridin-1-yl)-tri(propan-2-yl)silane Chemical group COC1=CN=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1F QEYOHUBBPSKXMV-UHFFFAOYSA-N 0.000 description 1
- VXWBQOJISHAKKM-UHFFFAOYSA-N (4-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)C=C1 VXWBQOJISHAKKM-UHFFFAOYSA-N 0.000 description 1
- AIJAFOFKGPWSSO-UHFFFAOYSA-N (5-bromo-4-fluoropyrrolo[2,3-b]pyridin-1-yl)-tri(propan-2-yl)silane Chemical compound BrC1=CN=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1F AIJAFOFKGPWSSO-UHFFFAOYSA-N 0.000 description 1
- DEQOVKFWRPOPQP-UHFFFAOYSA-N (5-formylthiophen-2-yl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)S1 DEQOVKFWRPOPQP-UHFFFAOYSA-N 0.000 description 1
- ZCUFJAORCNFWOF-UHFFFAOYSA-N (5-formylthiophen-3-yl)boronic acid Chemical compound OB(O)C1=CSC(C=O)=C1 ZCUFJAORCNFWOF-UHFFFAOYSA-N 0.000 description 1
- MWWSFMDVAYGXBV-MYPASOLCSA-N (7r,9s)-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;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-MYPASOLCSA-N 0.000 description 1
- DAXJNUBSBFUTRP-RTQNCGMRSA-N (8r,9s,10r,13s,14s)-6-(hydroxymethyl)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(CO)C2=C1 DAXJNUBSBFUTRP-RTQNCGMRSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- ROSZATIVXDPKMO-UHFFFAOYSA-N 1,2-difluoropyrrolidine;hydrochloride Chemical compound Cl.FC1CCCN1F ROSZATIVXDPKMO-UHFFFAOYSA-N 0.000 description 1
- WVWOOAYQYLJEFD-UHFFFAOYSA-N 1-(2-nitroimidazol-1-yl)-3-piperidin-1-ylpropan-2-ol Chemical compound C1=CN=C([N+]([O-])=O)N1CC(O)CN1CCCCC1 WVWOOAYQYLJEFD-UHFFFAOYSA-N 0.000 description 1
- OEWYWFJWBZNJJG-UHFFFAOYSA-N 1-(aziridin-1-yl)-3-(2-nitroimidazol-1-yl)propan-2-ol Chemical compound C1=CN=C([N+]([O-])=O)N1CC(O)CN1CC1 OEWYWFJWBZNJJG-UHFFFAOYSA-N 0.000 description 1
- FDWUFDIEKNWJQX-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-chloro-5-(trifluoromethyl)pyrrolo[2,3-b]pyridine Chemical compound C1=CC2=C(Cl)C(C(F)(F)F)=CN=C2N1S(=O)(=O)C1=CC=CC=C1 FDWUFDIEKNWJQX-UHFFFAOYSA-N 0.000 description 1
- NVNPLEPBDPJYRZ-UHFFFAOYSA-N 1-(bromomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CBr)C=C1 NVNPLEPBDPJYRZ-UHFFFAOYSA-N 0.000 description 1
- ATWXYVDFJLESJV-UHFFFAOYSA-N 1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrrolidine Chemical group O1C(C)(C)C(C)(C)OB1C1=CC=CC(N2CCCC2)=C1 ATWXYVDFJLESJV-UHFFFAOYSA-N 0.000 description 1
- SYYBDNPGDKKJDU-ZDUSSCGKSA-N 1-[5-bromo-4-methyl-2-[[(2S)-2-morpholinyl]methoxy]phenyl]-3-(5-methyl-2-pyrazinyl)urea Chemical compound C1=NC(C)=CN=C1NC(=O)NC1=CC(Br)=C(C)C=C1OC[C@H]1OCCNC1 SYYBDNPGDKKJDU-ZDUSSCGKSA-N 0.000 description 1
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
- XEEBVHGZQKYBCD-UHFFFAOYSA-N 1-benzyl-N-(4-fluoro-5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide Chemical compound Cc1cnc2[nH]cc(NC(=O)c3cnn(Cc4ccccc4)c3)c2c1F XEEBVHGZQKYBCD-UHFFFAOYSA-N 0.000 description 1
- AECWVFGDVCMGSC-UHFFFAOYSA-N 1-benzyl-N-(4-fluoro-5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide 4-fluoro-5-methyl-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound FC1=C2C(=NC=C1C)NC=C2N.FC2=C1C(=NC=C2C)NC=C1NC(=O)C=1C=NN(C1)CC1=CC=CC=C1 AECWVFGDVCMGSC-UHFFFAOYSA-N 0.000 description 1
- LFJWCFLAYFUGIZ-UHFFFAOYSA-N 1-benzyl-N-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazole-4-carboxamide 5-bromo-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound BrC=1C=C2C(=NC1)NC=C2N.BrC=2C=C1C(=NC2)NC=C1NC(=O)C=1C=NN(C1)CC1=CC=CC=C1 LFJWCFLAYFUGIZ-UHFFFAOYSA-N 0.000 description 1
- FNUNODOPANYPJX-UHFFFAOYSA-N 1-benzyl-N-[1-(4-methylphenyl)sulfonyl-5-[3-(1-methylpiperidin-3-yl)oxyphenyl]pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound CN1CC(CCC1)OC=1C=C(C=CC1)C=1C=C2C(=NC1)N(C=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)S(=O)(=O)C2=CC=C(C=C2)C FNUNODOPANYPJX-UHFFFAOYSA-N 0.000 description 1
- ZXPMQTKJDAVJIN-UHFFFAOYSA-N 1-benzyl-N-[5-(5-formylthiophen-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C(=O)C1=CC=C(S1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 ZXPMQTKJDAVJIN-UHFFFAOYSA-N 0.000 description 1
- VGAFMEAQTYKXFH-UHFFFAOYSA-N 1-benzyl-N-[5-[1-[2-(diethylamino)ethyl]pyrazol-4-yl]-1-(4-methylphenyl)sulfonylpyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C(C)N(CCN1N=CC(=C1)C=1C=C2C(=NC1)N(C=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)S(=O)(=O)C2=CC=C(C=C2)C)CC VGAFMEAQTYKXFH-UHFFFAOYSA-N 0.000 description 1
- HPJSOTCSLFGBGU-UHFFFAOYSA-N 1-benzyl-N-[5-[3-[(dimethylamino)methyl]phenyl]-1-(4-methylphenyl)sulfonylpyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound CN(C)CC=1C=C(C=CC1)C=1C=C2C(=NC1)N(C=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)S(=O)(=O)C2=CC=C(C=C2)C HPJSOTCSLFGBGU-UHFFFAOYSA-N 0.000 description 1
- XFPUFBHANVVZFG-UHFFFAOYSA-N 1-benzyl-N-[5-[4-[3-(dimethylamino)propoxy]phenyl]-1-(4-methylphenyl)sulfonylpyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound CN(CCCOC1=CC=C(C=C1)C=1C=C2C(=NC1)N(C=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)S(=O)(=O)C2=CC=C(C=C2)C)C XFPUFBHANVVZFG-UHFFFAOYSA-N 0.000 description 1
