CN101365679B - 制备cc-1065类似物的方法和化合物 - Google Patents
制备cc-1065类似物的方法和化合物 Download PDFInfo
- Publication number
- CN101365679B CN101365679B CN2006800491755A CN200680049175A CN101365679B CN 101365679 B CN101365679 B CN 101365679B CN 2006800491755 A CN2006800491755 A CN 2006800491755A CN 200680049175 A CN200680049175 A CN 200680049175A CN 101365679 B CN101365679 B CN 101365679B
- Authority
- CN
- China
- Prior art keywords
- compound
- unsubstituted
- group
- alkyl
- aryl
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 47
- 150000001875 compounds Chemical class 0.000 title claims description 145
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 93
- -1 CBI CC-1065 analogue Chemical class 0.000 claims description 65
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 43
- 125000001072 heteroaryl group Chemical group 0.000 claims description 34
- 229910052757 nitrogen Inorganic materials 0.000 claims description 29
- 230000000903 blocking effect Effects 0.000 claims description 23
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- XLJMAIOERFSOGZ-UHFFFAOYSA-N cyanic acid Chemical compound OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 10
- 150000001721 carbon Chemical group 0.000 claims description 10
- 125000004122 cyclic group Chemical group 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 239000004215 Carbon black (E152) Substances 0.000 claims description 5
- 230000029936 alkylation Effects 0.000 claims description 5
- 238000005804 alkylation reaction Methods 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 229930195733 hydrocarbon Natural products 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 229910052710 silicon Inorganic materials 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 230000008859 change Effects 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 150000002430 hydrocarbons Chemical class 0.000 claims description 4
- 125000001151 peptidyl group Chemical group 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 238000006073 displacement reaction Methods 0.000 claims description 3
- ICIWUVCWSCSTAQ-UHFFFAOYSA-M iodate Chemical compound [O-]I(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-M 0.000 claims description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims 2
- 238000010511 deprotection reaction Methods 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 abstract description 8
- 239000000543 intermediate Substances 0.000 abstract description 2
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 1
- 239000007858 starting material Substances 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 35
- 150000001413 amino acids Chemical class 0.000 description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 31
- 235000001014 amino acid Nutrition 0.000 description 31
- 150000003839 salts Chemical class 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 20
- 238000003756 stirring Methods 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 18
- 230000002194 synthesizing effect Effects 0.000 description 17
- 239000003814 drug Substances 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000002585 base Substances 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 239000002994 raw material Substances 0.000 description 13
- 206010028980 Neoplasm Diseases 0.000 description 12
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 10
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical group SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- UOWVMDUEMSNCAV-WYENRQIDSA-N rachelmycin Chemical class C1([C@]23C[C@@H]2CN1C(=O)C=1NC=2C(OC)=C(O)C4=C(C=2C=1)CCN4C(=O)C1=CC=2C=4CCN(C=4C(O)=C(C=2N1)OC)C(N)=O)=CC(=O)C1=C3C(C)=CN1 UOWVMDUEMSNCAV-WYENRQIDSA-N 0.000 description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- 125000002252 acyl group Chemical group 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 125000000547 substituted alkyl group Chemical group 0.000 description 8
- 125000003107 substituted aryl group Chemical group 0.000 description 8
- 125000001118 alkylidene group Chemical group 0.000 description 7
- 125000003277 amino group Chemical group 0.000 description 7
- 239000000427 antigen Substances 0.000 description 7
- 102000036639 antigens Human genes 0.000 description 7
- 108091007433 antigens Proteins 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 229940125898 compound 5 Drugs 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical class [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 125000005340 bisphosphate group Chemical group 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 229940126214 compound 3 Drugs 0.000 description 4
- 238000013016 damping Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000007614 solvation Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- UOORRWUZONOOLO-OWOJBTEDSA-N (E)-1,3-dichloropropene Chemical group ClC\C=C\Cl UOORRWUZONOOLO-OWOJBTEDSA-N 0.000 description 3
