HRP20040043A2 - Dolastatin 10 derivatives - Google Patents
Dolastatin 10 derivatives Download PDFInfo
- Publication number
- HRP20040043A2 HRP20040043A2 HR20040043A HRP20040043A HRP20040043A2 HR P20040043 A2 HRP20040043 A2 HR P20040043A2 HR 20040043 A HR20040043 A HR 20040043A HR P20040043 A HRP20040043 A HR P20040043A HR P20040043 A2 HRP20040043 A2 HR P20040043A2
- Authority
- HR
- Croatia
- Prior art keywords
- methyl
- butyl
- propyl
- methoxy
- carbamoyl
- Prior art date
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- OFDNQWIFNXBECV-VFSYNPLYSA-N dolastatin 10 Chemical class CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C=1SC=CN=1)CC1=CC=CC=C1 OFDNQWIFNXBECV-VFSYNPLYSA-N 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 218
- -1 carbamoyloxy Chemical group 0.000 claims description 203
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 125000001424 substituent group Chemical group 0.000 claims description 53
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 44
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 42
- 229910052736 halogen Chemical group 0.000 claims description 39
- 150000002367 halogens Chemical group 0.000 claims description 39
- 125000003545 alkoxy group Chemical group 0.000 claims description 37
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- 206010028980 Neoplasm Diseases 0.000 claims description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 29
- 238000002360 preparation method Methods 0.000 claims description 26
- 125000004414 alkyl thio group Chemical group 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 22
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 21
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 21
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 19
- 201000011510 cancer Diseases 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
- 125000004442 acylamino group Chemical group 0.000 claims description 11
- 125000006239 protecting group Chemical group 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 8
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 8
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical group C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 6
- UJJMBYCPDLMLTD-UHFFFAOYSA-N N-[1-[[3-methoxy-5-methyl-1-[2-[3-[(1-methylsulfanyl-2-phenylethyl)amino]-3-oxopropyl]pyrrolidin-1-yl]-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]-3-methyl-2-(methylamino)butanamide Chemical compound CCC(C)C(C(CC(=O)N1CCCC1CCC(=O)NC(CC1=CC=CC=C1)SC)OC)N(C)C(=O)C(NC(=O)C(NC)C(C)C)C(C)C UJJMBYCPDLMLTD-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 5
- XRLOGWLEHBAMOF-UHFFFAOYSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-N-[1-[2-[3-[[1-(2-hydroxyethylsulfanyl)-2-phenylethyl]amino]-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide Chemical compound CCC(C)C(C(CC(=O)N1CCCC1CCC(=O)NC(CC1=CC=CC=C1)SCCO)OC)N(C)C(=O)C(NC(=O)C(C(C)C)N(C)C)C(C)C XRLOGWLEHBAMOF-UHFFFAOYSA-N 0.000 claims description 5
- KKZIZHSDEBJQFG-UHFFFAOYSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-n-[1-[2-[1-ethylsulfanyl-3-[2-(3-hydroxyphenyl)ethylamino]-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-n,3-dimethylbutanamide Chemical compound C1CCN(C(=O)CC(OC)C(C(C)CC)N(C)C(=O)C(NC(=O)C(C(C)C)N(C)C)C(C)C)C1C(SCC)C(C)C(=O)NCCC1=CC=CC(O)=C1 KKZIZHSDEBJQFG-UHFFFAOYSA-N 0.000 claims description 5