- LIJLRHBIIZMMKG-UHFFFAOYSA-N 1-benzyl-n-[5-[3-(1-methylpiperidin-3-yl)oxyphenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1N(C)CCCC1OC1=CC=CC(C=2C=C3C(NC(=O)C4=CN(CC=5C=CC=CC=5)N=C4)=CNC3=NC=2)=C1 LIJLRHBIIZMMKG-UHFFFAOYSA-N 0.000 description 1
- FKVTXXBRIXJUQQ-UHFFFAOYSA-N 1-benzyl-n-[5-[3-(2-morpholin-4-ylethoxy)phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(C=1)=CC=CC=1OCCN1CCOCC1 FKVTXXBRIXJUQQ-UHFFFAOYSA-N 0.000 description 1
- XVRJHIDTMLOKPU-UHFFFAOYSA-N 1-benzyl-n-[5-[3-(2-pyrrolidin-1-ylethoxy)phenyl]-1h-pyrrolo[2,3-b]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound C1=NN(CC=2C=CC=CC=2)C=C1C(=O)NC(C1=C2)=CNC1=NC=C2C(C=1)=CC=CC=1OCCN1CCCC1 XVRJHIDTMLOKPU-UHFFFAOYSA-N 0.000 description 1
- FHBHSJSJYIRFMM-UHFFFAOYSA-N 1-benzylpyrazole-4-carboxylic acid 5-[3-[(3,3-difluoropiperidin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound NC(C1=C2)=CNC1=NC=C2C1=CC(CN(CCC2)CC2(F)F)=CC=C1.OC(C1=CN(CC2=CC=CC=C2)N=C1)=O FHBHSJSJYIRFMM-UHFFFAOYSA-N 0.000 description 1
- UCNGGGYMLHAMJG-UHFFFAOYSA-N 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical group C1=NN(C)C=C1B1OC(C)(C)C(C)(C)O1 UCNGGGYMLHAMJG-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- 125000004898 2,2-dimethylpropylamino group Chemical group CC(CN*)(C)C 0.000 description 1
- QJYHMWJJNWZWCH-UHFFFAOYSA-N 2-(bromomethyl)pyridine;hydrochloride Chemical compound Cl.BrCC1=CC=CC=N1 QJYHMWJJNWZWCH-UHFFFAOYSA-N 0.000 description 1
- KGTRXRJMKPFFHY-UHFFFAOYSA-N 2-amino-3,7-dihydropurine-6-thione;3,7-dihydropurine-6-thione Chemical compound S=C1N=CNC2=C1NC=N2.S=C1NC(N)=NC2=C1NC=N2 KGTRXRJMKPFFHY-UHFFFAOYSA-N 0.000 description 1
- ILJKKAIQFPEIBL-UHFFFAOYSA-N 2-cyclopropyl-2-hydroxyacetonitrile Chemical group N#CC(O)C1CC1 ILJKKAIQFPEIBL-UHFFFAOYSA-N 0.000 description 1
- LXXWYTNNMDSTEU-UHFFFAOYSA-N 2-iodooxetane Chemical compound IC1CCO1 LXXWYTNNMDSTEU-UHFFFAOYSA-N 0.000 description 1
- CTRPRMNBTVRDFH-UHFFFAOYSA-N 2-n-methyl-1,3,5-triazine-2,4,6-triamine Chemical compound CNC1=NC(N)=NC(N)=N1 CTRPRMNBTVRDFH-UHFFFAOYSA-N 0.000 description 1
- XEZLBMHDUXSICI-UHFFFAOYSA-N 3-(1-ethylpiperidin-4-yl)oxy-5,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaene-4-carbonitrile Chemical compound C1CN(CC)CCC1OC1=C(C#N)N=CC2=C1C1=CC=CN=C1N2 XEZLBMHDUXSICI-UHFFFAOYSA-N 0.000 description 1
- NUGLIYXAARVRPQ-UHFFFAOYSA-N 3-(2-nitroimidazol-1-yl)propane-1,2-diol Chemical compound OCC(O)CN1C=CN=C1[N+]([O-])=O NUGLIYXAARVRPQ-UHFFFAOYSA-N 0.000 description 1
- VZYZKPJAXWDZFT-UHFFFAOYSA-N 3-(bromomethyl)-1-methylpiperidine Chemical group CN1CCCC(CBr)C1 VZYZKPJAXWDZFT-UHFFFAOYSA-N 0.000 description 1
- IAYGCINLNONXHY-LBPRGKRZSA-N 3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-3-piperidinyl]-2-thiophenecarboxamide Chemical compound NC(=O)NC=1C=C(C=2C=C(F)C=CC=2)SC=1C(=O)N[C@H]1CCCNC1 IAYGCINLNONXHY-LBPRGKRZSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- LJQNMDZRCXJETK-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine;hydron;chloride Chemical compound Cl.CN(C)CCCCl LJQNMDZRCXJETK-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- RDJUBLSLAULIAT-UHFFFAOYSA-N 3-fluoropiperidine;hydrochloride Chemical group Cl.FC1CCCNC1 RDJUBLSLAULIAT-UHFFFAOYSA-N 0.000 description 1
- OABUKBBBSMNNPM-UHFFFAOYSA-N 4,4-difluoropiperidin-1-ium;chloride Chemical compound Cl.FC1(F)CCNCC1 OABUKBBBSMNNPM-UHFFFAOYSA-N 0.000 description 1
- ZAPMTSHEXFEPSD-UHFFFAOYSA-N 4-(2-chloroethyl)morpholine Chemical compound ClCCN1CCOCC1 ZAPMTSHEXFEPSD-UHFFFAOYSA-N 0.000 description 1
- PIAZYBLGBSMNLX-UHFFFAOYSA-N 4-(3-chloropropyl)morpholine Chemical group ClCCCN1CCOCC1 PIAZYBLGBSMNLX-UHFFFAOYSA-N 0.000 description 1
- GNRWXAUPOYGSJF-MRVPVSSYSA-N 4-[(3R)-3-aminopiperidin-1-yl]-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound COC1=CN=C2NC=C(N)C2=C1N1CCC[C@@H](N)C1 GNRWXAUPOYGSJF-MRVPVSSYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- KISUPFXQEHWGAR-RRKCRQDMSA-N 4-amino-5-bromo-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound C1=C(Br)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 KISUPFXQEHWGAR-RRKCRQDMSA-N 0.000 description 1
- CVOAUOJFTYKHJC-UHFFFAOYSA-N 4-azido-3-hydroxypiperidine-1-carboxylic acid Chemical compound OC1CN(C(O)=O)CCC1N=[N+]=[N-] CVOAUOJFTYKHJC-UHFFFAOYSA-N 0.000 description 1
- BZBNGPXWPOQJPT-UHFFFAOYSA-N 4-bromo-1,2-dihydropyrrolo[3,2-b]pyridine Chemical compound BrN1C=CC=C2NCC=C12 BZBNGPXWPOQJPT-UHFFFAOYSA-N 0.000 description 1
- WVGCPEDBFHEHEZ-UHFFFAOYSA-N 4-bromo-1h-pyrazole Chemical compound BrC=1C=NNC=1 WVGCPEDBFHEHEZ-UHFFFAOYSA-N 0.000 description 1
- LEZHTYOQWQEBLH-UHFFFAOYSA-N 4-bromo-1h-pyrrolo[2,3-b]pyridine Chemical compound BrC1=CC=NC2=C1C=CN2 LEZHTYOQWQEBLH-UHFFFAOYSA-N 0.000 description 1
- HNTZVGMWXCFCTA-UHFFFAOYSA-N 4-chloro-1h-pyrrolo[2,3-b]pyridine Chemical group ClC1=CC=NC2=C1C=CN2 HNTZVGMWXCFCTA-UHFFFAOYSA-N 0.000 description 1
- VPSJPRMYBKNGOI-UHFFFAOYSA-N 4-chloro-3-nitro-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=C(C(F)(F)F)C(Cl)=C2C([N+](=O)[O-])=CNC2=N1 VPSJPRMYBKNGOI-UHFFFAOYSA-N 0.000 description 1
