JP2015514101A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2015514101A5 JP2015514101A5 JP2015503835A JP2015503835A JP2015514101A5 JP 2015514101 A5 JP2015514101 A5 JP 2015514101A5 JP 2015503835 A JP2015503835 A JP 2015503835A JP 2015503835 A JP2015503835 A JP 2015503835A JP 2015514101 A5 JP2015514101 A5 JP 2015514101A5
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- indol
- carbonyl
- dihydro
- thieno
- 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.)
- Granted
Links
- -1 5-{[(8R) -8- (chloromethyl) -4-hydroxy-1-methyl-7,8-dihydro-6H-thieno [3,2-e] indol-6-yl] carbonyl} -1-methyl-1H-pyrrol-3-yl Chemical group 0.000 claims description 45
- 150000001875 compounds Chemical class 0.000 claims description 33
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000004568 DNA-binding Effects 0.000 claims description 2
- 108010016626 Dipeptides Proteins 0.000 claims description 2
- 239000002202 Polyethylene glycol Chemical group 0.000 claims description 2
- 125000003827 glycol group Chemical group 0.000 claims description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229920001223 polyethylene glycol Chemical group 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 13
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 6
- 150000002431 hydrogen Chemical group 0.000 claims 6
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims 5
- 125000000623 heterocyclic group Chemical group 0.000 claims 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 4
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- OERRZAJTKPMGBB-BYPYZUCNSA-N (2s)-2,5-diaminopentanamide Chemical compound NCCC[C@H](N)C(N)=O OERRZAJTKPMGBB-BYPYZUCNSA-N 0.000 claims 2
- ZTOQBFJTKSDMRF-CHIBUHFTSA-N C1=CC=C2NC(C(=O)NC3=CN=C4NC=C(C4=C3)/C=C/C(=O)N3C[C@H]4C[C@]44C5=C(C(C=C43)=O)SC=C5C)=CC2=C1 Chemical compound C1=CC=C2NC(C(=O)NC3=CN=C4NC=C(C4=C3)/C=C/C(=O)N3C[C@H]4C[C@]44C5=C(C(C=C43)=O)SC=C5C)=CC2=C1 ZTOQBFJTKSDMRF-CHIBUHFTSA-N 0.000 claims 2
- QNJQVYIXMYRTCY-UHFFFAOYSA-N CN1CCN(CC1)C(=O)OC1=C2C(=C3CC(NC3=C1)=C=O)C=CS2 Chemical compound CN1CCN(CC1)C(=O)OC1=C2C(=C3CC(NC3=C1)=C=O)C=CS2 QNJQVYIXMYRTCY-UHFFFAOYSA-N 0.000 claims 2
- 239000002246 antineoplastic agent Substances 0.000 claims 2
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims 2
- 229940127089 cytotoxic agent Drugs 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- GKTQKQTXHNUFSP-UHFFFAOYSA-N thieno[3,4-c]pyrrole-4,6-dione Chemical compound S1C=C2C(=O)NC(=O)C2=C1 GKTQKQTXHNUFSP-UHFFFAOYSA-N 0.000 claims 2
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 1
- YSNOHRGMXBLFEQ-NNTXTVRGSA-N (e)-1-[(8r)-8-(chloromethyl)-4-hydroxy-1-methyl-7,8-dihydrothieno[3,2-e]indol-6-yl]-3-(1h-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one Chemical compound C1=CC=C2C(/C=C/C(=O)N3C4=CC(O)=C5SC=C(C5=C4[C@@H](CCl)C3)C)=CNC2=N1 YSNOHRGMXBLFEQ-NNTXTVRGSA-N 0.000 claims 1