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 3
- HIYWOHBEPVGIQN-UHFFFAOYSA-N 1h-benzo[g]indole Chemical compound C1=CC=CC2=C(NC=C3)C3=CC=C21 HIYWOHBEPVGIQN-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 0 CC1=C(*)C2C=C(C(*(CC3)c4c3c3cc(*)ccc3c(O)c4)=*)NC2C(*)=C1C Chemical compound CC1=C(*)C2C=C(C(*(CC3)c4c3c3cc(*)ccc3c(O)c4)=*)NC2C(*)=C1C 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 238000011579 SCID mouse model Methods 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 235000013905 glycine and its sodium salt Nutrition 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- ZCOSUVZGFDGWFV-UHFFFAOYSA-N pyrrolo[2,3-e]indole Chemical compound C1=CC2=NC=CC2=C2N=CC=C21 ZCOSUVZGFDGWFV-UHFFFAOYSA-N 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 description 3
- 229940104230 thymidine Drugs 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- VZXULLNDXWTFLH-UHFFFAOYSA-N Cl.C(=O)(Cl)Cl.N1CCNCC1.CC1=C(C=C(C(=O)O)C=C1)C(=O)O Chemical compound Cl.C(=O)(Cl)Cl.N1CCNCC1.CC1=C(C=C(C(=O)O)C=C1)C(=O)O VZXULLNDXWTFLH-UHFFFAOYSA-N 0.000 description 2
- 101710112752 Cytotoxin Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 2
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000005576 amination reaction Methods 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 229940125644 antibody drug Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229960000846 camphor Drugs 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000022534 cell killing Effects 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 231100000599 cytotoxic agent Toxicity 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 239000002619 cytotoxin Substances 0.000 description 2
- 238000010612 desalination reaction Methods 0.000 description 2
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-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
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000003810 ethyl acetate extraction Methods 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical class 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 239000001294 propane Substances 0.000 description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- KZVLNAGYSAKYMG-UHFFFAOYSA-N pyridine-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=N1 KZVLNAGYSAKYMG-UHFFFAOYSA-N 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical compound OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 235000012976 tarts Nutrition 0.000 description 2
- 125000005309 thioalkoxy group Chemical group 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- QSSXJPIWXQTSIX-UHFFFAOYSA-N 1-bromo-2-methylbenzene Chemical compound CC1=CC=CC=C1Br QSSXJPIWXQTSIX-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical group CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- KTLUMOZOWZSJFC-UHFFFAOYSA-N 3-azatetracyclo[7.5.0.02,6.012,14]tetradeca-1,3,5,7,9,11,13-heptaene Chemical compound C1=C2C=CN=C2C2=C3C=C3C=CC2=C1 KTLUMOZOWZSJFC-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
- 206010056951 Actinic cheilitis Diseases 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- BMFMQGXDDJALKQ-BYPYZUCNSA-N Argininic acid Chemical class NC(N)=NCCC[C@H](O)C(O)=O BMFMQGXDDJALKQ-BYPYZUCNSA-N 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000013165 Bowen disease Diseases 0.000 description 1
- 208000019337 Bowen disease of the skin Diseases 0.000 description 1
- OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 1
- 101150114104 CROT gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 241000790917 Dioxys <bee> Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010060766 Heteroplasia Diseases 0.000 description 1
- 241000701806 Human papillomavirus Species 0.000 description 1
- 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 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical group C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010054949 Metaplasia Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- XUYPXLNMDZIRQH-LURJTMIESA-N N-acetyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC(C)=O XUYPXLNMDZIRQH-LURJTMIESA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 229910003849 O-Si Inorganic materials 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229910003872 O—Si Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241001415846 Procellariidae Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 241000133426 Streptomyces zelensis Species 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 235000007244 Zea mays Nutrition 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- PNDPGZBMCMUPRI-XXSWNUTMSA-N [125I][125I] Chemical compound [125I][125I] PNDPGZBMCMUPRI-XXSWNUTMSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 208000009621 actinic keratosis Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 125000005110 aryl thio group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 239000012496 blank sample Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 201000007455 central nervous system cancer Diseases 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N citrulline Chemical compound OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- 201000010989 colorectal carcinoma Diseases 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 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