- ATLADCFKPSZUNL-UHFFFAOYSA-N 4-chloro-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridine Chemical group FC(F)(F)C1=CN=C2NC=CC2=C1Cl ATLADCFKPSZUNL-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- DOXBRKCMQZDRGY-UHFFFAOYSA-N 4-fluoro-5-methyl-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical compound CC1=CN=C2NC=C(N)C2=C1F DOXBRKCMQZDRGY-UHFFFAOYSA-N 0.000 description 1
- KGXKQWVQHYQDAU-UHFFFAOYSA-N 5-bromo-3-nitro-1H-pyrrolo[2,3-b]pyridine 5-bromo-1H-pyrrolo[2,3-b]pyridin-3-amine Chemical compound BrC=1C=C2C(=NC1)NC=C2[N+](=O)[O-].BrC=2C=C1C(=NC2)NC=C1N KGXKQWVQHYQDAU-UHFFFAOYSA-N 0.000 description 1
- 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 1
- VYYZREPCHGSAKZ-UHFFFAOYSA-N 5-chloro-1H-pyrrolo[2,3-b]pyridin-3-amine N-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1-[(4-fluorophenyl)methyl]pyrazole-4-carboxamide Chemical compound ClC=1C=C2C(=NC1)NC=C2N.ClC=2C=C1C(=NC2)NC=C1NC(=O)C=1C=NN(C1)CC1=CC=C(C=C1)F VYYZREPCHGSAKZ-UHFFFAOYSA-N 0.000 description 1
- MFZQJIKENSPRSJ-UHFFFAOYSA-N 5-chloro-1h-pyrrolo[2,3-b]pyridine Chemical group ClC1=CN=C2NC=CC2=C1 MFZQJIKENSPRSJ-UHFFFAOYSA-N 0.000 description 1
- DEZAIQUWOITSPT-UHFFFAOYSA-N 5-chloro-3-nitro-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=C(Cl)C=C2C([N+](=O)[O-])=CNC2=N1 DEZAIQUWOITSPT-UHFFFAOYSA-N 0.000 description 1
- VNIZOYILFQHTJY-UHFFFAOYSA-N 5-chloro-4-fluoro-1H-pyrrolo[2,3-b]pyridine (4-fluoropyrrolo[2,3-b]pyridin-1-yl)-tri(propan-2-yl)silane Chemical compound FC1=C2C(=NC=C1)N(C=C2)[Si](C(C)C)(C(C)C)C(C)C.ClC=2C(=C1C(=NC2)NC=C1)F VNIZOYILFQHTJY-UHFFFAOYSA-N 0.000 description 1
- NXFUJGIWFYKQGK-UHFFFAOYSA-N 5-chloro-4-fluoro-1h-pyrrolo[2,3-b]pyridine Chemical group FC1=C(Cl)C=NC2=C1C=CN2 NXFUJGIWFYKQGK-UHFFFAOYSA-N 0.000 description 1
- UVDDIZSAAWVACA-UHFFFAOYSA-N 5-methyl-1h-pyrrolo[2,3-b]pyridin-3-amine Chemical group CC1=CN=C2NC=C(N)C2=C1 UVDDIZSAAWVACA-UHFFFAOYSA-N 0.000 description 1
- DJCJHFFRHKGOCQ-UHFFFAOYSA-N 5-methyl-1h-pyrrolo[2,3-b]pyridine Chemical group CC1=CN=C2NC=CC2=C1 DJCJHFFRHKGOCQ-UHFFFAOYSA-N 0.000 description 1
- OWGGSXQRLHNDGC-UHFFFAOYSA-N 5-methyl-3-nitro-1h-pyrrolo[2,3-b]pyridine Chemical group CC1=CN=C2NC=C([N+]([O-])=O)C2=C1 OWGGSXQRLHNDGC-UHFFFAOYSA-N 0.000 description 1
- GHHWPSOGKLMSCJ-UHFFFAOYSA-N 507462-26-2 Chemical compound C1=C(Br)C=C2C([N+](=O)[O-])=CNC2=N1 GHHWPSOGKLMSCJ-UHFFFAOYSA-N 0.000 description 1
- GMIZZEXBPRLVIV-SECBINFHSA-N 6-bromo-3-(1-methylpyrazol-4-yl)-5-[(3r)-piperidin-3-yl]pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=NN(C)C=C1C1=C2N=C([C@H]3CNCCC3)C(Br)=C(N)N2N=C1 GMIZZEXBPRLVIV-SECBINFHSA-N 0.000 description 1
- 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
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 239000012099 Alexa Fluor family Substances 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000937413 Axia Species 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 101100002068 Bacillus subtilis (strain 168) araR gene Proteins 0.000 description 1
- 108010070075 Bacteriochlorophyll A Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- MLSJIVAIYHWTIB-UHFFFAOYSA-N BrC=1C(=C2C(=NC1)NC=C2)F.BrC=2C(=C1C(=NC2)NC=C1[N+](=O)[O-])F Chemical compound BrC=1C(=C2C(=NC1)NC=C2)F.BrC=2C(=C1C(=NC2)NC=C1[N+](=O)[O-])F MLSJIVAIYHWTIB-UHFFFAOYSA-N 0.000 description 1
- NDUKPOJSCMSYHD-UHFFFAOYSA-N BrC=1C=C(C=CC1)O.BrC=1C=C(OCCN2CCCC2)C=CC1 Chemical compound BrC=1C=C(C=CC1)O.BrC=1C=C(OCCN2CCCC2)C=CC1 NDUKPOJSCMSYHD-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- KMIVSCKUNGGLBG-UHFFFAOYSA-N C(C)OP(=O)(OCC)N1C2CCNCC12 Chemical compound C(C)OP(=O)(OCC)N1C2CCNCC12 KMIVSCKUNGGLBG-UHFFFAOYSA-N 0.000 description 1
- CLOWZCJCZNXHOG-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.C(C)N(CCN1N=CC(=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)CC Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.C(C)N(CCN1N=CC(=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)CC CLOWZCJCZNXHOG-UHFFFAOYSA-N 0.000 description 1
- PCTMORGVTOSOJE-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN(C)CC=1C=C(C=CC1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN(C)CC=1C=C(C=CC1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 PCTMORGVTOSOJE-UHFFFAOYSA-N 0.000 description 1
- LCYOBKSVUQWFAB-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN(CCCOC1=CC=C(C=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)C Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN(CCCOC1=CC=C(C=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)C LCYOBKSVUQWFAB-UHFFFAOYSA-N 0.000 description 1
- PKVCTXDIQCVNNP-UQIIZPHYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN1[C@@H](CCC1)COC=1C=C(C=CC1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.CN1[C@@H](CCC1)COC=1C=C(C=CC1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 PKVCTXDIQCVNNP-UQIIZPHYSA-N 0.000 description 1
- XYLKLBGBIOBPEQ-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.COCCN(C)CC1=CC=C(C=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.COCCN(C)CC1=CC=C(C=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 XYLKLBGBIOBPEQ-UHFFFAOYSA-N 0.000 description 1