- FKAVHLMIWRHYKO-LQYUOIDQSA-N (e)-1-[(8s)-8-(chloromethyl)-4-hydroxy-1-methyl-7,8-dihydrothieno[3,2-e]indol-6-yl]-3-(1h-indol-3-yl)prop-2-en-1-one Chemical compound C1=CC=C2C(/C=C/C(=O)N3C4=CC(O)=C5SC=C(C5=C4[C@H](CCl)C3)C)=CNC2=C1 FKAVHLMIWRHYKO-LQYUOIDQSA-N 0.000 claims 1
- YSNOHRGMXBLFEQ-ISZGNANSSA-N (e)-1-[(8s)-8-(chloromethyl)-4-hydroxy-1-methyl-7,8-dihydrothieno[3,2-e]indol-6-yl]-3-(1h-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one Chemical compound C1=CC=C2C(/C=C/C(=O)N3C4=CC(O)=C5SC=C(C5=C4[C@H](CCl)C3)C)=CNC2=N1 YSNOHRGMXBLFEQ-ISZGNANSSA-N 0.000 claims 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- NTSUDTJWQYBXEV-QYWNIODHSA-N 2-[(8S)-8-(chloromethyl)-6-[5-(1H-indole-2-carbonylamino)-1H-indole-2-carbonyl]-1-methyl-7,8-dihydrothieno[3,2-e]indol-4-yl]piperazine-1-carboxylic acid Chemical compound CC1=CSC2=C1C3=C(C=C2C4CNCCN4C(=O)O)N(C[C@H]3CCl)C(=O)C5=CC6=C(N5)C=CC(=C6)NC(=O)C7=CC8=CC=CC=C8N7 NTSUDTJWQYBXEV-QYWNIODHSA-N 0.000 claims 1
- OSRXKJNSSYJDMG-SXEDBCOVSA-N 5-amino-n-[2-[(8s)-8-(chloromethyl)-4-hydroxy-1-methyl-5a,7,8,8a-tetrahydrothieno[3,2-e]indole-6-carbonyl]-1h-indol-5-yl]-1h-indole-2-carboxamide Chemical compound NC1=CC=C2NC(C(=O)NC=3C=C4C=C(NC4=CC=3)C(=O)N3C[C@@H](CCl)C4C5=C(C(=CC43)O)SC=C5C)=CC2=C1 OSRXKJNSSYJDMG-SXEDBCOVSA-N 0.000 claims 1
- YAPRKFOSQTXPNL-QTEAWJPNSA-N C1=C2C=CNC2=CC(C(=O)NC=2C3=CC=C(C=C3NC=2)C(=O)N2C[C@H]3C[C@]33C4=C(C(C=C32)=O)SC=C4C)=C1 Chemical compound C1=C2C=CNC2=CC(C(=O)NC=2C3=CC=C(C=C3NC=2)C(=O)N2C[C@H]3C[C@]33C4=C(C(C=C32)=O)SC=C4C)=C1 YAPRKFOSQTXPNL-QTEAWJPNSA-N 0.000 claims 1
- ROEQCXKLBIEWOD-JVUYMAJISA-N C1=CC=C2C(/C=C/C(=O)N3C[C@@H]4C[C@@]44C5=C(C(C=C43)=O)SC=C5C)=CNC2=N1 Chemical compound C1=CC=C2C(/C=C/C(=O)N3C[C@@H]4C[C@@]44C5=C(C(C=C43)=O)SC=C5C)=CNC2=N1 ROEQCXKLBIEWOD-JVUYMAJISA-N 0.000 claims 1
- ROEQCXKLBIEWOD-BKEYBNDJSA-N C1=CC=C2C(/C=C/C(=O)N3C[C@H]4C[C@]44C5=C(C(C=C43)=O)SC=C5C)=CNC2=N1 Chemical compound C1=CC=C2C(/C=C/C(=O)N3C[C@H]4C[C@]44C5=C(C(C=C43)=O)SC=C5C)=CNC2=N1 ROEQCXKLBIEWOD-BKEYBNDJSA-N 0.000 claims 1
- WAHUJUOBRIEUQF-MQFAKOPTSA-N C1=CC=C2N(C)C(C(=O)NC=3C=C4C=C(N(C4=CC=3)C)C(=O)N3C[C@@H]4C[C@@]44C5=C(C(C=C43)=O)SC=C5C)=CC2=C1 Chemical compound C1=CC=C2N(C)C(C(=O)NC=3C=C4C=C(N(C4=CC=3)C)C(=O)N3C[C@@H]4C[C@@]44C5=C(C(C=C43)=O)SC=C5C)=CC2=C1 WAHUJUOBRIEUQF-MQFAKOPTSA-N 0.000 claims 1
- OSEFAXCBOSRUPB-NYEHZQRNSA-N CC(C)[C@H](N)C(=O)N[C@@H](CCCNC(N)=O)C(=O)Nc1ccc(COC(=O)N(C)CCN(C)C(=O)Oc2cc3N(C[C@@H](CCl)c3c3c(C)csc23)C(=O)c2cc3cc(NC(=O)c4cc5cc(OCCN6CCCC6)ccc5[nH]4)ccc3[nH]2)cc1 Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCNC(N)=O)C(=O)Nc1ccc(COC(=O)N(C)CCN(C)C(=O)Oc2cc3N(C[C@@H](CCl)c3c3c(C)csc23)C(=O)c2cc3cc(NC(=O)c4cc5cc(OCCN6CCCC6)ccc5[nH]4)ccc3[nH]2)cc1 OSEFAXCBOSRUPB-NYEHZQRNSA-N 0.000 claims 1