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 125000004119 disulfanediyl group Chemical group *SS* 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- HCPOCMMGKBZWSJ-UHFFFAOYSA-N ethyl 3-hydrazinyl-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NN HCPOCMMGKBZWSJ-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000001261 hydroxy acids Chemical group 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229940044173 iodine-125 Drugs 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 201000011486 lichen planus Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000015689 metaplastic ossification Effects 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-O methylsulfide anion Chemical compound [SH2+]C LSDPWZHWYPCBBB-UHFFFAOYSA-O 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002829 nitrogen Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000013139 quantization Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000000163 radioactive labelling Methods 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 150000003527 tetrahydropyrans Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 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
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 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
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- FBTUMDXHSRTGRV-ALTNURHMSA-N zorubicin 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)=N\NC(=O)C=1C=CC=CC=1)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 FBTUMDXHSRTGRV-ALTNURHMSA-N 0.000 description 1
- 229960000641 zorubicin Drugs 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/60—Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US73080405P | 2005-10-26 | 2005-10-26 | |
| US60/730,804 | 2005-10-26 | ||
| PCT/US2006/060050 WO2007051081A1 (en) | 2005-10-26 | 2006-10-18 | Methods and compounds for preparing cc-1065 analogs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101365679A CN101365679A (zh) | 2009-02-11 |
| CN101365679B true CN101365679B (zh) | 2012-11-14 |
Family
ID=37766648
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2006800491755A Expired - Fee Related CN101365679B (zh) | 2005-10-26 | 2006-10-18 | 制备cc-1065类似物的方法和化合物 |
Country Status (23)
Families Citing this family (69)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002092771A2 (en) | 2001-05-11 | 2002-11-21 | Ludwig Institute For Cancer Research | Specific binding proteins and uses thereof |
| US20100056762A1 (en) | 2001-05-11 | 2010-03-04 | Old Lloyd J | Specific binding proteins and uses thereof |
| ES2527961T3 (es) | 2005-09-26 | 2015-02-02 | Medarex, L.L.C. | Anticuerpos monoclonales humanos para CD70 |
| MX2009007987A (es) | 2007-01-25 | 2010-03-01 | Dana Farber Cancer Inst Inc | Uso de anticuerpos anti-egfr en el tratamiento de enfermedad mediada por egfr mutante. |
| US9023356B2 (en) | 2007-03-15 | 2015-05-05 | Ludwig Institute For Cancer Research Ltd | Treatment method using EGFR antibodies and SRC inhibitors and related formulations |
| US9901567B2 (en) | 2007-08-01 | 2018-02-27 | Syntarga B.V. | Substituted CC-1065 analogs and their conjugates |
| JP5532486B2 (ja) | 2007-08-14 | 2014-06-25 | ルードヴィッヒ インスティテュート フォー キャンサー リサーチ | Ｅｇｆ受容体を標的とするモノクローナル抗体１７５ならびにその誘導体および用途 |
| EP2185188B1 (en) | 2007-08-22 | 2014-08-06 | Medarex, L.L.C. | Site-specific attachment of drugs or other agents to engineered antibodies with c-terminal extensions |
| CA2700860C (en) * | 2007-10-01 | 2016-07-19 | Jonathan A. Terrett | Human antibodies that bind mesothelin, and uses thereof |
| AR072999A1 (es) | 2008-08-11 | 2010-10-06 | Medarex Inc | Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos |
| MX2011004625A (es) | 2008-11-03 | 2011-07-20 | Syntarga Bv | Analogos cc-1065 novedosos y sus conjugados. |
| WO2010096394A2 (en) | 2009-02-17 | 2010-08-26 | Redwood Biosciences, Inc. | Aldehyde-tagged protein-based drug carriers and methods of use |
| PL2403878T3 (pl) | 2009-03-05 | 2017-12-29 | E. R. Squibb & Sons, L.L.C. | W pełni ludzkie przeciwciała specyficzne dla CADM1 |
| US8394922B2 (en) | 2009-08-03 | 2013-03-12 | Medarex, Inc. | Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof |
| PL2560645T3 (pl) | 2010-04-21 | 2017-01-31 | Syntarga B.V. | Koniugaty analogów CC-1065 i łączników dwufunkcyjnych |
| US8956859B1 (en) | 2010-08-13 | 2015-02-17 | Aviex Technologies Llc | Compositions and methods for determining successful immunization by one or more vaccines |
| JOP20210044A1 (ar) | 2010-12-30 | 2017-06-16 | Takeda Pharmaceuticals Co | الأجسام المضادة لـ cd38 |
| AU2012205301B2 (en) | 2011-01-14 | 2017-01-05 | Redwood Bioscience, Inc. | Aldehyde-tagged immunoglobulin polypeptides and method of use thereof |
| PE20141791A1 (es) | 2012-02-13 | 2014-11-19 | Bristol Myers Squibb Co | Compuestos de enediino, conjugados de los mismos y sus usos y metodos |
| UY34887A (es) | 2012-07-02 | 2013-12-31 | Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware | Optimización de anticuerpos que se fijan al gen de activación de linfocitos 3 (lag-3) y sus usos |
| WO2014126836A1 (en) | 2013-02-14 | 2014-08-21 | Bristol-Myers Squibb Company | Tubulysin compounds, methods of making and use |
| SG10201911860VA (en) | 2014-01-10 | 2020-02-27 | Synthon Biopharmaceuticals Bv | Duocarmycin adcs showing improved in vivo antitumor activity |
| MY177390A (en) | 2014-01-10 | 2020-09-14 | Byondis Bv | Method for purifying cys-linked antibody-drug conjugates |
| MX368234B (es) | 2014-01-10 | 2019-09-25 | Synthon Biopharmaceuticals Bv | Conjugados de anticuerpo-fármaco (adcs) que contienen duocarmicina para usarse en el tratamiento de cáncer endometrial. |
| EP3647322B1 (en) | 2014-03-20 | 2021-10-20 | Bristol-Myers Squibb Company | Stabilized fibronectin based scaffold molecules |
| SG11201610074YA (en) | 2014-06-06 | 2016-12-29 | Bristol Myers Squibb Co | Antibodies against glucocorticoid-induced tumor necrosis factor receptor (gitr) and uses thereof |
| US10077287B2 (en) | 2014-11-10 | 2018-09-18 | Bristol-Myers Squibb Company | Tubulysin analogs and methods of making and use |
| KR102569813B1 (ko) | 2014-11-21 | 2023-08-24 | 브리스톨-마이어스 스큅 컴퍼니 | Cd73에 대항한 항체 및 그의 용도 |
| EP3789399A1 (en) | 2014-11-21 | 2021-03-10 | Bristol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
| CN107207379B (zh) | 2014-11-25 | 2021-08-10 | 百时美施贵宝公司 | 用于生物制品的18f-放射性标记的方法和组合物 |
| ES2822990T3 (es) | 2014-11-25 | 2021-05-05 | Bristol Myers Squibb Co | Novedosos polipéptidos de unión a PD-L1 para obtención de imágenes |
| WO2016097865A1 (en) | 2014-12-19 | 2016-06-23 | Regenesance B.V. | Antibodies that bind human c6 and uses thereof |
| MX2017009144A (es) | 2015-01-14 | 2017-11-22 | Bristol Myers Squibb Co | Dimeros de benzodiazepina unidos con puentes de heteroarileno, conjugados de estos, y sus metodos de preparacion y uso. |
| ES2809125T3 (es) | 2015-09-23 | 2021-03-03 | Bristol Myers Squibb Co | Moléculas de armazón a base de fibronectina de unión a glipicano-3 |
| EA201891121A1 (ru) | 2015-11-19 | 2018-12-28 | Бристол-Майерс Сквибб Компани | Антитела к глюкокортикоид-индуцированному рецептору фактора некроза опухоли (gitr) и их применения |
| SG10201913033UA (en) | 2016-03-04 | 2020-03-30 | Bristol Myers Squibb Co | Combination therapy with anti-cd73 antibodies |
| AU2017257504A1 (en) | 2016-04-26 | 2018-10-25 | R.P. Scherer Technologies, Llc | Antibody conjugates and methods of making and using the same |
| CN109562195A (zh) | 2016-06-01 | 2019-04-02 | 百时美施贵宝公司 | 用pd-l1结合多肽进行pet成像 |
| US10994033B2 (en) | 2016-06-01 | 2021-05-04 | Bristol-Myers Squibb Company | Imaging methods using 18F-radiolabeled biologics |
| AU2017297506A1 (en) | 2016-07-14 | 2019-02-21 | Bristol-Myers Squibb Company | Antibodies against TIM3 and uses thereof |
| WO2018035391A1 (en) | 2016-08-19 | 2018-02-22 | Bristol-Myers Squibb Company | Seco-cyclopropapyrroloindole compounds, antibody-drug conjugates thereof, and methods of making and use |
| WO2018075842A1 (en) | 2016-10-20 | 2018-04-26 | Bristol-Myers Squibb Company | Condensed benzodiazepine derivatives and conjugates made therefrom |
| CA3051839A1 (en) | 2017-02-17 | 2018-08-23 | Bristol-Myers Squibb Company | Antibodies to alpha-synuclein and uses thereof |
| US11339218B2 (en) | 2017-05-10 | 2022-05-24 | Zhejiang Shimai Pharmaceutical Co., Ltd. | Human monoclonal antibodies against LAG3 and uses thereof |
| CA3064321A1 (en) | 2017-05-25 | 2018-11-29 | Bristol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
| US10508115B2 (en) | 2017-08-16 | 2019-12-17 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor |
| US10457681B2 (en) | 2017-08-16 | 2019-10-29 | Bristol_Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a tricyclic moiety, conjugates thereof, and methods and uses therefor |
| US10487084B2 (en) | 2017-08-16 | 2019-11-26 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a heterobiaryl moiety, conjugates thereof, and methods and uses therefor |