- CLQIDAZWLODOIW-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.N1(CCCCC1)CC1=CC=C(C=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.N1(CCCCC1)CC1=CC=C(C=C1)C=1C=C2C(=NC1)NC=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2 CLQIDAZWLODOIW-UHFFFAOYSA-N 0.000 description 1
- LPZVILVASREXHY-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.OC1=CC=C(C=C1)C=1C=C2C(=NC1)N(C=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)S(=O)(=O)C2=CC=C(C)C=C2 Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)C(=O)O.OC1=CC=C(C=C1)C=1C=C2C(=NC1)N(C=C2NC(=O)C=2C=NN(C2)CC2=CC=CC=C2)S(=O)(=O)C2=CC=C(C)C=C2 LPZVILVASREXHY-UHFFFAOYSA-N 0.000 description 1
- XYHIPVYMOMFFJL-UHFFFAOYSA-N C(C1=CC=CC=C1)OC(=O)N1CC(C(CC1)N=[N+]=[N-])O.C(C1=CC=CC=C1)OC(=O)N1CC(C(CC1)OS(=O)(=O)C1=CC=C(C=C1)C)N=[N+]=[N-] Chemical compound C(C1=CC=CC=C1)OC(=O)N1CC(C(CC1)N=[N+]=[N-])O.C(C1=CC=CC=C1)OC(=O)N1CC(C(CC1)OS(=O)(=O)C1=CC=C(C=C1)C)N=[N+]=[N-] XYHIPVYMOMFFJL-UHFFFAOYSA-N 0.000 description 1
- NBHQYAOHOVUDEG-UHFFFAOYSA-N C1(=CC=CC=C1)S(=O)(=O)N1C=CC=2C1=NC=C(C2Cl)C(F)(F)F.ClC2=C1C(=NC=C2C(F)(F)F)NC=C1 Chemical compound C1(=CC=CC=C1)S(=O)(=O)N1C=CC=2C1=NC=C(C2Cl)C(F)(F)F.ClC2=C1C(=NC=C2C(F)(F)F)NC=C1 NBHQYAOHOVUDEG-UHFFFAOYSA-N 0.000 description 1
- QADVVGDWFQYIHP-DEOSSOPVSA-N CN1[C@@H](CCC1)COC=1C=C(C=CC1)C=1C=C2C(=NC1)N(C=C2NC(=O)C=2C=NNC2)S(=O)(=O)C2=CC=C(C)C=C2 Chemical compound CN1[C@@H](CCC1)COC=1C=C(C=CC1)C=1C=C2C(=NC1)N(C=C2NC(=O)C=2C=NNC2)S(=O)(=O)C2=CC=C(C)C=C2 QADVVGDWFQYIHP-DEOSSOPVSA-N 0.000 description 1
- 101100004988 Caenorhabditis elegans cdh-3 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 description 1
- 102100031065 Choline kinase alpha Human genes 0.000 description 1
- 206010053138 Congenital aplastic anaemia Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 230000007118 DNA alkylation Effects 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 230000012746 DNA damage checkpoint Effects 0.000 description 1
- 239000012623 DNA damaging agent Substances 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000004150 EU approved colour Substances 0.000 description 1
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- GZOQXGCPGSHJTK-MVNLRXSJSA-N FC1=CNC(=O)NC1=O.O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 Chemical compound FC1=CNC(=O)NC1=O.O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 GZOQXGCPGSHJTK-MVNLRXSJSA-N 0.000 description 1
- 201000004939 Fanconi anemia Diseases 0.000 description 1
- SIXHCCPAJIVTOY-UHFFFAOYSA-N Flutimide Natural products CC(C)CC1=NC(=CC(C)C)C(=O)N(O)C1=O SIXHCCPAJIVTOY-UHFFFAOYSA-N 0.000 description 1
- 230000010337 G2 phase Effects 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DOMWKUIIPQCAJU-LJHIYBGHSA-N Hydroxyprogesterone caproate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)CCCCC)[C@@]1(C)CC2 DOMWKUIIPQCAJU-LJHIYBGHSA-N 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- ZZOQWWSGGCLCGB-UNTBIKODSA-N N-[4-[(3R)-3-aminopiperidin-1-yl]-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide 1-benzylpyrazole-4-carboxylic acid Chemical compound OC(=O)c1cnn(Cc2ccccc2)c1.N[C@@H]1CCCN(C1)c1c(Br)cnc2[nH]cc(NC(=O)c3cnn(Cc4ccccc4)c3)c12 ZZOQWWSGGCLCGB-UNTBIKODSA-N 0.000 description 1
- JYKXJFXHOZOUQK-QGZVFWFLSA-N N-[5-chloro-4-[(3R)-3-formamidopiperidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl]-1-(pyridin-4-ylmethyl)pyrazole-4-carboxamide Chemical compound Clc1cnc2[nH]cc(NC(=O)c3cnn(Cc4ccncc4)c3)c2c1N1CCC[C@H](C1)NC=O JYKXJFXHOZOUQK-QGZVFWFLSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- CXHXAOPLXLMETO-UHFFFAOYSA-N N1CCC=CC1.C(C1=CC=CC=C1)OC(=O)N1CCC=CC1 Chemical compound N1CCC=CC1.C(C1=CC=CC=C1)OC(=O)N1CCC=CC1 CXHXAOPLXLMETO-UHFFFAOYSA-N 0.000 description 1
- 101150081841 NBN gene Proteins 0.000 description 1
- YDPCBSVOQMJTJZ-UHFFFAOYSA-N NC(C1=C2)=CNC1=NC=C2Cl.NC(C1=C2)=CNC1=NC=C2Cl Chemical compound NC(C1=C2)=CNC1=NC=C2Cl.NC(C1=C2)=CNC1=NC=C2Cl YDPCBSVOQMJTJZ-UHFFFAOYSA-N 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- SYYAESWMOOAZTL-UHFFFAOYSA-L O.O.[Cl-].[Cl-].[Sn++].Nc1cnc2[nH]cc(Br)c(F)c12 Chemical compound O.O.[Cl-].[Cl-].[Sn++].Nc1cnc2[nH]cc(Br)c(F)c12 SYYAESWMOOAZTL-UHFFFAOYSA-L 0.000 description 1
- CMLHYLKBZFVRTI-UHFFFAOYSA-L O.O.[Sn](Cl)Cl.ClC=1C=C2C(=NC1)NC=C2N Chemical compound O.O.[Sn](Cl)Cl.ClC=1C=C2C(=NC1)NC=C2N CMLHYLKBZFVRTI-UHFFFAOYSA-L 0.000 description 1
- KEIXOXQZIIOWQD-UHFFFAOYSA-N OC=1C=C(C=CC=1)C=1C=C2C(=NC=1)N(C=C2NC(=O)C=1C=NN(C=1)CC1=CC=CC=C1)S(=O)(=O)C1=CC=C(C=C1)C Chemical compound OC=1C=C(C=CC=1)C=1C=C2C(=NC=1)N(C=C2NC(=O)C=1C=NN(C=1)CC1=CC=CC=C1)S(=O)(=O)C1=CC=C(C=C1)C KEIXOXQZIIOWQD-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 102100031075 Serine/threonine-protein kinase Chk2 Human genes 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 239000004133 Sodium thiosulphate Substances 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 229910052771 Terbium Inorganic materials 0.000 description 1
- PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- GMCGYLIRFCDMPS-RXMQYKEDSA-N [(3r)-piperidin-3-yl]carbamic acid Chemical compound OC(=O)N[C@@H]1CCCNC1 GMCGYLIRFCDMPS-RXMQYKEDSA-N 0.000 description 1