- IIHLTOJHVNXPRZ-VZYDHVRKSA-N Cl.CN1CCN(CC1)C(=O)Oc1cc2N(C[C@@H](CCl)c2c2c(C)csc12)C(=O)c1cc2cc(NC(=O)c3cc4cc(N)ccc4[nH]3)ccc2[nH]1 Chemical compound Cl.CN1CCN(CC1)C(=O)Oc1cc2N(C[C@@H](CCl)c2c2c(C)csc12)C(=O)c1cc2cc(NC(=O)c3cc4cc(N)ccc4[nH]3)ccc2[nH]1 IIHLTOJHVNXPRZ-VZYDHVRKSA-N 0.000 claims 1
- VSRXZPHBLOFJOX-ZQHDKMAOSA-N N-[2-[(1R,12S)-3-methyl-7-oxo-5-thia-10-azatetracyclo[7.4.0.01,12.02,6]trideca-2(6),3,8-triene-10-carbonyl]-1H-indol-5-yl]-5-nitro-1H-indole-2-carboxamide Chemical compound CC1=CSC2=C1[C@@]13[C@@H](CN(C1=CC2=O)C(=O)C=1NC2=CC=C(C=C2C=1)NC(=O)C=1NC2=CC=C(C=C2C=1)[N+](=O)[O-])C3 VSRXZPHBLOFJOX-ZQHDKMAOSA-N 0.000 claims 1
- VSRXZPHBLOFJOX-NOVUIFNWSA-N N-[2-[(1S,12R)-3-methyl-7-oxo-5-thia-10-azatetracyclo[7.4.0.01,12.02,6]trideca-2(6),3,8-triene-10-carbonyl]-1H-indol-5-yl]-5-nitro-1H-indole-2-carboxamide Chemical compound CC1=CSC2=C1[C@]13[C@H](CN(C1=CC2=O)C(=O)C=1NC2=CC=C(C=C2C=1)NC(=O)C=1NC2=CC=C(C=C2C=1)[N+](=O)[O-])C3 VSRXZPHBLOFJOX-NOVUIFNWSA-N 0.000 claims 1
- QJVOTMJXHJCVTN-NOVUIFNWSA-N NC1=CC=C2NC(C(=O)NC=3C=C4C=C(NC4=CC=3)C(=O)N3C[C@@H]4C[C@@]44C5=C(C(C=C43)=O)SC=C5C)=CC2=C1 Chemical compound NC1=CC=C2NC(C(=O)NC=3C=C4C=C(NC4=CC=3)C(=O)N3C[C@@H]4C[C@@]44C5=C(C(C=C43)=O)SC=C5C)=CC2=C1 QJVOTMJXHJCVTN-NOVUIFNWSA-N 0.000 claims 1
- QJVOTMJXHJCVTN-ZQHDKMAOSA-N NC1=CC=C2NC(C(=O)NC=3C=C4C=C(NC4=CC=3)C(=O)N3C[C@H]4C[C@]44C5=C(C(C=C43)=O)SC=C5C)=CC2=C1 Chemical compound NC1=CC=C2NC(C(=O)NC=3C=C4C=C(NC4=CC=3)C(=O)N3C[C@H]4C[C@]44C5=C(C(C=C43)=O)SC=C5C)=CC2=C1 QJVOTMJXHJCVTN-ZQHDKMAOSA-N 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- IIHLTOJHVNXPRZ-FTBISJDPSA-N [(8r)-6-[5-[(5-amino-1h-indole-2-carbonyl)amino]-1h-indole-2-carbonyl]-8-(chloromethyl)-1-methyl-7,8-dihydrothieno[3,2-e]indol-4-yl] 4-methylpiperazine-1-carboxylate;hydrochloride Chemical compound Cl.C1CN(C)CCN1C(=O)OC(C=1SC=C(C)C=11)=CC2=C1[C@@H](CCl)CN2C(=O)C1=CC2=CC(NC(=O)C=3NC4=CC=C(N)C=C4C=3)=CC=C2N1 IIHLTOJHVNXPRZ-FTBISJDPSA-N 0.000 claims 1
- DLGMWIQPGAEPPC-SFHVURJKSA-N [(8r)-8-(chloromethyl)-4-hydroxy-1-methyl-7,8-dihydrothieno[3,2-e]indol-6-yl]-[5-(2-pyrrolidin-1-ylethoxy)-1h-indol-2-yl]methanone Chemical compound C1([C@@H](CCl)C2)=C3C(C)=CSC3=C(O)C=C1N2C(=O)C(NC1=CC=2)=CC1=CC=2OCCN1CCCC1 DLGMWIQPGAEPPC-SFHVURJKSA-N 0.000 claims 1
- ZAYQWCHJZMUHGQ-QFIPXVFZSA-N [(8r)-8-(chloromethyl)-6-[5-[(5-hydroxy-1h-indole-2-carbonyl)amino]-1h-indole-2-carbonyl]-1-methyl-7,8-dihydrothieno[3,2-e]indol-4-yl] 4-methylpiperazine-1-carboxylate Chemical compound C1CN(C)CCN1C(=O)OC(C=1SC=C(C)C=11)=CC2=C1[C@@H](CCl)CN2C(=O)C1=CC2=CC(NC(=O)C=3NC4=CC=C(O)C=C4C=3)=CC=C2N1 ZAYQWCHJZMUHGQ-QFIPXVFZSA-N 0.000 claims 1
- DLGMWIQPGAEPPC-GOSISDBHSA-N [(8s)-8-(chloromethyl)-4-hydroxy-1-methyl-7,8-dihydrothieno[3,2-e]indol-6-yl]-[5-(2-pyrrolidin-1-ylethoxy)-1h-indol-2-yl]methanone Chemical compound C1([C@H](CCl)C2)=C3C(C)=CSC3=C(O)C=C1N2C(=O)C(NC1=CC=2)=CC1=CC=2OCCN1CCCC1 DLGMWIQPGAEPPC-GOSISDBHSA-N 0.000 claims 1