- MXERUZYPBDNRSK-UHFFFAOYSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-n-[1-[2-[3-[2-(3-hydroxyphenyl)ethylamino]-2-methyl-1-methylsulfanyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-n,3-dimethylbutanamide Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)CC)C(OC)CC(=O)N1CCCC1C(SC)C(C)C(=O)NCCC1=CC=CC(O)=C1 MXERUZYPBDNRSK-UHFFFAOYSA-N 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 5
- ZODZAMGATMBGTR-UHFFFAOYSA-N N-[1-[[1-[2-[3-[(1-ethylsulfanyl-2-phenylethyl)amino]-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]-3-methyl-2-(methylamino)butanamide Chemical compound CCSC(CC1=CC=CC=C1)NC(=O)CCC1CCCN1C(=O)CC(OC)C(C(C)CC)N(C)C(=O)C(NC(=O)C(NC)C(C)C)C(C)C ZODZAMGATMBGTR-UHFFFAOYSA-N 0.000 claims description 5
- 125000001769 aryl amino group Chemical group 0.000 claims description 5
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 238000009833 condensation Methods 0.000 claims description 5
- 230000005494 condensation Effects 0.000 claims description 5
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 208000020816 lung neoplasm Diseases 0.000 claims description 5
- KHUUDBXXZJCVTL-UHFFFAOYSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-n-[1-[2-[3-[2-(2-hydroxyphenyl)ethylamino]-1-methylsulfanyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-n,3-dimethylbutanamide Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)CC)C(OC)CC(=O)N1CCCC1C(SC)CC(=O)NCCC1=CC=CC=C1O KHUUDBXXZJCVTL-UHFFFAOYSA-N 0.000 claims description 4
- TWYMOCZMECAMCV-UHFFFAOYSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-n-[3-methoxy-5-methyl-1-[2-[1-methylsulfanyl-3-oxo-3-(2-pyridin-3-ylethylamino)propyl]pyrrolidin-1-yl]-1-oxoheptan-4-yl]-n,3-dimethylbutanamide Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)CC)C(OC)CC(=O)N1CCCC1C(SC)CC(=O)NCCC1=CC=CN=C1 TWYMOCZMECAMCV-UHFFFAOYSA-N 0.000 claims description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
- YOPKFWATQGUYGD-UHFFFAOYSA-N 3-[1-[4-[[2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methoxy-5-methylheptanoyl]pyrrolidin-2-yl]-3-methylsulfanylpropanoic acid Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)CC)C(OC)CC(=O)N1CCCC1C(CC(O)=O)SC YOPKFWATQGUYGD-UHFFFAOYSA-N 0.000 claims description 4
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 4
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- NIRXJUYBAYTMIZ-CWQSAYAXSA-N N-[1-[2-[3-[[(1R)-1-tert-butylsulfanyl-2-phenylethyl]amino]-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-N,3-dimethylbutanamide Chemical compound CCC(C)C(C(CC(=O)N1CCCC1CCC(=O)N[C@@H](CC1=CC=CC=C1)SC(C)(C)C)OC)N(C)C(=O)C(NC(=O)C(C(C)C)N(C)C)C(C)C NIRXJUYBAYTMIZ-CWQSAYAXSA-N 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 4
- 201000010881 cervical cancer Diseases 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- KWBIXTIBYFUAGV-UHFFFAOYSA-N ethylcarbamic acid Chemical compound CCNC(O)=O KWBIXTIBYFUAGV-UHFFFAOYSA-N 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000003395 phenylethylamino group Chemical group [H]N(*)C([H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- IYUPHNXLARLFHK-GNXDQWMXSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-N-[1-[2-[3-[[(1S)-1-(4-hydroxyphenyl)sulfanyl-2-phenylethyl]amino]-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide Chemical compound C(C)(CC)C(C(CC(=O)N1C(CCC1)CCC(N[C@H](CC1=CC=CC=C1)SC1=CC=C(C=C1)O)=O)OC)N(C(=O)C(C(C)C)NC(C(C(C)C)N(C)C)=O)C IYUPHNXLARLFHK-GNXDQWMXSA-N 0.000 claims description 3