| US10472361B2 (en) | 2017-08-16 | 2019-11-12 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a benzotriazole moiety, conjugates thereof, and methods and uses therefor |
| US10494370B2 (en) | 2017-08-16 | 2019-12-03 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a pyridine or pyrazine moiety, conjugates thereof, and methods and uses therefor |
| WO2019075090A1 (en) | 2017-10-10 | 2019-04-18 | Tilos Therapeutics, Inc. | ANTI-LAP ANTIBODIES AND USES THEREOF |
| WO2019140229A1 (en) | 2018-01-12 | 2019-07-18 | Bristol-Myers Squibb Company | Antibodies against tim3 and uses thereof |
| PE20210665A1 (es) | 2018-03-23 | 2021-03-31 | Bristol Myers Squibb Co | Anticuerpos contra mica y/o micb y sus usos |
| AR117566A1 (es) | 2018-04-02 | 2021-08-18 | Bristol Myers Squibb Co | Anticuerpos anti-trem-1 y sus usos |
| WO2019209811A1 (en) | 2018-04-24 | 2019-10-31 | Bristol-Myers Squibb Company | Macrocyclic toll-like receptor 7 (tlr7) agonists |
| US11884729B2 (en) | 2018-06-29 | 2024-01-30 | ApitBio, Inc | Anti-L1CAM antibodies and uses thereof |
| US11554120B2 (en) | 2018-08-03 | 2023-01-17 | Bristol-Myers Squibb Company | 1H-pyrazolo[4,3-d]pyrimidine compounds as toll-like receptor 7 (TLR7) agonists and methods and uses therefor |
| US11130802B2 (en) | 2018-10-10 | 2021-09-28 | Tilos Therapeutics, Inc. | Anti-lap antibody variants |
| EP3887397A1 (en) | 2018-11-28 | 2021-10-06 | Bristol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
| WO2020117627A1 (en) | 2018-12-03 | 2020-06-11 | Bristol-Myers Squibb Company | Anti-ido antibody and uses thereof |
| CN109762067B (zh) | 2019-01-17 | 2020-02-28 | 北京天广实生物技术股份有限公司 | 结合人Claudin 18.2的抗体及其用途 |
| BR112021014106A2 (pt) | 2019-01-22 | 2021-10-13 | Bristol-Myers Squibb Company | Anticorpos contra subunidade alfa de il-7r e usos dos mesmos |
| WO2021011681A1 (en) | 2019-07-15 | 2021-01-21 | Bristol-Myers Squibb Company | Antibodies against human trem-1 and uses thereof |
| JP2022540674A (ja) | 2019-07-15 | 2022-09-16 | ブリストル－マイヤーズ スクイブ カンパニー | 抗ｔｒｅｍ－１抗体およびその使用 |
| JP2023512456A (ja) | 2020-01-13 | 2023-03-27 | ネオイミューンテック， インコーポレイテッド | Ｉｌ－７タンパク質と二重特異性抗体の組み合わせで腫瘍を治療する方法 |
| TW202140564A (zh) | 2020-02-27 | 2021-11-01 | 大陸商正大天晴藥業集團股份有限公司 | 結合ｉｌ４ｒ的抗體及其用途 |
| US20230272056A1 (en) | 2020-04-09 | 2023-08-31 | Merck Sharp & Dohme Llc | Affinity matured anti-lap antibodies and uses thereof |
| CN114685669A (zh) | 2020-12-30 | 2022-07-01 | 和铂医药(苏州)有限公司 | 结合trop2的抗体及其用途 |
| EP4314068A1 (en) | 2021-04-02 | 2024-02-07 | The Regents Of The University Of California | Antibodies against cleaved cdcp1 and uses thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997012862A1 (en) * | 1995-10-03 | 1997-04-10 | The Scripps Research Institute | Cbi analogs of cc-1065 and the duocarmycins |
| WO1997045411A1 (en) * | 1996-05-31 | 1997-12-04 | The Scripps Research Institute | Analogs of cc-1065 and the duocarmycins |
| WO2001016104A1 (en) * | 1999-08-27 | 2001-03-08 | Spirogen Limited | Cyclopropylindole derivatives |
| WO2003086318A2 (en) * | 2002-04-05 | 2003-10-23 | Immunogen, Inc. | Improved prodrugs of cc-1065 analogs |
| WO2003087055A1 (en) * | 2002-04-05 | 2003-10-23 | Immunogen, Inc. | Improved cc-1065 analog synthesis |
| WO2005112919A2 (en) * | 2004-05-19 | 2005-12-01 | Medarex, Inc. | Self-immolative linkers and drug conjugates |
Family Cites Families (100)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4169888A (en) | 1977-10-17 | 1979-10-02 | The Upjohn Company | Composition of matter and process |
| US4391904A (en) | 1979-12-26 | 1983-07-05 | Syva Company | Test strip kits in immunoassays and compositions therein |
| US4671958A (en) | 1982-03-09 | 1987-06-09 | Cytogen Corporation | Antibody conjugates for the delivery of compounds to target sites |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4912227A (en) | 1984-02-21 | 1990-03-27 | The Upjohn Company | 1,2,8,8A-tetrahydrocyclopropa(c)pyrrolo(3,2-e)-indol-4-(5H)-ones and related compounds |
| US4978757A (en) | 1984-02-21 | 1990-12-18 | The Upjohn Company | 1,2,8,8a-tetrahydrocyclopropa (C) pyrrolo [3,2-e)]-indol-4(5H)-ones and related compounds |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| JPH0684377B1 (US07847105-20101207-C00016.png) | 1986-04-17 | 1994-10-26 | Kyowa Hakko Kogyo Kk | |
| US5332837A (en) | 1986-12-19 | 1994-07-26 | The Upjohn Company | CC-1065 analogs |
| US4975278A (en) | 1988-02-26 | 1990-12-04 | Bristol-Myers Company | Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells |
| US5773435A (en) | 1987-08-04 | 1998-06-30 | Bristol-Myers Squibb Company | Prodrugs for β-lactamase and uses thereof |
| US4952394A (en) | 1987-11-23 | 1990-08-28 | Bristol-Myers Company | Drug-monoclonal antibody conjugates |
| US4994578A (en) | 1987-11-27 | 1991-02-19 | Meiji Seika Kaisha, Ltd. | Certain anti-tumor duocarmycin antibiotics from streptomyces |