- ZAYQWCHJZMUHGQ-JOCHJYFZSA-N [(8s)-8-(chloromethyl)-6-[5-[(5-hydroxy-1h-indole-2-carbonyl)amino]-1h-indole-2-carbonyl]-1-methyl-7,8-dihydrothieno[3,2-e]indol-4-yl] 4-methylpiperazine-1-carboxylate Chemical compound C1CN(C)CCN1C(=O)OC(C=1SC=C(C)C=11)=CC2=C1[C@H](CCl)CN2C(=O)C1=CC2=CC(NC(=O)C=3NC4=CC=C(O)C=C4C=3)=CC=C2N1 ZAYQWCHJZMUHGQ-JOCHJYFZSA-N 0.000 claims 1
- 238000011319 anticancer therapy Methods 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 125000006575 electron-withdrawing group Chemical group 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- 125000001072 heteroaryl group Chemical group 0.000 claims 1
- 229950003188 isovaleryl diethylamide Drugs 0.000 claims 1
- ILKNYDYHSDRBKI-FQEVSTJZSA-N n-[2-[(8r)-8-(chloromethyl)-4-hydroxy-1-methyl-7,8-dihydrothieno[3,2-e]indole-6-carbonyl]-1-methylindol-5-yl]-1-methylindole-2-carboxamide Chemical compound C1=CC=C2N(C)C(C(=O)NC=3C=C4C=C(N(C4=CC=3)C)C(=O)N3C4=CC(O)=C5SC=C(C5=C4[C@@H](CCl)C3)C)=CC2=C1 ILKNYDYHSDRBKI-FQEVSTJZSA-N 0.000 claims 1
- DKHKILMWOTZNRZ-GHOSXJJBSA-N n-[3-[(e)-3-[(8r)-8-(chloromethyl)-4-hydroxy-1-methyl-7,8-dihydrothieno[3,2-e]indol-6-yl]-3-oxoprop-1-enyl]-1h-pyrrolo[2,3-b]pyridin-5-yl]-1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)NC3=CN=C4NC=C(C4=C3)/C=C/C(=O)N3C4=CC(O)=C5SC=C(C5=C4[C@@H](CCl)C3)C)=CC2=C1 DKHKILMWOTZNRZ-GHOSXJJBSA-N 0.000 claims 1
- DKHKILMWOTZNRZ-OVKVCFKUSA-N n-[3-[(e)-3-[(8s)-8-(chloromethyl)-4-hydroxy-1-methyl-7,8-dihydrothieno[3,2-e]indol-6-yl]-3-oxoprop-1-enyl]-1h-pyrrolo[2,3-b]pyridin-5-yl]-1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)NC3=CN=C4NC=C(C4=C3)/C=C/C(=O)N3C4=CC(O)=C5SC=C(C5=C4[C@H](CCl)C3)C)=CC2=C1 DKHKILMWOTZNRZ-OVKVCFKUSA-N 0.000 claims 1
- BKBWUCJJECCKNO-LJQANCHMSA-N n-[6-[(8s)-8-(chloromethyl)-4-hydroxy-1-methyl-7,8-dihydrothieno[3,2-e]indole-6-carbonyl]-1h-indol-3-yl]-1h-indole-6-carboxamide Chemical compound C1=C2C=CNC2=CC(C(=O)NC=2C3=CC=C(C=C3NC=2)C(=O)N2C3=CC(O)=C4SC=C(C4=C3[C@H](CCl)C2)C)=C1 BKBWUCJJECCKNO-LJQANCHMSA-N 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000003107 substituted aryl group Chemical group 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 2
- BTJIUGUIPKRLHP-UHFFFAOYSA-M 4-nitrophenolate Chemical compound [O-]C1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-M 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- 150000007942 carboxylates Chemical class 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 150000004996 alkyl benzenes Chemical class 0.000 description 1
- 125000005599 alkyl carboxylate group Chemical group 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- ZSCYJHGJGRSPAB-UHFFFAOYSA-N carbamic acid Chemical compound NC(O)=O.NC(O)=O ZSCYJHGJGRSPAB-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical class 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 1