- NPIHYFCXNIDUJZ-UHFFFAOYSA-N [2-chloro-6-[2,6-di(propan-2-yloxy)phenyl]phenyl]-dicyclohexylphosphane Chemical group ClC=1C(=C(C=CC=1)C1=C(C=CC=C1OC(C)C)OC(C)C)P(C1CCCCC1)C1CCCCC1 NPIHYFCXNIDUJZ-UHFFFAOYSA-N 0.000 description 1
- OPJPCDCKLCWJON-HSZRJFAPSA-N [3-[(1-benzylpyrazole-4-carbonyl)amino]-4-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]piperidin-1-yl]-1h-pyrrolo[2,3-b]pyridin-5-yl] 2,2-dimethylpropanoate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCCN1C1=C(OC(=O)C(C)(C)C)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 OPJPCDCKLCWJON-HSZRJFAPSA-N 0.000 description 1
- SIMJJYIGUQFXCG-UHFFFAOYSA-N [4-fluoro-1-tri(propan-2-yl)silylpyrrolo[2,3-b]pyridin-5-yl] 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC1=CN=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1F SIMJJYIGUQFXCG-UHFFFAOYSA-N 0.000 description 1
- LNTZXMUZGGMXTP-UHFFFAOYSA-N [Na].C(C1=CC=CC=C1)OC(=O)N1CC(C(CC1)OS(=O)(=O)C1=CC=C(C)C=C1)N Chemical compound [Na].C(C1=CC=CC=C1)OC(=O)N1CC(C(CC1)OS(=O)(=O)C1=CC=C(C)C=C1)N LNTZXMUZGGMXTP-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001780 adrenocortical effect Effects 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical class OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 229960000473 altretamine Drugs 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000036878 aneuploidy Diseases 0.000 description 1
- 231100001075 aneuploidy Toxicity 0.000 description 1
- RGHILYZRVFRRNK-UHFFFAOYSA-N anthracene-1,2-dione Chemical compound C1=CC=C2C=C(C(C(=O)C=C3)=O)C3=CC2=C1 RGHILYZRVFRRNK-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000003432 anti-folate effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940127074 antifolate Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940045686 antimetabolites antineoplastic purine analogs Drugs 0.000 description 1
- 229940045687 antimetabolites folic acid analogs Drugs 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 229940045688 antineoplastic antimetabolites pyrimidine analogues Drugs 0.000 description 1
- NOFOAYPPHIUXJR-APNQCZIXSA-N aphidicolin Chemical compound C1[C@@]23[C@@]4(C)CC[C@@H](O)[C@@](C)(CO)[C@@H]4CC[C@H]3C[C@H]1[C@](CO)(O)CC2 NOFOAYPPHIUXJR-APNQCZIXSA-N 0.000 description 1
- SEKZNWAQALMJNH-YZUCACDQSA-N aphidicolin Natural products C[C@]1(CO)CC[C@]23C[C@H]1C[C@@H]2CC[C@H]4[C@](C)(CO)[C@H](O)CC[C@]34C SEKZNWAQALMJNH-YZUCACDQSA-N 0.000 description 1
- 230000005756 apoptotic signaling Effects 0.000 description 1
- 101150044616 araC gene Proteins 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 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 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- NBWISEVVHNFKAQ-UHFFFAOYSA-N benzyl 3-amino-4-(4-methylphenyl)sulfonyloxypiperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1C(N)CN(C(=O)OCC=2C=CC=CC=2)CC1 NBWISEVVHNFKAQ-UHFFFAOYSA-N 0.000 description 1
- XOCCDWVWMPSHJU-UHFFFAOYSA-N benzyl 4-azido-3-hydroxypiperidine-1-carboxylate Chemical compound C1CC(N=[N+]=[N-])C(O)CN1C(=O)OCC1=CC=CC=C1 XOCCDWVWMPSHJU-UHFFFAOYSA-N 0.000 description 1
- BOZPVLJVKMWARN-UHFFFAOYSA-N benzyl 7-diethoxyphosphoryl-4,7-diazabicyclo[4.1.0]heptane-4-carboxylate Chemical compound C1C2N(P(=O)(OCC)OCC)C2CCN1C(=O)OCC1=CC=CC=C1 BOZPVLJVKMWARN-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 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 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003850 cellular structure Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000024321 chromosome segregation Effects 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- JZCCFEFSEZPSOG-UHFFFAOYSA-L copper(II) sulfate pentahydrate Chemical compound O.O.O.O.O.[Cu+2].[O-]S([O-])(=O)=O JZCCFEFSEZPSOG-UHFFFAOYSA-L 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 238000011393 cytotoxic chemotherapy Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- MXFYYFVVIIWKFE-UHFFFAOYSA-N dicyclohexyl-[2-[2,6-di(propan-2-yloxy)phenyl]phenyl]phosphane Chemical group CC(C)OC1=CC=CC(OC(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 MXFYYFVVIIWKFE-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 description 1
- 229960000452 diethylstilbestrol Drugs 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000013024 dilution buffer Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 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 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 230000005782 double-strand break Effects 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229940046085 endocrine therapy drug gonadotropin releasing hormone analogues Drugs 0.000 description 1
- 229960001842 estramustine Drugs 0.000 description 1
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
- 229960004750 estramustine phosphate Drugs 0.000 description 1
- ADFOJJHRTBFFOF-RBRWEJTLSA-N estramustine phosphate Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)OP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 ADFOJJHRTBFFOF-RBRWEJTLSA-N 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- WCDWBPCFGJXFJZ-UHFFFAOYSA-N etanidazole Chemical compound OCCNC(=O)CN1C=CN=C1[N+]([O-])=O WCDWBPCFGJXFJZ-UHFFFAOYSA-N 0.000 description 1