- GEHZHCFDPWGZNJ-UHFFFAOYSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-N-[1-[2-[3-[[1-(3-hydroxyphenyl)sulfanyl-2-phenylethyl]amino]-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide Chemical compound C(C)(CC)C(C(CC(=O)N1C(CCC1)CCC(NC(CC1=CC=CC=C1)SC1=CC(=CC=C1)O)=O)OC)N(C(=O)C(C(C)C)NC(C(C(C)C)N(C)C)=O)C GEHZHCFDPWGZNJ-UHFFFAOYSA-N 0.000 claims description 3
- ZXESHIUVGWQOGO-UHFFFAOYSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-N-[1-[2-[3-[[1-(furan-2-ylmethylsulfanyl)-2-phenylethyl]amino]-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide Chemical compound CCC(C)C(C(CC(=O)N1CCCC1CCC(=O)NC(CC1=CC=CC=C1)SCC1=CC=CO1)OC)N(C)C(=O)C(NC(=O)C(C(C)C)N(C)C)C(C)C ZXESHIUVGWQOGO-UHFFFAOYSA-N 0.000 claims description 3
- BGDDJBIDUBFBPL-UHFFFAOYSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-N-[3-methoxy-5-methyl-1-oxo-1-[2-[3-oxo-3-(2-phenylethylamino)-2-(1-phenylethylsulfanyl)propyl]pyrrolidin-1-yl]heptan-4-yl]-N,3-dimethylbutanamide Chemical compound C(C)(CC)C(C(CC(N1C(CCC1)CC(SC(C)C1=CC=CC=C1)C(NCCC1=CC=CC=C1)=O)=O)OC)N(C(=O)C(C(C)C)NC(C(C(C)C)N(C)C)=O)C BGDDJBIDUBFBPL-UHFFFAOYSA-N 0.000 claims description 3
- OOXJHBGWHMQRNQ-UHFFFAOYSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-N-[3-methoxy-5-methyl-1-oxo-1-[2-[3-oxo-3-[(1-pentylsulfanyl-2-phenylethyl)amino]propyl]pyrrolidin-1-yl]heptan-4-yl]-N,3-dimethylbutanamide Chemical compound CCCCCSC(CC1=CC=CC=C1)NC(=O)CCC1CCCN1C(=O)CC(OC)C(C(C)CC)N(C)C(=O)C(NC(=O)C(C(C)C)N(C)C)C(C)C OOXJHBGWHMQRNQ-UHFFFAOYSA-N 0.000 claims description 3
- ZWDUDEYRRNPVQF-UHFFFAOYSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-n-[1-[2-[3-[2-(3-hydroxyphenyl)ethylamino]-1-methylsulfanyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-n,3-dimethylbutanamide Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)CC)C(OC)CC(=O)N1CCCC1C(SC)CC(=O)NCCC1=CC=CC(O)=C1 ZWDUDEYRRNPVQF-UHFFFAOYSA-N 0.000 claims description 3
- GPFGIXVDYZCJBN-UHFFFAOYSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-n-[3-methoxy-5-methyl-1-[2-[1-methylsulfanyl-3-oxo-3-(2-thiophen-2-ylethylamino)propyl]pyrrolidin-1-yl]-1-oxoheptan-4-yl]-n,3-dimethylbutanamide Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)CC)C(OC)CC(=O)N1CCCC1C(SC)CC(=O)NCCC1=CC=CS1 GPFGIXVDYZCJBN-UHFFFAOYSA-N 0.000 claims description 3
- XICREFSYSCYVRC-UHFFFAOYSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-n-[3-methoxy-5-methyl-1-[2-[1-methylsulfanyl-3-oxo-3-(pyridin-4-ylmethylamino)propyl]pyrrolidin-1-yl]-1-oxoheptan-4-yl]-n,3-dimethylbutanamide Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)CC)C(OC)CC(=O)N1CCCC1C(SC)CC(=O)NCC1=CC=NC=C1 XICREFSYSCYVRC-UHFFFAOYSA-N 0.000 claims description 3
- PWJLIMNTXNTEIB-UHFFFAOYSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-n-[3-methoxy-5-methyl-1-[2-[3-[methyl(2-phenylethyl)amino]-1-methylsulfanyl-3-oxopropyl]pyrrolidin-1-yl]-1-oxoheptan-4-yl]-n,3-dimethylbutanamide Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)CC)C(OC)CC(=O)N1CCCC1C(SC)CC(=O)N(C)CCC1=CC=CC=C1 PWJLIMNTXNTEIB-UHFFFAOYSA-N 0.000 claims description 3
- JCMHQJKNNNDDAM-UHFFFAOYSA-N 2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-n-[3-methoxy-5-methyl-1-oxo-1-[2-[3-oxo-3-(2-phenylethylamino)-1-phenylsulfanylpropyl]pyrrolidin-1-yl]heptan-4-yl]-n,3-dimethylbutanamide Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)CC)C(OC)CC(=O)N1CCCC1C(SC=1C=CC=CC=1)CC(=O)NCCC1=CC=CC=C1 JCMHQJKNNNDDAM-UHFFFAOYSA-N 0.000 claims description 3