- 238000006265 spirocyclization reaction Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12163459.6 | 2012-04-05 | ||
| EP12163459 | 2012-04-05 | ||
| EP12176162.1 | 2012-07-12 | ||
| EP12176162 | 2012-07-12 | ||
| PCT/EP2013/056743 WO2013149948A1 (en) | 2012-04-05 | 2013-03-28 | New alkylating agents |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017199656A Division JP2018070599A (ja) | 2012-04-05 | 2017-10-13 | 新たなアルキル化剤 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015514101A JP2015514101A (ja) | 2015-05-18 |
| JP2015514101A5 true JP2015514101A5 (enExample) | 2016-05-19 |
| JP6314128B2 JP6314128B2 (ja) | 2018-04-18 |
Family
ID=48092927
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015503835A Active JP6314128B2 (ja) | 2012-04-05 | 2013-03-28 | 新たなアルキル化剤 |
| JP2017199656A Withdrawn JP2018070599A (ja) | 2012-04-05 | 2017-10-13 | 新たなアルキル化剤 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017199656A Withdrawn JP2018070599A (ja) | 2012-04-05 | 2017-10-13 | 新たなアルキル化剤 |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US9527863B2 (enExample) |
| EP (2) | EP2836494B1 (enExample) |
| JP (2) | JP6314128B2 (enExample) |
| CN (2) | CN107011358B (enExample) |
| DK (1) | DK2836494T3 (enExample) |
| ES (2) | ES2929759T3 (enExample) |
| HR (1) | HRP20221356T1 (enExample) |
| HU (1) | HUE060655T2 (enExample) |
| RU (1) | RU2632206C2 (enExample) |
| WO (1) | WO2013149948A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9561290B2 (en) * | 2012-04-05 | 2017-02-07 | Nerviano Medical Sciences S.R.L. | Functionalized thieno-indole derivatives for the treatment of cancer |
| ES2929759T3 (es) | 2012-04-05 | 2022-12-01 | Nerviano Medical Sciences Srl | Nuevos agentes alquilantes |
| US10266547B2 (en) * | 2013-09-25 | 2019-04-23 | Nerviano Medical Sciences S.R.L. | Thieno[2,3-e]indole derivatives as new antitumor agents |
| WO2016151432A1 (en) | 2015-03-20 | 2016-09-29 | Pfizer Inc. | Bifunctional cytotoxic agents containing the cti pharmacophore |
| EP3325489B1 (en) | 2015-07-21 | 2019-11-13 | Nerviano Medical Sciences S.R.L. | Asymmetric process for the preparation of thieno-indoles derivatives |
| CN107029242A (zh) | 2015-11-03 | 2017-08-11 | 财团法人工业技术研究院 | 抗体药物复合物及其制造方法 |
| ES2902179T3 (es) * | 2016-08-19 | 2022-03-25 | Bristol Myers Squibb Co | Compuestos de seco-ciclopropapirroloindol, conjugados de anticuerpo-fármaco de los mismos y métodos de elaboración y uso |
| EP4221705A1 (en) * | 2020-09-09 | 2023-08-09 | Clinuvel (UK) Ltd. | Pyrrolidine compounds to treat xeroderma pigmentosum |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0065393B1 (en) * | 1981-05-12 | 1984-12-27 | Imperial Chemical Industries Plc | Pyrrole derivatives |
| CA1238907A (en) * | 1984-02-21 | 1988-07-05 | Robert C. Kelly | 1,2,8,8a-tetrahydrocyclopropa¬c|pyrrolo(3,2-e)- indol-4(5h)-ones and related compounds |