- 229950006566 etanidazole Drugs 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 229960002568 ethinylestradiol Drugs 0.000 description 1
- OPTPGWNYYFAYHY-UHFFFAOYSA-N ethyl 1-[(1-methylsulfonylpyrrol-2-yl)methyl]pyrazole-4-carboxylate Chemical compound C1=C(C(=O)OCC)C=NN1CC1=CC=CN1S(C)(=O)=O OPTPGWNYYFAYHY-UHFFFAOYSA-N 0.000 description 1
- WSKYHWOFKSOCQN-UHFFFAOYSA-N ethyl 1H-pyrazole-4-carboxylate 1-[(4-fluorophenyl)methyl]pyrazole-4-carboxylic acid Chemical compound N1N=CC(=C1)C(=O)OCC.FC1=CC=C(CN2N=CC(=C2)C(=O)O)C=C1 WSKYHWOFKSOCQN-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
- 229960005420 etoposide Drugs 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- 229960005304 fludarabine phosphate Drugs 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229960001751 fluoxymesterone Drugs 0.000 description 1
- YLRFCQOZQXIBAB-RBZZARIASA-N fluoxymesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)C[C@@H]2O YLRFCQOZQXIBAB-RBZZARIASA-N 0.000 description 1
- SIXHCCPAJIVTOY-UITAMQMPSA-N flutimide Chemical compound CC(C)CC1=N\C(=C/C(C)C)C(=O)N(O)C1=O SIXHCCPAJIVTOY-UITAMQMPSA-N 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000004052 folic acid antagonist Substances 0.000 description 1
- 150000002224 folic acids Chemical class 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical class C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 210000005096 hematological system Anatomy 0.000 description 1
- VHHHONWQHHHLTI-UHFFFAOYSA-N hexachloroethane Chemical compound ClC(Cl)(Cl)C(Cl)(Cl)Cl VHHHONWQHHHLTI-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 229950000801 hydroxyprogesterone caproate Drugs 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000013332 literature search Methods 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 229940124302 mTOR inhibitor Drugs 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical class [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 235000012254 magnesium hydroxide Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VFZXMEQGIIWBFJ-UHFFFAOYSA-M magnesium;cyclopropane;bromide Chemical compound [Mg+2].[Br-].C1C[CH-]1 VFZXMEQGIIWBFJ-UHFFFAOYSA-M 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 229960002985 medroxyprogesterone acetate Drugs 0.000 description 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- GQJCAQADCPTHKN-UHFFFAOYSA-N methyl 2,2-difluoro-2-fluorosulfonylacetate Chemical compound COC(=O)C(F)(F)S(F)(=O)=O GQJCAQADCPTHKN-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- KTMKRRPZPWUYKK-UHFFFAOYSA-N methylboronic acid Chemical compound CB(O)O KTMKRRPZPWUYKK-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- OBBCSXFCDPPXOL-UHFFFAOYSA-N misonidazole Chemical compound COCC(O)CN1C=CN=C1[N+]([O-])=O OBBCSXFCDPPXOL-UHFFFAOYSA-N 0.000 description 1
- 229950010514 misonidazole Drugs 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 230000017205 mitotic cell cycle checkpoint Effects 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- ZDZOTLJHXYCWBA-BSEPLHNVSA-N molport-006-823-826 Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-BSEPLHNVSA-N 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- NMGVIZJUIPNHLI-UHFFFAOYSA-N n,n-dimethylpiperidin-3-amine Chemical group CN(C)C1CCCNC1 NMGVIZJUIPNHLI-UHFFFAOYSA-N 0.000 description 1
- CFLVRAZWHBQIGQ-QGZVFWFLSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(C(F)(F)F)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 CFLVRAZWHBQIGQ-QGZVFWFLSA-N 0.000 description 1
- ABZYQTQZJDCXJQ-QGZVFWFLSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(Cl)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 ABZYQTQZJDCXJQ-QGZVFWFLSA-N 0.000 description 1
- XCPWMFLYGXCEGF-QGZVFWFLSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-hydroxy-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(O)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 XCPWMFLYGXCEGF-QGZVFWFLSA-N 0.000 description 1
- PJOWZRBEUFUWFG-HSZRJFAPSA-N n-[4-[(3r)-3-aminopiperidin-1-yl]-5-phenyl-1h-pyrrolo[2,3-b]pyridin-3-yl]-1-benzylpyrazole-4-carboxamide Chemical compound C1[C@H](N)CCCN1C1=C(C=2C=CC=CC=2)C=NC2=C1C(NC(=O)C1=CN(CC=3C=CC=CC=3)N=C1)=CN2 PJOWZRBEUFUWFG-HSZRJFAPSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- MDJFHRLTPRPZLY-UHFFFAOYSA-N nimorazole Chemical compound [O-][N+](=O)C1=CN=CN1CCN1CCOCC1 MDJFHRLTPRPZLY-UHFFFAOYSA-N 0.000 description 1
- 229960004918 nimorazole Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 239000003956 nonsteroidal anti androgen Substances 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 229960005079 pemetrexed Drugs 0.000 description 1
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229960002340 pentostatin Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 229940109328 photofrin Drugs 0.000 description 1
- 229950010456 pimonidazole Drugs 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- KCBGRDTXDXIOPL-UHFFFAOYSA-M potassium ethyl 1-[(1-methylsulfonylpyrrol-2-yl)methyl]pyrazole-4-carboxylate 1-(1H-pyrrol-2-ylmethyl)pyrazole-4-carboxylate Chemical compound C(C)OC(=O)C=1C=NN(C1)CC=1N(C=CC1)S(=O)(=O)C.N1C(=CC=C1)CN1N=CC(=C1)C(=O)[O-].[K+] KCBGRDTXDXIOPL-UHFFFAOYSA-M 0.000 description 1