| US5147786A (en) | 1988-04-22 | 1992-09-15 | Monsanto Company | Immunoassay for the detection of α-haloacetamides |
| JP2642165B2 (ja) | 1988-07-22 | 1997-08-20 | 協和醗酵工業株式会社 | 新規ｄｃ−８９化合物およびその製造法 |
| US5084468A (en) | 1988-08-11 | 1992-01-28 | Kyowa Hakko Kogyo Co., Ltd. | Dc-88a derivatives |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| US5176996A (en) | 1988-12-20 | 1993-01-05 | Baylor College Of Medicine | Method for making synthetic oligonucleotides which bind specifically to target sites on duplex DNA molecules, by forming a colinear triplex, the synthetic oligonucleotides and methods of use |
| JP2598116B2 (ja) | 1988-12-28 | 1997-04-09 | 協和醗酵工業株式会社 | 新規物質ｄｃ１１３ |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| JP2510335B2 (ja) | 1989-07-03 | 1996-06-26 | 協和醗酵工業株式会社 | Ｄｃ―８８ａ誘導体 |
| US5187186A (en) | 1989-07-03 | 1993-02-16 | Kyowa Hakko Kogyo Co., Ltd. | Pyrroloindole derivatives |
| US5495009A (en) | 1989-10-24 | 1996-02-27 | Gilead Sciences, Inc. | Oligonucleotide analogs containing thioformacetal linkages |
| US5334528A (en) | 1989-10-30 | 1994-08-02 | The Regents Of The University Of California | Monoclonal antibodies to cyclodiene insecticides and method for detecting the same |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| WO1991010741A1 (en) | 1990-01-12 | 1991-07-25 | Cell Genesys, Inc. | Generation of xenogeneic antibodies |
| EP0527189A1 (en) | 1990-04-25 | 1993-02-17 | PHARMACIA & UPJOHN COMPANY | Novel cc-1065 analogs |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| US5137877B1 (en) | 1990-05-14 | 1996-01-30 | Bristol Myers Squibb Co | Bifunctional linking compounds conjugates and methods for their production |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| US6172197B1 (en) | 1991-07-10 | 2001-01-09 | Medical Research Council | Methods for producing members of specific binding pairs |
| DE69121334T2 (de) | 1990-07-26 | 1997-03-20 | Kyowa Hakko Kogyo Kk | DC-89-Derivate als Antitumor-Wirkstoffe |
| GB9017024D0 (en) | 1990-08-03 | 1990-09-19 | Erba Carlo Spa | New linker for bioactive agents |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| ES2108048T3 (es) | 1990-08-29 | 1997-12-16 | Genpharm Int | Produccion y utilizacion de animales inferiores transgenicos capaces de producir anticuerpos heterologos. |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| JPH0597853A (ja) | 1991-10-07 | 1993-04-20 | Kyowa Hakko Kogyo Co Ltd | Ｄｃ−８９誘導体の臭化水素酸塩 |
| ES2227512T3 (es) | 1991-12-02 | 2005-04-01 | Medical Research Council | Produccion de anticuerpos contra auto-antigenos a partir de repertorios de segmentos de anticuerpos fijados en un fago. |
| US5622929A (en) | 1992-01-23 | 1997-04-22 | Bristol-Myers Squibb Company | Thioether conjugates |
| CA2076465C (en) | 1992-03-25 | 2002-11-26 | Ravi V. J. Chari | Cell binding agent conjugates of analogues and derivatives of cc-1065 |
| GB9314960D0 (en) | 1992-07-23 | 1993-09-01 | Zeneca Ltd | Chemical compounds |
| JP3514490B2 (ja) | 1992-08-21 | 2004-03-31 | 杏林製薬株式会社 | トリフルオロメチルピロロインドールカルボン酸エステル誘導体及びその製造方法 |
| US5288514A (en) | 1992-09-14 | 1994-02-22 | The Regents Of The University Of California | Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support |
| US5324483B1 (en) | 1992-10-08 | 1996-09-24 | Warner Lambert Co | Apparatus for multiple simultaneous synthesis |
| DE4314091A1 (de) | 1993-04-29 | 1994-11-03 | Boehringer Mannheim Gmbh | Immunologisches Nachweisverfahren für Triazine |
| US6214345B1 (en) | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
| US5786377A (en) | 1993-11-19 | 1998-07-28 | Universidad De Santiago De Compostela | Pyrrolo 3,2-E!indol derivatives, process for the preparation thereof and applications |
| ES2220927T3 (es) | 1994-04-22 | 2004-12-16 | Kyowa Hakko Kogyo Co., Ltd. | Derivados de dc-89. |
| JPH07309761A (ja) | 1994-05-20 | 1995-11-28 | Kyowa Hakko Kogyo Co Ltd | デュオカルマイシン誘導体の安定化法 |
| US5773001A (en) | 1994-06-03 | 1998-06-30 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
| SI0769967T1 (sl) | 1994-08-19 | 2008-06-30 | Wallone Region | Konjugati vsebujoäśi protitumorna sredstva in njihova uporaba |
| EP0786252A4 (en) | 1994-09-30 | 1998-01-07 | Kyowa Hakko Kogyo Kk | ANTI-TUMOR AGENT |
| CA2205872A1 (en) | 1994-11-29 | 1996-06-06 | Kyorin Pharmaceutical Co., Ltd. | Acrylamide derivatives and process for production thereof |
| WO1996035451A1 (fr) | 1995-05-10 | 1996-11-14 | Kyowa Hakko Kogyo Co., Ltd. | Nouveau complexe de toxines |
| US5686237A (en) | 1995-06-05 | 1997-11-11 | Al-Bayati; Mohammed A. S. | Use of biomarkers in saliva to evaluate the toxicity of agents and the function of tissues in both biomedical and environmental applications |
| US5712374A (en) | 1995-06-07 | 1998-01-27 | American Cyanamid Company | Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates |
| US5646298A (en) * | 1995-06-07 | 1997-07-08 | Procoron, Inc. | Cyclopropylindole prodrugs |
| US5714586A (en) | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
| DE69632989T2 (de) | 1995-10-17 | 2005-08-25 | Combichem, Inc., San Diego | Matrize für die Synthese kombinatorischer Bibliotheken in Lösung |
| WO1997023243A1 (en) | 1995-12-22 | 1997-07-03 | Bristol-Myers Squibb Company | Branched hydrazone linkers |
| US6143901A (en) | 1996-07-31 | 2000-11-07 | Genesoft, Inc. | Complex formation between dsDNA and pyrrole imidazole polyamides |
| WO1997032850A1 (en) * | 1996-03-08 | 1997-09-12 | The Scripps Research Institute | Mcbi analogs of cc-1065 and the duocarmycins |
| US6130237A (en) | 1996-09-12 | 2000-10-10 | Cancer Research Campaign Technology Limited | Condensed N-aclyindoles as antitumor agents |
| JPH1087666A (ja) | 1996-09-18 | 1998-04-07 | Kyorin Pharmaceut Co Ltd | デュオカルマイシンｓａ及びその誘導体の製造中間体と製造方法 |
| US6759509B1 (en) * | 1996-11-05 | 2004-07-06 | Bristol-Myers Squibb Company | Branched peptide linkers |
| WO1998043663A1 (en) | 1997-03-28 | 1998-10-08 | The Scripps Research Institute | Sandramycin analogs |
| CA2289115A1 (en) | 1997-05-07 | 1998-11-12 | Bristol-Myers Squibb Company | Recombinant antibody-enzyme fusion proteins |
| JP2002503228A (ja) | 1997-05-22 | 2002-01-29 | ザ スクリップス リサーチ インスティテュート | デュオカルマイシンおよびｃｃ−１０６５の類似体 |
| CA2306420A1 (en) | 1997-10-14 | 1999-04-22 | The Scripps Research Institute | Iso-cbi and iso-ci analogs of cc-1065 and the duocarmycins |
| JP2001525382A (ja) * | 1997-12-08 | 2001-12-11 | ザ スクリップス リサーチ インスティテュート | Ｃｃ−１０６５／デュオカルマイシン類似体の合成 |
| 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 |
| US7425541B2 (en) | 1998-12-11 | 2008-09-16 | Medarex, Inc. | Enzyme-cleavable prodrug compounds |
| WO2001049698A1 (en) | 1999-12-29 | 2001-07-12 | Immunogen, Inc. | Cytotoxic agents comprising modified doxorubicins and daunorubicins and their therapeutic use |
| US6559125B1 (en) * | 2000-01-28 | 2003-05-06 | California Institute Of Technology | Polyamide-alkylator conjugates and related products and method |
| JP2003529609A (ja) | 2000-03-16 | 2003-10-07 | ジーンソフト インコーポレイティッド | 核酸結合部分を含む荷電した化合物およびその利用法 |
| JP4061819B2 (ja) | 2000-05-12 | 2008-03-19 | 独立行政法人科学技術振興機構 | インターストランドクロスリンク剤の合成方法 |
| JP2004510702A (ja) | 2000-06-14 | 2004-04-08 | メダレックス，インコーポレイティド | イソロイシンを有するプロドラッグ化合物 |
| CA2411545A1 (en) | 2000-06-14 | 2002-01-03 | Medarex, Inc. | Tripeptide prodrug compounds |
| EP1243276A1 (en) | 2001-03-23 | 2002-09-25 | Franciscus Marinus Hendrikus De Groot | Elongated and multiple spacers containing activatible prodrugs |
| US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
| US7256257B2 (en) | 2001-04-30 | 2007-08-14 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
| US20030083263A1 (en) | 2001-04-30 | 2003-05-01 | Svetlana Doronina | Pentapeptide compounds and uses related thereto |
| US6762179B2 (en) | 2001-05-31 | 2004-07-13 | Vertex Pharmaceuticals Incorporated | Thiazole compounds useful as inhibitors of protein kinase |
| KR20030033007A (ko) | 2001-05-31 | 2003-04-26 | 코울터 파머수티컬, 인코포레이티드 | 세포독소, 약물전구체, 링커 및 이에 유용한 안정화제 |
| CA2450316A1 (en) | 2001-06-11 | 2002-12-19 | Medarex, Inc. | Cd10-activated prodrug compounds |
| JP2005502703A (ja) | 2001-09-07 | 2005-01-27 | ザ スクリプス リサーチ インスティテュート | Ｃｃ−１０６５およびデュオカルマイシンのｃｂｉ類似体 |
| US7091186B2 (en) | 2001-09-24 | 2006-08-15 | Seattle Genetics, Inc. | p-Amidobenzylethers in drug delivery agents |
| US7816377B2 (en) | 2002-07-09 | 2010-10-19 | R&D-Biopharmaceuticals Gmbh | Tubulysin analogues |
| EP1521769B1 (de) | 2002-07-09 | 2015-09-09 | Dömling, Alexander | Tubulysinkonjugate |
| US20050026987A1 (en) | 2003-05-13 | 2005-02-03 | The Scripps Research Institute | CBI analogues of the duocarmycins and CC-1065 |
| US7714016B2 (en) * | 2005-04-08 | 2010-05-11 | Medarex, Inc. | Cytotoxic compounds and conjugates with cleavable substrates |
-
2006
- 2006-10-18 CA CA2627046A patent/CA2627046C/en not_active Expired - Fee Related
- 2006-10-18 EP EP06839458A patent/EP1940789B1/en active Active
- 2006-10-18 AU AU2006305842A patent/AU2006305842B2/en not_active Ceased
- 2006-10-18 KR KR1020087011981A patent/KR20080068084A/ko not_active Application Discontinuation
- 2006-10-18 EA EA200801176A patent/EA015324B1/ru not_active IP Right Cessation
- 2006-10-18 SI SI200631269T patent/SI1940789T1/sl unknown
- 2006-10-18 ES ES06839458T patent/ES2375843T3/es active Active
- 2006-10-18 AT AT06839458T patent/ATE534629T1/de active
- 2006-10-18 RS RS20120009A patent/RS52100B/en unknown
- 2006-10-18 PL PL06839458T patent/PL1940789T3/pl unknown
- 2006-10-18 JP JP2008538132A patent/JP5116686B2/ja not_active Expired - Fee Related
- 2006-10-18 US US12/090,445 patent/US7847105B2/en active Active
- 2006-10-18 WO PCT/US2006/060050 patent/WO2007051081A1/en active Application Filing