| US5659022A (en) * | 1996-01-05 | 1997-08-19 | Epoch Pharmaceuticals, Inc. | Oligonucleotide-cyclopropapyrroloindole conjugates as sequence specific hybridization and crosslinking agents for nucleic acids |
| JP3045706B1 (ja) | 1998-09-14 | 2000-05-29 | 科学技術振興事業団 | Ｄｎａの特定塩基配列をアルキル化する化合物及びその合成法 |
| GB2344818A (en) * | 1998-12-16 | 2000-06-21 | Pharmacia & Upjohn Spa | Anti-tumour thieno-indole derivatives |
| GB0015447D0 (en) * | 2000-06-23 | 2000-08-16 | Pharmacia & Upjohn Spa | Combined therapy against tumors comprising substituted acryloyl derivates and alkylating agents |
| EP1243276A1 (en) | 2001-03-23 | 2002-09-25 | Franciscus Marinus Hendrikus De Groot | Elongated and multiple spacers containing activatible prodrugs |
| US7087600B2 (en) * | 2001-05-31 | 2006-08-08 | Medarex, Inc. | Peptidyl prodrugs and linkers and stabilizers useful therefor |
| EP1423110A4 (en) * | 2001-09-07 | 2005-04-27 | Scripps Research Inst | CBI ANALOGUE OF CC-1065 AND DUOCARMYCINES |
| WO2003026577A2 (en) * | 2001-09-24 | 2003-04-03 | Seattle Genetics, Inc. | P-amidobenzylethers in drug delivery agents |
| US6756397B2 (en) * | 2002-04-05 | 2004-06-29 | Immunogen, Inc. | Prodrugs of CC-1065 analogs |
| US7705045B2 (en) | 2002-11-14 | 2010-04-27 | Syntarga, B.V. | Prodrugs built as multiple self-elimination-release spacers |
| WO2004069201A2 (en) * | 2003-02-03 | 2004-08-19 | Medlogics Device Corporation | Compounds useful in coating stents to prevent and treat stenosis and restenosis |
| TW200526204A (en) * | 2004-02-03 | 2005-08-16 | Pharmacia Italia Spa | 1h-thieno[2,3-c]pyrazole derivatives useful as kinase inhibitors |
| US7282590B2 (en) | 2004-02-12 | 2007-10-16 | The Research Foundation Of State University Of New York | Drug conjugates |
| WO2005105154A1 (en) | 2004-04-21 | 2005-11-10 | Alza Corporation | Polymer conjugate releasable under mild thiolytic conditions |
| US7691962B2 (en) * | 2004-05-19 | 2010-04-06 | Medarex, Inc. | Chemical linkers and conjugates thereof |
| US7517903B2 (en) | 2004-05-19 | 2009-04-14 | Medarex, Inc. | Cytotoxic compounds and conjugates |
| JP5149620B2 (ja) | 2004-07-23 | 2013-02-20 | エンドサイト，インコーポレイテッド | ２価リンカーおよびその結合体 |
| US8940784B2 (en) * | 2006-02-02 | 2015-01-27 | Syntarga B.V. | Water-soluble CC-1065 analogs and their conjugates |
| EP2120932B1 (en) * | 2006-12-20 | 2014-07-09 | Nerviano Medical Sciences S.r.l. | Indazole derivatives as kinase inhibitors for the treatment of cancer |
| WO2010009124A2 (en) | 2008-07-15 | 2010-01-21 | Genentech, Inc. | Anthracycline derivative conjugates, process for their preparation and their use as antitumor compounds |
| ES2929759T3 (es) | 2012-04-05 | 2022-12-01 | Nerviano Medical Sciences Srl | Nuevos agentes alquilantes |
| US9561290B2 (en) * | 2012-04-05 | 2017-02-07 | Nerviano Medical Sciences S.R.L. | Functionalized thieno-indole derivatives for the treatment of cancer |