- 239000001120 potassium sulphate Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical group OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- ZSKGQVFRTSEPJT-UHFFFAOYSA-N pyrrole-2-carboxaldehyde Chemical compound O=CC1=CC=CN1 ZSKGQVFRTSEPJT-UHFFFAOYSA-N 0.000 description 1
- 150000005255 pyrrolopyridines Chemical class 0.000 description 1
- 101150010682 rad50 gene Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000028617 response to DNA damage stimulus Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical class [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- 239000002278 tabletting lubricant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- GZCRRIHWUXGPOV-UHFFFAOYSA-N terbium atom Chemical compound [Tb] GZCRRIHWUXGPOV-UHFFFAOYSA-N 0.000 description 1
- GWIXKKVUKDHQOY-LLVKDONJSA-N tert-butyl n-[(3r)-1-(5-methoxy-3-nitro-1h-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl]carbamate Chemical compound COC1=CN=C2NC=C([N+]([O-])=O)C2=C1N1CCC[C@@H](NC(=O)OC(C)(C)C)C1 GWIXKKVUKDHQOY-LLVKDONJSA-N 0.000 description 1
- OGPCSYUFPBVGKD-SNVBAGLBSA-N tert-butyl n-[(3r)-1-[3-nitro-5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCCN1C1=C(C(F)(F)F)C=NC2=C1C([N+]([O-])=O)=CN2 OGPCSYUFPBVGKD-SNVBAGLBSA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- NVISSTNTBKVSPW-SNVBAGLBSA-N tert-butyl n-ethyl-n-[(3r)-piperidin-3-yl]carbamate Chemical group CC(C)(C)OC(=O)N(CC)[C@@H]1CCCNC1 NVISSTNTBKVSPW-SNVBAGLBSA-N 0.000 description 1
- RTXNDTNDOHQMTI-SECBINFHSA-N tert-butyl n-methyl-n-[(3r)-piperidin-3-yl]carbamate Chemical group CC(C)(C)OC(=O)N(C)[C@@H]1CCCNC1 RTXNDTNDOHQMTI-SECBINFHSA-N 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 229960001712 testosterone propionate Drugs 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000016596 traversing start control point of mitotic cell cycle Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 150000003918 triazines Chemical class 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1201566.5A GB201201566D0 (en) | 2012-01-30 | 2012-01-30 | New chemical compounds |
| GB1201566.5 | 2012-01-30 | ||
| PCT/GB2013/050212 WO2013114113A1 (en) | 2012-01-30 | 2013-01-30 | 1h-pyrrolo[2,3-b] pyridine derivatives and their use as kinase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2013213954A1 AU2013213954A1 (en) | 2014-08-07 |
| AU2013213954B2 true AU2013213954B2 (en) | 2016-02-25 |
Family
ID=45876325
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2013213954A Active AU2013213954B2 (en) | 2012-01-30 | 2013-01-30 | 1H-pyrrolo[2,3-b] pyridine derivatives and their use as kinase inhibitors |
Country Status (21)
| Country | Link |
|---|---|
| US (3) | US10000481B2 (en:Method) |
| EP (1) | EP2809670B1 (en:Method) |
| JP (1) | JP6199316B2 (en:Method) |
| CN (4) | CN106866658B (en:Method) |
| AU (1) | AU2013213954B2 (en:Method) |
| BR (1) | BR112014018795B1 (en:Method) |
| CA (1) | CA2862940C (en:Method) |
| DK (1) | DK2809670T3 (en:Method) |
| EA (1) | EA026657B1 (en:Method) |
| ES (1) | ES2637340T3 (en:Method) |
| GB (1) | GB201201566D0 (en:Method) |
| HK (1) | HK1200447A1 (en:Method) |
| HU (1) | HUE035332T2 (en:Method) |
| IL (1) | IL233595B (en:Method) |
| IN (1) | IN2014DN06104A (en:Method) |
| MX (1) | MX352927B (en:Method) |
| NZ (1) | NZ627361A (en:Method) |
| PL (1) | PL2809670T3 (en:Method) |
| PT (1) | PT2809670T (en:Method) |
| WO (1) | WO2013114113A1 (en:Method) |
| ZA (1) | ZA201405070B (en:Method) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201201566D0 (en) * | 2012-01-30 | 2012-03-14 | Vernalis R&D Ltd | New chemical compounds |
| CA2871436C (en) * | 2012-04-23 | 2020-07-28 | Genentech, Inc. | Intermediates and processes for preparing compounds for use as chk1 inhibitors |
| WO2015027092A1 (en) | 2013-08-22 | 2015-02-26 | Genentech, Inc. | Process for preparing a compound |
| CN104829609B (zh) * | 2014-02-11 | 2016-08-03 | 北大方正集团有限公司 | 取代的吡啶并嘧啶化合物及其制备方法和应用 |
| MA41559A (fr) | 2015-09-08 | 2017-12-26 | Taiho Pharmaceutical Co Ltd | Composé de pyrimidine condensé ou un sel de celui-ci |
| US10032914B2 (en) * | 2015-10-20 | 2018-07-24 | Taiwan Semiconductor Manufacturing Co., Ltd. | Semiconductor device and manufacturing method thereof |
| PT3269370T (pt) | 2016-02-23 | 2020-03-05 | Taiho Pharmaceutical Co Ltd | Novo composto de pirimidina condensada ou sal do mesmo |
| AU2018322286B2 (en) | 2017-08-21 | 2022-03-10 | Taiho Pharmaceutical Co., Ltd. | Fusion protein of DCTN1 protein with RET protein |
| TW202043198A (zh) | 2019-01-17 | 2020-12-01 | 美商Ｉｆｍ Ｄｕｅ有限公司 | 用於治療與sting活性相關之病況的化合物及組合物 |
| CN111518096B (zh) | 2019-02-02 | 2022-02-11 | 江苏威凯尔医药科技有限公司 | 两面神激酶jak家族抑制剂及其制备和应用 |
| EP4007757A4 (en) | 2019-08-01 | 2023-07-19 | Integral Biosciences Pvt. Ltd. | HETEROCYCLIC COMPOUNDS USED AS KINASE INHIBITORS AND THEIR USES |
| IT202000005527A1 (it) * | 2020-03-16 | 2021-09-16 | Univ Degli Studi Di Trento | Trattamento terapeutico di cromatinopatie |