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- MRFMGAGBQFQZGP-UHFFFAOYSA-N CCC(C)C(C(CC(=O)N1CCCC1CCC(=O)NC(CC1=CC=CC=C1)SC1=CC=C(F)C=C1)OC)N(C)C(=O)C(NC(=O)C(C(C)C)N(C)C)C(C)C Chemical compound CCC(C)C(C(CC(=O)N1CCCC1CCC(=O)NC(CC1=CC=CC=C1)SC1=CC=C(F)C=C1)OC)N(C)C(=O)C(NC(=O)C(C(C)C)N(C)C)C(C)C MRFMGAGBQFQZGP-UHFFFAOYSA-N 0.000 claims description 3
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- NIRXJUYBAYTMIZ-UHFFFAOYSA-N N-[1-[2-[3-[(1-tert-butylsulfanyl-2-phenylethyl)amino]-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-N,3-dimethylbutanamide Chemical compound C(C)(CC)C(C(CC(=O)N1C(CCC1)CCC(NC(CC1=CC=CC=C1)SC(C)(C)C)=O)OC)N(C(=O)C(C(C)C)NC(C(C(C)C)N(C)C)=O)C NIRXJUYBAYTMIZ-UHFFFAOYSA-N 0.000 claims description 3
- VJSGUGPEPUAPQQ-UHFFFAOYSA-N N-[1-[2-[3-[[1-(4-tert-butylphenyl)sulfanyl-2-phenylethyl]amino]-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-2-[[2-(dimethylamino)-3-methylbutanoyl]amino]-N,3-dimethylbutanamide Chemical compound C(C)(CC)C(C(CC(=O)N1C(CCC1)CCC(NC(CC1=CC=CC=C1)SC1=CC=C(C=C1)C(C)(C)C)=O)OC)N(C(=O)C(C(C)C)NC(C(C(C)C)N(C)C)=O)C VJSGUGPEPUAPQQ-UHFFFAOYSA-N 0.000 claims description 3
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 239000003744 tubulin modulator Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil 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
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- 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
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0205—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Crystallography & Structural Chemistry (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP01117410 | 2001-07-19 | ||
PCT/EP2002/007931 WO2003008378A1 (en) | 2001-07-19 | 2002-07-17 | Dolastatin 10 derivatives |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20040043A2 true HRP20040043A2 (en) | 2004-08-31 |
Family
ID=8178073
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20040043A HRP20040043A2 (en) | 2001-07-19 | 2004-01-19 | Dolastatin 10 derivatives |
Country Status (30)
Country | Link |
---|---|
US (1) | US6737409B2 (es) |
EP (1) | EP1412328B1 (es) |
JP (1) | JP2004534859A (es) |
KR (2) | KR20060057652A (es) |
CN (1) | CN1553897A (es) |
AR (1) | AR036175A1 (es) |
AT (1) | ATE341537T1 (es) |
BR (1) | BR0211289A (es) |
CA (1) | CA2453987A1 (es) |
CO (1) | CO5550462A2 (es) |
DE (1) | DE60215179T2 (es) |
DK (1) | DK1412328T3 (es) |
ES (1) | ES2272763T3 (es) |
GT (1) | GT200200154A (es) |
HR (1) | HRP20040043A2 (es) |
HU (1) | HUP0401253A2 (es) |
IL (1) | IL159890A0 (es) |
MX (1) | MXPA04000577A (es) |
MY (1) | MY127718A (es) |
NO (1) | NO20040198L (es) |
NZ (1) | NZ530655A (es) |
PA (1) | PA8551001A1 (es) |
PE (1) | PE20030258A1 (es) |
PL (1) | PL367682A1 (es) |
PT (1) | PT1412328E (es) |
RU (1) | RU2296750C2 (es) |
SI (1) | SI1412328T1 (es) |
UY (1) | UY27388A1 (es) |
WO (1) | WO2003008378A1 (es) |
ZA (1) | ZA200400334B (es) |
Families Citing this family (36)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7256257B2 (en) | 2001-04-30 | 2007-08-14 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
US7064211B2 (en) | 2002-03-22 | 2006-06-20 | Eisai Co., Ltd. | Hemiasterlin derivatives and uses thereof |