-
2013
- 2013-03-28 ES ES19184082T patent/ES2929759T3/es active Active
- 2013-03-28 HR HRP20221356TT patent/HRP20221356T1/hr unknown
- 2013-03-28 DK DK13715931T patent/DK2836494T3/da active
- 2013-03-28 ES ES13715931T patent/ES2755719T3/es active Active
- 2013-03-28 EP EP13715931.5A patent/EP2836494B1/en active Active
- 2013-03-28 WO PCT/EP2013/056743 patent/WO2013149948A1/en not_active Ceased
- 2013-03-28 US US14/390,644 patent/US9527863B2/en active Active
- 2013-03-28 CN CN201610942350.9A patent/CN107011358B/zh active Active
- 2013-03-28 HU HUE19184082A patent/HUE060655T2/hu unknown
- 2013-03-28 JP JP2015503835A patent/JP6314128B2/ja active Active
- 2013-03-28 EP EP19184082.6A patent/EP3587426B1/en active Active
- 2013-03-28 RU RU2014143994A patent/RU2632206C2/ru active
- 2013-03-28 CN CN201380016674.4A patent/CN104220442B/zh active Active
-
2016
- 2016-11-23 US US15/359,703 patent/US10071074B2/en active Active
-
2017
- 2017-10-13 JP JP2017199656A patent/JP2018070599A/ja not_active Withdrawn
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2587864T3 (es) | Derivados de pirimidina | |
| ES2925564T3 (es) | Derivados de azetidina tal como moduladores de receptores de quimiocinas y usos de los mismos | |
| FI4161935T3 (fi) | Brm:ään kohdennettuja yhdisteitä ja niihin liittyviä käyttömenetelmiä | |
| KR102343747B1 (ko) | 치환된 피롤리진 화합물 및 그의 용도 | |
| CN111788204B (zh) | 作为hbv复制抑制剂的取代吡咯嗪化合物 | |
| ES2989326T3 (es) | Compuestos de benzolactama como inhibidores de la proteína cinasa | |
| JP2006508981A (ja) | 癌を治療するためのインドリノンと化学療法剤との組み合わせ投与 | |
| CN106536480B (zh) | 吡咯烷-2,5-二酮衍生物、药物组合物及用作ido1抑制剂的方法 | |
| US8785438B2 (en) | Imidazopyridin-2-one derivatives | |
| RU2014143994A (ru) | Новые алкилирующие средства | |
| JP2025508702A5 (enExample) | ||
| CN112041311A (zh) | Pd-1/pd-l1抑制剂 | |
| CN108430993A (zh) | Tank-结合激酶抑制剂化合物 | |
| NZ532405A (en) | Treatment of acute myeloid leukemia with indolinone compounds | |
| AU2016263083A1 (en) | Benzimidazole and imadazopyridine carboximidamide compounds having activity as inhibitors of indoleamine 2,3-dioxygenase | |
| JP2019508384A (ja) | ５−置換２−（モルホリン−４−イル）−１，７−ナフチリジン | |
| JP2015523390A (ja) | 置換型ピラゾロン化合物及び使用方法 | |
| KR20150118102A (ko) | Pi3 키나제 모듈레이터로서의 헤테로방향족 화합물 | |
| KR20150083833A (ko) | Pi3 키나제 모듈레이터로서의 헤테로방향족 화합물 및 이의 이용 방법 | |
| WO2014193647A2 (en) | Alkenyl compounds and methods of use | |
| RU2014143992A (ru) | Функционализированные производные тиеноиндола для лечения ракового заболевания | |
| CA3089754A1 (en) | Antibody drug conjugates (adcs) with nampt inhibitors | |
| JP2019069990A (ja) | 癌を処置するためのセファロスポリンの新規誘導体 | |
| WO2014089280A1 (en) | Alkynyl compounds and methods of use | |
| WO2013177092A1 (en) | Substituted alkynyl pyridine compounds and methods of use |