| JP2023540673A (ja) | 2020-07-15 | 2023-09-26 | アイエフエム デュー インコーポレイテッド | Ｓｔｉｎｇ活性に関連する状態を治療するための化合物および組成物 |
| TW202216685A (zh) * | 2020-07-15 | 2022-05-01 | 美商Ｉｆｍ Ｄｕｅ有限公司 | 用於治療與sting活性相關的病狀之化合物及組合物 |
| JP2023540674A (ja) * | 2020-07-15 | 2023-09-26 | アイエフエム デュー インコーポレイテッド | Ｓｔｉｎｇ活性に関連する状態を治療するための化合物および組成物 |
| TW202235073A (zh) | 2021-01-08 | 2022-09-16 | 美商Ｉｆｍ Ｄｕｅ有限公司 | 用於治療與sting活性相關的病狀之化合物及組合物 |
| CN118613473A (zh) * | 2022-01-12 | 2024-09-06 | 艾福姆德尤股份有限公司 | 用于治疗与sting活性相关的病症的化合物和组合物 |
| CN116554170A (zh) * | 2023-04-26 | 2023-08-08 | 上海大学 | 4-氟-7-氮杂吲哚的制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009089352A1 (en) * | 2008-01-08 | 2009-07-16 | Array Biopharma Inc. | Pyrrolopyridines as kinase inhibitors |
| WO2009140320A1 (en) * | 2008-05-13 | 2009-11-19 | Array Biopharma Inc. | Pyrrolopyridines as kinase inhibitors |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1012976A (en) * | 1909-03-25 | 1911-12-26 | Adolf Bordt | Adding-machine. |
| WO2003028724A1 (en) * | 2001-10-04 | 2003-04-10 | Smithkline Beecham Corporation | Chk1 kinase inhibitors |
| US7531553B2 (en) * | 2003-03-21 | 2009-05-12 | Amgen Inc. | Heterocyclic compounds and methods of use |
| BRPI0416852A (pt) * | 2003-11-21 | 2007-02-27 | Array Biopharma Inc | inibidores da quinase akt |
| DK2294065T3 (da) * | 2008-01-22 | 2014-04-28 | Vernalis R&D Ltd | Indolyl-pyridonderivater med checkpoint kinase 1 inhibitorisk aktivitet |
| JP5677945B2 (ja) * | 2008-06-11 | 2015-02-25 | ジェネンテック， インコーポレイテッド | ジアザカルバゾール及びその使用方法 |
| KR20120055608A (ko) * | 2009-08-06 | 2012-05-31 | 메르크 파텐트 게엠베하 | 신규한 이환 우레아 화합물 |
| EP2571361A4 (en) * | 2010-05-19 | 2013-11-13 | Univ North Carolina | PYRAZOLOPYRIMIDINE COMPOUNDS FOR CANCER TREATMENT |
| GB201201566D0 (en) * | 2012-01-30 | 2012-03-14 | Vernalis R&D Ltd | New chemical compounds |
-
2012
- 2012-01-30 GB GBGB1201566.5A patent/GB201201566D0/en not_active Ceased
-
2013
- 2013-01-30 BR BR112014018795-9A patent/BR112014018795B1/pt active IP Right Grant
- 2013-01-30 DK DK13703121.7T patent/DK2809670T3/en active
- 2013-01-30 JP JP2014555310A patent/JP6199316B2/ja not_active Expired - Fee Related
- 2013-01-30 NZ NZ627361A patent/NZ627361A/en unknown
- 2013-01-30 US US14/375,353 patent/US10000481B2/en active Active
- 2013-01-30 PT PT137031217T patent/PT2809670T/pt unknown
- 2013-01-30 MX MX2014009112A patent/MX352927B/es active IP Right Grant
- 2013-01-30 EP EP13703121.7A patent/EP2809670B1/en active Active
- 2013-01-30 HU HUE13703121A patent/HUE035332T2/en unknown
- 2013-01-30 EA EA201491376A patent/EA026657B1/ru not_active IP Right Cessation
- 2013-01-30 CN CN201610920720.9A patent/CN106866658B/zh active Active
- 2013-01-30 HK HK15100794.1A patent/HK1200447A1/xx unknown
- 2013-01-30 CN CN201380014717.5A patent/CN104203948A/zh active Pending
- 2013-01-30 AU AU2013213954A patent/AU2013213954B2/en active Active
- 2013-01-30 PL PL13703121T patent/PL2809670T3/pl unknown
- 2013-01-30 CN CN202010405942.3A patent/CN111484493A/zh active Pending
- 2013-01-30 ES ES13703121.7T patent/ES2637340T3/es active Active
- 2013-01-30 IN IN6104DEN2014 patent/IN2014DN06104A/en unknown
- 2013-01-30 WO PCT/GB2013/050212 patent/WO2013114113A1/en active Application Filing
- 2013-01-30 CN CN201610920724.7A patent/CN107011341A/zh active Pending
- 2013-01-30 CA CA2862940A patent/CA2862940C/en active Active
-
2014
- 2014-07-10 IL IL233595A patent/IL233595B/en active IP Right Grant
- 2014-07-11 ZA ZA2014/05070A patent/ZA201405070B/en unknown
-
2018
- 2018-06-15 US US16/009,439 patent/US10889582B2/en active Active
-
2020
- 2020-11-30 US US17/107,176 patent/US20210206762A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009089352A1 (en) * | 2008-01-08 | 2009-07-16 | Array Biopharma Inc. | Pyrrolopyridines as kinase inhibitors |
| WO2009140320A1 (en) * | 2008-05-13 | 2009-11-19 | Array Biopharma Inc. | Pyrrolopyridines as kinase inhibitors |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2013213954B2 (en) | 1H-pyrrolo[2,3-b] pyridine derivatives and their use as kinase inhibitors | |
| AU2022228150B2 (en) | Polycyclic compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides | |
| CN106999479B (zh) | 可用作sumo活化酶抑制剂的杂芳基化合物 | |
| CA2712959C (en) | Indolyl-pyridone derivatives having checkpoint kinase 1 inhibitory activity | |
| KR102181915B1 (ko) | Trka 키나아제 억제제로서 n-피롤리디닐, n'-피라졸릴-우레아, 티오우레아, 구아니딘 및 시아노구아니딘 화합물 | |
| EA019785B1 (ru) | Бензофуропиримидиноны в качестве ингибиторов протеинкиназ, фармацевтические композиции, их содержащие, и их применение | |
| TW201000475A (en) | Heterocyclic urea derivatives and methods of use thereof | |
| WO2024097953A1 (en) | Naphthyridine compounds for inhibition of raf kinases | |
| HK1240217B (zh) | 1h-吡咯并[2,3-b]吡啶衍生物及它们作为激酶抑制剂的用途 | |
| HK40025567A (en) | 1h-pyrrolo[2,3-b] pyridine derivatives and their use as kinase inhibitors | |
| HK1240217A1 (en) | 1h-pyrrolo[2,3-b] pyridine derivatives and their use as kinase inhibitors | |
| HK1240227A1 (zh) | 1h-吡咯并[2，3-b]吡啶衍生物及他们作为激酶抑制剂的用途 | |
| WO2011010083A1 (en) | Indolyl-pyridone derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) |