IL163868A0 (en) * | 2002-03-22 | 2005-12-18 | Eisai Co Ltd | Hermiasterlin derivatives and uses thereof |
US7659241B2 (en) | 2002-07-31 | 2010-02-09 | Seattle Genetics, Inc. | Drug conjugates and their use for treating cancer, an autoimmune disease or an infectious disease |
BR122018071808B8 (pt) | 2003-11-06 | 2020-06-30 | Seattle Genetics Inc | conjugado |
US7312343B2 (en) * | 2004-06-02 | 2007-12-25 | Hoffmann-La Roche Inc. | Synthesis of α-amino-β-alkoxy-carboxylic acid esters |
AU2005332660A1 (en) | 2004-11-12 | 2006-12-14 | Seattle Genetics, Inc. | Auristatins having an aminobenzoic acid unit at the N terminus |
MX2007006746A (es) * | 2004-12-13 | 2007-07-09 | Hoffmann La Roche | Proceso novedoso para la manufactura de derivados del acido 3-pirrolidin-2-il-propionico. |
JP2008523002A (ja) * | 2004-12-13 | 2008-07-03 | エフ.ホフマン−ラ ロシュ アーゲー | 少なくとも1つのドラスタチン10誘導体を含有する新規な医薬組成物 |
US20060189893A1 (en) * | 2005-01-06 | 2006-08-24 | Diamics, Inc. | Systems and methods for detecting abnormal cells |
US20060161076A1 (en) * | 2005-01-06 | 2006-07-20 | Diamics, Inc. | Systems and methods for collection of cell clusters |
MX2007008349A (es) * | 2005-01-13 | 2007-07-25 | Hoffmann La Roche | Nueva sintesis de una etapa de aminas disustituidas utiles. |
EP1883627B1 (en) | 2005-05-18 | 2018-04-18 | Pharmascience Inc. | Bir domain binding compounds |
WO2007008848A2 (en) * | 2005-07-07 | 2007-01-18 | Seattle Genetics, Inc. | Monomethylvaline compounds having phenylalanine carboxy modifications at the c-terminus |
WO2007008603A1 (en) | 2005-07-07 | 2007-01-18 | Seattle Genetics, Inc. | Monomethylvaline compounds having phenylalanine side-chain modifications at the c-terminus |
US7750116B1 (en) | 2006-02-18 | 2010-07-06 | Seattle Genetics, Inc. | Antibody drug conjugate metabolites |
NZ572836A (en) | 2006-05-16 | 2011-12-22 | Pharmascience Inc | Iap bir domain binding compounds |
US20080003652A1 (en) * | 2006-06-28 | 2008-01-03 | Hans Iding | Novel enzymatic process for the manufacture of Boc-Dap-Oh priority to related application(s) |
CR20190516A (es) | 2007-07-16 | 2020-02-18 | Genentech Inc | ANTICUERPOS ANTI-CD79B E INMUNOCONJUGADOS (Divisional 2015-0040) |
PE20090481A1 (es) | 2007-07-16 | 2009-05-18 | Genentech Inc | Anticuerpos anti-cd79b e inmunoconjugados humanizados y metodos de uso |
CN101981055B (zh) | 2008-01-31 | 2016-03-09 | 健泰科生物技术公司 | 抗cd79b抗体和免疫偶联物及使用方法 |
PL2842575T3 (pl) | 2008-03-18 | 2018-02-28 | Seattle Genetics, Inc. | Koniugaty aurystatyny lek łącznik |
WO2011100403A1 (en) | 2010-02-10 | 2011-08-18 | Immunogen, Inc | Cd20 antibodies and uses thereof |
SG10201501095WA (en) | 2010-02-12 | 2015-04-29 | Pharmascience Inc | Iap bir domain binding compounds |
ES2528956T3 (es) | 2010-06-10 | 2015-02-13 | Seattle Genetics, Inc. | Nuevos derivados de auristatina y su uso |
CN103379912B (zh) | 2010-09-29 | 2016-03-16 | 西雅图基因公司 | 正羧烷基耳他汀及其应用 |
ES2543888T3 (es) * | 2011-03-16 | 2015-08-25 | Seattle Genetics, Inc. | N-carboxialquil-auristatinas y su utilización |
MX371526B (es) * | 2011-05-27 | 2020-01-31 | Ambrx Inc | Composiciones que contienen, metodos que incluyen, y usos de derivados de dolastatina enlazados a aminoacidos no naturales. |
BR112013030372A2 (pt) | 2011-05-27 | 2016-08-30 | Ambrx Inc | composições contendo, métodos envolvendo, e usos de derivados de dolastatin ligados ao aminoácido não natural |