- 2006-10-18 CN CN2006800491755A patent/CN101365679B/zh not_active Expired - Fee Related
- 2006-10-18 PT PT06839458T patent/PT1940789E/pt unknown
- 2006-10-18 DK DK06839458.4T patent/DK1940789T3/da active
- 2006-10-18 BR BRPI0619331-5A patent/BRPI0619331A2/pt not_active IP Right Cessation
-
2008
- 2008-04-17 IL IL190971A patent/IL190971A/en not_active IP Right Cessation
- 2008-05-15 NO NO20082243A patent/NO20082243L/no not_active Application Discontinuation
- 2008-05-23 ZA ZA200804521A patent/ZA200804521B/xx unknown
- 2008-09-11 HK HK08110088.4A patent/HK1118549A1/xx not_active IP Right Cessation
-
2012
- 2012-01-19 HR HR20120058T patent/HRP20120058T1/hr unknown
- 2012-02-21 CY CY20121100174T patent/CY1112533T1/el unknown
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997012862A1 (en) * | 1995-10-03 | 1997-04-10 | The Scripps Research Institute | Cbi analogs of cc-1065 and the duocarmycins |
| WO1997045411A1 (en) * | 1996-05-31 | 1997-12-04 | The Scripps Research Institute | Analogs of cc-1065 and the duocarmycins |
| WO2001016104A1 (en) * | 1999-08-27 | 2001-03-08 | Spirogen Limited | Cyclopropylindole derivatives |
| WO2003086318A2 (en) * | 2002-04-05 | 2003-10-23 | Immunogen, Inc. | Improved prodrugs of cc-1065 analogs |
| WO2003087055A1 (en) * | 2002-04-05 | 2003-10-23 | Immunogen, Inc. | Improved cc-1065 analog synthesis |
| WO2005112919A2 (en) * | 2004-05-19 | 2005-12-01 | Medarex, Inc. | Self-immolative linkers and drug conjugates |
Also Published As
| Publication number | Publication date |
|---|---|
| EA015324B1 (ru) | 2011-06-30 |
| WO2007051081A1 (en) | 2007-05-03 |
| JP2009513676A (ja) | 2009-04-02 |
| JP5116686B2 (ja) | 2013-01-09 |
| AU2006305842B2 (en) | 2011-11-03 |
| EP1940789B1 (en) | 2011-11-23 |
| PT1940789E (pt) | 2012-02-01 |
| PL1940789T3 (pl) | 2012-04-30 |
| BRPI0619331A2 (pt) | 2011-09-27 |
| HK1118549A1 (en) | 2009-02-13 |
| US20080281102A1 (en) | 2008-11-13 |
| SI1940789T1 (sl) | 2012-03-30 |
| CY1112533T1 (el) | 2015-12-09 |
| ATE534629T1 (de) | 2011-12-15 |
| US7847105B2 (en) | 2010-12-07 |
| KR20080068084A (ko) | 2008-07-22 |
| IL190971A0 (en) | 2008-12-29 |
| AU2006305842A1 (en) | 2007-05-03 |
| EP1940789A1 (en) | 2008-07-09 |
| ZA200804521B (en) | 2009-04-29 |
| WO2007051081A8 (en) | 2010-12-16 |
| EA200801176A1 (ru) | 2009-02-27 |
| DK1940789T3 (da) | 2012-03-19 |
| WO2007051081B1 (en) | 2007-07-19 |
| NO20082243L (no) | 2008-07-21 |
| RS52100B (en) | 2012-06-30 |
| CN101365679A (zh) | 2009-02-11 |
| CA2627046A1 (en) | 2007-05-03 |
| HRP20120058T1 (hr) | 2012-02-29 |
| CA2627046C (en) | 2015-09-15 |
| IL190971A (en) | 2013-02-28 |
| ES2375843T3 (es) | 2012-03-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101365679B (zh) | 制备cc-1065类似物的方法和化合物 | |
| US20230143751A1 (en) | Aromatic Compound And Use Thereof In Preparing Antineoplastic Drugs | |
| EP1948242B9 (en) | Cytotoxic compounds | |
| CN104109149B (zh) | 氘代的二氨基嘧啶化合物以及包含该化合物的药物组合物 | |
| CN102448951B (zh) | 丙酮酸激酶m2调节剂、治疗组合物和相关使用方法 | |
| KR20200064059A (ko) | 프로그램가능한 수지상 약물 | |
| JP2015078232A (ja) | 治療組成物および関連する使用方法 | |
| CN101778629A (zh) | 用作激酶调节剂的取代的吡咯并吡啶和吡唑并吡啶化合物 | |
| CN111362967B (zh) | 苯并氧杂二氮杂十四碳烯衍生物及其用途 | |
| EA016577B1 (ru) | Конъюгаты антитело-лекарство и их применение | |
| EA017196B1 (ru) | Цитотоксические агенты, включающие новые производные томаймицина, конъюгаты, способы получения конъюгатов, фармацевтическая композиция, включающая конъюгат, и их терапевтическое применение | |
| AU2004215428A1 (en) | Aminoheteroaryl compounds as protein kinase inhibitors | |
| JP2022515335A (ja) | 置換ピラゾロ［１，５－ａ］ピリジン化合物、該化合物を含む組成物およびその使用 | |
| CN114760994A (zh) | HIF-2α的抑制剂 | |
| JP2001504857A (ja) | ３−ピリジルエナンチオマーおよび鎮痛薬としてのその使用 | |
| JP7096817B2 (ja) | 三環式複素環式誘導体及びその使用 | |
| UA116534C2 (uk) | Піразолопіримідинілові інгібітори убіквітинактивуючого ферменту | |
| CA3083616A1 (en) | Myst family histone acetyltransferase inhibitors | |
| CN101193877A (zh) | 造血系统肿瘤治疗剂 | |
| US8952002B2 (en) | Aminoheteroaryl compounds and preparation method and use thereof | |
| ES2893006T3 (es) | 1-(4-amino-5-bromo-6-(1 H-pirazol-1-il)pirimidin-2-il)-1 H-pirazol-4-ol y su uso en el tratamiento del cáncer | |
| EP3325454A1 (en) | Deuterated meclizine | |
| CN1997402B (zh) | 化学连接基团及其缀合物 | |
| CN108602834B (zh) | 一种布鲁顿酪氨酸激酶抑制剂 | |
| CN113354630A (zh) | 一种5,6-二氢苯并[h]喹唑啉类化合物及其应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20130724 Address after: new jersey Patentee after: MEDAREX,INC Address before: American New Jersey Patentee before: Medarex Inc. |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20161019 Address after: new jersey Patentee after: E.R. expensive precious & Sheng Si limited liability company is executed Address before: new jersey Patentee before: MEDAREX,INC |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121114 Termination date: 20161018 |