JP6089108B2 (ja) | 2012-09-20 | 2017-03-01 | セルトリオン, インク. | ドラスタチン10誘導体、その製造方法およびそれを含む抗癌剤組成物 |
WO2015095953A1 (en) | 2013-12-27 | 2015-07-02 | The Centre For Drug Research And Development | Sulfonamide-containing linkage systems for drug conjugates |
PT3262071T (pt) | 2014-09-23 | 2020-06-16 | H Hoffnabb La Roche Ag | Métodos de utilização de imunoconjugados anti-cd79b |
CN105949277B (zh) * | 2015-05-05 | 2019-03-01 | 成都永泰诺科技有限公司 | 一种抗肿瘤化合物及其用途 |
US10792365B2 (en) * | 2016-03-29 | 2020-10-06 | Toray Industries, Inc. | Peptide derivative and use thereof |
CN109021065B (zh) * | 2017-06-08 | 2021-10-01 | 复旦大学 | 一种制备海兔毒素Dolastatin10的方法 |
AU2022338463A1 (en) | 2021-09-03 | 2024-03-21 | Toray Industries, Inc. | Pharmaceutical composition for cancer treatment and/or prevention |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6323315B1 (en) | 1999-09-10 | 2001-11-27 | Basf Aktiengesellschaft | Dolastatin peptides |
-
2002
- 2002-07-15 US US10/195,698 patent/US6737409B2/en not_active Expired - Fee Related
- 2002-07-17 UY UY27388A patent/UY27388A1/es not_active Application Discontinuation
- 2002-07-17 AR ARP020102678A patent/AR036175A1/es not_active Application Discontinuation
- 2002-07-17 DK DK02764710T patent/DK1412328T3/da active
- 2002-07-17 HU HU0401253A patent/HUP0401253A2/hu unknown
- 2002-07-17 KR KR1020067008692A patent/KR20060057652A/ko not_active Application Discontinuation
- 2002-07-17 SI SI200230447T patent/SI1412328T1/sl unknown
- 2002-07-17 WO PCT/EP2002/007931 patent/WO2003008378A1/en active IP Right Grant
- 2002-07-17 NZ NZ530655A patent/NZ530655A/en unknown
- 2002-07-17 KR KR1020047000854A patent/KR100611540B1/ko not_active IP Right Cessation
- 2002-07-17 PT PT02764710T patent/PT1412328E/pt unknown
- 2002-07-17 MX MXPA04000577A patent/MXPA04000577A/es active IP Right Grant
- 2002-07-17 AT AT02764710T patent/ATE341537T1/de not_active IP Right Cessation
- 2002-07-17 PL PL02367682A patent/PL367682A1/xx not_active Application Discontinuation
- 2002-07-17 JP JP2003513938A patent/JP2004534859A/ja active Pending
- 2002-07-17 CN CNA028177622A patent/CN1553897A/zh active Pending
- 2002-07-17 RU RU2004105145/04A patent/RU2296750C2/ru not_active IP Right Cessation
- 2002-07-17 EP EP02764710A patent/EP1412328B1/en not_active Expired - Lifetime
- 2002-07-17 CA CA002453987A patent/CA2453987A1/en not_active Abandoned
- 2002-07-17 ES ES02764710T patent/ES2272763T3/es not_active Expired - Lifetime
- 2002-07-17 MY MYPI20022704A patent/MY127718A/en unknown
- 2002-07-17 IL IL15989002A patent/IL159890A0/xx unknown
- 2002-07-17 BR BR0211289-2A patent/BR0211289A/pt not_active IP Right Cessation
- 2002-07-17 DE DE60215179T patent/DE60215179T2/de not_active Expired - Fee Related
- 2002-07-18 PA PA20028551001A patent/PA8551001A1/es unknown
- 2002-07-18 GT GT200200154A patent/GT200200154A/es unknown
- 2002-07-19 PE PE2002000643A patent/PE20030258A1/es not_active Application Discontinuation
-
2004
- 2004-01-15 ZA ZA2004/00334A patent/ZA200400334B/en unknown
- 2004-01-16 NO NO20040198A patent/NO20040198L/no not_active Application Discontinuation
- 2004-01-19 HR HR20040043A patent/HRP20040043A2/hr not_active Application Discontinuation
- 2004-01-20 CO CO04003736A patent/CO5550462A2/es not_active Application Discontinuation
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